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812 Poster HDR hyperfractionated interstitial brachytherapy for mobile tongue cancer at the Osaka University Hospital
Posters
809
Friday/Saturday, 20-21 September 2002 $241
Poster
Frequency and types of TP53 mutations in squamous cell carcinomas of the head and neck - a comparison of two methods used on formalin fixed paraffin embedded tissue sampies J.G, Eriksen. J. Alsner, SB. Sorensen, J. Overgaard Aarhus University Hospital, Dept. of Experimental Clinical Oncology, Aarhus C, Denmark Introduction: Mutations in TP53 and expression of p53 protein have been shown to influence the radiosensitivity in tumour cells from head and neck carcinomas. Immunohistochemistry is an often used method for analysis in formalin fixed paraffin embedded tissue sections, but the PCR-based mutation screening method Denaturing Gradient Gel Electrophoresis (DGGE) is also an attractive method to use. By use of this technique we have earlier shown, that functional (missense or null) mutations in exon 5 to 9 of TP53 has prognostic importance for the outcome of HNSCC(1). Recently developed techniques increases the sensitivity of mutation detection, and our aim was to compare the mutation profiles obtained by screening exon 4C (C-terminal) to 10 of TP53 when using Denaturing High Pressure Liquid Chromatography (DHLPC) and DGGE, respectively, Material and methods: DNA extracted from 114 formalin fixed paraffin embedded pro-treatment biopsies of HNSCC was analysed by DGGE. The characteristics of this group were compared to a cohort of similar size (n=110) of HNSCC screened by DHPLC (WAWE®) in exon 4C to 10 of TP53. Mutations found in both groups were further characterised by sequencing, Further analysis Of the DGGE-group using DHPLC on exon 4Cq 0 is ongoing. Results: No relation was found in any of the two methods between the clinical parameters: tumour size, nodal status, anatomical site, stage or differentiation and TP53-status. DHPLC registered 8% more mutations in the core region of TP53 (exon 5-9) compared to the DGGE-results(1). DHPLCanalysis including exon 4C and exon 10 increased the TP53-mutation rate from 52% to 67%. An increase in incidence of multiple mutations in the same tumour was found by the DHPLC-method compared to DGGE, but this was not significant. Conclusion:,ln total 51 functional mutations were found in the DGGE-serie: 82% point mutations, 14% deletions and 4% insertions. In total 70 functional mutations were detected by DHPLC: 91% point mutations, 7% deletions and 2% insertions. The DHPLC-method is at least as sensitive screening method for TP53-mutations as DGGE. Based on this study it is reasonable to screen exons outside the DNA-binding area because additional functional mutations are located there. (1): Alsner J, Sorensen SB and Overgaard J:TP53 mutation is related to poor prognosis after radiotherapy, but not surgery, in squamous cell carcinoma of the head and neck. 810
Poster
Quality of life in patients with oral-oropharynx tumors treated with curative radiotherapy: an open randomised phase III study on recombinant human GM-CSF (molgramostim, leucomax*)
Y, Brandber_o.M. Karimi, G. Masucci Karolinska Instituter, Oncology-Pathology, Stockholm, Sweden The majority, of patients with locally advanced tumors of the head and neck who receives pre or post-operative radiotherapy (RT) present mucositis/epitelitis, which have a negative impact on the patients quality of life (QoL), The effects of GM-CSF on QoL were studied within the framework of an open randomised phase-Ill-study. A total of 45 patients from two of the participating centres were included in the QoL-study. They completed the EORTC Quality of Life Questionnaire (QLQ C-30) and the EORTC Head & Neck module (EORTC-H&N35) six times once a week during RT, The first questionnaire was completed before randomisation, Differences between the two randomisation arms are analysed, using ANOVA repeated measurement, with respect to the five functional QLQ-30 variables, "global health status" , the fatigue scale, and H&N-variables "weight loss", "pain", "swallowing", "speech problems", "teeth", "opening mouth", "dry mouth", "felt ill" and "pain killers", The data are currently being analysed and will be presented at the conference. Preliminary analyses suggest differences between the two randomisation arms in the head- and neck cancer specific symptom scales.
