727 poster A prospective study on postoperative reirradiation (report) for recurrent and second primary head and neck squamous cell carcinoma

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4Gazi University, Radiation Oncology, Ankara, Turkey 5Dokuz Eylul, Radiation Oncology, Izmir, Turkey Purpose: The current study reports on long-term Quality of life (QoL) status following conventional radiotherapy in 187 nasopharyngeal carcinoma patients from 14 centers in Turkey. Patients and Methods: Patients with the diagnosis of nasopharyngeal carcinoma treated in 14 centers in Turkey with minimum 6 months of follow-up in complete remission were asked to complete Turkish version of EORTC QLQ C30 and HN 35 questionnaires. Each center participated with the required information of clinical data including age at diagnosis, gender, symptoms on admission, follow-up period, treatment modalities, radiotherapy dose and AJCC 1997 tumor stage. Each patient's 33 QoL scores including function, global health status and symptoms were calculated as instructed in EORTC C30 QLQ scoring manual. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems. KruskaI-Wallis and Mann-Whitney U non-parametric tests were used for comparisons. Results: One hundred eighty-seven patients with median age of 46 years (range; 16-79 years) participated to complete the questionnaires. Median follow-up time was 3.4 years (range 6 months-24 years). All patients have received external beam radiotherapy. Beside external radiotherapy, 59 patients underwent brachytherapy boost, 70 patients received concomittant and 85 patients received adjuvant/neoadjuvant chemotherapy. Most of the patients in the analysis (75%) were in advanced stage [(Stage III, n=85 (45.4%); stage IV, n=55(29%)]. Median global health status was calculated as 66. Parameters that increase global health status were male gender, early stage disease and patients with less than 4 year follow up (p<0.05). Functional parameters were better in male and early stage disease. Factors yielding better symptom scores were short interval after treatment (10 scores), male gender (7 scores) and lower radiation dose (6 scores). Neoadjuvant or adjuvant chemotherapy did not have any effect on quality of life whereas concomitant chemotherapy adversely affected 4 symptom scores. Conclusion: It is remarkable that quality of life is adversely affected in our nasopharyngeal carcinoma patients treated with combined treatments. The factors that adversely affect quality of life are advanced tumor stage, female gender and long term follow up. Further controlled studies evaluating both pre and post-radiotherapy status are necessary to clarify the contribution of each treatment modality in quality of life. 726 poster Concomitant chemo-radiotherapy (chemo-CAIR) in patients with advanced head and neck cancers - early results of phase II study

W. Sasiadek~ M. Golen, T. Rutkowski, A. Wygoda, M. Sygula, B. Plecki, W. Przeorek, B. Hejduk, Z. Kolosza, K. Skladowski Centre of Oncology - MSC Institute, I Radiotherapy, Gliwice, Poland Aim: As the CAIn fractionation - 7 fractions given in 7 days has become in Gliwice a standard radiation treatment for moderately advanced head and neck cancer, we decided to combine its high local effectiveness with systemic therapy in

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Iocoregionally advanced lesions. Phase II study of "ChemoCAIn" - an original organ-preservation approach consisted in platinum-based chemotherapy given concomitantly with accelerated conformal radiotherapy was done in patients with advanced, fairly unresectable head and neck cancers. Material and methods: Forty seven male patients with median age of 51 years, treated between March 1999 and December 2003 were prospectively evaluated. The most frequent primary tumour location was pharynx 33pts (70%) and 36pts (77%) were in stage IV. Treatment consisted in 4 cycles of cisplatin and vinorelbin administered with 21 days interval, beginning from 1st completing at 64th day. Radiation therapy administered as continuous radiation with 7 fractions per week has started at 22nd day and has completed at the day 63 with total dose of 68Gy in 40 fractions. Results: Only one patient death could be related to the treatment. Compliance of total radiation dose was 96% but 57% of patients finished full course of chemotherapy (only 19% received less then 3 cycles). Between 15 and 48 day of treatment all patients developed confluent mucositis, which lasted medially 60 days. Median follow-up was 25 months. Two-year Ioco-regional control (LRC) and disease free survival (DFS) rates were respectively 70% and 60%. Overall survival (OS) after 24 months ranged 78%. During follow-up 10 patients died, 9 of them from cancer disease. In 6 patients salvage surgery was performed: 5 lymph node resections and one resection of residual tumour. The most important negative prognostic factor effected LRC, DFS and OS was N3 stage. The presence of neurological symptoms effected negatively LRC. Higher LRC and DFS rates were observed for patients with egzophytic tumour growth pattern and younger age. Multivariate analysis revealed that N3 stage was the independent negative prognostic factor. Conclusions: Concomitant chemo-radiotherapy (ChemoCAIR) in patients with advanced head and neck tumours produces very promising early results and we plan to perform a multicenter phase III study. 727 poster A prospective study on postoperative reirradiation (report) for recurrent and second primary head and neck squamous cell carcinoma

