ARTICLE | doi:10.20944/preprints202208.0182.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: oncology; nutrition; supportive care; integrative oncology; metabolism; mitochondria
Online: 9 August 2022 (15:02:55 CEST)
Cancer-related fatigue is a common, burdensome symptom of cancer and side-effect of chemotherapy. While a Mediterranean Diet (MedDiet) promotes energy metabolism and overall health, its effects on cancer-related fatigue remain unknown. In a randomized controlled trial, we evaluated a rigorous MedDiet intervention for feasibility and safety as well as preliminary effects on cancer-related fatigue and metabolism compared to usual care. Participants had stage I-III cancer and at least 6 weeks of chemotherapy scheduled. After baseline assessments, randomization occurred 2:1, MedDiet:usual care. Measures were collected at baseline, week 4, and week 8 including MedDiet adherence, dietary intake, and blood-based metabolic measures. Mitochondrial respiration from freshly isolated T cells was measured at baseline and 4 weeks. Participants (n=33) were 51.0±14.6 years old, 94% were female, and 91% were being treated for breast cancer. The study was feasible, with 100% completing the study and >70% increasing their MedDiet adherence at 4 and 8 weeks compared to baseline. Overall, the MedDiet intervention vs. usual care had a small-moderate effect on change in fatigue at weeks 4 and 8. For those with a baseline MedDiet score<5 (n=21), the MedDiet intervention had a moderate-large effect of 0.67 and 0.48 at weeks 4 and 8, respectively. The MedDiet did not affect blood-based lipids, though it had a beneficial effect on fructosamine (ES= -0.55). Fatigue was associated with mitochondrial dysfunction including lower basal respiration, maximal respiration, and spare capacity (p<0.05 for FACIT-F fatigue subscale and BFI, usual fatigue). In conclusion, the MedDiet was feasible and attenuated cancer-related fatigue among patients undergoing chemotherapy, especially those with lower MedDiet scores at baseline.
REVIEW | doi:10.20944/preprints201812.0006.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: oncology; ectopic RAS cancer cells; epigenetic stimulation PAC in oncology
Online: 3 December 2018 (04:27:03 CET)
Analyzed the literature devoted to the changes in the expression of the RAS proteins of cancer cells. A brief review of protein expression dynamics PAC in malignant tumors and the possible role of epigenetic mechanisms in these processes. Through research epigenetic mechanisms state for cancer have been developed principally new techniques for their correction, based on the use of selective regulators systems covalent modification-histone proteins (for example, deacetylase inhibitor) and microRNA synthesis technologies. Literature data show promising pharmacological correction epigenetic modification of chromatin in the treatment of cancer.
REVIEW | doi:10.20944/preprints202208.0285.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Breast; cancer; metastasis; oncology
Online: 16 August 2022 (09:52:17 CEST)
Regardless of the advances in our ability to detect early and treat breast cancer, it is still one of the common types of malignancy worldwide, with the majority of patients decease upon metastatic disease. Nevertheless, due to these advances, we have extensively characterized the drivers and molecular profiling of breast cancer and further dividing it into subtypes. These subgroups are based on immunohistological markers (Estrogen Receptor-ER, Progesterone Receptor-PR and Human Epidermal Growth Factor Receptor 2-HER-2) and transcriptomic signatures, with distinct therapeutic approaches and regiments. These therapeutic approaches include targeted therapy (HER-2+), endocrine therapy (HR+) or chemotherapy (TNBC) with optional combination radiotherapy, depending on clinical stage. Technological and scientific advances in the identification of molecular pathways that contribute to therapy-resistance and establishment of metastatic disease, have provided the rationale for revolutionary targeted approaches against Cyclin-Dependent Kinases 4/6 (CDK4/6), PI3 Kinase (PI3K), Poly ADP Ribose Polymerase (PARP) and Programmed Death-Ligand 1 (PD-L1), among others. In this review, we focus on the comprehensive overview of epidemiology and current standard of care treatment of metastatic breast cancer, along with ongoing clinical trials. Towards this goal, we utilized available literature from PubMed and ongoing clinical trial information from clinicaltrials.gov to reflect the up to date and future treatment options for metastatic breast cancer.
ARTICLE | doi:10.20944/preprints202004.0527.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Radiation oncology; COVID-19; Radiation therapist COVID-19 policy; Radiation oncology departmental Policy
Online: 30 April 2020 (11:02:58 CEST)
Abstract: This brief policy is written after experience treating COVID-19 positive radiation therapy patients to reduce risk to therapy staff and patients in radiation oncology department. It is important to prioritize the safety of staff and non-infected patients while ensuring the continuation of radiation oncology services. Radiation therapists have sustained contact with covid-19 patients in an enclosed vault. Protocols for correct disinfecting of equipment and room and therapists following methods for less transmission of virus is crucial. This policy covers prevention methods from COVID-19 transmission from patient to patient, patient to staff, staff to patient and staff to staff as follows A.Risk reduction by screening and preparing staff and rooms B.Radiation Therapist Policy for COVID-19 positive patient with CCC (Critical Cancer Care)
REVIEW | doi:10.20944/preprints202309.0834.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: atrial fibrillation; management; cardio-oncology
Online: 13 September 2023 (07:27:42 CEST)
Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with can-cer. Indeed, cancer patients have a significantly higher incidence of AF than that ob-served in the general population. A reciprocal relationship between these two diseases has been observed, as much as some assume AF as a marker for occult cancer screen-ing, especially in older adults. The pathophysiological mechanisms are many and var-ied, including the underlying pro-inflammatory state, specific treatments (chemo and radiotherapy) and surgery. The therapeutic management of patients with cancer and AF involves the same rhythm and frequency control strategies as the general popula-tion; however, the numerous interactions with chemotherapeutics, which lead to a sig-nificant increase in side effects, as well as the extreme fragility of the patient should be considered. Anticoagulant therapy is also a complex challenge to address, as bleeding and stroke risk scores have not been fully assessed in this subpopulation. Furthermore, in large studies establishing the efficacy of direct oral anticoagulants (DOACs), cancer patients have been underrepresented. In this review, we elaborate on mechanisms linking AF to cancer patients with a particular focus on therapeutic challenges in this population.
HYPOTHESIS | doi:10.20944/preprints202304.0041.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Hepatology; Oncology; Biomarkers; Hepatocellular Carcinoma
Online: 4 April 2023 (09:28:52 CEST)
In this study, novel biomarkers in Blood Mononuclear Cells (PBMCs) of Hepatocellular Carcinoma (HCC) patients were identified through microarray data analysis. The problem that prompted the study was the lack of reliable biomarkers for early diagnosis and monitoring of HCC. The purpose of this study was to discover potential biomarkers in PBMCs of HCC patients that can be used for early diagnosis and monitoring of the disease. The main hypothesis was that there are genes that are overexpressed in PBMC of HCC patients compared to healthy individuals. The results showed that genes HBB, WBP2, HBA2, and HBA1 were overexpressed in PBMCs of HCC patients. Additionally, nine genes were found to be upregulated in HCC patients and had a relation between KEGG pathways of RA, suggesting a link between the two diseases. These genes are TLR4, IL1B, CXCL5, IL11, HLA-DQA1, HLA-DRA, LBT, ATP6V1B2 and ATP6V1C1. The Gene ontology analysis revealed biological processes used in the process of how these genes play a role in development of HCC. In conclusion, this study identified potential biomarkers in PBMC of HCC patients that can aid in early diagnosis and monitoring of the disease. The findings of this study have important implications for improving the clinical management of HCC patients.
ARTICLE | doi:10.20944/preprints201911.0342.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: spirometry; VAS Pain; oncology rehabilitation
Online: 27 November 2019 (09:53:58 CET)
The aim of the following paper was to determine the influence of soft tissue therapy on respiratory efficiency and chest mobility of women suffering from breast cancer. This study was a controlled randomized trial. Tests were carried out in a group of patients (n=49), who were hospitalized in the Province Polyclinic Hospital, Konin, Poland. In the study group, irrespective of the standard physical therapy program, an additional therapy program was run. The program consisted in applying specific techniques of soft tissue treatment. All patients in the each term were subject to pulmonary function test, chest mobility and pain assessment. Statistical analysis of the obtained results of spirometry and chest mobility assessment have revealed no differences in the analyzed parameters between the examined groups in the period of joint therapeutic treatment. In the period between the 3rd examination and the end of the 11-month- rehabilitation treatment, statistically significant differences were observed in the analyzed spirometry parameters, however, there was no difference in the parameters describing airflow in small airways (MEF50,PEF) between individual groups, during consecutive examinations in the course of diversified therapeutic treatment. Chest mobility assessment of the patients, performed during diversified therapeutic treatment, revealed statistically significant differences between the groups. However, there was no difference between the examined groups, as far as pain sensation is concerned. Enhancing the regular rehabilitation program by including additional therapeutic methods, which are based on myofascial release and post-isometric relaxation techniques, had a beneficial effects regarding respiratory system efficiency.
REVIEW | doi:10.20944/preprints202306.1321.v1
Subject: Medicine And Pharmacology, Transplantation Keywords: Transplant Oncology; Liver Transplant; Gastrointestinal Malignancies
Online: 19 June 2023 (08:33:55 CEST)
Transplant oncology is a relatively new field in which transplantation is used to treat patients who would otherwise be unresectable. New anticancer treatment paradigms using tumor and transplant immunology and cancer immunogenomics are emerging. In turn, liver transplantation (LT) has become a potential therapy for certain patients with colorectal cancer (CRC) with liver metastasis, hepatocellular (HCC), cholangiocarcinoma (CCA), and metastatic neuroendocrine tumor (NET) to the liver. Although there are established criteria for LT in HCC, the evidence regarding LT as a treatment modality for certain gastrointestinal malignancies is still debated. The aim of this review is to highlight updates in the role of LT for certain malignancies, including HCC, metastatic CRC, hilar CCA, and neuroendocrine tumor (NET), as well as contextualize LT use and discuss controversies in transplant oncology.
ARTICLE | doi:10.20944/preprints202209.0012.v1
Subject: Engineering, Control And Systems Engineering Keywords: Computational Oncology; Cancer; Antifragility; Control Theory
Online: 1 September 2022 (07:45:27 CEST)
A therapy’s outcome is determined by a tumor’s response to treatment which, in turn, depends on multiple factors such as the severity of the disease and the strength of patient’s immune response. Gold standard cancer therapies are in most cases fragile when sought to break the ties to either tumor kill ratio or patient toxicity. Lately, research has shown that cancer therapy can be at most robust when handling adaptive drug resistance and immune escape patterns developed by evolving tumors. This is due to the stochastic and volatile nature of the interactions, at the tumor environment level, tissue vasculature, and immune landscape, induced by drugs. Herein, we explore the path towards antifragile therapy control, that generates treatment schemes that are not fragile but go beyond robustness. More precisely, we describe a first instantiation of a control-theoretic method to make therapy schemes cope with the systemic variability in the tumor–immune–drug interactions and gain more tumor kill with less patient toxicity. Considering the anti-symmetric interactions within a model of the tumor–immune–drug network, we introduce the antifragile control framework that demonstrates promising results in simulation. We evaluate our control strategy against state-of-the-art therapy schemes on various experiments and discuss the insights we gained on the potential that antifragile control could have in treatment design in clinical settings.
REVIEW | doi:10.20944/preprints202202.0078.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Cardiology; Oncology; CSC; TNBC; TGF-β
Online: 7 February 2022 (11:19:03 CET)
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. While there is immense focus on the development of novel therapies for TNBC treatment, a persistent and critical issue is the rate of heart failure and cardiomyopathy which is a leading cause of mortality and morbidity amongst cancer survivors. In this review, we highlight mechanisms of cardiotoxicity post-chemotherapeutic exposure, assess how this is assessed clinically and highlight the transforming growth factor-beta family (TGF-β) pathway and discuss its role as a mediator of cardiomyopathy. We highlight recent findings demonstrating TGF-β inhibition as a potent method to prevent cardiac re-modeling, fibrosis and cardiomyopathy. We describe how dysregulation of the TGF-β pathway is associated with negative patient outcomes across 32 types of cancer including TNBC. We then highlight how TGF-β modulation may be a potent method to target mesenchymal (CD44+/CD24-) and epithelial (ALDHhigh) cancer stem cell (CSC) populations in TNBC models. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to plasticity and differential regulation these populations remain difficult to target and persist as a major barrier barring successful therapy. TGF-β inhibition represents an intersection of two fields: cardiology and oncology. Through inhibiting cardiomyopathy, cardiac damage and heart failure may be prevented and through CSC targeting, patient prognosis may be improved. Together, both approaches, if successfully implemented would target the two greatest causes of cancer-related morbidity in patients and potentially lead to a breakthrough therapy.
REVIEW | doi:10.20944/preprints202102.0393.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Microbiome; Personalized Medicine; Integrative Oncology; Oncobiotic
Online: 17 February 2021 (13:29:27 CET)
Sound evidence recognizes the microbiota as one of the major players in human health and disease, including cancer. Every human being is an holobiont, a shared human and microbial ecosystem, in which microbial composition is individually set by behaviours and environmental factors during the first years of life. Thereafter it is modulated by diet, physical activity, emotions and drugs (in particularly antibiotics and chemotherapeutics). As a consequence, a shift in medicine is needed toward a more comprehensive practice that takes into account every individual's genoma and, in addition, his or her metagenome, known as microbiome: a "microbiota revolution". As regards breast cancer (BC), a clear link between microbiota and oncogenesis is still to be confirmed. Specific microbes display unique features regulating their host niche in a number of body sites, which can result in an increased risk of cancer; in addition, gut microbiota composition plays a role in immune modulation within the intestinal barrier, affecting local and systemic inflammation, recognized drivers of cancer. Moreover, part of the bacterial gene mass inside the gut, constituting the so called “estrobolome”, influences the sexual hormonal balance and subsequentely may impact on the onset, progression and treatment of hormonal dependent cancers. Microbiota is also clearly involved in modulating the response to anticancer treatments, and above all to the emerging immunotherapy. Based on these premises, the microbiome is becoming a potential target, in order to enhance efficacy of antitumoral treatments as well as to lower their toxicity. The complex scenario that links microbiome composition to oncogenesis and response to anticancer treatments defines the frames of a new “oncobiotic” perspective.
