Sophie Dussart

Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial

BACKGROUND How best to treat rising prostate-specific antigen (PSA) concentration after radical prostatectomy is an urgent clinical question. Salvage radiotherapy delays the need for more aggressive treatment such as long-term androgen suppression, but fewer than half of patients benefit from it. We aimed to establish the effect of adding short-term androgen suppression at the time of salvage radiotherapy on biochemical outcome and overall survival in men with rising PSA following radical prostatectomy. METHODS This open-label, multicentre, phase 3, randomised controlled trial, was done in 43 French study centres. We enrolled men (aged ≥18 years) who had received previous treatment for a histologically confirmed adenocarcinoma of the prostate (but no previous androgen deprivation therapy or pelvic radiotherapy), and who had stage pT2, pT3, or pT4a (bladder neck involvement only) in patients who had rising PSA of 0·2 to less than 2·0 μg/L following radical prostatectomy, without evidence of clinical disease. Patients were randomly assigned (1:1) centrally via an interactive web response system to standard salvage radiotherapy (three-dimensional [3D] conformal radiotherapy or intensity modulated radiotherapy, of 66 Gy in 33 fractions 5 days a week for 7 weeks) or radiotherapy plus short-term androgen suppression using 10·8 mg goserelin by subcutaneous injection on the first day of irradiation and 3 months later. Randomisation was stratified using a permuted block method according to investigational site, radiotherapy modality, and prognosis. The primary endpoint was progression-free survival, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00423475. FINDINGS Between Oct 19, 2006, and March 30, 2010, 743 patients were randomly assigned, 374 to radiotherapy alone and 369 to radiotherapy plus goserelin. Patients assigned to radiotherapy plus goserelin were significantly more likely than patients in the radiotherapy alone group to be free of biochemical progression or clinical progression at 5 years (80% [95% CI 75-84] vs 62% [57-67]; hazard ratio [HR] 0·50, 95% CI 0·38-0·66; p<0·0001). No additional late adverse events occurred in patients receiving short-term androgen suppression compared with those who received radiotherapy alone. The most frequently occuring acute adverse events related to goserelin were hot flushes, sweating, or both (30 [8%] of 366 patients had a grade 2 or worse event; 30 patients [8%] had hot flushes and five patients [1%] had sweating in the radiotherapy plus goserelin group vs none of 372 patients in the radiotherapy alone group). Three (8%) of 366 patients had grade 3 or worse hot flushes and one patient had grade 3 or worse sweating in the radiotherapy plus goserelin group versus none of 372 patients in the radiotherapy alone group. The most common late adverse events of grade 3 or worse were genitourinary events (29 [8%] in the radiotherapy alone group vs 26 [7%] in the radiotherapy plus goserelin group) and sexual disorders (20 [5%] vs 30 [8%]). No treatment-related deaths occurred. INTERPRETATION Adding short-term androgen suppression to salvage radiotherapy benefits men who have had radical prostatectomy and whose PSA rises after a postsurgical period when it is undetectable. Radiotherapy combined with short-term androgen suppression could be considered as a reasonable option in this population. FUNDING French Ministry of Health, AstraZeneca, and La Ligue Contre le Cancer.

Impact of 18F-Fluoro-2-Deoxyglucose Positron Emission Tomography on Treatment Strategy and Radiotherapy Planning for Stage I–II Hodgkin Disease: A Prospective Multicenter Study

