Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Defining an Optimal Time Window for Salvage Surgery: Primary Radiochemotherapy Does Not Induce Radiomically Assessable Short-Term Alterations of Skeletal Muscle Composition in Head and Neck Squamous Cell Carcinoma

Version 1 : Received: 25 August 2023 / Approved: 1 September 2023 / Online: 4 September 2023 (02:41:55 CEST)

A peer-reviewed article of this Preprint also exists.

Santer, M.; Riechelmann, H.; Hofauer, B.; Schmutzhard, J.; Freysinger, W.; Runge, A.; Gottfried, T.M.; Zelger, P.; Widmann, G.; Kranebitter, H.; Mangesius, S.; Mangesius, J.; Kocher, F.; Dejaco, D. Radiomic Assessment of Radiation-Induced Alterations of Skeletal Muscle Composition in Head and Neck Squamous Cell Carcinoma within the Currently Clinically Defined Optimal Time Window for Salvage Surgery—A Pilot Study. Cancers 2023, 15, 4650. Santer, M.; Riechelmann, H.; Hofauer, B.; Schmutzhard, J.; Freysinger, W.; Runge, A.; Gottfried, T.M.; Zelger, P.; Widmann, G.; Kranebitter, H.; Mangesius, S.; Mangesius, J.; Kocher, F.; Dejaco, D. Radiomic Assessment of Radiation-Induced Alterations of Skeletal Muscle Composition in Head and Neck Squamous Cell Carcinoma within the Currently Clinically Defined Optimal Time Window for Salvage Surgery—A Pilot Study. Cancers 2023, 15, 4650.

Abstract

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.

Keywords

head and neck neoplasms; head and neck cancer; head and neck squamous cell carcinoma; radiotherapy; radiochemotherapy; salvage surgery; time interval; body composition; skeletal muscle; computed tomography scan; radiomics

Subject

Medicine and Pharmacology, Otolaryngology

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