REVIEW | doi:10.20944/preprints202008.0528.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Hemangiosarcoma; neoplasia; oncology; metastasis; doxorubicin; hemoabdomen
Online: 24 August 2020 (10:08:43 CEST)
Canine Hemangiosarcoma (HSA) is a devastating cancer affecting blood vessels in numerous sites within the body that is primarily seen in middle to older aged dogs. It is marked by its rapid aggressive metastatic pathology that often results in a lack of apparent symptoms in early stages. In most cases, disease becomes apparent due to hemorrhagic events following the rupture of the malignant vascular cell structures that can capture and pool blood cells, resulting in necrosis of the affected tissues. The poor survival times in affected patients cause a hindrance to the ability to carry out large scale studies, leaving numerous knowledge gaps to be filled in future research. The pathologic similarities between this and human angiosarcoma (HA) provides the potential for translatable research to be carried out that would improve outcomes across species. Here, current knowledge is outlined in order to improve understanding HSA holistically and suggest future direction. Emphasis is placed on the potential to improve veterinary practices in ways that will improve the ability to quickly and accurately diagnose patients in order to establish better client communication and provide clarity in collaborating to create the best informed treatment plan possible.
ARTICLE | doi:10.20944/preprints202312.0124.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: palliative care; thoracic oncology; high-value care
Online: 4 December 2023 (03:54:29 CET)
Although cancer care is often contextualized in terms of survival, there are other important cancer care outcomes, such as quality of life and cost of care. The ASCO Value Framework assesses the value of cancer therapies not only in terms of survival but with consideration of quality of life and financial cost. Early palliative care for patients with advanced cancer is associated with improved quality of life, mood, symptoms, overall survival, and cost savings. While palliative care has been shown to have numerous benefits, the impact of real-world implementation of outpatient embedded palliative care on value-based metrics is not fully understood. We sought to describe the association of outpatient embedded palliative care in a multidisciplinary thoracic oncology clinic on inpatient value-based metrics. We performed a retrospective cohort study of 215 patients being treated for advanced thoracic malignancies with non-curative intent. We evaluated the association of outpatient embedded palliative care with inpatient clinical outcomes including emergency room visits, hospitalizations, intensive care unit admissions, hospital charges, as well as hospital quality metrics including 30-day readmissions, admissions within 30 days of death, inpatient mortality, and inpatient hospital charges. Outpatient embedded palliative care was associated with lower hospital charges per day ($3,807 versus $4,695, p=0.024). Furthermore, patients who received outpatient embedded palliative care had decreased hospital admissions within 30 days of death (O.R. 0.50; 95% CI 0.34, 0.74; P<0.001) and decreased inpatient mortality (O.R. 0.46; 95%CI 0.23, 0.94; p=0.032). Our study further supports that outpatient palliative care is a high-value intervention and alternative models of palliative care, including one embedded into a multidisciplinary thoracic oncology clinic, is associated with improved value-based metrics.
REVIEW | doi:10.20944/preprints202309.1196.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: frailty; cardiovascular disease; cancer; cardio-oncology; multimorbidity
Online: 19 September 2023 (04:05:23 CEST)
Advances in cardiovascular therapies and cancer treatments result in longer patient survival. The coexistence of cancer and cardiovascular disease has been recognized as a complex clinical scenario. Beside cardiovascular disease, older people with cancer are at greater risk of experiencing multimorbidity and the geriatric syndromes such as frailty. In older people, the concurrent presence of cancer and cardiovascular disease increased the risk of mortality, and the presence of frailty can exacerbate their conditions and hinder the treatment effectiveness. Given the significant intersection among frailty, cardiovascular disease and cancer in older people, this paper aims to provide an overview of the current research in this field and identifies gaps in research to understand the burden and impact of frailty in these populations. While many studies have examined the prevalence and impact of frailty on adverse outcomes in patients with cancer or with cardiovascular disease, evidence of frailty in individuals with both conditions is lacking. There is no universally accepted definition of frailty, which leads to inconsistencies in identifying and measuring frailty in older adults with cardiovascular disease and cancer. The frailty index seems to be a preferred frailty definition in studies in patients with cancer, while the frailty phenotype seems to be more commonly used in cardiovascular research. However, differences in how the frailty index was categorised and in how patients were classified as ‘frail’ depending on the cut points may have negative effect on understanding the impact of frailty in the studied populations. This makes it challenging to compare findings across different studies and limits our understanding of the prevalence and impact of frailty in these populations. Addressing these research gaps will contribute to our understanding of the burden of frailty in older people with cardiovascular disease and cancer, and improved clinical care protocols in this vulnerable population.
Subject: Arts And Humanities, Art Keywords: Pediatric oncology; Artistic clown doctors; Narrative analysis
Online: 6 September 2023 (05:52:04 CEST)
Using a humanistic and qualitative approach, the present study aims to (1) bring light on 1 the impact of clown doctors’ artistic work in pediatric oncology and, as a consequence, (2) contribute 2 to the refinement and improvement of the clown doctors’ intervention quality, in the context of 3 pediatric oncology, bringing hypotheses of reflection hardly met with quantitative approaches. We 4 are interested in the subjective experience of the artists, and the perceived subjective experience of 5 the child as reported by the clown doctors. The present analysis was developed from the clown 6 doctors’ final reports, their narrative, after visiting the pediatric oncology ward in a Portuguese public 7 hospital, for a continuous period of six months. The visits were performed by a clown doctor dyad, 8 and the audience was a young adolescent girl, with cancer, and her constant mother.9
ARTICLE | doi:10.20944/preprints202306.1932.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: malnutrition; digestive surgery; oncology; gastrointestinal malignancies; prevalence
Online: 27 June 2023 (14:58:11 CEST)
A prospective, observational, multicenter, and exploratory study was conducted in 469 gastrointestinal cancer patients undergoing elective surgery. The Malnutrition Universal Screening Tool (MUST) and the Global Leadership Initiative on Malnutrition (GLIM) criteria were used to assess nutritional risk. On admission, 17.9% and 21.1% of patients were at moderate (MUST score 1) and severe (MUST score ≥ 2) nutritional risk, respectively. GLIM criteria used in patients with MUST score ≥ 2 showed moderate malnutrition in 35.3% of patients and severe in 64.6%. Forty-seven percent of patients with MUST score ≥ 2 on admission had the same score at discharge, and 20.7% with MUST score 0 had moderate/severe risk at discharge. Small bowel, esophageal and gastric cancer, and diabetes were predictors of malnutrition on admission. Complications were significantly higher among patients with MUST score 1 or ≥ 2 either on admission (p = 0.001) or at discharge (p < 0.0001). In patients who received nutritional therapy (n = 231), 43% continued to have moderate/severe nutritional risk on discharge, and 54% of those with MUST ≥ 2 on admission maintained this score at discharge. In gastrointestinal cancer patients undergoing elective surgery, there is an urgent need for improving nutritional risk screening before and after surgery, as well as improving nutritional therapy during hospitalization
ARTICLE | doi:10.20944/preprints202212.0218.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Monoclonal antibodies; Variable dosing; Fixed dosing; Oncology
Online: 13 December 2022 (02:25:03 CET)
Oncological patients need the proper doses of medications to facilitate their recovery. The two basic approaches used in dosing Monoclonal Antibodies (mAbs) are fixed-dose combination and variable dosing. In Fixed-Dose Combination Drugs (FDCs), two or more active components are combined in a single formulation at a predetermined dose. Variable dosage, which has long been the industry standard, is the polar opposite of this approach. The body changes over time; the Body Surface Area (BSA) in square meters is often used as a Measure (m2). This study uses a systematic review. Most mAbs used in oncology are predominantly given as cytotoxic anticancer drugs using body-size-based (variable) regimens. Despite the benefits of fixed-dose, variable dosing has become the industry standard, despite being criticized for ineffectiveness. While variable dosing has some advantages, the prevalent view is that continuous dosing has significant advantages based on the balance of probabilities. After assessing each alternative, including its benefits and drawbacks, history of use, and suitability in the current context, fixed dosing emerges as a viable option.
REVIEW | doi:10.20944/preprints201810.0327.v1
Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: LC-MS/MS, Rapid, Quantification, Oncology Drugs
Online: 15 October 2018 (16:57:44 CEST)
In the last decade, the tremendous improvement in the sensitivity and also affordability of Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) have revolutionized its application in pharmaceutical analysis, resulting in wide-spread of employing LC-MS/MS for determining pharmaceutical compounds including anticancer drugs in pharmaceutical research and also industries. Currently, LC-MS/MS has been widely used to quantify small molecule oncology drugs in various biological matrices to support preclinical and clinical Pharmacokinetic studies in R & D of oncology drugs. This mini-review article will describe the state-of-the art LC-MS/MS and its application in rapid quantification of small molecule anticancer drugs. In addition, efforts have also been made in this review to address several key aspects in the development of rapid LC-MS/MS methods, including sample preparation, chromatographic separation and matrix effect evaluation.
ARTICLE | doi:10.20944/preprints202310.1175.v1
Subject: Medicine And Pharmacology, Urology And Nephrology Keywords: machine learning; testicular cancer; personalised oncology; precision imaging
Online: 18 October 2023 (11:52:35 CEST)
Radiomics refers to the extraction and analysis of a wide range of medical imaging features in a non-invasive and cost-effective manner to comprehensively characterise tumours. In this study, machine learning models combining radiomics and clinical factors were developed to predict retroperitoneal lymph node metastasis in testicular germ cell tumours (TGCTs), with the aim of reducing unnecessary treatment in this group of young patients. Ninety-one patients with surgically proven testicular germ cell tumours and contrast-enhanced CT were included in this retrospective study. After segmenting 273 retroperitoneal lymph nodes using dedicated radiomics software, we developed machine-learning prediction models using Random Forest (RF), Light Gradient Boosting Machine (LGBM), Support Vector Machine Classifier (SVC), and K-Nearest Neighbours (KNN). For each classifier, we developed a radiomics-only, clinical-only, and combined radiomics-clinical prediction model. The models’ performances were evaluated using the area under the receiver operating characteristic curves (AUCs). The RF-based combined clinical and radiomic model showed the most robust performance in predicting LNM with an area under the curve (AUC) of 0.95 (±0.03; 95% CI), accuracy 87%, precision 89%, recall 86% and F1 score 87%, followed by the LGBM model with an area under the curve (AUC) of 0.93 (±0.05; 95% CI), accuracy 83%, precision 87%, recall 80% and F1 score 82%. Decision curve analysis demonstrated the clinical utility of our proposed RF-based combined clinical–radiomics model. Our study has identified reliable and predictive machine-learning techniques for predicting lymph node metastasis in early-stage testicular cancer. Identifying the most effective machine-learning approaches for predictive analysis based on radiomics integrating clinical risk factors can expand the applicability of radiomics in precision oncology and cancer treatment. Multi-centre validation is required to provide high-quality evidence for clinical application.
ARTICLE | doi:10.20944/preprints202307.1170.v1
Subject: Medicine And Pharmacology, Urology And Nephrology Keywords: Hybrid operating room; Kidney cancer; Laparoscopy; Oncology; Surgery
Online: 18 July 2023 (07:55:56 CEST)
Laparoscopic partial nephrectomy (LPN) after hyperselective embolization of tumor vessels (HETV) in a hybrid operating room (HOR) that combines traditional surgical equipment with advanced imaging technology, is a non-clamping surgical approach to treat localized kidney tumors that have shown promising short-term results. The aim of this study was to evaluate the long-term oncological and functional outcomes of this procedure. All consecutive patients treated for a localized kidney tumor by LPN after HETV between May 2015 and October 2022 in a single academic institution were included in the study. Clinical, pathological and biological data were collected prospectively in the uroCCR database. We evaluated perioperative data, postoperative complications, surgical margin and modification of renal function after surgery. We included 245 patients. Median tumor size was 3.2 (2.5-4.4) cm. The R.E.N.A.L. complexity was low, medium and high for 104 (43.5%), 109 (45.6%) and 26 (10.9%) patients, respectively. Median LPN time was 75 (65 -100) min and median blood loss was 100 (50-300) mL. Surgical postoperative complications occurred in 56 (22.9%) patients with 17 (5.7%) major complications. The median preoperative Glomerular Function Rate (GFR) was 90.5 (77-101.8) mL/min and the median GFR variation at 6 months was -7.5 (-15- -2) mL/min. Malignant tumors were present in 211 (86.1%) patients and 12 (4.9%) patients had positive surgical margins. After a median follow-up of 27 (8-49) months, 20 (8.2%) patients had a tumor recurrence and 4 (1.6%) died from cancer. The use of a HOR to perform LPN after HETV is a safe and efficient non-clamping approach to treat localized kidney tumors.
ARTICLE | doi:10.20944/preprints202307.1121.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: children; cancer; oncology; music therapy; quality of life
Online: 17 July 2023 (15:12:48 CEST)
Background: Music therapy (MT) is a non-pharmacological treatment increasingly used to reduce stress and anxiety in hospitalized children affected by cancers. The aim of this study was to eval-uate the impact of MT on quality of life of children with cancer. Methods: We have conducted a quasi-experimental study between April 1 and August 31, 2021 at Bechir Hamza children's Hos-pital in Tunis, including children treated for cancer. The child or the parent completed PedsQL Module Cancer french version 3.0 questionnaires before and after four weekly music therapy ses-sions. Child's respiratory and heart rate were measured before and after each session. Results: We included 20 children whose mean age was 7 ± 4.5 years [2-14]. The median value of the total questionnaire score increased from 57 [46; 70] to 72 [67; 85] (p < 10-3) with a significant reduction in pain (p = 0.02), nausea (p = 0.009), anxiety related to medical procedures (p = 0.009) and worry about the future (p = 0.005). We highlighted a significant decrease in respiratory and heart rate after MT (p<0,05). Conclusions: MT has positive impact of on quality of life of children with cancer.
