Differentiation of irradiation and cetuximab induced skin reactions in patients with locally advanced head and neck cancer undergoing radioimmunotherapy: the HICARE protocol (head and neck cancer: immunochemo and radiotherapy with erbitux) - a multicenter phase IV trial.

BACKGROUND: In order to improve the clinical outcome of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable to receive platinum-based chemoradiation, radiotherapy can be intensified by addition of cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible treatment option showing a favourable toxicity profile. The most frequent side effect of radiotherapy is radiation dermatitis, the most common side effect of treatment with cetuximab is acneiform rash. Incidence and severity of these frequent, often overlapping and sometimes limiting skin reactions, however, are not well explored. A clinical and molecular differentiation between radiogenic skin reactions and skin reactions caused by cetuximab which may correlate with outcome, have never been described before. METHODS/DESIGN: The HICARE study is a national, multicenter, prospective phase IV study exploring the different types of skin reactions that occur in patients with LASCCHN undergoing radioimmun(chemo)therapy with the EGFR inhibitor cetuximab. 500 patients with LASCCHN will be enrolled in 40 participating sites in Germany. Primary endpoint is the rate of radiation dermatitis NCI CTCAE grade 3 and 4 (v. 4.02). Radioimmunotherapy will be applied according to SmPC, i.e. cetuximab will be administered as loading dose and then weekly during the radiotherapy. Irradiation will be applied as intensity-modulated radiation therapy (IMRT) or 3D-dimensional radiation therapy. DISCUSSION: The HICARE trial is expected to be one of the largest trials ever conducted in head and neck cancer patients. The goal of the HICARE trial is to differentiate skin reactions caused by radiation from those caused by the monoclonal antibody cetuximab, to evaluate the incidence and severity of these skin reactions and to correlate them with outcome parameters. Besides, the translational research program will help to identify and confirm novel peripheral blood based molecular predictors and surrogates for treatment response and resistance. TRIAL REGISTRATION: Clinical Trial Identifier, NCT01553032 (clinicaltrials.gov)EudraCT number: 2010-019748-38.

Impact of Primary Staging with Fibroblast Activation Protein Specific Enzyme Inhibitor (FAPI)-PET/CT on Radio-Oncologic Treatment Planning of Patients with Esophageal Cancer.

PURPOSE: Quinoline-based ligands targeting cancer-associated fibroblasts have emerged as promising radiopharmaceuticals in different tumor entities. The aim of this retrospective study was to explore the potential of FAPI-PET/CT in the initial staging of esophageal cancer patients and its usefulness in radiotherapy planning as a first clinical analysis. METHODS: Seven patients with treatment-naive esophageal cancer underwent FAPI-PET/CT. Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean. Six patients received definitive and one neoadjuvant (chemo)radiation therapy. Endo-esophageal clipping, the gold standard to define tumor margins not delineable per CT, was performed in three patients. RESULTS: Primary tumors demonstrated high FAPI uptake with a median SUVmax of 17.2. Excellent tumor-to-background ratios resulted in accurate target volume delineation and were found in perfect match with clipping. Detection of regional lymph node metastases facilitated the use of simultaneous integrated boost radiotherapy plans for these patients. CONCLUSION: FAPI-PET/CT may be beneficial for the management of esophageal cancer particularly in planning radiotherapy, but further research is necessary to increase patient number and statistical reliability.

Intrafractional dose variation and beam configuration in carbon ion radiotherapy for esophageal cancer.

BACKGROUND: In carbon ion radiotherapy (CIR) for esophageal cancer, organ and target motion is a major challenge for treatment planning due to potential range deviations. This study intends to analyze the impact of intrafractional variations on dosimetric parameters and to identify favourable settings for robust treatment plans. METHODS: We contoured esophageal boost volumes in different organ localizations for four patients and calculated CIR-plans with 13 different beam geometries on a free-breathing CT. Forward calculation of these plans was performed on 4D-CT datasets representing seven different phases of the breathing cycle. Plan quality was assessed for each patient and beam configuration. RESULTS: Target volume coverage was adequate for all settings in the baseline CIR-plans (V95 > 98% for two-beam geometries, > 94% for one-beam geometries), but reduced on 4D-CT plans (V95 range 50-95%). Sparing of the organs at risk (OAR) was adequate, but range deviations during the breathing cycle partly caused critical, maximum doses to spinal cord up to 3.5x higher than expected. There was at least one beam configuration for each patient with appropriate plan quality. CONCLUSIONS: Despite intrafractional motion, CIR for esophageal cancer is possible with robust treatment plans when an individually optimized beam setup is selected depending on tumor size and localization.