811
Poster
The role of radiotherapy for the treatment of etmoidal cancer: a retrospective analysis of 100 cases treated in Brescia (19702000) S.M. Maerini. A. Somensari, A. Scheda, B. La Face, S, Tonoli Istituto del Radio Ofindo Alberti, Radiation Oncology, Brescia, Italy Purpose: This study aims at a definition of the results of radiotherapy for the treatment of ethmoid cancer, mainly in the context of a combined radlo-surgical approach. Methods and Materials: A relatively large series of t00 consecutive ptS treated at our Institution has been retrospectively analysed, also according to the accrual period (Group 1, 1970-88; Group 2, 1989-00). The vast majority of the pts had T3 or T4 disease (79%) and 21% had undlfferentiated (G3) tumours. Radical surgery was more common in Group 2 pts (81% vs 52%). Average ICRU dose varied according to the extent (~f p0stsurgical residual disease (Group 1 : R0, 58 Gy; R1, 66 Gy (1 pts); R2, 62 Gy; Rx, 61 Gy; Group 2: R0, 55 Gy; R1, 58 Gy; R2, 66 Gy; Rx, 57 Gy), ReSults:The 5-year actuarial overall survival of the entire series was 43% (39,4% versus 44,5%, respectively for Group 1 and 2), 5°year disease-specific survival (DSS) 52% (Group 1: 43,3% versus Group 2: 57,7%) and 5year relapse free survival (RFS) 46% (Group 1: 38,8%; Group 2: 50,4%). DSS and RFS were significantly better (Log-rank) for early stage pts (T1T2), and for those with low-grade disease; RFS was also better for pts who had radical Surgery and for those with less extended post-sUrgical residue. Higher cumulative doses (> 60 Gy) are related to a not significantly lower recurrence probability in R1-R2 cases (54% vs 62%). Conclusions: The relevance of radical surgery is evident but radiotherapy has an important role for loco regional Control and for survival, being able by itself to cure 20% of the negatively selected biopsy-only cases. The prognostic relevance of the different clinical therapeutic features will be discussed in detail, along with the possible interatton betwean surgery and radiotherapy. 812
Poster
HDR hyperfractionated interstitial brachytherapy for m o b i l e tongue cancer at the Osaka University Hospital T. /noue 1, T. /noue 1, E. Tanaka2, K. Shimizutani2, N. Kaklmoto 3, S. Furukawa3 1OsakaUniversity Graduate School of Medicine, Division of Mu/tidiscip/inary Radiotherapy, Suita, Osaka, Japan 2Osaka University Graduate School of Medicine, Department of Radiology, Suit& Osaka, Japan 3Osaka University Graduate School of Dentistry, Department of Oral & Maxillofacial Radiology, Suita, Osaka, Japan Purpose: To present 11-year experience of HDR hyperfractionated intersti° tial brachytherapy for early mobile tongue cancer through phase I/ii study for oral cancer, and phase Ill study of HDR versus LDR brachytherapy for T1-2N0 carcinoma of the mobile tongue. In July 1991, we began HDR interstitial brachytherapy using microSelectron-HDR with plastic tube technique for tongue cancer through submandibular approach, At that time, there was no standardized dose schedule for HDR interstitial brachytherapy for oral cancer. Methods: From July to December 1991, 9 patients with oral cancer entered phase 1/11study, We performed dose escalation study of 20% intervals from starting dose of 35 Gy using hyperfractionated interstitial brachytherapy. From April 1992 to October 1996, a total of 59 patients entered phase III study. Twenty4ive patients in HDR group and 26 patients in LDR group were eligible for the final assessment, There were no differences of patient and treatment characteristics between two groups, except for the thickness of the tumor. HDR group included more patients with thicker tumor. In LDR arm (70 Gy/4-9 days) we used guide gutter technique with intraoral handltng, while in HDR arm (60 Gy/10 fractions/5-7 days) we treated patients with linked double-button technique through submandibular approach. This technique resulted in more correct arrangement with equal spacing by suturing these buttons, and sufficient dosage to the dorsal end of thetongue by means of one additional buttons attached to the upper end of catheter. Dose optimization was able to perform in HDR. Results: According to the phase 1/11study, HDR interstitial brachytherapy of 60 Gy in 10 fractions Over one week had the same effect to LDR of 70 Gy over one week for the mobile tongUe cancer, as to the early mucosal reaction and local tumor control. From the phase III study, 5-year cause specific survivals of HDR and LDR groups were 88% and 87%, respectively. Corresponding 5-year local control rates were 88% and 84%, and 5-year nodal recurrence free survivals were 76% and 77%. Adverse effects including the
