Background. This study aims to estimate the rate of death by cancer, according to Radio Base Stations (RBS) radiofrequency exposure, especially for the types of breast, cervix, lung and esophagus cancer. Methods. We collected information about the number of deaths by cancer, gender, age group, Gross Domestic Product per capita, death year and the amount of exposure over the lifetime. We investigated all cancer types and some specific types (breast, cervix, lung and esophagus cancers). Results. In capitals where RBS radiofrequency exposure was higher than 2,000/antennas-year, the average mortality rate was 112/100,000 for all cancers. The adjusted analysis showed that the higher the exposure to RBS radiofrequency, the higher cancer mortality. The highest adjusted risk was observed for cervix cancer (Rate Ratio = 2.18). The spatial analysis showed that the highest RBS radiofrequency exposure was observed in a city in southern Brazil, which also showed the highest mortality rate for all types of cancer and specifically for lung and breast cancer. Conclusion. The balance of our results indicates that the exposure to radiofrequency electromagnetic fields from RBS increases the rate of death by all types of cancer.

The real-world outcomes of patients with metastatic prostate cancer (mPCa) are largely unexplored. We investigated the improvements in overall survival (OS) and cancer-specific survival (CSS) in patients with de novo mPCa in latest years. The USA SEER Research Data (2000-2017) were analyzed using the SEER*Stat software. The Kaplan-Meier method and Cox regression were used. Patients with de novo mPCa were allocated to 3 cohorts based on year of diagnosis: A (2000-2003), B (2004-2010), C (2011-2014). Maximum follow-up was fixed to 5 years. Overall, 26434 patients were included. Age, race and metastatic stage significantly affected OS and CSS. After adjustment for age and race, patients in cohort C showed 9% reduced risk of death (HR:0.91 [95% CI, 0.87-0.95], p<0.001) and 8% reduced risk of cancer-specific death (HR:0.91 [95% CI, 0.87-0.95], p<0.001) compared to those in cohort A. After adjustment for age, race and metastatic stage, patients in cohort C showed an improvement in OS and CSS compared to cohort B (HR:0.94 [95% CI, 0.91-0.97], p=0.001 and HR:0.89 [95% CI, 0.85-0.92], p<0.001). Patients with M1c disease had a more pronounced improvement in OS and CSS compared with the other stages. No differences were found between cohort B and C. In conclusion, the prognosis of de novo mPCa remains poor with a median OS of 30 months and a median CSS of 35 months. Limited OS and CSS improvements were observed in latest years.

The purpose of this study was to determine the change in overall survival (OS) for patients with de novo metastatic breast cancer (dnMBC) over time. We conducted a retrospective cohort study with 1981 patients with dnMBC diagnosed between January 1995 and December 2017 at The University of Texas MD Anderson Cancer Center. OS was measured from the date of diagnosis of dnMBC. OS was compared between patients diagnosed during different time periods: 5-year periods and periods defined according to when key agents were approved for clinical use. The median OS was 3.4 years. The 5- and 10-year OS rates improved over time across both types of time periods. A subgroup analysis showed that OS improved significantly over time for the estrogen-receptor-positive/HER2-positive (ER+/HER2+) subtype, and exhibited a tendency toward improvement over time for the ER-negative (ER-)/HER2+ subtype. Median OS was significantly longer in patients with non-inflammatory breast cancer (P = .02) and in patients with ER+ disease, progesterone-receptor-positive disease, HER2+ disease, lower nuclear grade, locoregional therapy, and metastasis to a single organ (all P <.0001). These findings showed that OS at 5 and 10 years after diagnosis in patients with dnMBC improved over time. The significant improvements in OS over time for the ER+/HER2+ subtype and the tendency toward improvement for ER-/HER2+ subtype suggest the contribution of HER2-targeted therapy to survival.

Background: Coffee is the second most popular drink in the worldwide, and it has different components with antioxidant and antitumor properties. The objective of this study was to explore the relationship between coffee consumption and the incidence and mortality of stomach cancer in the main consuming countries. Methods: An observational study was performed. Dataset of coffee consumption was obtained from WorldAtlas, and incidence and mortality rates from GLOBOCAN database. Spearman's rank correlation coefficient was calculated. All statistical analysis were performed using STATA software. Results: A total of 25 countries were included in the study. There was a significant linear correlation between coffee consumption kg per person per year and an estimated age-adjusted incidence (r=0.5984, p=0.0016) and mortality (r=0.5877, p=0.0020). Conclusion: Coffee consumption could potentially have beneficial effects on incidence and mortality by stomach cancer.

Myeloid neoplasms and acute leukemias include different entities that have been recently re-classify taking into account molecular and clinicopathological features. The myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) category comprises a heterogeneous group of hybrid neoplastic myeloid diseases characterized by the co-occurrence of clinical and pathologic features of both myelodysplastic and myeloproliferative neoplasms. The most frequent entity in this category is chronic myelomonocytic leukemia (CMML) which is, after acute myeloid leukemia (AML), the main myeloid disorder prone to develop cutaneous manifestations. Skin lesions associated with myelodysplastic and myeloproliferative neoplasms include a broad clinical, histopathological and molecular spectrum of lesions, poorly understood and without a clear-cut classification in the current medical literature. The aim of this review is to describe and classify the main clinical, histopathological and molecular patterns of cutaneous lesions in the setting of MDS/MPN in order to improve the diagnostic skills of dermatologists, hematologist and pathologist who deal with these patients.

We investigated the diagnostic capacity of selected circulating biomarkers (CBMs) for the early detection of bone metastasis (BMets) in patients with pancreatic neuroendocrine neoplasms (PanNENs). 115 patients with PanNENs and 40 controls were enrolled. We measured the serum levels of ferritin, cytokeratin 18 (CY18), CA19-9, CA125, AFP, CEA, and beta-2 microglobulin (B2M). 8 PanNENs patients developed BMets, and 107 remained BMets-free. We observed a significantly higher level of CA125 and CY18 in BM-PanNENs patients vs. non-BM-PanNENs patients (p = 0.01 and p = 0.04, respectively). CA125, CY18, and B2M area under receiver operator characteristic (AUROC) analyses differentiated BM-PanNENs from non-BM-PanNENs patients; CA125 area under the curve (AUC) 0.77, p < 0.01; CY18 AUC data were 0.72, p = 0.03, and B2M AUC 0.67, p = 0.02. Based on CBMs metrics in both subgroups, we reached a sensitivity/specificity for CA125 of 75/76%; for CY18 of 75/69%, for B2M of 100/50%, for CA125 and CY18 combination 93/90%, respectively. The useful CBMs for BM-PanNENs patients detection were CA125, CY18, and B2M. They seem to have the diagnostic capacity as a fair single biomarker and CA125&CY18 combination panel for the detection of BMets.

