Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial.

BACKGROUND: Concomitant chemoradiotherapy and accelerated radiotherapy independently improve outcomes for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC). We aimed to assess the efficacy and safety of a combination of these approaches. METHODS: In our open-label phase 3 randomised trial, we enrolled patients with locally advanced, stage III and IV (non-metastatic) HNSCC and an Eastern Cooperative Oncology Group performance status of 0-2. We randomly allocated patients centrally with a computer program (with centre, T stage, N stage, and localisation as minimisation factors) in a 1:1:1 ratio to receive conventional chemoradiotherapy (70 Gy in 7 weeks plus three cycles of 4 days' concomitant carboplatin-fluorouracil), accelerated radiotherapy-chemotherapy (70 Gy in 6 weeks plus two cycles of 5 days' concomitant carboplatin-fluorouracil), or very accelerated radiotherapy alone (64·8 Gy [1·8 Gy twice daily] in 3·5 weeks). The primary endpoint, progression-free survival (PFS), was assessed in all enrolled patients. This trial is completed. The trial is registered with ClinicalTrials.gov, number NCT00828386. FINDINGS: Between Feb 29, 2000, and May 9, 2007, we randomly allocated 279 patients to receive conventional chemoradiotherapy, 280 to accelerated radiotherapy-chemotherapy, and 281 to very accelerated radiotherapy. Median follow-up was 5·2 years (IQR 4·9-6·2); rates of chemotherapy and radiotherapy compliance were good in all groups. Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy (HR 1·02, 95% CI 0·84-1·23; p=0·88) or very accelerated radiotherapy (0·83, 0·69-1·01; p=0·060); conventional chemoradiotherapy improved PFS compared with very accelerated radiotherapy (0·82, 0·67-0·99; p=0·041). 3-year PFS was 37·6% (95% CI 32·1-43·4) after conventional chemoradiotherapy, 34·1% (28·7-39·8) after accelerated radiotherapy-chemotherapy, and 32·2% (27·0-37·9) after very accelerated radiotherapy. More patients in the very accelerated radiotherapy group had RTOG grade 3-4 acute mucosal toxicity (226 [84%] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205 [76%] of 271 patients) or conventional chemoradiotherapy (180 [69%] of 262; p=0·0001). 158 (60%) of 265 patients in the conventional chemoradiotherapy group, 176 (64%) of 276 patients in the accelerated radiotherapy-chemotherapy group, and 190 (70%) of 272 patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment (p=0·045). INTERPRETATION: Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy and acceleration of radiotherapy cannot compensate for the absence of chemotherapy. We noted the most favourable outcomes for conventional chemoradiotherapy, suggesting that acceleration of radiotherapy is probably not beneficial in concomitant chemoradiotherapy schedules. FUNDING: French Ministry of Health.

Nutritional factors as predictors of response to radio-chemotherapy and survival in unresectable squamous head and neck carcinoma.

BACKGROUND AND PURPOSE: This study sought to evaluate nutritional prognostic factors before treatment in patients with unresectable head and neck cancer treated by concomitant radio-chemotherapy. METHODS AND MATERIALS: Seventy-two consecutive patients were treated. We studied the potential effects of CRP, Alb, preAlb, orosomucoid, weight, weight history, BMI, PINI, OPR and NRI on response to treatment, Event-Free Survival (EFS) and Overall Survival (OS). Effects of potential risk factors on OS and on EFS were analyzed by computing Kaplan-Meier estimates, and curves were compared using the log-rank test. RESULTS: All biological nutritional factors were statistically correlated with the response to radio-chemotherapy. In multivariate analysis, only CRP (p=0.004) remained statistically significant. A statistical correlation was found between Alb and EFS in multivariate analysis (p=0.04). The factors influencing OS in univariate analysis were Alb (p=0.008), CRP (p=0.004), orosomucoid (p=0.01) and NRI (p=0.01), response to radio-chemotherapy (p<0.001) and staging (p=0.04). In multivariate analysis, only the response to radio-chemotherapy (p<0.001) remained significant. CONCLUSIONS: This study illustrates the prognostic value of nutritional status. CRP and Alb may be useful in the assessment of advanced head and neck cancer patients at diagnosis and for stratifying patients taking part in randomized trials.

Very accelerated radiotherapy or concurrent chemoradiotherapy for N3 head and neck squamous cell carcinoma: Pooled analysis of two GORTEC randomized trials.

OBJECTIVE: To analyze the outcome of N3 patients treated with very accelerated radiotherapy (VART) or different schedules of concurrent chemoradiotherapy (CRT) within two phase III trials. PATIENTS AND METHODS: Data of 179 patients with N3 HNSCC from two GORTEC randomized trials (96-01 and 99-02) were pooled. Patients received either VART: 64.8Gy/3.5weeks or one of the 3 following CRT regimens: Conventional CRT: 70Gy/7weeks+3 cycles carboplatin-5FU; Moderately accelerated CRT: 70Gy/6weeks+2 cycles carboplatin-5FU; Strongly intensified CRT: 64Gy/5weeks+cisplatin (days 2, 16, 30) and 5 FU (days 1-5, 29-33) followed by 2 cycles adjuvant cisplatin-5FU. RESULTS: Median follow-up was 13.3 and 5.2years for GORTEC 96-01 and GORTEC 99-02, respectively. Five-year overall survival (OS) was 13.8%. No significant difference was observed between CRT versus VART in terms of OS (hazard ratio [HR]: 0.93, p=0.68), loco-regional progression (HR: 0.70, p=0.13), or distant progression (HR: 0.86, p=0.53). OS was worse for patients with T3-4 tumors versus early T stage (11.0% versus 25.7%, p=0.015). In multivariate analysis, the oropharyngeal subsite presented a higher risk of distant metastasis (as first event 46.5% vs 19.2%, p<0.001),). A significant interaction between treatment modalities and subsites has been observed concerning loco-regional and distant failures. CONCLUSION: The outcome of N3 HNSCC was extremely poor despite treatment intensification and no difference between CRT and VART. Both distant metastases and loco-regional failures remain important treatment challenge.