PURPOSE To quantify the impact of preradiotherapy 18F-fluoro-2-deoxyglucose positron-emission tomography (FDG-PET) on treatment strategy and radiotherapy planning for patients with Stage I/II Hodgkin disease included in a large prospective multicenter study. PATIENTS AND METHODS Conventional computed tomography and FDG-PET were performed just before the planned radiotherapy. The radiotherapy plan was first elaborated under blinded conditions for FDG-PET data. Then, the medical staff was asked to confirm or not confirm the treatment strategy and, if appropriate, to modify the radiotherapy plan based on additional information from FDG-PET. RESULTS Between January 2004 and January 2006, 137 patients were included (124 were available for analysis) in 11 centers (108 adults, 16 children). All but 1 patient had received chemotherapy before inclusion. Prechemotherapy work-up included FDG-PET for 61 patients, and data were available for elaboration of the first radiotherapy plan. Based on preradiotherapy FDG-PET data, the radiotherapy was cancelled in 6 patients (4.8%), and treatment plan modifications occurred in 16 patients (12.9%): total dose (11 patients), CTV volume (5 patients), number of beam incidences (6 patients), and number of CTV (6 patients). The concordance between the treatment strategies with or without preradiotherapy FDG-PET was 82.3%. Concordance results were not significantly different when prechemotherapy PET-CT information was available. CONCLUSION Preradiotherapy FDG-PET for treatment planning in Hodgkin lymphoma may lead to significant modification of the treatment strategy and the radiotherapy planning in patients with Stage I or II Hodgkin disease, even in those who have undergone FDG-PET as part of the prechemotherapy work-up.

Impact of 18F-FDG PET on Treatment Strategy and 3D Radiotherapy Planning in Non–Small Cell Lung Cancer: A Prospective Multicenter Study

OBJECTIVE The purpose of our study was to quantify the impact of preradiotherapy (18)F-FDG PET when deciding whether radiotherapy should be curative or palliative in intent and defining its detailed planning in patients with non-small cell lung cancer referred for 3D conformal radical radiotherapy within a large prospective multicenter study. SUBJECTS AND METHODS Conventional CT and FDG PET were performed 2-3 weeks before radiotherapy was scheduled to start. As an initial step, the medical team was asked to plan radiotherapy while blinded to the results of FDG PET. In a second step, the FDG PET data were revealed, and the medical team had to decide whether or not to confirm their radical radiotherapy strategy and, if so, whether any modifications were required to the treatment plan. RESULTS Of the 134 patients (79% with stage III disease) who were included in the analysis, 110 patients (82%) had received induction chemotherapy. Prechemotherapy FDG PET also was available for 25 patients. Knowledge of preradiotherapy FDG PET data caused treatment to be cancelled or changed from curative to palliative intent in 15 patients (11%). Of the 119 patients in whom radical radiotherapy was confirmed, the treatment plan was modified in 37 (31%). The concordance rate between the treatment strategies with or without preradiotherapy FDG PET was 62%. Concordance was improved but was still not complete (80%) when the prechemotherapy workup included FDG PET. CONCLUSION Preradiotherapy FDG PET for non-small cell lung cancer patients referred for 3D conformal radiotherapy may lead to significant modification of treatment strategy and radiotherapy planning.

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer

PURPOSE Intensity-modulated radiation therapy (IMRT) has shown its interest for head and neck cancer treatment. In parallel, cetuximab has demonstrated its superiority against exclusive radiotherapy. The objective of this study was to assess the acute toxicity, local control and overall survival of cetuximab associated with different IMRT modalities compared to platinum-based chemotherapy and IMRT in the ARTORL study (NCT02024035). PATIENTS AND METHOD This prospective, multicenter study included patients with epidermoid or undifferentiated nasopharyngeal carcinoma, epidermoid carcinoma of oropharynx and oral cavity (T1-T4, M0, N0-N3). Acute toxicity, local control and overall survival were compared between groups (patients receiving cetuximab or not). Propensity score analysis at the ratio 1:1 was undertaken in an effort to adjust for potential bias between groups due to non-randomization. RESULTS From the 180 patients included in the ARTORL study, 29 patients receiving cetuximab and 29 patients treated without cetuximab were matched for the analysis. Ten patients (34.5%) reported acute dermal toxicity of grade 3 in the cetuximab group versus three (10.3%) in the non-cetuximab group obtained after matching (P=0.0275). Cetuximab was not significantly associated with more grade 3 mucositis (P=0.2563). There were no significant differences in cutaneous or oral toxicity for patients treated with cetuximab between the different IMRT modalities (P=1.000 and P=0.5731, respectively). There was no significant difference in local relapse-free survival (P=0.0920) or overall survival (P=0.4575) between patients treated with or without cetuximab. CONCLUSION Patients treated with cetuximab had more cutaneous toxicities, but oral toxicity was similar between groups. The different IMRT modalities did not induce different toxicity profiles.