ARTICLE | doi:10.20944/preprints202305.0482.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Mitochondria; Personalized Oncology; cancer stem cell; T Cell
Online: 8 May 2023 (08:48:56 CEST)
Energy is needed by cancer cells to stay alive and communicate with their surroundings. The primary organelles for cellular metabolism and energy synthesis are mitochondria. Researchers recently proved that cancer cells can steal immune cells' mitochondria using nanoscale tubes. This finding demonstrates the dependence of cancer cells on normal cells for their living and function. It also denotes the importance of mitochondria in cancer cells’ biology. Emerging evidence has demonstrated how mitochondria are essential for cancer cells to survive in the harsh tumor microenvironment, evade the immune system, obtain more aggressive features, and resist treatments. For instance, functional mitochondria can improve cancer resistance against radiotherapy by scavenging the released reactive oxygen species. Therefore, targeting mitochondria can potentially enhance oncological outcomes, according to this notion. The patients' reactions to radiation are varied, ranging from a complete response to even cancer progression during treatment. This concept illustrates how different levels of mitochondrial metabolism might contribute to this heterogeneity. Considering this notion can help to improve personalized oncological treatments. This article outlines the importance of mitochondrial metabolism in cancer biology and personalized treatments.
REVIEW | doi:10.20944/preprints202304.0340.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Africa; cancer; immunotherapy; oncology; Tanzania; therapeutic; tumor microenvironment
Online: 14 April 2023 (03:30:46 CEST)
The tumor microenvironment (TME) plays a critical role in cancer progression and treatment outcomes. Despite advances in cancer research, many therapeutic strategies have failed to provide the desired clinical outcomes. In this integrated review, aimed to explore the role of TME in cancer biology and develop novel therapeutic strategies that target not only cancer cells but also the surrounding microenvironment. Study conducted a comprehensive literature search using PubMed, Embase, and Web of Science databases for articles published between 2016 and 2022. Inclusion of articles that discussed the impact of TME on cancer development and progression, as well as articles that proposed novel therapeutic strategies targeting the TME. The analysis of the literature revealed that the TME plays a crucial role in cancer development and progression by promoting cancer cell survival, angiogenesis, invasion, and metastasis, and by interfering with the efficacy of cancer therapies. The TME is composed of a complex network of non-cancerous cells, extracellular matrix components, and signaling molecules that interact with cancer cells. Several novel therapeutic strategies have been proposed based on the modulation of TME components. One of the most promising approaches is the use of immunotherapy, which aims to enhance the immune system's ability to recognize and attack cancer cells. Immunotherapy drugs such as checkpoint inhibitors, chimeric antigen receptor (CAR) T cells, and immune-stimulatory monoclonal antibodies have been approved for the treatment of different cancer types. These approaches have shown promising results in preclinical studies and clinical trials. The TME plays a critical role in cancer development and progression, and targeting its components represents a promising avenue for cancer therapy. Novel therapeutic strategies such as immunotherapy, extracellular matrix-targeting drugs, and nanoparticle-based therapies have shown promising results in preclinical studies and clinical trials. However, further research is needed to identify the most effective strategies and to overcome the challenges associated with TME targeting.
ARTICLE | doi:10.20944/preprints202107.0281.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Glioblastoma; Precision Medicine; Targeted Therapy; Genomics; Neuro-Oncology
Online: 13 July 2021 (09:28:35 CEST)
BACKGROUND: Glioblastoma (GBM) is driven by various genomic alterations. Next generation sequencing (NGS) could yield targetable alterations that may impact outcomes. The goal of this study was to describe how NGS can inform targeted therapy (TT) in this patient population. METHODS: The medical records of patients (pts) with a diagnosis of GBM from 2017-2019 were reviewed. Records of patients with recurrent GBM and genomic alterations were evaluated. Objective response rates and disease control rates were deter-mined. RESULTS: A total of 87 pts with GBM underwent NGS. Forty percent (n = 35) were considered to have actionable alterations. Of the 35, 40% (n=14) pts had their treatment changed due to an alteration. The objective response rate (ORR) of this population was 43%. The disease control rate (DCR) was 100%. The absolute mean decrease in contrast enhancing disease was 50.7% (95% CI 34.8 – 66.6). CONCLUSION: NGS for GBM, particularly in the recurrent setting, yields a high rate of actionable alterations. We observed a high ORR and DCR, reflecting the value of NGS in deciding on TT to match alterations that are likely to respond. In conclusion, patient selection and availability of NGS may impact outcomes in select pts with recurrent GBM.
ARTICLE | doi:10.20944/preprints202104.0374.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Covid-19; Radiation Oncology; Operation; Survey; Adaptability; Resilience
Online: 14 April 2021 (12:30:40 CEST)
Background: A comprehensive response to the unprecedented SARS-CoV-2 (COVID-19) chal-lenges for public health and its impact on radiation oncology patients and personnel for resilience and adaptability is presented. Methods: The general recommendations included working remote-ly when feasible, implementation of screening/safety and personal protective equipment (PPE) guidelines, social distancing, regular cleaning of treatment environment, and testing for high-risk patients/procedures. All teaching conferences, tumor boards, and weekly chart rounds were con-ducted using a virtual platform. Additionally, specific recommendations were given to each sec-tion to ensure proper patient treatments. The impact of these measures, especially adaptability and resilience, were evaluated through specific questionnaire surveys. Results: These comprehen-sive COVID-19 related measures resulted in most staff expressing a consistent level of satisfaction in regards to personal safety, maintaining a safe work environment, continuing quality patient care and continuing educational activities during the pandemic. There was a significant reduction in patient treatments and on-site patient visits with an appeciable increase in the number of tele-medicine e-visits. Conclusions: Survey results demonstrated substantial adaptability and resili-ence, including in the rapid recovery of departmental activities during the reactivation phase. In the event of a future public health emergency, the measures implemented may be adopted with good outcomes by radiation oncology departments across the globe.
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: female dog; cell culture; mammary cancer; veterinary; oncology
Online: 15 April 2020 (07:59:18 CEST)
Mammary neoplasm affects a population of intact and elderly female dogs and 50% are malignant. In order to study this disease, cell culture is as a promising preclinical model, creating the opportunity to deposit cell lines at a cell bank, allowing a great reproducibility of the assays and making the validation of the results more reliable. Another important aspect is the possibility to establish models for better understanding tumour characteristics, such as vasculogenic mimicry. Due the importance of cancer cell lines in preclinical models, this study aimed to establish and characterize primary cell lines from canine mammary gland tumours according to immunophenotype and tumorigenicity, and with its ability to form vasculogenic mimicry-like structures in vitro and in vivo. Cell cultures were evaluated for morphology, phenotype, vasculogenic mimicry and tumorigenicity abilities. We collected 17 primary mammary carcinoma and 3 metastasis and had a satisfactory result in 10 of them. All cell lines presented spindle shape or polygonal morphology and expressed concomitant pan-cytokeratin and cytokeratin 8/18. Four cell lines had vasculogenic mimicry ability in vitro and two of them showed in vivo tumorigenic potential and forming VM in the xenotransplant tumour. Cell characterization of those lines will help to create a database for more knowledge of mammary carcinomas in dogs, including studies of tumour behaviour and new therapeutic targets.
ARTICLE | doi:10.20944/preprints201902.0042.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: RNA-Seq; Oncology; DNA repair; Survival; PCNA metagene
Online: 4 February 2019 (16:55:20 CET)
Removal of the proliferation component of gene expression by PCNA adjustment has been addressed in numerous survival prediction studies for breast cancer and all cancers in the TCGA. These studies indicate that widespread co-regulation of proliferation upwardly biases survival prediction when gene selection is performed on a genome-wide basis. In addition, removal of the correlative effects of proliferation does not reduce the random bias associated with survival prediction using random gene selection. Since most cancers become addicted to DNA repair as a result of forced cellular replication, increased oxidation, and repair deficiencies from oncogenic loss or genetic polymorphisms, we pursued an investigation to remove the proliferation component of expression in DNA repair genes to determine survival prediction. This translational hypothesis-driven focus on DNA repair genes is directly amenable to finding new sets of DNA repair genes that could potentially be studied for inhibition therapy. Overall survival (OS) prediction was evaluated in 18 cancers by using normalized RNA-Seq data for 126 DNA repair genes with expression available in TCGA. Transformations for normality and adjustments for age at diagnosis, stage, and PCNA metagene expression were performed for all DNA repair genes. We also analyzed genomic event rates (GER) for somatic mutations, deletions, and amplification in driver genes and DNA repair genes. After performing empirical p-value testing with use of randomly selected gene sets, it was observed that OS could be predicted significantly by sets of DNA repair genes for 61% (11/18) of the cancers. Interestingly, PARP1 was not a significant predictor of survival for any of the 11 cancers. Results from cluster analysis of GERs indicates that the most opportunistic cancers for inhibition therapy may be AML, colorectal, and renal papillary, because of potentially less confounding due to lower GERs for mutations, deletions, and amplifications in DNA repair genes. However, the most opportunistic cancer for inhibition therapy is likely to be AML, since it showed the lowest GERs for mutations, deletions, and amplifications in DNA repair genes. In conclusion, our hypothesis-driven focus to target DNA repair gene expression adjusted for the PCNA metagene as a means of predicting OS in various cancers resulted in statistically significant sets of genes.
REVIEW | doi:10.20944/preprints201811.0525.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: immuno-oncology; CAR T-cell; lymphoma; one health
Online: 21 November 2018 (11:34:58 CET)
The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T-cells for targeted cancer therapy. CAR T-cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T-cell therapies were approved by the U. S Food and Drug Administration; one for the treatment of pediatric Acute Lymphoblastic Leukemia (ALL), the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T-cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B-cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin’s lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T-cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This Commentary summarizes the current state of knowledge on CAR T-cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.
ARTICLE | doi:10.20944/preprints201707.0075.v1
Subject: Social Sciences, Sociology Keywords: pediatric oncology; cancer; social worker; burn out; stress
Online: 26 July 2017 (08:41:09 CEST)
As professionals, social workers have a special position in relation to considering the needs of children with cancer and their families. Hence, it is important to recognize the experiences and challenges of social workers to improve care of their clients. This study was a qualitative content analysis that aimed to determine a comprehensive understanding of 19 pediatric oncology social workers’ experiences in Iran. Data were collected using semi structured interviews and field observations, analyzed through face content analysis. Concepts extracted from social workers’ experiences consisted of the nature of oncology work, lack of professional competence, low organizational support and professional inferiority that were related to main concept of "exhausting and stressful service". The results indicated that social workers' involvement in stressful and emotionally demanding situations and professional and organizational challenges caused personal exhaustion. In addition to explaining the social workers’ experiences and related factors, the results emphasize the importance of taking care of service providers to prevent them becoming stressed and exhausted. It is also important to protect patients from the consequences of stressed and exhausted care providers so further research is recommended to develop specific intervention.
ARTICLE | doi:10.20944/preprints202306.1555.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: research; oncology; Arab; Middle East; North Africa; cancer management
Online: 21 June 2023 (12:53:49 CEST)
The increasing cancer burden is a major health concern in Arab countries with variations in cancer profiles. Given the limited oncology research output and scarce data on cancer trial participation in the Arab region, this study explored the therapeutic cancer trial landscape in Arab countries over the past 20 years. A bibliometric analysis of the PubMed database was conducted on primary publications of therapeutic trials with a participating Arab center. Arab countries participated in 320 published cancer-related therapeutic trials (2000‒2021). There was a consistent increase in the number of trials, sample size, multiregional site participation, and number of randomized trials. However, most trials were small, did not receive external funding, and included a single Arab site. Compared with Arab-only trials, trials with joint non-Arab sites were larger (p = .003) and more likely to be externally funded (p < .001). Citation numbers and journal impact factors were higher in trial publications with joint non-Arab authorship than those without (p < .001, for both). Despite improving conduct and publication records of oncology trials with Arab centers, cancer trial participation remains limited in Arab countries. Concerted efforts are required to encourage sponsorship and international collaboration in this region.
ARTICLE | doi:10.20944/preprints202305.0393.v1
Subject: Public Health And Healthcare, Other Keywords: Virtual assistants; Gynecologic; Oncology; Siri; Alexa; Google; Cortana; Validity
Online: 6 May 2023 (08:42:27 CEST)
1) Background: This study focused on the validity of audible replies to voice queries in gyneco-logic oncology by Siri, Alexa, Google, and Cortana virtual assistants (VAs).; (2) Methods: 21 evaluators analyzed VA audible answers to voice queries related to gynecologic oncology. A 3-tier template was utilized for each voice query: “X?” (A), “What is X?” (B), and “Define X?” (C) in a 24-question panel, allowing questions to be posed in different formats to assess the VAs at a greater depth. Responses were scored using a rubric designed to assess the validity and quality of each answer; (3) Results: For general queries, Google provided the most correct audible replies (ncorrect = 20; 83.3% correct), followed by Alexa (ncorrect = 16; 66.7% correct), Siri (ncorrect = 11; 45.8% correct), and Cortana (ncorrect = 5; 20.8% correct.; For Gynecologic Oncology related queries, Google also provided the most correct audible replies (ncorrect=222; 18.14%), followed by Alexa (ncorrect=75; 6.51%), Siri (ncorrect=55; 5.46%), and Cortana (ncorrect=23; 2.28%). (4) Conclusions: The audible replies to oral queries on gynecologic oncology topics varied between Siri, Alexa, Google, and Cortana. Google’s audible reply accuracy was superior to audible replies by Siri, Alexa, and Cortana. Since there is room for considerable improvement in VA performance, the authors advise caution when using VAs for medical queries in gynecologic oncology.