Infrastructure of radiation oncology in France: a large survey of evolution of external beam radiotherapy practice.

PURPOSE: To study the structural characteristics of radiation oncology facilities for France and to examine how technological evolutions had to be taken into account in terms of accessibility and costs. This study was initiated by the three health care financing administrations that cover health care costs for the French population. The needs of the population in terms of the geographic distribution of the facilities were also investigated. The endpoint was to make proposals to enable an evolution of the practice of radiotherapy (RT) in France. METHODS AND MATERIALS: A survey designed by a multidisciplinary committee was distributed in all RT facilities to collect data on treatment machines, other equipment, personnel, new patients, and new treatments. Medical advisors ensured site visits in each facility. The data were validated at the regional level and aggregated at the national level for analysis. RESULTS: A total of 357 machines had been installed in 179 facilities: 270 linear accelerators and 87 cobalt units. The distribution of facilities and megavoltage units per million inhabitants over the country was good, although some disparities existed between areas. It appeared that most megavoltage units had not benefited from technological innovation, because 25% of the cobalt units and 57% of the linear accelerators were between 6 and 15 years old. Computed tomography access for treatment preparation was not sufficient, and complete data management systems were scarce (15% of facilities). Seven centers had no treatment planning system. Electronic portal imaging devices were available in 44.7% of RT centers and in vivo dosimetry in 35%. A lack of physicians and medical physicists was observed; consequently, the workload exceeded the normal standard recommended by the French White Book. Discrepancies were found between the number of patients treated per machine per year in each area (range, 244.5-604). Most treatments were delivered in smaller facilities (61.6%). CONCLUSION: On the basis of the findings of this study, measures were taken to update the infrastructure of RT in France. A first evaluation showed an improvement of care supply in RT in the country.

Impact of radiation oncology practice on pain: a cross-sectional survey.

PURPOSE: A cross-sectional study was performed to evaluate the prevalence of pain in our radiotherapy (RT) department. The impact of RT practice on pain and pain management were analyzed. METHODS AND MATERIALS: Of 126 patients, 93 (73.8%) completed the questionnaire proposed in this survey. It was designed to assess the proportion of patients experiencing pain in the department, the impact of RT practice on pain, and patients' estimate of the quality of management of their pain by the medical staff. Pain intensity and patient satisfaction were assessed using an 11-point numeric rating scale. RESULTS: Of the 93 patients, 66 experienced pain during RT, 13 of whom were totally relieved by analgesic treatment. The mean pain intensity was 3.9 (SD 2.3). A total of 26 patients had a numeric rating >/=4, indicating that their pain was not sufficiently treated. The objective length of waiting time for a session, transportation, and mobilization for session positioning worsened the pain of a substantial proportion of patients. A total of 56% of patients had a favorable opinion about pain management in our department. A high percentage (72.2%) of patients found that the time spent by the medical staff for pain management was inadequate, and 54.5% believed that the psychological support they received was insufficient. Personnel in the RT department remained the primary source of information regarding pain control. However, 17.5% of patients did not report their pain or talked about it to non-health care professionals. CONCLUSION: The prevalence of pain was high in the department. The specific practice of RT worsened pain and nearly one-half of patients were not satisfied with its management. The necessity for medical staff to be more available was highlighted by patients.

Impact of the prophylactic gastrostomy for unresectable squamous cell head and neck carcinomas treated with radio-chemotherapy on quality of life: Prospective randomized trial.

BACKGROUND AND PURPOSE: Concomitant radio-chemotherapy is the gold standard treatment for unresectable head and neck carcinomas. Placement of prophylactic gastrostomy has been proposed to provide adequate nutrition during the therapeutic sequence. The objectives of this study were to assess the impact of prophylactic gastrostomy on the 6-month quality of life, and to determine the factors related to this quality of life. MATERIALS AND METHODS: Design. randomized, controlled, open study ("systematic percutaneous gastrostomy" versus "no systematic gastrostomy"). Patients. squamous cell head and neck carcinoma (stages III and IV, UICC 1997). Setting. oncological departments of French university teaching hospitals. Treatment. optimal concomitant radio-chemotherapy. Evaluations. T0 baseline evaluation, T1 during the treatment, T2 end of the treatment, and T3 6-month post-inclusion. Primary endpoint. 6-month quality of life (Qol) assessed using SF36, EORTC QLQ-C30, EORTC QLQ H&N35 questionnaires. RESULTS: The Qol changes from baseline included a decline (T1 and T2) followed by an improvement (T3). Qol at 6 months was significantly higher in the group receiving systematic prophylactic gastrostomy (p=10(-3)). Higher initial BMI and lower initial Karnofsky index were significant factors related to a higher 6-month Qol. CONCLUSIONS: The study results suggest that prophylactic gastrostomy improves post-treatment quality of life for unresectable head and neck cancer patients, after adjusting for other potential predictive quality of life factors.