N. Kasperts 1, P. Doornaert ~, B.J. Slotman ~, C.R. Leemans 2, J.A. Langendijk ~ ~VU University medical center, Radiation Oncology, Amsterdam, The Netherlands 2VU University medical center, Otolorayngology/Head and Neck Surgery, Amsterdam, The Netherlands Introduction: The purpose of this prospective study was to evaluate the results of post-operative re-irradiation (REPORT) on Iocoregional control (LRC), overall survival (OS), toxicity and quality of life (QoL) among patients who underwent curative surgery of a second primary tumour (SPT) or Iocoregional recurrent head and neck tumour in previously irradiated areas. Material and methods: A total of 40 patients with SPT (n=19) or Iocoregional recurrence (n=21) were treated with adjuvant radiotherapy, Indications for RE-PORT were extranodal spread (49%), positive surgical margins (44%), or other risk factors (8%). Patients with severe (=grade III) late complications from the first irradiation were not accepted. The interval between former radiotherapy had to be at least 1 year in case of SPT and 2 years in case of recurrent tumor. The CTV for RE-PORT included the high-risk area only. No elective radiotherapy was applied in regions that were situated in the formerly high-dose area (> 50 Gy). Pre- and postoperative CT-scans were used for planning.

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Radiotherapy plans were evaluated by means of DVH's. A reirradiation dose of 46 Gy was applied to elective areas, a boost to 60 Gy was given if the high-risk area was situated in the high-dose area of the formerly irradiation. If not, the highrisk area was boosted to 62.5-66 Gy. The results of REPORT were compared to the results of 178 patients treated with primary postoperative radiotherapy (PRI-PORT) at our department in the same period. QoL was evaluated using the EORTC QLQ-C30 and EORTC H&N35 at baseline and 6 weeks and 6 and 12 months after radiotherapy. Seventeen REPORT patients completed all questionnaires. Results: RE-PORT was generally well tolerated with only grade II and III objective and functional mucositis and acute xerostomia. The LRC at 3-year was 68% and the 3-year OS was 44% (not significant), as compared to 74% and 54% (not significant) in the PRI-PORT patients, respectively. As compared to patients treated with PRI-PORT, a significant increase was noted with regard to Ithe following late complicatons: grade Ill-IV xerostomia (17% vs 5%); grade IllIV neck fibrosis (25% vs 3%), grade Ill-IV laryngeal reactions (14% vs 2%) and grade Ill-IV swallowing complaints (50% vs 18%). In the RE-PORT group 23% of the patients depended fully upon a gastrostomy tube as compared to 13% in the PRI-PORT group. Osteoradionecrosis occurred in 8% and formation of fistulae was seen in 5% of patients. QoL analysis revealed more local problems in RE-PORT patients including sticky saliva, xerostomia, reduced smell and taste and difficulties with swallowing compared to PRI-PORT patients. No significant differences were seen regarding the more general QoL dimensions. Conclusion: Postoperative re-irradiation after salvage surgery among patients at high risk for Iocoregional recurrence is feasible and leads to promising results regarding LRC and OS. Although the incidence of late morbidity was significantly higher in RE-PORT patients compared to PRI-PORT patients, with more self-reported local symptoms, no differences were noted for the more general QoL dimensions. Therefore, RE-PORT should be considered in patients at high risk for Iocoregional recurrence after salvage surgery.