REVIEW | doi:10.20944/preprints202305.0180.v1
Subject: Chemistry And Materials Science, Nanotechnology Keywords: Green Chemistry; Vegetable oils; Bio-based nanoparticles; Oncology APIs
Online: 4 May 2023 (04:04:06 CEST)
Latterly, the development of green synthesized polymeric nanoparticles with anticancer studies has been an emerging field in academia, and in the pharmaceutical and chemical industry. Vegetable oils are potential substitutes for petroleum derivatives, as they present themselves as a clean and environmentally friendly alternative and are available in high quantities at relatively low prices. Biomass-derived chemicals can be converted into monomers with unique structures, generating materials with new properties for the synthesis of sustainable monomers and polymers. In this way, the production of bio-based polymeric nanoparticles appears as a great application of green chemistry for biomedical uses. There is an increasing demand for biocompatible and biodegradable materials for specific applications in biomedical as cancer therapy, encouraging scientists in working on research towards designing polymers, with enhanced properties and clean processes, containing oncology active pharmaceutical ingredients (APIs). The nanoencapsulation of these APIs in bio-based polymeric nanoparticles can control the release of the substances, increase bioavailability, reduce problems with volatility and degradation, reduce side effects, and increase treatment efficiency. Thus, this review aims to discuss the use of green chemistry for bio-based nanoparticle production and its application in anticancer medicine. The use of vegetable oils for the production of renewable monomers and polymers will be discussed, bringing castor oil as an ideal candidate for such application, as well as more suitable methods for the production of bio-based nanoparticles and some oncology APIs available for anticancer application.
ARTICLE | doi:10.20944/preprints202301.0568.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: cancer, pediatrics, psycho-oncology, family, COVID-19, risk, resilience
Online: 31 January 2023 (02:49:26 CET)
Previous literature highlights the impact of COVID-19 on family functioning. Less is known about the impact of the pandemic on families of pediatric cancer patients. In order to determine universal and unique risk and resilience factors of these families during the pandemic, a qualitative analysis was conducted on families currently receiving cancer treatment at a midwestern hospital. Results of the data analysis depict ways in which these families have been impacted by and have adapted to COVID-19. These findings suggest that families of pediatric cancer patients have unique experiences in the context of COVID-19, in addition to universal experiences outlined in previous literature.
REVIEW | doi:10.20944/preprints202105.0376.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Gene Editing; Gene Therapy; Oncology; Comparative Medicine; One Health
Online: 17 May 2021 (09:45:43 CEST)
With rapid advances in gene editing and gene therapy technologies, the development of genetic, cell, or protein-based cures to disease are no longer the realm of science fiction but that of today’s practice. The impact of these technologies are rapidly bringing them to the veterinary market as both enhanced therapeutics and towards modeling their outcomes for translational application. Simply put, gene editing enables scientists to modify an organism’s DNA a priori through the use of site-specific DNA targeting tools like clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9). Gene therapy is a broader definition that encompasses the addition of exogenous genetic materials into specific cells to correct a genetic defect. More precisely, the U.S Food and Drug Administration (FDA) defines gene therapy as “a technique that modifies a person’s genes to treat or cure disease” by either (i) replacing a disease-causing gene with a healthy copy of the gene; (ii) inactivating a disease-causing gene that was not functioning properly; or (iii) introducing a new or modified gene into the body to help treat a disease. In some instances, this can be accomplished through direct transfer of DNA or RNA into target cells of interest or more broadly through gene editing. While gene therapy is possible through the simple addition of genetic information into cells of interest, gene editing allows the genome to be reprogrammed intentionally through the deletion of diseased alleles, reconstitution of wild type sequence, or targeted integration of exogenous DNA to impart new function. Cells can be removed from the body, altered, and reinfused, or edited in vivo. Indeed, manufacturing and production efficiencies in gene editing and gene therapy in the 21st century has brought the therapeutic potential of in vitro and in vivo reprogrammed cells, to the front lines of therapeutic intervention (Brooks et al., 2016). For example, CAR-T cell therapy is revolutionizing hematologic cancer care in humans and is being translated to canines by us and others, and gene therapy trials are ongoing for mitral valve disease in dogs.
REVIEW | doi:10.20944/preprints202103.0114.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: organoid; stem cell; cancer; glioblastoma; glioma; oncology; precision medicine
Online: 2 March 2021 (21:59:47 CET)
The emergence of three-dimensional human organoids has opened the door for development of patient-derived cancer organoid (PDO) models, which closely recapitulate parental tumor tissue. Mainstays of preclinical cancer modeling include in vitro cell lines and patient-derived xenografts, but these models lack the cellular heterogeneity seen in human tumors. Moreover, xenograft establishment is resource- and time-intensive, rendering these models difficult to use to inform clinical trials and decisions. PDOs, however, can be created efficiently and retain tumor-specific properties such as cellular heterogeneity, cell-cell and cell-stromal interactions, tumor microenvironment, and therapeutic responsiveness. PDO models and drug screening protocols have been described for several solid tumors and, more recently, for gliomas. Since PDOs can be developed in clinically relevant timeframes and share many characteristics of parent tumors, they may enhance the ability to provide precision oncologic care for patients. This review explores the current literature on cancer organoids, highlighting the history of PDO development, organoid models of glioma, and potential clinical applications of PDOs.
REVIEW | doi:10.20944/preprints202310.1680.v1
Subject: Medicine And Pharmacology, Obstetrics And Gynaecology Keywords: ovarian cancer; gynecologic oncology; gynecologic surgery; debulking surgery; PDS; laparoscopy
Online: 26 October 2023 (10:12:52 CEST)
Ovarian cancer affects thousands of women every year and represents the female cancer with the highest mortality rate. Surgery is currently the cornerstone of the treatment of this disease and several methods have been analyzed and developed to predict the possibility of obtaining a residual tumor of 0 (RT=0). The aim of this review is to analyze the data available in the literature about minimally invasive surgical methods to predict the optimal cytoreduction of patients with advanced epithelial ovarian cancer undergoing primary debulking surgery (PDS). A review of the literature has been performed on the available data about the criteria of cytoreducibility during PDS for the surgical treatment of advanced epithelial ovarian cancer. The assessment of the extent of intra and extrabdominal pathology is essential to guide the surgeon in the most appropriate therapeutic choice for patients with ovarian cancer, so radiological methods (MRI, PET-scan and CT), surgical (mini-laparotomy, laparoscopy) and serological (CA-125, HE4) can provide a huge help for tailoring the therapeutic approach of these patients.
ARTICLE | doi:10.20944/preprints202306.2115.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: exercise oncology; telehealth; synchronous delivery; supervised exercise; group-based exercise
Online: 29 June 2023 (11:37:23 CEST)
Alberta Cancer Exercise (ACE) is an exercise oncology program that transitioned from in-person to online delivery during COVID-19. The purpose of this work was to understand participants’ experiences in both delivery modes. Specifically, survivors' exercise facilitators and barriers, delivery mode preference, and experience with program elements targeting behaviour change were gathered. A retrospective cohort design using explanatory sequential mixed methods was used. 57 participants completed a survey, and 19 subsequent, optional interviews were conducted. Most participants indicated preferring in-person programs (58%), followed by online (32%), and no preference (10%). There were significantly fewer barriers (i.e., commute time) (p<0.01), but also fewer facilitators (i.e., social support) (p<0.01), to exercising online. Four themes were generated from the qualitative data surrounding participant experiences in both delivery modes. Key differences in barriers and facilitators highlighted a more convenient experience online relative to a more socially supportive environment in-person. For future work that includes solely online, focusing on building social support and a sense of community will be critical to optimizing program benefits. Beyond the COVID-19 pandemic, results of this research will remain relevant as we aim to increase the reach of online exercise oncology programming to more underserved populations of individuals living with cancer.
ARTICLE | doi:10.20944/preprints202306.0407.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Boron neutron capture therapy; BNCT; radiation oncology; medical physics; Canada
Online: 6 June 2023 (08:09:25 CEST)
Background: Boron Neutron Capture Therapy (BNCT) is an emerging radiotherapy. There are ongoing efforts to develop a Canadian accelerator-based BNCT center. However, it remains unclear how Canadian radiation oncologists (RO), medical physicists (MP), and their trainees perceive BNCT and its impact on radiation oncology as a discipline. Methods: A survey was created to explore knowledge of BNCT, its clinical role, and support for Canadian research. It was distributed through the Canadian Association of Radiation Oncology (CARO) and Canadian Organization of Medical Physicists (COMP). Results: We received 118 valid responses from all 10 provinces, from 70 RO (59.3%) and 48 MP (40.7%), including 9 residents. Most knew of BNCT and its indications (60.2%). Although many were unaware of reasons behind early failures (44.1%), common reasons were lack of clinical trials and inaccessibility of neutron sources (42.4%) and reactor unsuitability (34.7%). Additionally, 90.6% showed definite (66.9%) or possible (23.7%) support for Canadian BNCT research, while 89% indicated definite (56.8%) or possible (32.2%) willingness for BNCT referrals. Conclusions: Most RO and MP supported Canadian BNCT research and would refer patients. However, limited awareness and lack of experiences remain a challenge. Educational sessions are needed to realize this innovative cancer treatment in Canada.
CASE REPORT | doi:10.20944/preprints202305.2169.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Cardiac Metastasis; Cardio-oncology; Cardiac Disease; Acute myocardial infarction; Cardiology
Online: 31 May 2023 (04:04:21 CEST)
Abstract Background: Most cardiac metastases emerge from primary lung, breast, and hematologic malignancies. The clinical manifestations of cardiac metastasis vary depending on tumor location and size. Cardiac metastasis from cervical squamous cell carcinoma is extremely rare and is mostly found on autopsy. We report a case of cervical cancer metastasis to the interventricular septum. Case Summary. This report discusses the case of a 48-year-old woman with interventricular septal metastases, originating from squamous cell carcinoma of the cervix. The woman came to our hospital after experiencing a fainting spell. Her hospital stay was notable for a brief syncopal event during a 30-second asystole episode, which ended spontaneously. Upon awakening, she reported severe chest pain. In response, she was quickly taken to the catheterization laboratory. There, a coronary angiography revealed an 80% blockage in her left anterior descending artery. Two years prior, our patient was diagnosed with invasive squamous cell cervical carcinoma with PET/CT showing no evidence of metastatic disease. A repeat PET/CT scan was done following cardiac catheterization and was significant for a mass along the interventricular septum of the heart. Discussion. Cardiac metastasis from primary cervical squamous cell carcinomas is scarcely reported in medical literature. Among these rare cases, the majority involved the right ventricle, with only three involving the left ventricle. There are no documented instances of metastasis to the interventricular septum. To our knowledge, this would be the first such case.
ARTICLE | doi:10.20944/preprints202111.0399.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: clinical assistants; pediatric oncology; assistance activity; new roles; skill mix
Online: 22 November 2021 (14:00:03 CET)
Background: There is a high bureaucratic and administrative burden associated with health care tasks (test requesting, visits scheduling, supporting documents provision) that has historically largely fallen on health care professionals, which is one among the factors contributing to low job satisfaction and lower productivity. Incorporating new professional roles that help to better respond to the needs of both patients and professionals can increase the quality and efficiency of service provision. Objective: To evaluate the impact of the clinical assistant’s introduction in the Sant Joan de Déu Barcelona Children’s Hospital’s pediatric oncology department, in terms of displacement of activity loads carried out by this new professional role and the consequent time freed up for physicians. Methodology: Observational and retrospective study using administrative data based on the analysis of the type of activity performed by clinical assistants and the measurement of the time freed up in favor of the physicians, based on in situ timekeeping, to approximate the potential skill mix productivity increase. Results: Since its implementation in the pediatric oncology department, clinical assistants have performed 13,553 requests (69.93% of the total), representing a total saving of 266.83 hours or 6.67 workweeks of 40 hours. They performed 74.25% of outpatient surgical requests in the oncology department, 87.5% of day hospital requests and 54.13% of total requests in the outpatient consultations area. Conclusion: The introduction of clinical assistants in the oncology department could be efficient to the extent that it displaces a good part of the bureaucratic and administrative tasks previously performed by health care professionals. This delegation allows them to work more closely to the maximum of their competences and the physicians to have more time for higher added value clinical tasks. In terms of efficiency, this role change enables to optimize the clinical process, reducing the cost by 56% compared to the conventional model.
REVIEW | doi:10.20944/preprints202110.0307.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: SARS-Cov-2; COVID-19; oncology; cancer screening; clinical trials
Online: 21 October 2021 (12:45:12 CEST)
The coronavirus disease 2019 (COVID-19) pandemic has caused considerable global disruption to clinical practice. This article will review the impact that the pandemic has had on oncology clinical trials. It will assess the effect of the COVID-19 situation on the initial presentation and investigation of patients with suspected cancer. It will also discuss the impact of the pandemic on the subsequent management of cancer patients and how clinical trial approval, recruitment and conduct were affected during the pandemic. An intriguing aspect of the pandemic is that clinical trials investigating treatments for COVID-19 and vaccinations against the causative virus, SARS-CoV-2, have been approved and conducted at unprecedented speed. In light of this, this re-view will also discuss the potential that this enhanced regulatory environment could have on the running of oncology clinical trials in the future.