The current management of colorectal cancer liver metastasis (CRCLM) patients involves a multidisciplinary approach with surgical resection remaining the primary curative option. The advances in liver surgery have improved outcomes, enabling more patients to undergo surgery successfully. In addition, the development of imaging software has improved the preoperative planning and patient selection for surgery and other interventions. Systemic therapies, such as targeted therapies and immunotherapies have enhanced the chances of complete resection. Targeted agents in combination with chemotherapy, have shown efficacy in downstaging tumors and increasing resectability.

(1) Background: Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC) is a rare low-grade, neuroendocrine-differentiated, cutaneous adnexal tumour, officially recognized by the World Health Organization (WHO) Skin Tumours Classification in 2018 as a separate entity and homologue of endocrine ductal carcinoma in situ (eDCIS)/solid papillary carcinoma of the breast. Although it is more frequent in the female sex, between the sixth and seventh decade, in the peri-orbital region, EMPSGC has also been described in the male sex, in subjects under 60 and over 80, and in extra-eyelid localizations (cheek, temple, scalp), but also in extra-facial localizations (chest and scrotum). (2) Methods: We present the clinical case of a 71-year-old woman with an undated lesion of the scalp, which presented as a nodule, skin-coloured, 2.5 cm in maximum diameter. We also conduct a comprehensive literature review from 1997 to the end of 2022, consulting PubMed, Scopus and Web of Science (WoS), using the following keywords: "Endocrine mucin-producing sweat gland carcinoma" and/or "EMPSGC" and/or "skin" AND "cutaneous neoplasms", and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 248 patients were recorded with the majority, 146 females (58,8%) and 102 males (41,1%). The vast majority of the lesions were in the elides (peri-ocular region) and only a minority of cases involved the cheeks, supra-auricular, retro-auricular and occipital region, with very rare cases in the scalp, to which the present is also added (4) Conclusions: The morphological and immunophenotypical features are essential both for the correct diagnosis and to be able to classify this lesion among the corresponding eDCIS/solid papillary carcinoma of the breast, with neuroendocrine differentiation. Recent papers have attempted to shed light on the molecular features of EMPSGC and much remains to be done in the attempt to subtype the molecular profiles of these entities. Future studies with large case series, and especially with molecular biology techniques, will be needed to further add information about EMPSGC and its relationship in the PCMC spectrum.

Nuclear protein of testis (NUT), a protein product of the NUTM1 gene (located on the long arm of chromosome 15) with highly restricted physiologic expression in post-meiotic spermatids, is the oncogenic driver of a group of emerging neoplasms when fused with genes involved in transcription regulation. Although initially identified in a group of lethal midline carcinomas in which NUT forms fusion proteins with bromodomain proteins, NUTM1-rearrangement has since been identified in tumors at non-midline locations, with non-bromodomain partners and with varied morphology. The histologic features of these tumors have also expanded to include sarcoma, skin adnexal tumors, and hematologic malignancies that harbor various fusion partners and are associated with markedly different clinical courses varying from benign to malignant. Most of these tumors have nondescript primitive morphology and therefore should be routinely considered in any undifferentiated neoplasm. The diagnosis is facilitated by the immunohistochemical use of the monoclonal C52 antibody, fluorescence in situ hybridization (FISH), and, recently, RNA-Sequencing. The pathogenesis is believed to be altered expression of oncogenes or tumor suppressor genes by NUT-mediated genome-wide histone modification. NUTM1-rearranged neoplasms respond poorly to classical chemotherapy and radiation therapy. Targeted therapies such as bromodomain and extraterminal domain inhibitor (BETi) therapy are being developed. This current review provides an update of NUTM1-rearranged neoplasms, focusing on the correlation between basic sciences and clinical aspects.

Although pancreatic neuroendocrine neoplasms (PNENs) are relatively rare tumors, their number is increasing with advances in diagnostic imaging modalities. Even small lesions that are difficult to detect using computed tomography or magnetic resonance imaging can be detected with endoscopic ultrasound (EUS). Contrast-enhanced EUS is useful, and not only diagnosis but also malignancy detection have become possible by evaluating the vascularity of tumors. Pathological diagnosis using EUS with fine-needle aspiration (EUS-FNA) is useful when diagnostic imaging is difficult. EUS-FNA can also evaluate the grade of malignancy. Pooling the data of the studies which compared the PNENs grading between EUS-FNA samples and surgical specimen, the concordance rate was 77.5% (κ-statistic: 0.65, 95% confidence interval = 0.59 - 0.71, P< 0.01). EUS is a particularly important modality for the treatment of PNENs.

MicroRNAs are small non-coding RNAs that are implicated in several physiological processes such as cell development, proliferation, differentiation, apoptosis, immune response and angiogenesis. In the last couple of decades, several studies on miRNA profiling in OSCC have tried to associate miRNAs with clinical characteristics such as relapse, metastasis, and survival, however, the results have been found to vary considerably, sometimes even being contradictory. The main objective of our study was to analyse and verify miRNA expression in oral squamous cell carcinoma in a Spanish population. Second, we attempted to associate the identified deregulated miRNAs with molecular pathways. 8 Oral Squamous Cell Carcinoma patients and 8 healthy control samples were analysed by a microarray Affymetrix® miRNA 4.1 array plate and validated with 8 more cases using RT-qPCR. Deregulated miRNAs were studied using Diana Tools miRPath 3.0 to associate miRNA targets with molecular pathways. Microarray analysis identified 80 deregulated miRNAs (35 over-expressed and 45 under-expressed). Only miR-497-5p and miR-4417 maintained its deregulated expression after validation with qPCR. Among the molecular pathways in which deregulated miRNAs could be implicated, the most statistically significant pathway was ‘proteoglycans in cancer’. No relationship was found between miR-497-5p or miR-4417 expression and clinical or pathological parameters except of nodular affectation (high miR-4417 expression in patients with nodular affectation, p = 0.035) and radiotherapy (diminished miR-497-5p expression in patients who needed radiotherapy, p = 0.05). We have verified the altered expression of miR-497-5p and miR-4417 in Oral Squamous Cell Carcinoma samples and related the deregulated miRNAs with the ‘proteoglycans in cancer’ pathway.

