118 Concomitant Boost Radiation and Concurrent Cisplatin for Advanced Head and Neck Carcinomas: Preliminary Results of a Phase II Trial of the RTOG (99-14) K.K. Ang 1 , J. Harris 2 , A.S.Garden 1 , C.U.Jones 3 , A. Trotti 4 , J. Cheng 5 , S.A.Spencer 6 , R.S.Weber 7 1 M.D. Anderson Cancer Center, Houston, TX, 2 Radiation Therapy Oncology Group, Philadelphia, PA, 3 Radiation Oncology Center, Sacramento, CA, 4 Moffitt Cancer Center at University of South Florida, Tampa, FL, 5 Fox Chase Cancer Center, Philadelphia, PA, 6 University of Alabama, Birmingham, AL, 7 University of Pennsylvania, Philadelphia, PA Purpose/Objective: A phase II trial was undertaken to assess the feasibility, acute and late toxicity, rate of local-regional control (LRC), and survival of the combination of accelerated fractionation by concomitant boost (AFX-CB) and cisplatin f the treatment of patients with locally advanced head and neck squamous cell carcinomas (HNSCC). Materials/Methods: Between April and November 2000, 84 patients with histologic proof of stage III or IV carcinoma of oralcavity,oropharynx, hypopharynx, or larynx and having Zubrod performance status of 0-1 and adequate hematologic, hepatic, and renal functions were registered. Three patients were found to be ineligible, 1 did not receive protocol therap 3 had no follow up data resulting in a total of 77 (92%) analyzable patients. Age ranged from 40 to 76 with a median of 57 years. Sixty-one (79%) patients were men, 51 (66%) had oropharyngeal cancer, 64 (83%) had stage IV disease. The radia dose was 72 Gy in 42 fractions over 6 weeks, delivered in one daily fraction of 1.8 Gy during the first 3.5 weeks and two fractions per day, 1.8 Gy and 1.5 Gy separated by ⱖ6 h interval, during the last 2.5 weeks. Cisplatin, 100 mg/m 2 , was given in short iv infusion at week 1 and week 3 or 4. Tumor status and side effects were assessed every 2-3 months the first yea subsequently 3-4 months. Results: Of the 77 analyzable patients, 92% received radiation dose within 5% of the protocol guideline and 89% receive both cycles of cisplatin. Overall,51 (66%) patients had grade 3 acute reactions, 19 (25%) had grade 4 toxicity, and 3 patients (4%) died of sepsis or pneumonia. Dysphagia, bone morrow suppression, nausea, and vomiting were the most common side effects, which were mainly associated with cisplatin administration. Grade 3 and 4 acute mucositis occurred in 39 (51%) and 2 (3%) patients, respectively. At the time of analysis, 63 (82%) patients were still alive.At a median follow-up of 1 year for patients at risk, the estimated 1-year survival rate was 81.3% (95% confidence interval: 71.8-90.7) Grade 3 and 4 late toxicities developed in 17 (23%) and 6 (8%) patients, respectively, with chronic dysphagia being the leading problem. Conclusions: Results ofphase IIItrials in patients with locally advanced HNSCC showed that AFX-CB improved the likelihood of LRC and cisplatin given concurrently with SF yielded better LRC and survival rates relative to SF radiothera This phase II study was launched to test the feasibility of combining AFX-CB and cisplatin in patients with advanced HNC The data showed that the acute and late toxicities of the combination of AFX-CB with cisplatin were similar to those obse with other concurrent radiation-chemotherapy regimens (e.g., cisplatin-5FU given during the boost phase of SF, hydroxyu 5FU plus split-course radiation, and cisplatin-taxol and SF as studied in RTOG 97-03). The 1-year survival rate of 81.3% is encouraging given that 83% of patients had stage IV disease. Therefore, a phase III trial comparing AFX-CB plus cisplatin SF plus cisplatin will be activated to test whether accelerated fractionation provides an additional benefit in the concurrent radiation-chemotherapy setting. 119 Conventional vs Modified Fractionated Radiotherapy. Meta-Analysis of Radiotherapy in Head & Neck Squamous Cell Carcinoma : A Meta-Analysis Based on Individual Patient Data J. Bourhis 1 , N.Syz 2 , J. Overgaard 2 , K.K. Ang 2 , S. Dische 2 , J. Horiot 2 , A. Hilniak 2 , M. Poulsen 2 , B. O’Sullivan 2 , W. Dobrowsky 2 , C. Fallai 2 , L. Pinto 2 , K. Skladowski 2 , J.H.Hay 2 , K.K. Fu 2 , R. Sylvester 2 , J. Pignon 2 1 Department of Radiotherapy, Institut Gustave-Roussy, Villejuif, France, 2 MARCH Collaborative Group, Institut Gustave- Roussy, Villejuif, France Purpose/Objective: The aim of the project was to study the role of modified radiotherapy (RT) on overall survival. Materials/Methods: The Meta-Analysis of Radiotherapy in Carcinomas of Head & Neck (MARCH) group performed a meta-analysis using updated individual patient data comparing conventional RT to hyperfractionated or accelerated RT, o as radical treatment, in locally advanced head and neck squamous cell carcinoma Trials including only nasopharyngeal carcinoma were not eligible. The logrank-test, stratified by trial, was used for comparison and the hazard ratio (HR) of de or loco-regional failure (LRF) was calculated. Results: Fifteen randomized trials (1970-1998) with 6,515 patients wereincluded.One trialhad four-armsand contributed to three comparisons. Its control group was counted three time in the analysis that was then performed on 7,073 patients. The median follow-up period was 5.8 years. The pooled HR of death was 0.91 (95% confidence interval: 0.86-0.97; pⱖ0.003) corresponding to an absolute survival benefit of 3% for modified RT, from 36% to 39%, at 5 years. The pooled HR of LRF was 0.82 (0.77-0.88; p⬍0.0001) corresponding to an absolute benefit on loco-regional control of 7% for modified RT, from 46% to 53%, at 5 years. Three groups of trials were defined according to the total dose in the modified RT arm as compared to the conventional arm:increased (hyperfractionated RT), similar (accelerated RT) and decreased (very accelerated RT). There was a significant interaction (pⱖ0.03) for survival,butnotfor loco-regional control (pⱖ0.14), between the type of RT and treatment effect (table). The largest effect was observed with increased tota dose. The heterogeneity of treatment effect between trials disappeared after exclusion of the 3 trials having included less than 110 patients for both endpoints. There was no evidence that any subgroup of patients defined according to tumor site benefited more or less of modified RT than any other group. 71 Proceedings of the 44th Annual ASTRO Meeting