REVIEW | doi:10.20944/preprints202108.0258.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Deep Learning; Pelvic Cancer Segmentation; Radiology; Radiation Oncology; Radiotherapy Planning
Online: 11 August 2021 (12:17:31 CEST)
The recent rise of deep learning (DL) and its promising capabilities in capturing non-explicit detail from large datasets have attracted substantial research attention in the field of medical image processing. DL provides ground for technology development for computer-aided diagnosis and segmentation in radiology and radiation oncology. Amongst the anatomical locations where recent auto-segmentation algorithms have been employed, the pelvis remains one of the most challenging due to large intra- and inter-patient soft-tissue variabilities. This review provides a comprehensive and clinically-oriented overview of DL-based segmentation studies for bladder, prostate, cervical and rectal cancers, highlighting the key findings, challenges and limitations.
HYPOTHESIS | doi:10.20944/preprints202104.0516.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: spontaneous regression; tumors; cancer; bacterial therapy; Coley; immunotherapy; hyperthermia; oncology
Online: 19 April 2021 (21:03:16 CEST)
Neither tumor growth nor regression is truly spontaneous, but both may under special circumstances be driven by similar events. We describe a sequence of processes that typically leads to tumor progression but may on occasion inadvertently result in regression. A possible procedure for reducing tumor mass through a controlled intervention is also outlined.
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: CML; Imatinib; early detection; cancer; tumor progression; oncology; Gleevec; Glivec
Online: 18 October 2019 (07:18:47 CEST)
Chronic myelogenous leukemia (CML) was the first malignancy for which clinical outcome was drastically improved by kinase inhibitor therapy. Kinase inhibitors targeting other well-known oncogenes have been introduced into clinical practice, but none have shown the same magnitude of clinical benefit as ABL1 inhibition in CML. We argue that early detection is an underappreciated, but critically important factor in success of ABL1 inhibitors in treatment of CML. We show that CML provides a window into how many types of cancer may look and behave at an early stage, prior to diagnosis and the development of additional genomic alterations. The remarkable clinical benefits of ABL1 inhibition is likely due to early detection of CML at a stage in which the tumor is driven by single oncogenic alteration which can be successfully controlled by the inhibitor. Thinking of CML as a prototype for effective systemic treatment based on early cancer detection may help to develop strategies for improving treatment for other types of cancer.
REVIEW | doi:10.20944/preprints202307.0891.v1
Subject: Medicine And Pharmacology, Obstetrics And Gynaecology Keywords: endometrial microbiota; microbiome; fertility; chronic endometritis; uterus; reproductive outcomes; endometriosis, oncology
Online: 13 July 2023 (09:25:34 CEST)
Contrary to popular belief, we have known for many years that the endometrium is not a sterile environment and is considered to be a low-biomass milieu compared to the vagina. Numerous trials and studies have attempted to establish a valid sampling method and assess its physiological composition, but no consensus has been reached. Many factors such as ethnicity, age and inflammation, can influence the microbiome. Moreover, it possesses a higher alpha-diversity and therefore contains more diverse bacteria than the vagina. For instance, Lactobacillus has been shown to be a predominant genus in the vaginal microbiome of healthy women. Consequently, even if a majority of scientists postulate that a predominance of Lactobacillus inside the uterus improves reproductive outcomes, vaginal contamination by these bacteria during sampling cannot be ruled out. Certain pathologies, such as chronic endometritis, have been identified as inflammation perpetrators that hinder the embryo implantation process. This pro-inflammatory climate created by dysbiosis of the endometrial microbiota could induce secondary inflammatory mediators via Toll-like receptors, creating an environment conducive to the development of endometriosis and even promoting carcinogenesis. However, studies to this day have focused on small populations. In addition, there is no clearly defined healthy uterine composition yet. At most, only a few taxa have been identified as pathogenic. As sampling and analysis methods become increasingly precise, we can expect the endometrial microbiota to be incorporated into future diagnostic tools and treatments for women’s health.
ARTICLE | doi:10.20944/preprints202302.0025.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: radiomics signature; prediction; machine learning; testicular cancer; personalised oncology; precision imaging
Online: 2 February 2023 (03:15:05 CET)
Accurate retroperitoneal lymph node metastasis (LNM) prediction in early-stage testicular germ cell tumours (TGCT) harbours the potential to significantly reduce over- or undertreatment and treatment-related morbidity in this group of young patients as an important survivorship imperative. We investigated the role of computed tomography (CT) radiomics models integrating clinical predictors for the individualized prediction of LNM in early-stage TGCT. Ninety-one patients with surgically proven testicular germ cell tumours and contrast-enhanced CT were included in this retrospective study. Dedicated radiomics software was used to segment 273 retroperitoneal lymph nodes and extract features. After feature selection, radiomics-based machine learning models were developed to predict LN metastasis. The robustness of the procedure was controlled by 10-fold cross-validation. Using multivariable logistic regression modelling, we developed three prediction models: A radiomics-only model, a clinical-only model and a combined radiomics-clinical model. The models' performance was evaluated using the area under the receiver operating characteristic curve (AUC). Finally, decision curve analysis was performed to estimate the clinical usefulness of the predictive model. The radiomics-only model for predicting lymph node metastasis reached a greater discrimination power than the clinical-only model, with an AUC of 0.84 (± 0.17; 95% CI ) vs 0.60 (± 0.22; 95% CI) in our study cohort. The combined model integrating clinical risk factors and selected radiomics features outperformed the clinical-only and the radiomics-only prediction models and showed good discrimination with an area under the curve of 0.94 ( ± 0.10; 95% CI). The decision curve analysis demonstrated the clinical usefulness of our proposed combined model. The presented combined CT-based radiomics-clinical model represents an exciting non-invasive prediction tool for individualized prediction of LN metastasis in testicular germ cell tumours. Multi-centre validation is required to generate high-quality evidence for its clinical application.
REVIEW | doi:10.20944/preprints202208.0452.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: lactate; lactic acid; glycolysis; carcinogenesis; malignant tumor; evolutionary oncology; Warburg effect
Online: 26 August 2022 (07:13:46 CEST)
The role of lactic acid (lactate) in cell metabolism has been significantly revised in recent dec-ades. Initially, lactic acid was attributed to the role of a toxic end product of metabolism, which accumulation in the cell and extracellular space leads to acidosis, muscle pain and other adverse effects. However, it has now become obvious that lactate is not only a universal fuel molecule and the main substrate for gluconeogenesis, but also one of the most ancient metabolites with signaling function, which has a wide range of regulatory activity. The Warburg effect described 100 years ago (that means intensification of glycolysis associated with high lactate production), which is characteristic of many malignant tumors, confirms the key role of lactate not only in physiological conditions, but also in pathologies. The study of lactate’s role in the malignant transformation becomes more relevant in the light of the “atavistic theory of carcinogenesis,” which suggests that tumor cells return to a more primitive hereditary phenotype during micro-evolution. In this review, we attempted to summarize the accumulated knowledges about the functions of lactate in cell metabolism and its role in the process of carcinogenesis, and to con-sider the possible evolutionary significance of the Warburg effect.
REVIEW | doi:10.20944/preprints202109.0453.v3
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: BNCT; targeted therapy; biological dosimetry; boron imaging; personalized oncology; personalized medicine
Online: 16 May 2022 (15:22:13 CEST)
Boron Neutron Capture Therapy (BNCT) is a promising binary disease-targeted therapy, as neutrons preferentially kill cells labeled with boron (10B), which makes it a precision medicine treatment modality that provides a therapeutic effect exclusively on patient-specific tumor spread. Contrary to what is usual in radiotherapy, BNCT proposes cell-tailored treatment planning rather than to the tumor mass. The success of BNCT depends mainly on the sufficient spatial biodistribution of 10B located around or within neoplastic cells to produce a high-dose gradient between the tumor and healthy tissue. However, it is not yet possible to precisely determine the concentration of 10B in a specific tissue in real-time using noninvasive methods. Critical issues remain to be resolved if BNCT is to become a valuable, minimally invasive, and efficient treatment. Moreover, functional imaging technologies such as PET can be applied to determine biological information that can be used for the combined-modality radiotherapy protocol for each specific patient. Anyway, not only imaging methods but also proteomics and gene expression methods will facilitate BNCT becoming a modality of personalized medicine. This work provides an overview of the fundamental principles, recent advances, and future directions of BNCT as cell-targeted cancer therapy for personalized radiation treatment.
ARTICLE | doi:10.20944/preprints201912.0382.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: glioblastoma multiforme; MGMT; IDH1; EGFR; P53; ATRX; Ki67; neurosurgery; oncology; epilepsy
Online: 29 December 2019 (13:04:12 CET)
Glioblastoma is a solid, infiltrating and the most frequent highly malignant primary brain tumor. Our aim was to find the prognostic value of mutations of IDH1, MGMT, EGFR, p53, ATRX, Ki67 genes and the correlation between sex, age, presenting with seizures, number of interventions, extent of resection with Overall Survival (OS), Progression Free Survival (PFS) and Karnofsky performance status (KPS) score. A randomized retrospective analysis of 122 patients treated by a single operator at Sapienza University of Rome, was carried out. After surgery patients followed standard treatment Stupp protocol . Exclusion criteria were: patients with primitive brainstem and spinal cord gliomas and patients who underwent partial resections (resection < 90%) and cases of brain biopsy exclusively for diagnostic purposes. Statistical analysis with a simultaneous regression model was carried on by SPSS 25 ® (IBM) program. Results showed statistically significant survival increase in four groups: 1) patients treated with gross total resection (p< 0.03); 2) patients with methylated MGMT promoter (p<0.005); 3) patients with non EGFR amplification or EGFRvIII mutation (p<0.035); 4) mutated IDH1/IDH2 (p<0.0161). Higher survival rates (but not statistically significant) were observed also in patients with: age < 75 years, Ki 67 <10%, lesions in non eloquent areas, ATRX gene mutation and presentation with seizures.
REVIEW | doi:10.20944/preprints201807.0071.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: precision medicine; next generation sequencing; oncology, patient outcomes; health insurance coverage
Online: 4 July 2018 (11:06:43 CEST)
Precision medicine seeks to use genomic data to help provide the right treatment to the right patient at the right time. Next-generation sequencing technology allows for the rapid and accurate sequencing of many genes at once. This technology is becoming more common in oncology, though the clinical benefit of incorporating it into precision medicine strategies remains under significant debate. In this manuscript, we discuss the early findings of the impact of next-generation sequencing on cancer patient outcomes. We investigate why not all patients with genomic variants linked to a specific therapy receive that therapy and describe current barriers. Finally, we explore the current state of health insurance coverage for individual genome sequencing and targeted therapies for cancer. Based on our analysis, we recommend increased transparency around the determination of “actionable mutations” and a heightened focus on investigating the variations in health insurance coverage across patients receiving sequencing-matched therapies.
REVIEW | doi:10.20944/preprints202310.1655.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Graph Neural Network; GNN; Deep Learning; Cancer; Oncology; Graphical Model; Bayesian Network
Online: 26 October 2023 (03:33:36 CEST)
Next-generation cancer and oncology research needs to take full advantage of the multi-modal structured, or graph, information, with the graph datatypes ranging from molecular structures to spatially resolved imaging and digital pathology to biological networks to knowledge graphs. Graph Neural Networks (GNNs) efficiently combine the graph structure representations with the high predictive performance of deep learning, especially on the large multi-modal datasets. In this review article, we survey the landscape of recent (2020-present) GNN applications in the context of cancer and oncology research, and delineate six currently predominant research areas. Subsequently, we identify the most promising directions for future research. We compare GNNs with graphical models and "non-structured" deep learning, and devise the guidelines for cancer and oncology researchers or physician-scientists asking the question of whether they should adopt the GNN methodology in their research pipelines.
REVIEW | doi:10.20944/preprints202308.0404.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: aortic stenosis, cancer, valve replacement, cardio-oncology, transcatheter valve implantation, radiation therapy
Online: 4 August 2023 (11:44:10 CEST)
Aortic valve stenosis and malignancy frequently coexist and share the same risk factors as atherosclerotic disease. Data reporting the prognosis of patients with severe aortic stenosis and cancer are limited. Tailoring the correct and most optimal care for cancer patients with severe aortic stenosis is complex. Cancer patients may be further disadvantaged by aortic stenosis if it interferes with their treatment by increasing the risk associated with oncologic surgery and compounding the risks associated with cardiotoxicity and heart failure (HF). Nowadays, several therapeutic options are available for aortic valve stenosis (surgical valve replacement , transcatheter valve implantation, balloon valvuloplasty, or medical therapy), but in presence of malignancy, the use of one of these versus the others should be decided on a case-by-case approach, depending on cancer stage and associated treatment, expected outcome, comorbidities and after an accurate physical examination and Doppler-echocardiography which are the key tools for diagnosing and evaluating aortic stenosis. The current review considers the available data on the association between aortic stenosis and cancer, and therapeutic options.
REVIEW | doi:10.20944/preprints202306.1788.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Meningioma; Cabozantinib; VEGF; Targeted treatment Cabozantinib; METs; VEGFR2; Inhibitors; Angiogen-esis; Oncology
Online: 26 June 2023 (10:57:00 CEST)
Meningiomas are cerebral cancers that arise from abnormal cell development in the meninges and defensive layers covering the mind and spinal line. They can attack areas close to the cerebrum tissue and apply tension to neighboring designs, prompting different neurological side effects. Recent advances in atomic science and genomics have revealed insights into the fundamental subatomic adjustments and flagging pathways involved in the improvement of meningoma. Cabozantinib, a chemotherapeutic agent, has shown promising results in preclinical and clinical studies in various malignancies, including meningia. It inhibits angiogenesis, reduces cancer development, and prompts cell passage, providing areas of strength for clinical examination. Inhibition of VEGFR2 signaling has shown promise results in clinical trials in various cancer types, including a variety of cancers. This review summarizes the current knowledge on the pathophysiology and potential therapeutic effects of cabozanteb as a therapeutic agent for intracranial meninga.