Background: To investigate the safety and efficacy of palliative arterial embolization for metastases of the scapula. Materials and Methods: We studied the files of the patients who underwent palliatrive arterial embolization for metastases of the scapula from January 2016 to January 2023, 15 patients (8 M, and 7 F) with a mean age of 62 years (SD 10.2) with two patients receiving a second procedure, for a total of 17 embolizations. Data on technical and clinical success, as well as changes in tumor size, were collected. All embolization-related complications were evaluated according to the CIRSE classification system for complications. Results: The average follow-up was 18 months (Range 6-36 months). The main primary tumor were renal, lung and breast cancer. The primary arteries embolized were the circumflex scapular artery, the dorsal scapular artery, and the thoracoacromial trunk. A mixture of Glubran and Lipiodol in a 1:2 ratio was used for embolization, with an average of 1.1 mL (Range 0.5-1.5 mL) used per procedure. The efficacy of embolization was measured using the Visual Analogue Scale (VAS), with values recorded at baseline, at 1, 3, 6, and 12 months post-embolization, and at 6-month intervals after. Baseline VAS scores averaged 7.2 (SD 1.5), decreasing to 2.8 (SD 0.9) at one month. Progressive reduction was observed at 3, 6, and 12 months with scores of 2.3 (SD 0.8), 1.9 (SD 0.7), and 1.6 (SD 0.6) respectively. Metastatic tumor size was reduced from a mean of 192.2 cm3 (range 38.7 to 480.1 cm3) pre-embolization to a mean of 177.3 cm3 (range 37.2 to 455.5 cm3) at the 12-month follow-up (p

Recently, immunotherapy has arisen as a novel treatment approach for patients with colorectal cancer (CRC), but the effectiveness of immunotherapy varies in these patients. We hypothesized that immune checkpoint molecules (ICMs), which are the targets of immunotherapy, are often exhibit concomitantly. Our objective was to investigate the patterns of ICM expression in patients with CRC and the differences in ICM expression based on the microsatellite instability status. Immunohistochemical expression of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), and lymphocyte-activation gene 3 (LAG-3) in the tumor center and periphery was assessed in patients with non-metastatic colorectal cancer. We enrolled 83 patients with CRC: 40 with microsatellite stable (MSS) and 43 with microsatellite instability-high (MSI-H). PD-L1 was more frequently expressed in the tumor center in patients with MSI-H than that in patients with MSS (18 [41.9 %] vs. 3 [7.5 %], respectively; P &lt; 0.001), and the same trend was observed for TIM-3 expression (30 [69.8 %] vs. 19 [47.5 %], respectively; P = 0.047). Concomitant expression of two or more ICMs was more frequently observed than no expression or expression of a single molecule in both MSS and MSI-H groups; 34 (79.7 %) patients with MSI-H and 23 (57.5 %) with MSS showed ICM expression at the tumor center, whereas 34 (79.7 %) patients with MSI-H and 22 (55 %) with MSS showed expression at the tumor periphery. Patients with the genetic characteristics of MSI-H showed higher expression levels of ICMs than that in patients with MSS, and predominantly, two or more ICMs were concurrently expressed. Our findings highlight the potential efficacy of the dual-blockade approach in immunotherapy, particularly in patients with MSI-H CRC.

In recent years, the emergence of cancer drug resistance is one of the crucial tumor hallmarks which is supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters and stemness are among the several key contributing molecular and cellular response mechanisms. Topo-active drugs, e.g., doxorubicin and topotecan, are clinically active and are utilized extensively against a wide variety of human tumors and often results in the development of resistance and failure to therapy. Thus, there is an urgent need for an incremental and comprehensive understanding of mechanisms of cancer drug resistance specifically in the context of topo-active drugs. This review delves into the intricate mechanistic aspects of these intracellular and extracellular topo-active drug resistance mechanisms and explores use of potential combinatorial approaches by utilizing various topo-active drugs and inhibitors of pathways involved in drug resistance. We believe that this review will help guide basic scientists, pre-clinicians, clinicians, and policymakers toward holistic and interdisciplinary strategies that transcend resistance, renewing optimism in the ongoing battle against cancer.

Myxoid endometriosis is a rare entity that is part of the histological changes that can occur in endometriosis. It is extremely important that the pathologist has knowledge of the histological guidelines for the morphological recognition of this entity, as well as the histochemical and immunohistochemical techniques that will support the diagnosis. Define the morphological characteristics of myxoid endometriosis. In the present work we propose diagnostic approach guidelines, as well as the main differential diagnoses with the use of special histochemical techniques and immunohistochemical reactions to recognize this entity.

Background: The front-line treatment of advanced NeuroEndocrine Neoplasms (NENs) depends on clinical and pathological factors but there are no standard second-line therapies. Methods: Metastatic NENs patients were treated at the ENETS (European NeuroEndocrine Tumor Society) center of excellence of Naples (Italy), from 2014 to 2017 with second-line metronomic temozolomide, 75 mg/m2 per os “one week on/one week off”. Toxicity was graded with NCI-CTC criteria v4.0; objective responses with RECIST v1.1 and performance status (PS) according to ECOG. Results: Twenty-six consecutive patients were treated. Median age was 65.5 years. The predominant primary organs were pancreas and lung. Grading was G2 in 11 patients, G3 in 15. Eleven patients presented with PS 1 and 15 with PS 2. The median time-on-temozolomide therapy was 12.2 months (95% CI: 11.4-19.6). No G3/G4 toxicities were registered. Complete response was obtained in 1 patient, partial response in 4, stable disease in 19 (disease control rate: 92.3%), and progressive disease in 2. The median overall survival from temozolomide start was 28.3 months. PS improved in 73% of patients. Conclusions: Metronomic temozolomide is a safe and active treatment for G2 and G3 NENs. Prospective and larger trials are needed to confirm these results.

Background: Poroid neoplasms (PN) are a heterogeneous group of tumors deriving from sweat glands and folliculo-sebaceous units. Their histological classification and clinical features are challenging. Our aim was to report clinicopathological features of poroid neoplasms. Methods: it is a retrospective study including all cases of poroid neoplasms registered at our Pathology laboratory of Niamey National Hospital (from February 2020 to February 2024). Results: We registered 13 cases of benign poroid neoplasms: 10 classic poromas (CP) (76.9%), 2 poroid hidradenomas (PH) (15.4%) and 1 dermal duct tumor (DDT) (7.7%). Nine cases (69.2%) had preoperative clinical diagnosis of malignancy. The mean age was 41.1 years (range of 12 – 70 years) with a slight female predominance (sex ratio = 1.16). Only 4/13 cases (30.8%) had classical palmoplantar locations. The tumors mean size was 3.7 cm (range of 0.4 – 8 cm). All cases were well-circumscribed solid (7/13 cases, 53.8%) or solido-cystic whitish nodules (6/13 cases, 46.2%). Clear cells were present in 7 cases (53.8%), apocrine ductal differentiation (mixed or pure) in 6 cases (46.2%), keratin horns in 2 cases (15.4%), squamous eddies in 6 cases (46.2%), melanin pigments in 1 case (7.7%) and sebaceous differentiation in 2 cases (15.4%). Conclusions: Unlike what is classically reported, our study shows that apocrine ductal differentiation, younger age and non-palmoplantar locations are common in poroid neoplasms. Also, PN are often diagnosed as malignant tumors by clinicians before histopathological analysis.