$242 Friday/Saturday, 20-21 September 2002
late tongue atrophy of HDR were the same to that of LDR brachytherapy, Conclusions: Treatment results of HDR hyperfractionated interstitial brachytherapy for tongue cancer were higher or the same as that of LDR continuous one through 11-year experience at the Osaka University Hospital. 813
Poster
Hemoglobin as an independent prognostic factor in the radiotherapy of head and neck tumors U. Sch&fer 1, O. Micke 1, C. RObe2, P. SchOIler I, N. Willich 1 1University of MOnster, Department of Radiotherapy, MOnster, Germany 2University-Hospital of the Saarland, Department of Radiotherapy, Homburg, Germany Purpose: The purpose of this study was to analyze the prognostic value of pre-treatment hemoglobin prior to radiotherapy in patients with head and neck tumors. Material and methods: In a retrospective study with a median follow-up of 33 months, we analyzed the results of 228 patients irradiated for head and neck cancer between 1-1-1990 and 1-1-1998 (197 men and 31 women with a median age of 58 years). The treatment concept was adjuvant radiotherapy in 67 patients, 77 patients received definitive radiochemotherapy (RCT), 38 patients definitive radiotherapy (RT), and 46 patients re-irradiation for in-field recurrence (re-RT). Several known prognostic factors like sex, age (< median vs. > median), tumor stage (AJCC stage I-IV), tumor grade (G1-G4), general condition (AJCC 0-1 vs. 2-3), and treatment concept were analyzed for their influence on overall survival and correlated with pre-treatment hemoglobin values (< 12 g/100 ml vs. > 12 g/100 ml). Results: Median survival of all patients amounted to 13 months (adjuvant treatment: 49 months, RCT 13 months, RT 8 months, re-RT 4 months). In univariate analysis, the following variables were significant prognostic factors for overall survival: treatment concept (p<0.0001), tumor stage (p=0:004), general condition (p<0.0001), and pre-treatment hemoglobin (p=0.039). Multivariate analysis (Cox) showed all these parameters to be independent from each other (treatment concept p=0.01, tumor stage p=0.0001, general condition p=0.001, pre-treatment hemoglobin p=0.024). Conclusion: In this retrospective analysis, pre-treatment hemoglobin proved to be an independent significant prognostic factor in the radiotherapy of head and neck cancer patients. Therefore there might be a sensible indication for the use of erythropoietin in patients treated for malignancies of the head and neck region, 814
Poster
Repopulation and tumour response to postoperative irradiation with or without adjuvant chemotherapy in head and neck c a n c e r patients V. Pedraza Murie/1, M. Guerrero Tejada 2, J. Luna de/Castil/o 3 1University Hospital, Radiation Oncology, Granada, Spain 2University Hospital, Radiation Oncology, Granada, Spain 3Faculty of Medicine, Biostatistics, Granada, Spain Background and purpose: Based on the radiobiological data relating to accelerated tumour repopulation following radiotherapy, it is rational to expect that the same kinetic changes would occur in residual tumour cells after surgery. Recent results from series of head and neck Cancer patients suggest that postoperative irradiation should not be unduly prolonged in order to minimize the amount of tumour cell proliferation: That this phenomenon is not specifically related to irradiation but it also occurs after effective chemotherapy is shown by the lack of improvement in local control rates from adding pretreatment chemotherapy to radiation therapy for head and neck cancers. The aim of the present study is to demonstrate that a similar effect can occur in such patients if adjuvant chemotherapy is given after surgery prior to postoperative irradiation, Methods and materials: From 1985 to 1995, 214 patients with head and neck squamous cell