REVIEW | doi:10.20944/preprints202306.0428.v1
Subject: Public Health And Healthcare, Health Policy And Services Keywords: quality of life; health-related quality of life; psychosocial factors; psycho-oncology
Online: 6 June 2023 (09:36:11 CEST)
The quality of life (QOL) is an important indicator of human satisfaction and wellbeing. QOL is significantly and persistently affected for patients after a cancer diagnosis. Despite some evidence suggesting that psycho-oncologic interventions can provide lasting benefits, the inclusion of such interventions in cancer therapy is not universal. This article overviews known approaches to the evaluation of QOL in cancer patients and various interventions for improving patients’ outcomes with a focus on the Eastern European regional and specific Romanian context. With a mortality rate above and cancer care performance below the EU average and unequally distributed, Roma-nia urgently needs a national coordination program which is discussed in our review highlighting the main psychological tools needed for the assessment and its challenges towards implementing the program. In the end, we suggest some directions for future development of the psycho-oncologic approach in the context of social, policy and unexpected financial challenges the nation provides
REVIEW | doi:10.20944/preprints202212.0354.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Anthracyclines; Cardiotoxicity; Heart failure; Chemotherapy toxicity; Cardio-Oncology; Breast cancer; Haematological cancer
Online: 20 December 2022 (04:26:21 CET)
Background: Anthracyclines form the backbone of many systemic chemotherapy regimens but dose-limiting cardiotoxicity can also lead to reduction in cardiac function and an increased risk of heart failure. Methods: This review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD42022373496). Results: 26 studies met the eligibility criteria including a total of 910 patients. Overall reduction in pooled mean left ventricular ejection fraction (LVEF) post‐anthracyclines in the placebo arms of included randomised-controlled trials was 4.6% (95% CI, 2.7 to 6.6). The trend in LVEF showed a progressive decline until approximately 180 days after which there was no significant change. Those receiving a cumulative anthracycline dose 300 mg/m2 experienced a more profound reduction. The risk of a 10% absolute decline in LVEF from baseline or decline to an LVEF below 50%, the overall pooled risk was 16% (95% CI: 11 to 21; I2 = 77%). Sensitivity analyses by baseline LVEF and trastuzumab treatment status did not yield significant differences. Conclusion: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines are required.
ARTICLE | doi:10.20944/preprints202107.0578.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: docetaxel; combination therapy; nanoparticles; head and neck squamous cell carcinoma; oncology; therapies
Online: 26 July 2021 (14:04:49 CEST)
Objective: The combination of docetaxel (DTX) with Laser-Activated NanoTherapy (LANT), as a treatment for head and neck cancer (HNC) may enhance the therapeutic efficacy of lower doses of DTX, thereby minimizing the effective dosage, side effects and treatment times. Material and methods: Three HNSCC cell lines, Detroit 562, FaDu, and CAL 27, were treated with four combinations of DTX + LANT to evaluate DTX dose reduction and cell viability. Results: The 1 nM DTX + 5 nM LANT combination was the most effective treatment, increasing cell death over its corresponding DTX monotreatment with approximately 86.6%, 80.7%, and 92.1% cell death for Detroit 562, FaDu, and CAL 27, respectively. In Detroit 562, the 1 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 84.6%; in FaDu and CAL 27, the 0.5 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 78.2% and 82.4%, respectively. Conclusion: LANT may increase the therapeutic efficacy of DTX at significantly lower doses, which could improve patient outcomes.
COMMUNICATION | doi:10.20944/preprints202003.0350.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: COVID-19; SARS-CoV-2; coronavirus; novel coronavirus; department policy; radiation oncology
Online: 23 March 2020 (09:55:24 CET)
The COVID-19 pandemic is placing unprecedented stress on healthcare systems around the world. Although Radiation Oncology Departments are not at the frontline of fighting this infectious disease, it is important to implement COVID-19 policies to reduce risk of staff and patient exposure, and to limit the risk of department shutdown or downtime. This brief report describes the policy implemented at George Washington University Radiation Oncology to manage the risks of COVID-19. This includes a General Statement related to the priorities of the Radiation Oncology department, a screening procedure for new and follow-up patients, management policies for critical and non-critical patients with COVID-19 or under quarantine, a policy for the management of patients currently under treatment who are diagnosed or placed in quarantine, a clinical escalation action plan, guidelines for staff meetings and travel, and procedure management. This policy was implemented at George Washington University Radiation Oncology after the first case of COVID-19 was reported in Washington DC on March 7, 2020.
REVIEW | doi:10.20944/preprints202310.1750.v1
Subject: Medicine And Pharmacology, Hematology Keywords: Atherosclerotic; Inflammation; Bone marrow; Clonal Hematopoiesis; Myeloproliferative Neoplasm; Autoimmunity; Cardiovascular Risk; Cardio-Oncology
Online: 30 October 2023 (06:54:10 CET)
: For a long time, atherosclerosis has been regarded as a mere lipid deposit in the blood vessels. However, in the recent years a growing body of experimental and clinical evidence have highlighted the role of inflammation and immunity as a central mechanism of disease. Moreover, in the last decade the coming of next-generation sequencing and its application to large human population has broken the barrier between inflammation and cancer. Indeed, acquired mutation in key genes related to the control of hematopoiesis and myeloproliferation have paved the way to establish the new concept of clonal hematopoiesis of indeterminate potential. This phenomenon is being considered not such “indeterminate”, but as an emerging cardiovascular risk factor. Thus, this may explain the mechanisms of myeloproliferation and inflammation in atherosclerosis. And in a bidirectional journey, it has helped to explain the extremely high cardiovascular risk in cancer survivors, in particular in myeloprolfierative neoplasm patients. A deeper understanding of these mechanisms may pave the way for the future early diagnosis and potential preemptive treatments of the leading worldwide cause of death.
ARTICLE | doi:10.20944/preprints202305.0884.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: food for special medical purposes; FSMP; qualitative research; nutritional needs for oncology patients
Online: 12 May 2023 (05:01:14 CEST)
This study aimed to investigate Romanian physicians' awareness, recommendation practices, and opinions regarding using Foods for Special Medical Purposes (FSMPs) products. A total of ten physicians were interviewed using a structured questionnaire, and their responses were analysed using thematic content analysis. The study found that physicians were aware of FSMPs and recommended them to their patients based on nutritional deficits, weight loss, or deglutition impairments. In addition, disease stage, treatment scheme, taste, affordability, and availability were identified as factors influencing the recommendation and use of FSMPs. While physicians generally did not consult clinical trials, clinical experience was deemed essential for recommending FSMPs to patients. Patients' feedback regarding the usage and sourcing of FSMPs was generally positive, with some expressing concerns about the availability of different flavours and the costs of purchasing the products. The study concludes that physicians play a vital role in recommending FSMPs to patients and ensuring they have the necessary nutritional support during treatment. However, more patient education materials and collaboration with nutritionists may be required to improve patient outcomes and reduce patient financial burden.
REVIEW | doi:10.20944/preprints202212.0300.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: medulloblastoma; TP53 mutation; molecular classification; diagnostics; liquid biopsy; animal models; transcriptome; precision oncology
Online: 16 December 2022 (08:47:35 CET)
A recent paradigm shift in diagnostics of medulloblastoma allows the distinction of four major groups defined by genetic data rather than histology. This new molecular classification correlates better with prognosis and will allow better clinical management for therapies targeting druggable mutations, but also offers a new combination of monitoring tumor development in real-time and treatment response by sequential liquid biopsy. This review highlights recent developments after a century of milestones in neurosurgery, radio- and chemotherapy, but also controversial theories on the cell of origin, animal models and the use of liquid biopsy.
REVIEW | doi:10.20944/preprints202004.0541.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: humanized mice; human immune system; preclinical oncology model; metastasis model; immunotherapy; efficacy; safety
Online: 30 April 2020 (17:10:32 CEST)
Metastases cause high mortality in several cancers and immunotherapies are expected to be effective in the prevention and treatment of metastatic disease. However, only a minority of patients benefit from immunotherapies. This creates a need for novel therapies that are efficacious regardless of the cancer types and metastatic environments they are growing in. Preclinical immuno-oncology models for studying metastases have long been limited to syngeneic or carcinogenesis-inducible models that have murine cancer and immune cells. However, the translational power of these models has been questioned. Interactions between tumor and immune cells are often species-specific and regulated by different cytokines in mice and humans. For increased translational power, mice engrafted with functional parts of human immune system have been developed. These humanized mice are utilized to advance understanding the role of immune cells in the metastatic process, but increasingly also to study the efficacy and safety of novel immunotherapies. From these aspects, this review will discuss the role of immune cells in the metastatic process and the utility of humanized mouse models in immuno-oncology research for metastatic cancers, covering several models from the perspective of efficacy and safety of immunotherapies.
REVIEW | doi:10.20944/preprints202308.0109.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: preclinical; oncology; 3D culture; organ-on-a-chip; spheroid; organoid; 3D bioprinting; drug screening
Online: 2 August 2023 (02:48:00 CEST)
Prior to clinical trials, preclinical testing of oncology drug candidates is performed by evaluating drug candidates with in vitro and in vivo platforms. For in vivo testing, animal models are used to evaluate the toxicity and efficacy of drug candidates. However, animal models often display poor translational results as many drugs that pass preclinical testing fail when tested in humans, with oncology drugs exhibiting especially poor acceptance rates. The FDA Modernization Act 2.0 promotes alternative preclinical testing techniques, presenting the opportunity to use higher complexity in vitro models as an alternative to in vivo testing, including 3D cell culture models. 3D tissue cultures address many of the shortcomings of 2D cultures by more closely replicating the tumour microenvironment through a combination of realistic drug diffusion, paracrine signaling, cellular phenotype, and vascularization that can better mimic native human tissue. This review will discuss the common forms of 3D cell culture, including cell spheroids, organoids, organs-on-a-chip, and 3D bioprinted tissues. Their advantages and limitations will be presented, aiming to discuss the use of these 3D models to accurately represent human tissue and as an alternative to animal testing. The use of 3D culture platforms for preclinical drug development is expected to accelerate as these platforms continue to improve in complexity, reliability, and translational predictivity.
ARTICLE | doi:10.20944/preprints202207.0262.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: sarcoma; multidisciplinary team / MDT; sarcoma surgery; orthopedic oncology; real-world data registry; exposure; experience
Online: 18 July 2022 (10:18:33 CEST)
Purpose: To meet the challenges of the precision medicine era, quality assessment of shared sarcoma care becomes pivotal. The MDT approach is the most important parameter for succesfull outcome. Because of all MDTs disciplines surgery is the key step to render sarcoma patients disease free, defining the spectrum of a sarcoma surgeon is critical. To the best of the authors knowledge, a comprehensive interoperable digital platform to assess the scope of sarcoma surgery and the experience of a sarcoma surgeon in its full complexity is lacking. Methods: A web-based real-world data (RWD) registry on sarcoma surgery has been created to assess the clinical exposure, tumor characteristics, and surgical settings and techniques applied for both resections and reconstructions of sarcomas and thereby the surgical exposure of an individual surgeon over time. Results: During 10 years, there were 723 sarcoma board/MDT meetings discussing 3130 patients. A total of 1094 patients underwent 1250 surgical interventions on mesenchymal tumors by one single sarcoma surgeon. These included 615 deep soft tissue tumors (197 benign, 102 intermediate, 281 malignant, 27 simulator, 7 metastasis, 1 blood), 116 superficial soft tissue tumors (45 benign, 12 intermediate, 40 malignant, 18 simulator, 1 blood) and 519 bone tumors (129 benign, 112 intermediate, 182 malignant, 18 simulator, 46 metastasis, 14 blood and 18 sequelae of 1st treatment). Detailed types of resections and reconstructions were analyzed. Conclusion: A web-based RWD sarcoma surgeon registry with transparent real-time descriptive analytics is feasible and enables large scale definition of the surgical complexity and ultimately quality of sarcoma care.
REVIEW | doi:10.20944/preprints202201.0208.v1
Subject: Medicine And Pharmacology, Hematology Keywords: End of Life; Advance Directives; Advance Care Planning; Intensive Care, Medical Oncology; malignant hemopathy
Online: 14 January 2022 (11:34:51 CET)
Patients living with cancer often experience serious adverse events due to their condition or its treatments. Those events may lead to a critical care unit admission or even result in death. One of the most important but challenging part of care is to build a caring plan according to the patient’s wishes, meeting his goals and values. Advance directives (ADs) allow everyone to give their preferences in advance regarding life sustaining treatments, continuation, and withdrawal or withholding of treatments in case one is not able to speak his mind anymore. While the absence of ADs is associated with a greater probability of receiving unwanted intensive care around the end of his life, their existence correlates with the respect of the patient’s desires and his greater satisfaction. Although progress has been made to promote ADs’ completion, they are still scarcely used among cancer patients in many countries. Several limitations to their acceptation and use can be detected. Efforts should be made to provide tailored solutions for the identified hindrances. This narrative review aims to depict the situation of ADs in the oncology context, and to highlight the future areas of improvement.
ARTICLE | doi:10.20944/preprints202012.0166.v1
Subject: Computer Science And Mathematics, Algebra And Number Theory Keywords: Mathematical oncology; CAR-T cells; mathematical immunology; mathematical modelling; immunotherapy of solid tumours; glioblastoma
Online: 7 December 2020 (15:06:37 CET)
Chimeric antigen receptor (CAR)-T cell-based therapies have achieved substantial successes against B-cell malignancies, what has led to a growing scientific and clinical interest on extending their use to solid cancers. However, results for solid tumours have been limited up to now, in part due to the immuno-suppressive tumour microenvironment, that is able to inactivate CAR-T cell clones. In this paper we put forward a mathematical model describing the competition of CAR-T and tumour cells, accounting for their immunosuppressive capabilities. Using the mathematical model, we show that the use of large numbers of CAR-T cells targeting the solid tumour antigens could overcome the cancer immunosuppressive potential. To achieve such high levels of CAR-T cells we propose and study computationaly, the manufacture and injection of CAR-T cells targeting two antigens: CD19 and a tumour-associated antigen. We study in-silico the resulting dynamics of the disease after the injection of this product and find that the expansion of the CAR-T cell population in the blood and lymphopoietic organs could lead to the massive generation of an army of CAR-T cells targetting the solid tumour, and potentially overcoming its inmune suppression capabilities. That strategy could benefit from the combination with PD-1 inhibitors and of low tumour loads. Our computational results provide a theoretical support for the treatment of different types of solid tumours using T-cells engineered with combination treatments of dual CARs with on- and off-tumour activity and anti-PD1 drugs after completion of classical cytoreductive treatments.