(1) Background. Intracavitary hyperthermic chemotherapy (HITHOC) remains a part of the complex mosaic which is the multimodal approach in advanced stage thymomas and pleural malignancies, and its role is still widely debated. In recent years, several studies have demonstrated the feasibility and the efficacy of HITHOC combined with cytoreductive surgery in the treatment of thymoma relapses and malignant pleural mesothelioma (MPM). However, there are currently no studies available on pleurectomy/removal of pleural lesions using the robotic technique, in association with intrathoracic chemotherapy. The aim of this narrative review is to evaluate the feasibility and safety of robotic pleurectomy/removal of relapses and HITHOC in patients with pleural recurrence of thymoma or MPM, after having analyzed the literature concerning this controversial topic, and to report our experience with robotic surgery. (2) Methods: A review of papers published on this topic, from 1980, was conducted. Later, the data of consecutive patients affected by thymoma relapses or MPM who underwent robotic surgery in combination with HITHOC will be collected and analyzed. The surgery performed, prior to intrathoracic infusion of the high-temperature chemotherapy, consisted of the removal of the recurrences or pleurectomy, depending on the pathology. All surgeries were performed with a 4-port-fully robotic technique. (3) Results: Between 2017 and 2022, nine patients underwent robotic cytoreductive surgery in combination with HITHOC. No intraoperative complications occurred. One patient had a grade II Clavien-Dindo postoperative complication. Oncological follow-up showed results in line with the literature. (4) Conclusion: With the limitation of the small number of patients, considering the results, robotic surgery may represent the surgical approach of choice, in combination with HITHOC, in patients with pleural relapses of thymoma and early-stage MPM.

This study aimed to evaluate the optimal extent of lymphadenectomy in patients with nonfunctioning pancreatic neuroendocrine neoplasms. We retrospectively analyzed the clinicopathological data of patients with nonfunctioning pancreatic neuroendocrine neoplasms who underwent surgical resection. We investigated the frequency of metastases at each lymph node station according to tumor location and analyzed the factors contributing to poor overall survival (OS) and disease-free survival (DFS). Overall, data of 84 patients were analyzed. For pancreatic head tumors, metastases at stations 8, 13, and 17 were found in one (3.1%), four (12.5%), and three (9.3%) patients, respectively. However, none of the other stations showed metastases. For pancreatic body and tail tumors, only metastases at station 11 were found in two (5.1%) patients. Additionally, multivariate DFS and OS analyses showed that lymph node metastasis was the only independent prognostic factor. Lymph node metastasis was found near the primary tumor and was the only independent factor of poor prognosis in patients with nonfunctioning pancreatic neuroendocrine neoplasms after undergoing curative surgery. Peri-pancreatic lymphadenectomy might be recommended for nonfunctioning pancreatic neuroendocrine neoplasms.

Chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck cancer; however, CRT may cause post-treatment dysphagia. Transcutaneous electrical sensory stimulation (TESS), developed in recent years for swallowing rehabilitation, has been used at many medical facilities. Although TESS has been used for dysphagia in several fields, its safety and efficacy in patients with head and neck cancer remain to be clarified. Therefore, this study evaluated the safety of TESS in ten patients with head and neck cancers undergoing CRT. Swallowing rehabilitation intervention and TESS implementation were performed for all patients during CRT. Non-blood toxicity adverse events (AEs), such as dermatitis and mucositis, occurred during CRT; however, the severity was less than Grade 3. No patient experienced pain due to TESS. As survival time analysis using the Kaplan–Meier method for interferential current device implementation rates revealed a feasibility of 100% for up to 60 Gy and a feasibility of 78% for up to 70 Gy, it concludes that TESS was feasible until 70 Gy. This study confirmed the feasibility and safety of TESS in the head and neck region, even during CRT. Although the precise mechanism of TESS on dysphagia is not yet clear, its continued use has great potential for improving sensory disturbance.

PURPOSE: Breast cancer tumors frequently have intratumor heterogeneity. Tumors with high intratumor heterogeneity have caused therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to poor prognosis for HER2-targeted adjuvant therapies resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with HER2 gene copy number within a tumor sample. Those heterogeneity classified each tumor into the biphasic grade graph (high heterogeneity [HH]) group and the monophasic grade graph (low heterogeneity [LH]) group. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: P < 0.001 (HH:63% vs LH:91% at 10 years), and OS: P = 0.012 (HH:78% vs LH:95% at 10 years). CONCLUSION: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach of heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

Mesentery was discovered as a new organ in 2017. It is a continuous membranous tissue from the duodenojejunal flexure to the anorectal junction. It has distinct anatomy, physiology, and disease states. Primary mesenteropathies include vascular and non-vascular diseases. Some of them are common, and some of them are rarely seen in clinical practice. Secondary mesenteropathies occur when infection or malignancy in another organ spreads to the mesentery. Each entity has specific diagnostic and treatment protocols.

BACKGROUND: Head and Neck Sarcomas (HNSs) are rare malignant tumors derived from mesenchymal cells characterized by rapid growth, local aggressive behavior, and multiple re-lapses. The Rhabdomyosarcoma (RMS) and the Osteosarcoma (OS) are the more frequent HNS. The present study aims to evaluate the clinical impact of multimodal treatment in patients diagnosed with HNS. METHODS: A retrospective analysis of medical records from patients diagnosed with HNS multimodal treated, four groups were formed: a) surgery and chemotherapy (CTX); b) surgery, CTX, and RT; c) surgery and RT; d) CTX and RT exclusively. The overall survival (OSS), disease-free survival (DFS) and progression-free survival (PFS) rates were calculated using the Kaplan-Meier test. RESULTS: Among 39 patients, 23.1% were diagnosed with RMS , 66.7% with OS and 10.3% with other subtypes of HNS. Moreover, 59% showed initial clinical staging (T1/T2) and of those 35.9% were T1. Surgery was performed in 87.2% patients, RT in 35.9% and CTX in 84.7%. RT performed showed not statistically significant clinical role regarding OSS (p=0.74), DFS (p=0.09) and PFS (p=0.90) rates independent of histological subtype. Finally, OSS (p=0.89), DFS (p=0.13) and PFS (p=0.50) rates were not statistically different for patients treated with monotherapy or multimodal therapy. CONCLUSION: RT has not showed a clinically important role referred to improve OSS, DFS and PFS rates in patients with HNS, regardless of the histological subtype of the primary tumor. Multimodal treatment could influence in survival rates and locoregional control of the disease; however, longitudinal studies such as randomized clinical trials must be conducted.

Persistent Organic Pollutants (POP) such as dichlorodimethyltrichloroethane (DDT) are present and ubiquitous in the environment due to their resilient nature. DDT is a prevalent endocrine disruptor still found in detectable amounts in organisms and the environment even after its use was banned in the 1970s. Studies show that exposure to DDT can cause adverse health effects in humans and animals, impairing fertility and increasing the risk of developing cancer. The aim of this work is to provide a comprehensive overview of the available literature on the effect of DDT and its metabolites on female reproductive tract, leading to infertility and cancer. Medline and Google Scholar were systematically searched to detect all relevant animal and human studies published in the last 20 years (January 2003 to February 2023) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. In total, 38 studies were included for qualitative synthesis. This systematic search and review indicated that exposure to DDT is associated with female reproductive health decline and that DDT acts as a sufficient carcinogen instigating reproductive cancers.