carcinomas were irradiated after radical surgical or single tumour resection. The total doses given ranged between 50 and 75 Gy to the primary bed and between 42 to 56 Gy to the neck with fraction sizes of 1.7-2Gy/day. A subgroup of 61 patients (28% of the total) were treated with adjuvant chemotherapy prior to irradiation, generally with cis-platinum+5-fluouracil (x3). The end-point analized was the local-regional tumour control rate at the primary tumour bed and the neck for 5 years from the begining of radiotherapy, Results: The actuarial 5-year tumour control rate for the entire group was 72%. Tumour control was inversely related to T stage and N status. Patients who received chemotherapy had a lower index of local control than those who did not (63% vs 75%, p= 0.0342). In contrast, the multivariate analysis
Posters
showed that the time interval between surgery and radiotherapy (<50/>50 days) had an independent significant impact on local control [hazard ratio, 2.43; CI (95%), 1.01-5.83] and the univariate analysis showed that the total time of treatment (<150/"150 days) also significantly influenced the local control rate (77% vs 63%, p= 0.015). Conclusions: It therefore seems likely that adjuvant chemotherapy not only afforded no tangible benefit to the patients but may also have worsened the prognosis. This paradoxical effect can be explained assuming that the cell kill produced by the cytotoxic systemic therapy was offset by the tumour celt regeneration occurring during the prolonged overall course of treatment. 815
Poster
Moderately accelerated radiotherapy w i t h w e e k l y Carboplatin for stage Ill-IV head and neck carcinoma: the experience o f the district of Le Havre Normandy L. Martin 1, A. Moran2, E. Sevin 3, M. Richard4, M. Damour 5, S. Durand 3, P. Oudinot 1, G. Plot 5, P. Pie 4 1Centre Guillaume Le Conquerant, Oncologie, Le Havre, France 2petit Colmoulins, Oncologie, Harfleur, France 3HOpital Monod, Oncologie, Montivilfiers, France 4H5pital-Clinique Val de Seine, Oncologie, Lillebonne, France 50rmeaux, Oncologie, Le Havre, France As a regional group, we present a retrospective study of a moderately accelerated radiotherapy with concomitant chemotherapy protocol that we routinely perform for every patient with advanced head and neck tumor. Material and method: between March 98 and September 2001, 63 censecutive patients, OMS < 2, mean age= 51 (31-75). non previously treated stage Ill-IV non metastatic advanced head and neck squamous carcinoma were treated as follow: Radiotherapy was: 70 G y / 6 weeks/40 fractions with 30 Gy, 1,5 Gy/f twice daily, 3 Gy/d during the first 2 weeks and then 40 Gy 2 Gy/d in 4 weeks. Chemotherapy was carboplatin: 100 mg/m 2 every week. Tumors sites were: 30 hypopharyngeal (47%), 27 oropharyngeal (43%), 6 oral cavity (10%). Acute and late toxicities were assessed using RTOG scales. Disease free survival and overall survival were calculated using the Kaplan-Meier product limit estimator and were controlled by independent observator. Results: Median follow-up is 22 months (7-48).. Mucositis grade Ill-IV were reported in 72% of the patients (median duration = 70 days). Median loss of weight was 15% (2-32). feeding tube was necessary in 55% of the patients (median duration =131 days (18-624)). 53% of the patients were concerned by toxicity-related hospitalisation. Median duration of hospitalisation was 22 days (4-102). 9 patients (14%) interrupted radiotherapy for a 17 days median duration: 8 for mucositis and 1 for symptoms linked to progressive disease. All completed the treatment. 8% of the carboplatin infusions (32) were cancelled in 12 patients for haematologic toxicity (14) or other acute toxicities (18). Grade Ill-IV neutropenia occurred for six (10%) patients (2% of the cycles) and thrombopenia occurred for five (8%) patients (1%/cycles). 2 deaths could be linked to acute to acute toxicity and 3 deaths to late toxicities (necrosis). Complete remission (CR) rate was 66%. 3 years disease free survival (DFS) rate was 31% (median=9,4 months). 3 years overall survival (OS) rate was 33% (median=21months). Among CR patients, 10 local-regional failure (median delay = 7,5 months), 8 metastasis failure (median delay = 7,5 months) were noted. 25 patients were evaluable for late reaction at one year: 3 (12%) patients developed a grade 4 mucositis (necrosis). 2 patients were still alimented by feeding tube (8%). 2 patients got a full-time job. Conclusion: this scheme of treatment is feasible as routine treatment if intensive background is provided. 816