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Acute Lymphoblastic Leukaemia; Flow Cytometry Data; Fisher’s Ratio; CD38; mathematical oncology; response biomarkers; personalized medicine
Online: 27 October 2020 (15:20:10 CET)
Artificial intelligence methods may help in unveliling information hidden in high-dimensional oncological data. Flow cytometry studies of haematological malignancies provide quantitative data with the potential to be used for the construction of response biomarkers. Many computational methods from the bioinformatics toolbox can be applied to these data but have not been exploited in their full potential in leukaemias, specifically for the case of childhood B-cell acute lymphoblastic leukemia. In this paper we analysed flow cytometry data obtained on diagnosis from 54 paediatric B-cell acute lymphoblastic leukemia patients from two local institutions. We constructed classifiers based on the Fisher’s Ratio to quantify differences in expression levels of immunophenotypical markers between patients with relapsing and non-relapsing disease. The distribution of the marker CD38 was found and validated to have a strong discriminating power between both patient cohorts, thus providing a classifier.
COMMENTARY | doi:10.3390/sci2030070
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: small molecule inhibitor; personalized medicine; precision medicine; oncology; targeted therapy; drug delivery; drug screening; chemotherapy
Online: 8 September 2020 (00:00:00 CEST)
The development of targeted therapeutics for cancer continues to receive intense research attention as laboratories and pharmaceutical companies seek to develop drugs and technologies that improve treatment efficacy and mitigate harmful side effects. In the aftermath of World War I, it was discovered that mustard gas destroys rapidly dividing cells and could be used to treat cancer. Since then, chemotherapy has remained a predominant treatment for cancer; however, the destruction of dividing cells throughout the body yields devastating side effects including off-target damage of the digestive tract, bone marrow, skin, and reproductive tract. Furthermore, the high mutation rate of cancerous cells often renders chemotherapy ineffective long-term. Therapies with improved specificity, localization, and efficacy are redefining cancer treatment. Herein, we define and summarize the principal advancements in targeted cancer treatment and briefly comment on the march towards personalized medicine in the treatment of human cancer.
REVIEW | doi:10.20944/preprints201912.0242.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: animal-assisted interventions; animal-assisted activities; animal-assisted therapy; oncology; cancer; human-animal bond; quantitative
Online: 19 December 2019 (06:41:38 CET)
Animal-assisted interventions (AAI) use human-animal interactions to positive effect in various contexts including cancer care. This systematic literature review is the first part of a two-part paper series focusing on the research methods and quantitative results of AAI studies in oncology. We find methodological consistency in the use of canines as therapy animals, in the types of high-risk patients excluded from studies, and in the infection precautions taken with therapy animals throughout cancer wards. The investigated patient endpoints are not significantly affected by AAI, with the exceptions of improvements in oxygen consumption, quality of life, depression, mood, and satisfaction with therapy. The AAI field in oncology has progressed significantly since its inception and has great potential to positively impact future patient outcomes. To advance the field, AAI research in oncology should consistently improve the methodological design of studies, report data more completely, and focus on the therapy animal’s well-being.
REVIEW | doi:10.20944/preprints202305.1637.v2
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: computational; drug repurposing; drug repositioning; cancer; combination therapy; network biology; machine learning; deep learning; precision oncology
Online: 20 July 2023 (05:02:16 CEST)
As cancer remains resistant to several modes of treatment, novel therapeutics are still under active investigation to overcome treatment inefficacy in cancer. Given the high attrition rate of de novo drug discovery, drug screening, and drug repurposing have offered time- and cost-effective alternative strategies for the identification of potentially effective therapeutics. In contrast to large-scale drug screens, computational approaches for drug repurposing leverage the increasing amounts of biomedical data to predict candidate therapeutic agents prior to testing in biological models. Current studies in drug repurposing for cancer therapy prediction have increasingly focused on the prediction of combination therapies, as combination therapies have numerous advantages over monotherapies. These include increased effect from synergistic interactions, reduced toxicity from lowered drug doses, and a reduced risk of resistance due to multiple non-overlapping mechanisms of action. This review provides a summary of several classes of computational methods used for drug combination therapy prediction in cancer research, including networks, regression-based machine learning, classifier machine learning models, and deep learning approaches, with the goal of presenting current progress in the field, particularly to non-computational cancer biologists. We conclude by discussing the need for further advancements in technologies that incorporate disease mechanisms, drug characteristics, multi-omics data, and clinical considerations to generate effective patient-specific drug combinations, as holistic data integration will inevitably result in optimal targeted therapeutics for cancer.
ARTICLE | doi:10.20944/preprints202304.1077.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: Multimodal Data Integration; Radiotherapy Standard Name mapping; Radiation Oncology; Machine Learning; Deep Learning; TG-263 Names
Online: 27 April 2023 (11:01:18 CEST)
Physicians often label anatomical structure sets in Digital Imaging and Communications in Medicine (DICOM) images with nonstandard names. As these names vary widely, the standardization of the nonstandard names in the Organs at Risk (OARs), Planning Target Volumes (PTVs), and 'Other' organs inside the area of interest is a vital problem. Prior works considered traditional machine learning approaches on structure sets with moderate success. This paper presents integrated deep learning methods applied to structure sets by integrating the multimodal data compiled from the radiotherapy centers administered by the US Veterans Health Administration (VHA) and the Department of Radiation Oncology at Virginia Commonwealth University (VCU). The de-identified radiation oncology data collected from VHA and VCU radiotherapy centers have 16,290 prostate structures. Our method integrates the heterogeneous (textual and imaging) multimodal data with Convolutional Neural Network (CNN)-based deep learning approaches like CNN, Visual Geometry Group (VGG) network, and Residual Network (ResNet). Our model presents improved results in prostate (RT) structure name standardization. Evaluation of our methods with macro-averaged F1 Score shows that our deep learning model with single-modal textual data usually performs better than the previous studies. We also experimented with various combinations of multimodal data (masked images, masked dose) besides textual data. The models perform well on the textual data alone, while the addition of imaging data shows that deep neural networks can achieve improved performance using information present in the other modalities. Additionally, using masked images and masked doses along with text leads to an overall performance improvement with the various CNN-based architectures than using all the modalities together. Undersampling the majority class leads to further performance enhancement. The VGG network on the masked image-dose data combined with CNNs on the text data performs the best and establishes the state-of-the-art in this domain.
REVIEW | doi:10.20944/preprints202207.0256.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: cancer; immunotherapy; adverse events; immune checkpoints inhibitors; chimeric antigen receptor therapy; bispecific antibodies; toxicity; renal; oncology
Online: 18 July 2022 (09:21:56 CEST)
Modern oncological therapy utilizes various types of immunotherapy. Immune checkpoint inhib-itors (ICIs), chimeric antigen receptor T cells (CAR-T) therapy, cancer vaccines and bispecific an-tibodies are improving patients’ outcomes. However, stimulation of the immune system, benefi-cial in terms of fighting against cancer, generates the risk of harm to other cells in a patient's body. Kidney damage belongs to the relatively rare adverse events (AEs). Best described, but still, su-perficially, are renal AEs in patients treated with ICIs. International guidelines issued by Euro-pean Society for Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) cover the management of immune-related adverse events (irAEs) during ICI therapy. There are scarce data concerning renal adverse drug reactions of other immunotherapeutic methods. This implicates the need for the collection of safety data during ongoing clinical trials and in the re-al-life world to characterize the hazard related to the use of new immunotherapies and manage-ment of irAEs.
ARTICLE | doi:10.20944/preprints202112.0306.v2
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: learning health system; ambulatory clinic; block schedule; disease site teams; interdisciplinary care; cancer operations; oncology value stream
Online: 26 April 2022 (04:37:15 CEST)
Abstract: Ambulatory cancer centers face fluctuating patient demand and deploy specialized personnel who have variable availability. This undermines operational stability through misa-lignment of resources to patient needs, resulting in overscheduled clinics, budget deficits, and wait times exceeding provincial targets. We describe deployment of a Learning Health System framework for operational improvements within the entire ambulatory center. Known methods of value stream mapping, operations research and statistical process control were applied to achieve organizational high performance that is data-informed, agile and adaptive. We transitioned from a fixed template model by individual physician to a caseload management by disease site model that is realigned quarterly. We adapted a block schedule model for the ambulatory oncology clinic to align the regional demand for specialized services with optimized human and physical resources. We demonstrated improved utilization of clinical space, increased weekly consistency and im-proved distribution of activity across the workweek. Increased value, represented as the ratio of monthly encounters per nursing worked hours, and increased percentage of services delivered by full-time nurses were benefits realized in our cancer system. The creation of a data-informed demand capacity model enables application of predictive analytics and business intelligence tools that will further enhance clinical responsiveness..
REVIEW | doi:10.20944/preprints202103.0342.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: glioblastoma; high-grade glioma; refractory glioma; direct delivery; convection enhanced delivery; neuro-oncology; refractory glioblastoma; clinical trials
Online: 12 March 2021 (15:01:51 CET)
Development of effective treatments for high-grade glioma (HGG) is hampered by 1) the blood-brain barrier (BBB), 2) an infiltrative growth pattern, 3) rapid development of therapeutic resistance, and, in many cases, 4) dose-limiting toxicity due to systemic exposure. Convec-tion-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and in-crease therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.
REVIEW | doi:10.20944/preprints202012.0239.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: glioblastoma; high-grade glioma; refractory glioma; virotherapy; oncolytic viruses; neuro-oncology; refractory glioblastoma; chimeric viruses; clinical trials
Online: 9 December 2020 (20:13:56 CET)
As new treatment modalities are being explored in neuro-oncology, viruses are emerging as a promising class of therapeutics. Virotherapy consists of introduction of either wild-type or engineered viruses to the site of disease, where they exert anti-tumor effect. These viruses can either be non-lytic, in which case they are used to deliver gene therapy, or lytic, which induce tumor cell lysis and subsequent host immunologic response. Replication-competent viruses can then go on to further infect and lyse neighboring glioma cells. This treatment paradigm is being explored extensively in both preclinical and clinical studies for a variety of indications. Virus-based therapies are advantageous due to the natural susceptibility of glioma cells to viral infection, which improves therapeutic selectivity. Furthermore, lytic viruses expose glioma antigens to the host immune system and subsequently stimulate an immune response that specifically targets tumor cells. This review surveys the current landscape of oncolytic virotherapy clinical trials in high-grade glioma, summarizes preclinical experiences, identifies challenges associated with this modality across multiple trials, and highlights potential to integrate this therapeutic strategy into promising combinatory approaches.
REVIEW | doi:10.20944/preprints201912.0243.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: animal-assisted interventions; animal-assisted activities; animal-assisted therapy; oncology; cancer; human-animal bond; mechanisms; theoretical frameworks
Online: 19 December 2019 (06:45:23 CET)
Animal-assisted interventions (AAI) are a unique class of complementary medical treatments that can improve a patient’s quality of life, both physically and psychologically. Part I of this two-paper systematic literature review series focused on the study methods and quantitative results of researchers in this field. We continue this in-depth review here in Part II by discussing the common theories associated with AAI in the context of cancer. Of all the factors at work in human-animal interactions, researchers explicitly cite compatible animal personality, physical touch, physical movement, distraction/entertainment, and increased human interaction as the mechanisms responsible for the positive clinical outcomes observed in AAI. In various combinations, these mechanisms group under broader theoretical frameworks that attempt to fully explain the AAI context as it relates to cancer care. The social support hypothesis and the conception of a human-animal bond are the most referenced overarching frameworks. The cognitive activation theory of stress, the science of unitary human beings, and the self-object hypothesis are also referenced. We briefly consider other relevant theories commonly noted in the human-animal interactions literature that have the potential to clarify aspects of cancer-related AAI. We also discuss the neurobiological transduction mechanisms needed to connect theoretical frameworks and their mechanisms directly to the observed clinical outcomes. To advance the field, researchers should consider overarching theories with testable hypotheses when designing studies, and use consistent terminology when reporting results. This review lays a foundation for progress towards a unified theoretical framework and for effective treatment of the whole cancer patient.
REVIEW | doi:10.20944/preprints202311.0017.v1
Subject: Public Health And Healthcare, Primary Health Care Keywords: nanomedicine; CNS cancer; therapeutics; blood-brain barrier; personalized medicine; nanoparticles; COVID-19; drug delivery; regulatory landscape; precision oncology
Online: 1 November 2023 (08:31:47 CET)
Central Nervous System (CNS) cancers pose a formidable challenge in the medical world, characterized by aggressive behaviors and limited therapeutic options. The emergence of nanomedicine has offered new hope in CNS cancer treatment. The COVID-19 pandemic has further accelerated the need for innovative therapeutic strategies, emphasizing the significance of nanomedicine in this era. This mini review explores the current status of nanomedicine in CNS cancer therapy, with a particular focus on the post-COVID-19 landscape. We discuss the unique challenges presented by CNS cancers, the potential of nanomedicine in overcoming these challenges, and the recent developments in the field. Additionally, we highlight the lessons learned from the pandemic and how they can be applied to improve CNS cancer therapeutics. We also shed light on the evolving regulatory landscape and the prospects of personalized nanomedicine in CNS cancer treatment. The integration of nanomedicine in CNS cancer therapy is becoming increasingly promising, and its role in the post-COVID-19 era is poised to shape the future of neuro-oncology.