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher exercise frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.

Cervical cancer is a public health issue with high disease burden and mortality in Brazil. The objectives of the present study were analyzing age, period, and cohort effects on cervical cancer mortality in women 20 years old or older from 1980 to 2019 in the North, South, and Southeast Regions of Brazil; and evaluating whether the implementation of a national screening program and the expansion of access to public health services caused impacts over the examined period and reduced the risk of death over the past years and among younger cohorts. The effects were estimated by applying Poisson regression models with estimable functions. The highest mortality rate by 100,000 women was found in Amazonas (24.13), and the lowest in São Paulo (10.56). A positive gradient was obtained for death rates as women’s age increased. The states in the most developed regions (South and Southeast) showed a reduction in the risk of death in the period that followed the implementation of the screening program and in cohort from the 1960s onwards. The North Region showed a decreased risk of death only in Amapá (2000–2004) and Tocantins (1995–2004; 2010–2019). The findings indicated that health inequities remain in Brazil and suggested that the health system has limitations regarding decreasing mortality associated with this type of cancer in regions with lower socioeconomic development.

The epidermal growth factor receptor (EGFR) exon-19 deletion is one of the most common mutations detected in lung cancer patients. Although exon-19 deletion is frequently detected in adenocarcinoma, observing this mutation in germline cells is very rare. Besides, the co-occurrence of homozygous and heterozygous mutations in dual primary cancers in a person is very uncommon. This article presents a 53-year-old Iranian woman with no history of smoking who was diagnose with two primary cancers; invasive ductal carcinoma, and primary pulmonary lung adenocarcinoma. The case reported a history of breast cancer in her sister and a history of lung cancer in her father. To select the best choice of treatment the EGFR gene was analyzed with Sanger’s sequencing method from DNA extracted from the patient’s lung tissue sample. Observing two primary cancers in this patient and considering her family pedigree, germline cells were also analyzed using samples recruited from the patient’s peripheral blood to investigate any EGFR mutations in her germline cells. The obtained data revealed that the lung tissue of the patient carried a homozygous form of EGFR exon-19 deletion while her peripheral blood contained a heterozygous form of this mutation, which is exceptionally rare.

Ruxolitinib has been approved by FDA for the treatment of myeloproliferative neoplasms such as polycythemia vera and idiopathic myelofibrosis. Although ruxolitinib has been in the clinic for more than ten years, surprisingly, no JAK2 drug resistant mutations have been identified in patients. At the moment, it is not clear whether the absence of JAK2 mutations in MPN patients is due to a lack of JAK2 addiction or residues that mediate the drug resistance compromising the JAK2 function. To find out this, we established a Ba/F3 cell-based screening strategy to predict mutations in JAK2-V617F that cause resistance towards ruxolitinib. In this study, we have recovered seven residues in the kinase domain of JAK2 that affect ruxolitinib sensitivity. All these mutations confer cross-resistance across the panel of JAK2 kinase inhibitors except JAK2-L983F. JAK2-L983F reduces the sensitivity towards ruxolitinib. However, it is sensitive towards fedratinib indicating that our screen identifies the drug-specific resistance profiles. All the ruxolitinib resistant JAK2 variants displayed sensitivity towards Type II JAK2 inhibitor CHZ-868. Finally, our study also shows that HSP90 inhibitors are potent against ruxolitinib resistant variants through the JAK2 degradation and provides the rationale for clinical evaluation of potent HSP90 inhibitors in genetic resistance driven by JAK2 inhibitors.

To the best of the author’s knowledge, studies of mature plasmacytoid dendritic cell proliferation associated with T lymphoblastic lymphoma were extremely rare in the literature. Here, we report a patient who underwent both mature plasmacytoid dendritic cell proliferation and T lymphoblastic lymphoma. With the findings of lymph node biopsy taken from the right cervical and inguinal regions, we identified eye-catching mature plasmacytoid dendritic cells that were considered to be responsible for this lesion at the beginning, until the immunostaining of Ki67 and TDT showed a small group of positive cells hiding in these plasmacytoid dendritic cells. Bone marrow biopsy was also performed in this patient. Microscopically, the hematopoietic tissue was almost completely replaced by lymphoblastoid cells with condensed chromatin, inconspicuous nucleoli and scanty cytoplasm, which were basically the same as those seen in the lymph nodes in morphology. However, there was no sign of plasmacytoid dendritic cells or Langerhans cells in the bone marrow biopsy. With the help of bone marrow biopsy, our final diagnosis of the lymph node was T lymphoblastic lymphoma coexisting with mature plasmacytoid dendritic cell proliferation . Although accumulations of plasmacytoid dendritic cells may occur in some infections or reactive lymphadenopathy, the presence of extensive nodules or infiltration of plasmacytoid dendritic cells strongly reminds the pathologist to carefully evaluate the bone marrow or peripheral blood status of the patient to exclude a hidden myeloid or other neoplasm.

The abnormal accumulation of cells in the human brain, if left untreated, may cause brain damage. Management and treatment of these tumours require an early and accurate diagnosis, while their prognostic characterisation can also be beneficial in the choice of care planning for the patient. CDSSs are being continuously developed and integrated into routine clinical practice as they assist clinicians and radiologists to deal with an enormous amount of medical data, reduce clinical errors, and improve diagnostic capabilities. They assist detection, classification, and grading of brain tumours as well as alerting physicians of requirement of change in treatment plans. The aim of this systematic review is to identify various CDSSs used in brain tumour diagnosis and prognosis, that rely on data captured by any imaging modality. Based on the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, the literature search was conducted in PubMed and Engineering Village Compendex databases. This review examines various CDSS tool types, system features, techniques used, accuracy, and outcome, to provide the latest evidence available in the field of neuro-oncology. An overview of different types of CDSSs used to support clinical decision-making in the management and treatment of brain tumours, along with highlighting their benefits, challenges, and future perspectives has been provided.

Myelodysplastic syndromes and myeloproliferative neoplasms both represent hematologic diseases associated with bone marrow failure often resulting in anemia. For those patients, transfusion of red blood cell (RBC) units is essential, but results in iron overload (IOL) that may affect various organ functions. Therefore, iron chelation therapy plays a major role in anemic patients, not only because it reduces IOL, but also because it may improve hematopoietic function by increasing hemoglobin or diminishing requirement of RBC transfusions. To assess the utility, efficacy and safety of the different iron chelation medication approved in Germany as well as to examine the effect of chelation on hematopoietic insufficiency, a prospective, multicenter, non-interventional study named EXCALIBUR was designed. In total, 502 patients from 106 German hospitals and medical practices were enrolled. A large proportion of patients switched from deferasirox dispersible tablet to deferasirox film-coated tablet, mainly due to more convenient application which was reflected in the treatment satisfaction questionnaire for medication scores. Iron chelation was effective in lowering serum ferritin levels, with the observed adverse drug reactions being in line with the known safety profile. Hematologic response occurred in a few patients, comparable to other studies that examined hematologic improvement in patients with MDS.

