Radiotherapy related skin toxicity (RAREST-01): Mepitel® film versus standard care in patients with locally advanced head-and-neck cancer.

BACKGROUND: The aim of the present trial is to investigate a new option of skin protection in order to reduce the rate of grade ≥ 2 skin toxicity in patients receiving radiotherapy alone or radiochemotherapy for locally advanced squamous cell carcinoma of the head-and-neck (SCCHN). METHODS / DESIGN: This is a randomized, active-controlled, parallel-group multi-center trial that compares the following treatments of radiation dermatitis in patients with head-and-neck cancer: Mepitel® Film (Arm A) vs. standard care (Arm B). The primary aim of this trial is to investigate the rate of patients experiencing grade ≥ 2 radiation dermatitis (according to Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03) until 50 Gy of radiotherapy. Evaluation until 50 Gy of radiotherapy has been selected as the primary endpoint, since up to 50 Gy, the irradiated volume includes the primary tumor and the bilateral cervical and supraclavicular lymph nodes, and, therefore, is similar in all patients. After 50 Gy, irradiated volumes are very individual, depending on location and size of the primary tumor, involvement of lymph nodes, and the treatment approach (definitive vs. adjuvant). In addition, the following endpoints will be evaluated: Time to grade 2 radiation dermatitis until 50 Gy of radiotherapy, rate of patients experiencing grade ≥ 2 radiation dermatitis during radio(chemo)therapy, rate of patients experiencing grade ≥ 3 skin toxicity during radio(chemo)therapy, adverse events, quality of life, and dermatitis-related pain. Administration of Mepitel® Film will be considered to be clinically relevant, if the rate of grade ≥ 2 radiation dermatitis can be reduced from 85% to 65%. DISCUSSION: If administration of Mepitel® Film instead of standard care will be able to significantly reduce the rate of grade ≥ 2 radiation dermatitis, it could become the new standard of skin care in patients irradiated for SCCHN. TRIAL REGISTRATION: clinicaltrials.gov NCT03047174 . Registered on 26th of January, 2017. First patient included on 9th of May, 2017.

Prognostic Value of Urokinase-Type Plasminogen Activator Receptor PET/CT in Head and Neck Squamous Cell Carcinomas and Comparison with 18F-FDG PET/CT: A Single-Center Prospective Study.

The aim of this phase II clinical trial (NCT02965001) was to evaluate the prognostic value of urokinase-type plasminogen activator receptor (uPAR) PET/CT with the novel ligand 68Ga-NOTA-AE105 in head and neck cancer and compare it with 18F-FDG. Methods: Patients with head and neck squamous cell carcinoma referred for curatively intended radiotherapy were eligible and prospectively included in this study. 68Ga-uPAR and 18F-FDG PET/CT were performed before initiation of curatively intended radiotherapy, and the SUVmax of the primary tumor was measured on both PET/CT studies by 2 independent readers. Relapse-free survival (RFS) and overall survival (OS) were calculated, and optimal cutoffs were established for 68Ga-uPAR and 18F-FDG PET independently and compared using log rank and Kaplan-Meier statistics, as well as univariate and multivariate analysis in a Cox proportional-hazards model. Results: In total, 57 patients were included and followed for a median of 33.8 mo (range, 2.30-47.2, mo). The median SUVmax of the primary tumors was 2.98 (range, 1.94-5.24) for 68Ga-uPAR and 15.7 (range, 4.24-45.5) for 18F-FDG. The optimal cutoffs for 68Ga-NOTA-AE105 SUVmax in the primary tumor were 2.63 for RFS and 2.66 for OS. A high uptake of 68Ga-NOTA-AE105 (SUVmax above cutoff) was significantly associated with poor RFS and OS (log-rank P = 0.012 and P = 0.022). 68Ga-NOTA-AE105 uptake in the primary tumor was significantly associated with poor RFS in univariate analysis (hazard ratio [HR], 8.53 [95% CI, 1.12-64.7]; P = 0.038), and borderline-associated with OS (HR, 7.44 [95% CI, 0.98-56.4]; P = 0.052). For 18F-FDG PET, the optimal cutoffs were 22.7 for RFS and 22.9 for OS. An 18F-FDG SUVmax above the cutoff was significantly associated with reduced RFS (log-rank P = 0.012) and OS (log-rank P = 0.000). 18F-FDG uptake was significantly associated with reduced RFS (HR, 3.27 [95% CI, 1.237-8.66]; P = 0.017) and OS (HR, 7.10 [95% CI, 2.60-19.4]; P < 0.001) in univariate analysis. In a multivariate analysis including 68Ga-uPAR SUVmax, 18F-FDG SUVmax, TNM stage, and p16 status, only 68Ga-uPAR SUVmax remained significant (HR, 8.51 [95% CI, 1.08-66.9]; P = 0.042) for RFS. For OS, only TNM stage and 18F-FDG remained significant. Conclusion: The current trial showed promising results for the use of 68Ga-uPAR PET SUVmax in the primary tumor to predict RFS in head and neck squamous cell carcinoma patients referred for curatively intended radiotherapy when compared with 18F-FDG PET, TNM stage, and p16 status. 68Ga-uPAR PET could potentially become valuable for identification of patients suited for deescalation of treatment and risk-stratified follow-up schemes.

A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas.

INTRODUCTION: Gemcitabine based regimens have been widely used in patients with advanced cholangiocarcinoma (CC), but no standard therapy exists. In this study we aimed to find the maximally tolerated dose (MTD) of a two-week schedule of fixed dose rate (FDR) gemcitabine (G), oxaliplatin (O) and capecitabine (C), and evaluate the safety and efficacy of this regimen in patients with advanced cholangiocarcinoma (CC). METHODS: In the Phase I part of the study a dose-escalation schedule of FDR G, O and C, administered every two weeks, was performed in patients with solid tumours and no other treatments or advanced CC. In the Phase II part response rate, toxicity, progression-free survival (PFS) and overall survival was evaluated in patients with newly diagnosed advanced CC. RESULTS: Thirty-six patients entered the Phase I part and G 1 000 mg/m(2) day 1 and 15, O 60 mg/m(2) day 1 and 15, and C 1 000 mg/m(2) BID day 1-7 and day 15-21 were established as MTD. In the Phase II part, 41 patients with advanced CC were included. Overall response rate was 34% and 51% had stable disease, resulting in a clinical benefit rate of 85%. Grade III and IV adverse events were rare. Median survival was 12.5 months (95% CI 9.2-15.9) and median progression-free survival (PFS) was 6.9 months (95% CI 5.1-8.6). CONCLUSIONS: This outpatient regimen was very feasible with significant activity and a favourable safety profile. Further studies will explore this combination with addition of newer targeted agents.