728 poster A new prognostic classification scheme derived from recursive partitioning analysis (RPA) for postoperative radiotherapy in squamous cell head and neck cancer

J.A. Lanqendiik ~, C.R. Leemans2, P. Doornaert 1, H. Berkhof, B.J. Sloiman 1 VU University Medical Center, Radiation Oncolegy, Amsterdam, The Netherlands 2VU University Medical Center, Otolaryngology/Head and Neck Surgery, Amsterdam, The Netherlands 3VU Medical Center, Clinical Epidemiology and Biostatistics, Amsterdam, The Netherlands Introduction: Postoperative radiotherapy after curative surgery for head and neck squamous cell carcinoma (HNSCC) is widely accepted as adjuvant treatment in case of one or more adverse prognostic factors. For the selection of patients who may benefit of other treatment modalities, including altered fractionation, chemoradiation and/or biological modifiers, the definition of subsets of patients with different prognosis is extremely important. Therefore, the aim of this study was to define different prognostic groups with regard to Iocoregional control (LRC) derived from recursive partitioning analysis (RPA). Material and methods: This study included 801 patients with HNSCC, who were treated between 1985 and 2000 with primary-surgery and postoperative radiotherapy. For the

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definition of prognostic groups, the method of classification and regression trees was performed, including a large number of well known prognostic factors. The partitioning procedure was stopped if no allowable split existed, i.e., if the p-value > 0.05 and/or if the size of a subgroup was < 15 cases. Results: The final model was composed of six prognostic factors for LRC, resulting in 7 terminal nodes. RPA class I (intermediate risk) consisted of 381 patients with no N3 nodes, free surgical margins (> 5 mm) and no extranodal spread (ENS). RPA class II (high risk) consisted of 189 patients with one positive node with ENS or T1, T2 or T4 tumours with close or positive surgical margins. RPA class III (very high risk) consisted of 231 patients with a N3 neck, 2 or more positive nodes with ENS or T3 with close or positive surgical margins. The 5-years LRC was 88%, 73% and 58%, in RPA class I, II and III, resp. (p< 0.0001). The hazard ratio (HR) relative to RPA class I was 2.3 (95%-ci: 1.5-3.6) for RPA class II and 4.2 (95-ci: 2.8-6~1) for RPA class II1. This classification scheme was also significantly associated with distant metastases free interval (DMFI) and the overall survival (OS). The DMFI was 89%, 79% and 68% after 5 years for RPA class I, II and III resp. (p<0.0001). The 5-years OS was 64%, 43% and 36%, resp. (p<0.0001). Conclusion: The RPA classification scheme allows for a clear definition of three prognostic groups with regard to LRC, which could be useful in the design of future prospective randomised studies investigating the additional value of chemotherapy and biological modifiers and/or altered fractionation schedules. 729 poster Still a place for induction therapy in chemoradiation of advanced squamous cancer of the head and neck?

C. Martin 1, D. Premachandra 2, P. Montgomery~, A. Bardslej, R. Rees ~, L. Swift3, F. Dixon 1, T. Bradnam 1, D. Smith 2 ~Norfolk and Norwich Hospital, Head and Neck Cancer Group, Norwich, United Kingdom 2james Paget Hospital, ENT, Gorleston, United Kingdom 3University of East Anglia, Statistics, Norwich, United Kingdom A meta-analysis of 63 randomised trials of chemotherapy (CT) added to Iocoregional treatment for head and neck squamous cell carcinoma (HNSCC) claimed little benefit for induction chemotherapy. This paper challenges this. 66 patients with advanced non-metastatic HNSCC were treated with 2 or 3 cycles of cisplatin - 5 fluorouracil infusion followed by radiotherapy (RT) 66Gy-70Gy/33-35F or 54-55Gy/20F using daily treatments. Sex ratio was M:F 58:8, staging il, III, IVA, IVB 5, 14, 31, 16 respectively and tumour sites oropharynx 41, larynx 15, pyriform 8, oral cavity 2. All patients were assessed by multi-disciplinary team. 5 patients underwent interval neck surgery following chemoradiation (CRT) but in all cases neck dissection gave negative histology. 10 patients (14%) underwent salvage surgery or CT either for initial chemo-resistant disease (2/10) or relapse (8/10). Median follow-up was 43 months (range 20 - 91 months). 5 year overall survival (OS), disease-free survival (DFS) and cause-specific survival (CSS) for stage Ill-IV cases was 52%, 48% and 68% respectively. 5 year DFS for II, III, IVA and IVB was 100%, 57%, 57% and 28% respectively. Performance status was a highly significant survival predictor between PS 0 and PS 1 (p=0.002, 0.003, 0.031 for OS, DFS, CSS respectively). Patients who showed complete response at end of CRT had significantly better OS than those that did not (p=0.000) and patients who completed CRT as planned than those who did not (p=0.000). Patients