(1) Background: This study aimed to identify the recurrence and survival rates according to the mismatch repair (MMR), p53, and L1 cell adhesion molecule (L1CAM) states in patients with advanced and recurrent endometrial cancer receiving systemic chemotherapy.; (2) Methods: This single-center retrospective cohort study included chemotherapy-naïve patients (n=156) with advanced-stage (III/IV) or recurrent endometrial cancer who were administered chemotherapy as adjuvant therapy (n=112) or first-line palliative treatment (n=44) between January 2015 and June 2022. MMR and p53 states were assessed using PCR, and L1CAM was tested using immunohistochemistry in the no specific molecular profile (NSMP) group. The primary outcomes were progression-free survival (PFS) and overall survival (OS).; (3) Results: Of the 156 patients, 62 (39.7%), 53 (34.0%), and 41 (26.3%) had NSMP, abnormal p53 (p53abn), and an MMR deficiency (MMR-D), respectively. PFS and OS were longest in MMR-D, followed by NSMP, and were the least in p53abn tumors (PFS: p=0.0006, OS: p=0.0013). After NSMP was classified according to positive or negative L1CAM status, the L1CAM-negative group exhibited significantly lower survival rates than the L1CAM-positive group (PFS: p=0.0001, OS: p=0.0027); p53abn tumors were independent prognostic factors for poor PFS (p=0.039 on the multivariable analysis).; (4) Conclusions: In chemotherapy-naïve patients with advanced and recurrent endometrial cancer, the best prognosis after chemotherapy was obtained using MMR-D, followed by NSMP and p53abn tumors. The L1CAM status is a useful new marker for stratifying NSMP in advanced and recurrent patients.

Background: The currently advised follow-up scheme of PSA-testing after robot-assisted radical prostatectomy (RARP) is strict and might pose a burden to our healthcare system. We aimed to optimize the 1-year follow-up scheme for patients who undergo RARP. Methods: All patients with histologically-proven prostate cancer (PCa) who underwent RARP between 2018 and August 2022 in the Prostate Cancer Network the Netherlands were retrospectively evaluated. We excluded patients who underwent salvage RARP and patients who had &lt;1 year of PSA follow-up. Postoperative PSA-values were collected. Biochemical persistence (BCP) was defined as PSA-level &gt;0.10 ng/mL at 0-4 months after RARP, whereas biochemical recurrence (BCR) was defined as PSA-level &gt;0.2 ng/mL at any time point after RARP. We aimed to identify a group of patients who had a very low risk of BCR at different time-points after surgery. Results: Of all 1155 patients, BCP was observed in 151 (13%), of whom 79 (6.8%) had PSA ≥0.2 ng/mL. BCR further developed in 51 (4.7%), and 37 (3.4%) patients at 5-8 and 9-12 months after RARP, respectively. In 12 patients, BCR was found at 5-8 months after RARP in absence of BCP. These patients represented 1.2% (12/1004) of the entire group. In other words, 98.8% (992/1004) of patients who had an unmeasurable PSA-level at 0-4 months after RARP also had unmeasurable PSA-level 5-8 months after surgery. Limitations are the retrospective design and incomplete follow-up. Conclusions: Patients with an unmeasurable PSA-level at 3-4 months after RARP may not need to be retested until 12 months of follow-up as almost 100% of patients will not have biochemically recurrent disease at 5-8 months of follow-up. This will reduce PSA-testing substantially at the costs of hardly any missed patients with recurrent disease.

BACKGROUND Krukenberg tumor is a rare metastatic tumor of the ovary with characteristic histopathological features known as signet-ring cells. It usually presents in women around 45 years of age, however, we present an uncommon case in a 38-year-old pregnant woman. We report this case because of the unusual findings, the uncommon presentation in this younger age bracket, its diagnostic challenge, and poor prognosis. CASE PRESENTATION We describe an unusual case of a young woman with a history of painful vaginal bleeding at 13 weeks of pregnancy and treated for abruptio placentae. In her routine prenatal visit at week 20 of pregnancy, she was found to have a uterine fundus greater than her gestational age and referred to the hospital to discard polyhydramnios. At her admission a pelvic ultrasound was performed with normal findings of a 25 weeks pregnancy, also showing bilateral enlarged ovaries with heterogeneous echogenicity. The MRI showed a left tumoral lesion with dimensions of 22.1 x 13.6 x 16.3 cm, with lobulated regular contours with displacement of peripheral structures and mild compression of the bladder, the left ureter, and the inferior vena cava. The lesion was heterogeneous with irregular borders. The patient was programmed for a cesarean section; during the operation, the abdominal cavity showed bilateral tumors compatible with MRI findings, the ovarian tumors were sent to pathology and the results showed poorly differentiated mucinous adenocarcinoma (WHO III) with extensive signet-ring cells, an indicative of Krukenberg tumor. CONCLUSION: The case presented is rare due to its presentation in a pregnant woman without identifiable risk factors for gastric cancer. The incidental finding suggests the pregnancy masked the clinical presentation of gastric cancer, and the rapid deterioration of the patient is consistent with the aggressiveness described in the literature. The limited descriptions of this neoplasm in our country and the torpid evolution of this case highlight the importance of further studies of this cancer in Mexico.

This narrative review delves into the evolving landscape of fertility preservation techniques with a particular focus on their use in patients undergoing oncology treatment that carries a risk of ovarian insufficiency. Advances in established methods such as cryopreservation of oocytes and embryos are highlighted and the increasing use of gonadotropin-releasing hormone (GnRH) agonists is discussed. The review also addresses the complexities and controversies associated with these approaches, such as the 'flare-up' effect associated with GnRH agonists and the potential of GnRH antagonists to reduce the risk of ovarian hyperstimulation syndrome. Despite advances in fertility preservation, the report highlights the challenges we face, including the need for personalized treatment protocols and management of associated risks. It calls for continued research and collaboration between healthcare professionals to refine these techniques and ultimately improve reproductive outcomes for patients facing the prospect of fertility-impairing treatment.

The identification of cancer predisposition syndromes (CPSs) plays a crucial role in understanding the etiology of pediatric cancers. CPSs are genetic mutations that increase the risk of developing cancer at an earlier age compared to the risk for the general population. This article aims to provide a comprehensive analysis of three unique cases involving pediatric patients with CPS who were diagnosed with multiple simultaneous or metachronous cancers. The first case involves a child with embryonal rhabdomyosarcoma, nephroblastoma, glioma, and subsequent medulloblastoma. Genetic analysis identified two pathogenic variants in the BRCA2 gene. The second case involves a child with alveolar rhabdomyosarcoma, Xanthogranuloma Juvenile, gliomas, and subsequent JMML/MDS/MPS. A pathogenic variant in the NF1 gene was identified. The third case involves a child with pleuropulmonary blastoma and pediatric cystic nephroma/nefroblastoma in whom a pathogenic variant in the DICER1 gene was identified. Multiple simultaneous and metachronous cancers in pediatric patients with CPSs are a rare but significant phenomenon. Comprehensive analysis and genetic testing play crucial roles in understanding the underlying mechanisms and guiding treatment strategies for these unique cases. Early detection and targeted interventions are crucial for improving outcomes in these individuals.