REVIEW | doi:10.20944/preprints202308.1613.v1
Subject: Medicine And Pharmacology, Internal Medicine Keywords: Albumin levels; pre-Albumin levels; Emergency Department; Nephrology; Cardiology; Oncology; Infectious Diseases; Intensive Care Units; Rheumatologig Autoimmune Diseases.
Online: 23 August 2023 (09:14:44 CEST)
Serum albumin (ALB), one of the most important proteins in human physiology, has the main functions of maintaining plasma oncotic pressure and plasma volume, transporting hormones, vitamins, oligominerals and drugs, and exerting a powerful antioxidant-antiinflammatory role. Its prognostic value in liver and malabsorption syndromes is well known. In this narrative review, an analysis of the most important studies evaluating the prognostic significance of low serum ALB levels in hospitalized patients was performed. Specifically, the risk in emergency medicine, cardiovascular diseases, COVID-19 infection, nephrology, oncology and autoimmune rheumatic diseases has been examined to fully explore its clinical value. ALB is a negative acute-phase reactant and the reduction of its serum levels represents a threatening parameter for long-term survival in several clinical settings, and a strong poor prognostic biomarker in most diseases. Therefore, clinicians should consider serum ALB as a valuable tool to assess the efficacy of specific therapies, both in hospitalized patients and in chronic follow-up.
ARTICLE | doi:10.20944/preprints202307.0781.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: DNA repair; homologous recombination deficiency; biomarkers; precision oncology; loss of heterozygosity; inhibitors of poly (ADP-ribose) polymerase (PARP)
Online: 12 July 2023 (07:50:04 CEST)
Several tumor types have been efficiently treated with PARPis, which are now approved for the treatment of ovarian, breast, prostate, and pancreatic cancer. The BRCA1/2 genes and mutations in many additional genes involved in the HR pathway may be responsible for the HRD phenomenon. In the present study, an NGS assay was used to analyze 513 genes associated with targeted and immuno-oncology therapies in 406 samples. In addition, the %gLOH values of 24 samples were also calculated using the Affymetrix technology to compare the results obtained by the two methodologies. HR variations occurred in 20.93% of the malignancies, while BRCA1/2 gene alterations in 5.17%. %LOH was highly correlated with alterations in the BRCA1/2 genes since 76.19% (16/21) of the BRCA1/2 positive tumors had a high %LOH value (p=0.007). Moreover, the LOH status was highly correlated with the TP53 and KRAS statuses, but there was no association with the TMB value. Lin's Concordance Correlation Coefficient for the 24 evaluable samples simultaneously examined by both assays was 0.87, indicating a nearly perfect agreement. In conclusion, the addition of gLOH analysis could assist the detection of additional patients eligible for PARPis
ARTICLE | doi:10.20944/preprints202309.1880.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: FLAIR infiltration; brain tumors; extent of surgical resection; glioblastoma; overall survival; progression-free survival; pseudocapsule; neuro-oncology; tumor volume
Online: 28 September 2023 (03:26:09 CEST)
Background: Glioblastoma is the most common primary brain neoplasm in adults, with still a poor prognosis despite a constant effort to improve patients’ survival. Some neuroradiological volumetric parameters seem to play a predictive role on Overall Survival (OS) and Progression Free Survival (PFS). The aim of this study is to analyze the impact that the volumetric areas of contrast-enhancing tumor and perineoplastic edema have on survival of patients treated for glioblastoma; Methods: A series of 87 patients who underwent surgery was retrospectively analyzed; OS and PFS were considered as the end points of the study. For each patient a multidisciplinary revision was conducted in collaboration with the Neuroradiology and Neuro-Oncology board. A manual and semi-automatic measurement were adopted to perform the radiological evaluation: contrast Enhancement Preoperative (CE-PTV) and Postoperative Tumor Volume (CE-RTV), Edema/Infiltration Preoperative (T2/FLAIR-PV) and Postoperative Volume (T2/FLAIR-RV); necrosis volume inside the tumor (NV); total tumor volume, including necrosis (TV); Results: The median OS value was 9 months and the median PFS value was 4 m; the mean values were respectively 12,3 m and 6,9 m. Multivariate analysis showed that the OS related factors were: adjuvant chemo-radiotherapy (p < 0,0001), CE-PTV < 15 cm³ (p=0,03), surgical resection > 95% (p=0,004) and the presence of a “pseudo-capsulated” radiological morphology (p=0,04); Conclusions: maximal safe resection is one of the most relevant predictive factors for patients’ survival. The semi-automatic pre-operative MRI evaluation could play a key role in prognostically categorizing these tumors.
ARTICLE | doi:10.20944/preprints202301.0421.v3
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Oncology; Immune Checkpoint Inhibition; PD-1; PD-L1; CTLA-4; Immune Related Adverse Events; Immunotherapy; Tumor Plasticity; Tumor Microenvironment; Optimum Therapy Duration
Online: 6 March 2023 (01:53:16 CET)
Immune checkpoint inhibition therapy (ICIT) is an emerging field in oncology especially opening new horizons to chemotherapy refractory patients. This paper provides deep insight into immune related adverse events (irAEs) posing a major challenge and drawback to ICIT, and presents right management strategies for very complex complications. Moreover, for the first time in literature, a non-linear mathematical model is introduced to measure the ICIT success rate and to decide about the optimum ICIT duration. Furthermore, a strategy is presented to overcome or to delay the progression after initial good response in a subset of patients.
ARTICLE | doi:10.20944/preprints202301.0073.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: metabotropic glutamate 5 receptor; anti-mGluR5 encephalitis; neuroimmunology; pediatric neu-rology; pediatric oncology; transcriptome analysis; Hodgkin lymphoma; Ophelia syndrome
Online: 4 January 2023 (08:47:37 CET)
Ophelia syndrome is characterized by the coincidence of severe neuropsychiatric symptoms, classical Hodgkin lymphoma, and the presence of antibodies to the metabotropic glutamate 5 receptor (mGluR5). Little is known about the pathogenetic link between these symptoms and the role that anti-mGluR5-antibodies play. We investigated lymphoma tissue from patients with Ophelia syndrome and with isolated classical Hodgkin lymphoma by quantitative immunocytochemistry for mGluR5-expression. Further, we studied the L-1236, L-428, L-540, SUP-HD1, KM-H2, and HDLM-2 classical Hodgkin lymphoma cell lines by FACS and Western blot for mGluR5-expression, and by transcriptome analysis. mGluR5 surface expression differed significantly in terms of receptor density, distribution pattern, and percentage of positive cells. Highest expression levels were found in the L-1236 line. RNA-sequencing revealed more than 800 genes that were higher expressed in the L-1236 line in comparison to the other classical Hodgkin lymphoma cell lines. High mGluR5-expression was associated with upregulation of PI3K/AKT and MAPK pathways and of downstream targets (e.g. EGR1) known to be involved in classical Hodgkin lymphoma progression. Finally, mGluR5 expression was increased in the classical Hodgkin lymphoma-tissue of our Ophelia syndrome patient in contrast to five classical Hodgkin lymphoma-patients without autoimmune encephalitis. Given the association of encephalitis and classical Hodgkin lymphoma in Ophelia syndrome, it is possible that mGluR5-expression on classical Hodgkin lymphoma cells not only drives tumor progression but also triggers anti-mGluR5 encephalitis even before classical Hodgkin lymphoma becomes manifest.
ARTICLE | doi:10.20944/preprints202312.0035.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Adolescents and young adults (AYA) cancer; molecular profiling; precision oncology; genomics; whole genome sequencing; next-generation sequencing; sarcoma; diagnostic biomarkers
Online: 1 December 2023 (08:09:28 CET)
Sarcomas are a heterogenous group of tumours that commonly carry poor prognosis with limited therapeutic options. Adolescents and young adults (AYA) with sarcoma are a unique and under-studied patient population that have only achieved modest survival gains compared to other groups. We present our institutional experience of AYA with sarcoma who underwent comprehensive molecular profiling (CMP) using either large-panel targeted DNA sequencing or whole genome and transcriptome sequencing and evaluated the feasibility and clinical impact of this approach. Genomic variants detected were determined to be clinically relevant and actionable following the Molecular Tumour Board evaluation. Clinicians provided feedback regarding the utility of testing three months after reporting. Twenty-five patients who were recruited for CMP are included in this analysis. The median time from consent to final molecular report was 45 days (interquartile range 37-57). Potentially actionable variants were detected for 14 patients (56%) and new treatment recommendations were identified for 12 patients (48%). Pathogenic germline variants were identified in three patients (12%), and one patient had a change of diagnosis. Implementation for CMP for AYA with sarcoma is clinically valuable, feasible and should be increasingly integrated into routine clinical practice as technologies and turnaround times continue to improve.
ARTICLE | doi:10.20944/preprints201808.0227.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: melanocyte; melanoma; oncology; precision medicine; immunotherapy; pigmentation; vitiligo; albinism; melasma; melanin; dermatology; skin; UV; cancer prevention; IFPCS; PASPCR; SMR; IPCC
Online: 13 August 2018 (11:04:12 CEST)
In this perspective, we identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology.
REVIEW | doi:10.20944/preprints202311.1426.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Complementary medicine; alternative medicine; integrative medicine; cancer care; oncology; nutritional supplements; natural products; dietary supplements; unmet needs; patient centered care; Patient doctor communication
Online: 23 November 2023 (17:26:32 CET)
Dietary supplements are widely embraced by cancer patients seeking complementary and integrative approaches to their care. Unfortunately, many patients do not discuss supplement use with physicians, often due to perceptions of physician indifference or negativity toward supplements. This communication gap exposes patients to unreliable information sources and, potentially, unnecessary risk. As the healthcare landscape evolves, patients increasingly value physicians who recognize their pivotal role in shaping healthcare decisions. This patient-centered perspective emphasizes the provision of evidence-based information tailored to individual needs, open discussions on potential risks, and shared decision-making. It underscores the importance of respecting patient autonomy, offering alternative options, documenting preferences, and ensuring ongoing support while coordinating with the healthcare team. To address these needs, healthcare providers should transform their perspectives and become expert guides who embrace patients as informed, empowered participants. This approach prioritizes open dialogue that considers both facts and uncertainties regarding dietary supplement use, allowing for mutually informed decision-making. Here, we review the literature and present a practical approach emphasizing open discussions, transparency, and respect for patient autonomy. Following this approach, healthcare providers can empower patients to navigate the complexities of dietary supplement use in the context of cancer care, ultimately safeguarding patient safety and well-being.
ARTICLE | doi:10.20944/preprints202311.0691.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: faecal microbiota transplantation; autologous faecal microbiota transplantation; autologous haematopoietic stem cell transplantation; haematopoietic stem cell transplantation; HSCT; bone marrow transplantation, multiple myeloma, gut microbiome, gut microbiota; supportive care, supportive oncology
Online: 10 November 2023 (11:56:32 CET)
Haematopoietic stem cell transplantation (HSCT) is a curative approach for blood cancers, yet its efficacy is undermined by a range of acute and chronic complications. In light of mounting evidence to suggest that these complications are linked to a dysbiotic gut microbiome, we aimed to evaluate the feasibility of faecal microbiota transplantation (FMT) delivered during the acute phase after HSCT. Of note, this trial opted for FMT prepared using the individual’s own stool (autologous FMT) to mitigate risks of disease transmission from donor stool. Adults (>18 years) with multiple myeloma were recruited from a single centre. Stool was collected prior to starting first-line therapy. Patients that progressed to HSCT were offered FMT via 3 x re-tention enemas before day +5 (HSCT = day 0). Feasibility was determined by recruitment rate, number and volume of enemas administered, and retention time. Longitudinally collected stool samples were also col-lected to explore the influence of auto-FMT using 16S rRNA gene sequencing. N=4 (2F:2M) participants received auto-FMT in 12 months. Participants received an average of 2.25(1-3) enemas (43.67(25-50)mL total, retained for an average of 60.78(10-145)minutes). No AEs, attributed to the FMT, were identified. Although minimum requirements were met for the volume and retention of auto-FMT, recruitment was significantly impacted by the logistical challenges of pre-therapy stool collection. This ultimately under-mined the feasibility of this trial and suggests that third party (donor) FMT should be prioritised.
REVIEW | doi:10.3390/sci2030068
Subject: Medicine And Pharmacology, Tropical Medicine Keywords: COVID-19; pooling clinical trials; hyperinfection; steroids; treatment; targeted healthcare; population health management; cancer treatment; clinical research; clinical trials; developing vaccines; ranking and rating hospital quality; school closures; interventions for delirium; assessments of COVID-19 death inequities; regulatory safeguards; preventing child abuse and maltreatment; prevalence of health care worker burnout; nursing home ratings; challenging oncology practice; addressing racial; ethnic; social and economic divides; violence against sexual minority adolescents; primary tumors; metastasis; stages of cancer; reforming cancer clinical trials; supporting carers; protection and prevention; benign and malignant tumors; reforming cancer clinical trials; protection of healthcare personnel; comparing excess deaths in NYC; 1918 influenza pandemic; the possibility of full recovery from COVID-19; mental health impact of COVID-19 on young adults; ranking and rating nursing home quali
Online: 21 August 2020 (00:00:00 CEST)
The SARS-CoV-2 virus that causes the COVID-19 disease has wreaked havoc on the world community in terms of every imaginable parameter. The research output on COVID-19 has been nothing short of phenomenal, especially in the medical and biomedical sciences, where the search for a potential vaccine is being conducted in earnest. Much of the advanced research has been distributed in the leading medical journals, including the Journal of the American Medical Association (JAMA), where the latest research is distributed on a daily basis. The purpose of this paper is to provide some perspectives on 44 interesting and highly topical research papers that have been published in JAMA, at the time of writing, within the past two weeks. The diverse topics include public health, general medicine, internal medicine, oncology, paediatrics, geriatrics, and biostatistics.