Fever range whole body hyperthermia for re-irradiation of head and neck squamous cell carcinomas: Final results of a prospective study.

OBJECTIVES: Fever-range whole body hyperthermia (FRWBH) has been shown to improve tumor oxygenation in vivo. A prospective pilot study addressed the question if addition of FRWBH to re-irradiation is feasible in recurrent head and neck squamous cell carcinomas (HNSCC) with unfavorable prognostic features. MATERIALS AND METHODS: The study completed accrual with the recruitment of ten patients between April 2018 and March 2020. Re-irradiation was administered using volumetric arc hyperfractionated radiotherapy with bi-daily 1.2 Gray (Gy) single fractions and a total dose of 66 Gy to all macroscopic tumor lesions. Concomitant chemotherapy consisted mostly of cisplatin (7 patients). FRWBH was scheduled weekly during re-irradiation. The study was registered in the clinicaltrials.gov database (NCT03547388). RESULTS: Only five patients received all cycles of FRWBH. Poor patient compliance, active infections during treatment and study restrictions due to the Covid-19 pandemic were the main reasons for omitting FRWBH. No increase of acute toxicity was observed by FRWBH. Exploratory evaluation of outcome data suggests that FRWBH treatment according to protocol does not seem to have a detrimental effect on tumor control or survival and might even increase treatment efficacy. CONCLUSION: FRWBH is difficult to apply concomitant to re-irradiation in HNSCC. No excess toxicity was observed in patients receiving FRWBH and exploratory analyses suggest potential anti-tumor activity and decreased patient-reported depression scores after FRWBH.

Prognostic value of baseline [18F]-fluorodeoxyglucose positron emission tomography parameters MTV, TLG and asphericity in an international multicenter cohort of nasopharyngeal carcinoma patients.

PURPOSE: [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) parameters have shown prognostic value in nasopharyngeal carcinomas (NPC), mostly in monocenter studies. The aim of this study was to assess the prognostic impact of standard and novel PET parameters in a multicenter cohort of patients. METHODS: The established PET parameters metabolic tumor volume (MTV), total lesion glycolysis (TLG) and maximal standardized uptake value (SUVmax) as well as the novel parameter tumor asphericity (ASP) were evaluated in a retrospective multicenter cohort of 114 NPC patients with FDG-PET staging, treated with (chemo)radiation at 8 international institutions. Uni- and multivariable Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), event-free survival (EFS), distant metastases-free survival (FFDM), and locoregional control (LRC) was performed for clinical and PET parameters. RESULTS: When analyzing metric PET parameters, ASP showed a significant association with EFS (p = 0.035) and a trend for OS (p = 0.058). MTV was significantly associated with EFS (p = 0.026), OS (p = 0.008) and LRC (p = 0.012) and TLG with LRC (p = 0.019). TLG and MTV showed a very high correlation (Spearman's rho = 0.95), therefore TLG was subesequently not further analysed. Optimal cutoff values for defining high and low risk groups were determined by maximization of the p-value in univariate Cox regression considering all possible cutoff values. Generation of stable cutoff values was feasible for MTV (p<0.001), ASP (p = 0.023) and combination of both (MTV+ASP = occurrence of one or both risk factors, p<0.001) for OS and for MTV regarding the endpoints OS (p<0.001) and LRC (p<0.001). In multivariable Cox (age >55 years + one binarized PET parameter), MTV >11.1ml (hazard ratio (HR): 3.57, p<0.001) and ASP > 14.4% (HR: 3.2, p = 0.031) remained prognostic for OS. MTV additionally remained prognostic for LRC (HR: 4.86 p<0.001) and EFS (HR: 2.51 p = 0.004). Bootstrapping analyses showed that a combination of high MTV and ASP improved prognostic value for OS compared to each single variable significantly (p = 0.005 and p = 0.04, respectively). When using the cohort from China (n = 57 patients) for establishment of prognostic parameters and all other patients for validation (n = 57 patients), MTV could be successfully validated as prognostic parameter regarding OS, EFS and LRC (all p-values <0.05 for both cohorts). CONCLUSIONS: In this analysis, PET parameters were associated with outcome of NPC patients. MTV showed a robust association with OS, EFS and LRC. Our data suggest that combination of MTV and ASP may potentially further improve the risk stratification of NPC patients.