Objective: The COVID-19 pandemic inferred on neuro-oncological patients (PTS) and the caregivers regarding tumor care and emotional functioning. This study aimed to understand how COVID-19 affects their psychological state and relations between PTS and health personnel in neuro-oncology. Methods: A cross-sectional study on neuro-oncological PTS and their caregivers. Results: A total of 162 PTS and 66 caregivers completed the questionnaire. The 37.5% of PTS perceived greater risk of contracting the COVID-19 compared to the general population. On the 0-10 scale, PTS tumor-related anxiety score was 5.8 and COVID-related 4.6. The caregivers reported 7.7 and 5.5 respectively. The QoL was described at least as good in 75% of both PTS and caregivers; the caregivers’ care burden increased in 22.7% during the pandemic, with no correlation with QoL. Future perception often changed both in PTS and in the caregivers. Cancer treatment schedule was changed in 18.5%, including for PTS decision. However, the 93.5% of PTS was satisfied with the overall care. Conclusion: A considerable proportion of PTS and caregivers still perceived the tumor disease as more burdensome than the pandemic, and perceived their future as more uncertain. Such data rinforce the need to build a proficient alliance between PTS and health personnel.

Background. To describe the characteristics of anterior mediastinal masses on conventional magnetic resonance imaging (MRI) and to assess the role of the Apparent Diffusion Coefficient (ADC) value in distinguishing benign from malignant mediastinal lesions. Methods. We conducted a retrospective cross-sectional study on 55 patients with anterior mediastinal mass who performed MRI before treatment. Biopsy and histopathological assessments were done after that. A radiologist evaluates the changes of signal intensity on these sequences: T1- weighted VIBE DIXON pre and post-contrast with Gadolinium, T2 HASTE, T2 TIRM, DWI/ADC, to determine the size, margin of the lesion, the presence of fat, cystic in it. ADCs values were calculated from the ADC maps which were constructed from b = 0 and b = 2000 Results. The study was composed of 55 patients, with 5 benign lesions and 50 malignant lesions. The ADCmean, ADCmedian, ADC10, and ADC90 in the histogram-based approach and hot-spot-ROI-based mean ADC for the malignant lesions was significantly lower than those found in benign lesions (P-value <0.05). The hot-spot-ROI-based mean ADC had the highest value in differentiation between benign and malignant mediastinal lesions, between group A (benign lesions, thymoma A, AB, B1) and group B (thymoma B2, B3 and other malignant lesions). The cut-off point of the ADC value differentiating malignant from benign mediastinal lesions was 1,17x10-3mm2/s with sensitivity of 80%, and specificity of 80%. The cut off point of the ADC value differentiating group A from group B was 0.99 x10-3mm2/s with sensitivity of 78,4%, and specificity of 88.9%. The cut-off point of the ADC value differentiating lymphoma from other malignant lesions was 0,91 x10-3mm2/s with sensitivity of 100%, and specificity of 60.5%. Conclusion. Diffusion-weighted MRI and measurement of ADC value in histogram-based approach and hot-spot-ROI-based mean ADC are very helpful in the differentiation between benign and malignant anterior mediastinal lesions.

Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are rare cancers consisting of neuroendocrine carcinomas (NECs) and neuroendocrine tumors (NETs), which have been increasing in incidence in recent years. Few cell lines and pre-clinical models exist for the study of GEP NECs and NETs, limiting the ability to discover novel imaging and treatment modalities. To address this gap, we isolated tumor cells from cryopreserved patient GEP NECs and NETs and injected them into the flanks of immunocompromised mice to establish patient-derived xenograft (PDX) models. Two of 6 mice developed tumors (NEC913 and NEC1452). Over 90% of NEC913 and NEC1452 tumor cells stained positive for Ki67. NEC913 PDX tumors expressed neuroendocrine markers such as chromogranin A (CgA), synaptophysin (SYP), and somatostatin receptor-2 (SSTR2) whereas NEC1452 PDX tumors do not express SSTR2. Exome sequencing revealed loss of p53 and RB1 in both tumors. To demonstrate an application of these novel NEC PDX models for SSTR2-targeted peptide imaging, the NEC913 and NEC1452 cells were bilaterally injected into mice. Near infrared-labelled octreotide was administered and fluorescent signal was specifically observed for the NEC913 SSTR2 positive tumors. These 2 GEP NEC PDX models serve as valuable resource for GEP NEN therapy testing.

Immunotherapy has been considered for years as a viable and attractive treatment option for patients with cancer. Among immunotherapy arsenal, the targeting of intratumoral immune cells by immune-checkpoint inhibitory agents has recently revolutionized the treatment of several subtypes of tumours. These approaches aimed at restoring an effective anti-tumour immunity, rapidly reached the market thanks to the simultaneous identification of inhibitory signals that dampen an effective antitumor response in a large variety of neoplastic cells, and the clinical development of monoclonal antibodies targeting checkpoint receptors. Leading therapies in solid tumours are mainly focused on the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed-death 1 (PD-1) pathways. These approaches have found a promising testing ground in both Hodgkin lymphoma and non-Hodgkin lymphoma, mainly because in these diseases the malignant cells interact with the immune system and commonly provide signals that regulate immune function. Although several trials have already demonstrated evidence of therapeutic activity with some checkpoint inhibitors in lymphoma, many of the immunologic lessons learned from solid tumours may not directly translate to lymphoid malignancies. In this sense, the mechanisms of effective antitumor responses are different between the different lymphoma subtypes, while the reasons for this substantial difference remain partially unknown. This review will discuss the current advances of immune-checkpoint blockade therapies in B-cell lymphoma and will build a projection of how the field may evolve in the near future. In particular, we will analyze the current strategies being evaluated both preclinically and clinically with the aim to foster the use of immune-checkpoint inhibitors in non-Hodgkin lymphoma, including combination approaches with chemotherapeutics, biological agents and/or different immunologic therapies.

The HER2-targeted antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and Trastuzumab deruxtecan (T-DXd) improved outcomes in breast cancer. Novel combinations and sequential approaches are under investigation to overcome resistance to T-DM1 and T-DXd. Furthermore, the landscape of HER2-targeted therapy is rapidly advancing with the development of ADCs designed to attack cancer cells with greater precision and reduced toxicity. Disitamab Vedotin (RC48) incorporates a HER2 antibody with unique binding epitope and a potent microtubule inhibitor as its cytotoxic moiety. ARX-788 comprises a non-cleavable linker and a novel maytansinoid derivative as the cytotoxic drug, engineered for increased stability and a higher drug-to-antibody ratio. SYD985, a duocarmycin-based ADC, is designed to be activated only in the acidic environment of the tumor, thus reducing off-target effects. BL-M0701 targets a different epitope on the HER2 protein, which might be beneficial in circumventing resistance that affects the binding of other ADCs and incorporate a camptothecin derivative as its payload. Zanidatamab zovodotin (ZW25) is an ADC that binds to two different HER2 epitopes simultaneously, enhancing the internalization and delivery of its cytotoxic payload. These and other ADCs in phase I trials hold the potential to improve outcomes for HER2-positive and HER2-Low breast cancer and possibly other solid tumors.

The rapid expansion of transcriptomics from increased affordability of next-generation sequencing (NGS) technologies generates rocketing amounts of gene expression data across biology and medicine, and notably in cancer research. Concomitantly, many bioinformatics tools were developed to streamline gene expression analysis and quantification. We tested the concordance of NGS RNA sequencing (RNA-seq) analysis outcomes between the two predominant programs for reads alignment, HISAT2 and STAR, and the two most popular programs for quantifying gene expression in NGS experiments, edgeR and DESeq2, using RNA-seq data from a series of breast cancer progression specimens, which include histologically confirmed normal, early neoplasia, ductal carcinoma in situ and infiltrating ductal carcinoma samples microdissected from formalin fixed, paraffin embedded (FFPE) breast tissue blocks. We identified significant differences in aligners’ performance: HISAT2 was prone to misalign reads to retrogene genomic loci, STAR generated more precise alignments, especially for early neoplasia samples. edgeR and DESeq2 produced similar lists of differentially expressed genes in stage comparisons, with edgeR producing more conservative, though shorter, lists of genes. Albeit, Gene Ontology (GO) enrichment analysis revealed no skewness in significant GO categories identified among differentially expressed genes by edgeR vs DESeq2. As transcriptome analysis of archived FFPE samples becomes a vanguard of precision medicine, identification and fine-tuning of bioinformatics tools becomes critical for clinical research. Our results indicate that STAR and edgeR are well-suited tools for differential gene expression analysis from FFPE samples.

The study of cell-free DNA (cfDNA) and other peripheral blood components (known as “liquid biopsies”) is promising and has been investigated especially in solid tumors. Nevertheless, it is increasingly showing greater utility in the diagnosis, prognosis, and response to treatment of hematological malignancies; in the future, it could prevent invasive techniques, such as bone marrow (BM) biopsy. Most of the studies about this topic have been focused on B cell lymphoid malignancies; some of them have shown that cfDNA can be used as a novel way for diagnosis and minimal residual monitoring in B cell lymphomas, using techniques such as next-generation sequencing (NGS). In myelodysplastic syndromes, multiple myeloma, or chronic lymphocytic leukemia, liquid biopsies may allow for an interesting genomic representation of the tumor clones affecting different lesions (spatial heterogeneity). In acute leukemias, it can be helpful in the monitoring of early treatment response and the prediction of treatment failure. In chronic lymphocytic leukemia, the evaluation of cfDNA permits the definition of clonal evolution and drug resistance in real-time. However, there are limitations such as the difficulty in obtaining sufficient circulating tumor DNA for achieving a high sensitivity to assess minimal residual disease or the lack of standardization of the method and clinical studies to confirm its prognostic impact. This review focuses on clinical applications of cfDNA on minimal residual disease in hematological malignancies.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies mainly originated from hormones secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout MEN-1 gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signaling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally, act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the roles and the potential therapeutic implications of gene mutations and NOTCH signaling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential roles across all NEN subtypes is required.

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) frequently require primary radiochemotherapy (RCT). Despite intensity-modulation, desired radiation-induced effects observed in HNSCC, may also be observed as side-effects in healthy tissue e.g. the sternocleidomastoideus muscle (SCM). These side-effects (e.g. tissue fibrosis) depend on the interval between completion of RCT and restaging-CT. For salvage surgery, the optimal time window for surgery is currently postulated between 6 and 12 weeks after completion of RCT. Thus, no extensive tissue fibrosis is to be expected. This interval is based on studies exploring surgical complications. Studies directly exploring radiation-induced changes of the SCM in HNSCC-patients are sparse. The present study quantifies tissue alterations in SCM and paravertebral musculature (PVM) after RCT applying radiomics to determine the optimal time window for salvage surgery. Three radiomic key parameters 1) volume, 2) mean positivity of pixels (MPP) and 3) uniformity were extracted with mint lesionTM in the staging-CTs and restaging-CTs of 98 HNSCC-patients. Of these, 25 were female, the mean age was 62 (±9.6) years and 80.9% were UICC Stage IV. The mean restaging-interval was 55 (±28; range29-229) days. Only the mean volume significantly decreased after RCT from 9.0 to 8.4 and 96.5 to 91.9 ml for SCM and PVM, respectively (both p=0.007, both Cohen’s d=0.28). In addition, the mean body mass index (BMI) decreases from 23.9 (±4.2) to 21.0 (±3.6) kg/m² (p<0.001); Cohen's d = 0.9). The mean BMI-decrease significantly correlated with the volume decrease for SCM (r=0.27; p=0.007) and PVM (r=0.41; p<0.001). If t-test p-values were adjusted for the BMI-decrease, no significant change in volumes for SCM and PVM was observed (both p>0.05). The present data supports the postulated optimal interval for salvage surgery of 6 to 12 weeks. Irrespective of the remaining risk-benefit ratio of salvage surgery, the risk of additional surgical complications due to fibrosis is not supported by the present observations.

The vast majority of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia. Although cachexia results from concurrent loss of adipose and muscle tissue, most studies focus on muscle alone. Emerging data demonstrate the prognostic value of fat loss in cachexia. Here we sought to identify the muscle and adipose gene profiles and pathways regulated in cachexia. Matched rectus abdominis muscle and subcutaneous adipose tissue were obtained at surgery from patients with benign conditions (n=11) and patients with PDAC (n=24). Self-reported weight loss and body composition measurements defined cachexia status. Gene profiling was done using Ion proton sequencing. Results were queried against external datasets for validation. 961 DE genes were identified from muscle and 2000 from adipose tissue, demonstrating greater response of adipose than muscle. In addition to known cachexia genes such as FOXO1, novel genes from muscle, including PPP1R8 and AEN correlated with cancer weight loss. All the adipose correlated genes including SCGN and EDR17 are novel for PDAC cachexia. Pathway analysis demonstrated shared pathways but largely non-overlapping genes in both tissues. Age related muscle loss predominantly had a distinct gene profiles compared to cachexia. This analysis of matched, externally validate gene expression points to novel targets in cachexia.