Poster
The patterns of taste loss after radiotherapy for head and neck cancer A. Maes 1, I. Huygh 2, C. We~tens1, G. Vandeve/de 1, P. De/aere 3, G. Evers 4, W. Van den Bogaert 1 1UZ Gasthuisberg, Radiotherapy, Leuven, Belgium 2AIgemeen Ziekenhuis Heilig Hart, Asse, Belgium 3UZ Gasthuisberg, Otorhinolaryngology, Leuven, Belgium 4Catholic University Leuven, Centre for Health Services and Nursing Research, Leuven, Belgium Background and purpose: Taste loss is a frequent complaint of head and neck cancer patients during and after radiotherapy (RT). The aim of the study was to quantify the prevalence of taste loss at different time periods
809
Friday/Saturday, 20-21 September 2002 $241
Poster
Frequency and types of TP53 mutations in squamous cell carcinomas of the head and neck - a comparison of two methods used on formalin fixed paraffin embedded tissue sampies J.G, Eriksen. J. Alsner, SB. Sorensen, J. Overgaard Aarhus University Hospital, Dept. of Experimental Clinical Oncology, Aarhus C, Denmark Introduction: Mutations in TP53 and expression of p53 protein have been shown to influence the radiosensitivity in tumour cells from head and neck carcinomas. Immunohistochemistry is an often used method for analysis in formalin fixed paraffin embedded tissue sections, but the PCR-based mutation screening method Denaturing Gradient Gel Electrophoresis (DGGE) is also an attractive method to use. By use of this technique we have earlier shown, that functional (missense or null) mutations in exon 5 to 9 of TP53 has prognostic importance for the outcome of HNSCC(1). Recently developed techniques increases the sensitivity of mutation detection, and our aim was to compare the mutation profiles obtained by screening exon 4C (C-terminal) to 10 of TP53 when using Denaturing High Pressure Liquid Chromatography (DHLPC) and DGGE, respectively, Material and methods: DNA extracted from 114 formalin fixed paraffin embedded pro-treatment biopsies of HNSCC was analysed by DGGE. The characteristics of this group were compared to a cohort of similar size (n=110) of HNSCC screened by DHPLC (WAWE®) in exon 4C to 10 of TP53. Mutations found in both groups were further characterised by sequencing, Further analysis Of the DGGE-group using DHPLC on exon 4Cq 0 is ongoing. Results: No relation was found in any of the two methods between the clinical parameters: tumour size, nodal status, anatomical site, stage or differentiation and TP53-status. DHPLC registered 8% more mutations in the core region of TP53 (exon 5-9) compared to the DGGE-results(1). DHPLCanalysis including exon 4C and exon 10 increased the TP53-mutation rate from 52% to 67%. An increase in incidence of multiple mutations in the same tumour was found by the DHPLC-method compared to DGGE, but this was not significant. Conclusion:,ln total 51 functional mutations were found in the DGGE-serie: 82% point mutations, 14% deletions and 4% insertions. In total 70 functional mutations were detected by DHPLC: 91% point mutations, 7% deletions and 2% insertions. The DHPLC-method is at least as sensitive screening method for TP53-mutations as DGGE. Based on this study it is reasonable to screen exons outside the DNA-binding area because additional functional mutations are located there. (1): Alsner J, Sorensen SB and Overgaard J:TP53 mutation is related to poor prognosis after radiotherapy, but not surgery, in squamous cell carcinoma of the head and neck. 810
Poster
Quality of life in patients with oral-oropharynx tumors treated with curative radiotherapy: an open randomised phase III study on recombinant human GM-CSF (molgramostim, leucomax*)
Y, Brandber_o.M. Karimi, G. Masucci Karolinska Instituter, Oncology-Pathology, Stockholm, Sweden The majority, of patients with locally advanced tumors of the head and neck who receives pre or post-operative radiotherapy (RT) present mucositis/epitelitis, which have a negative impact on the patients quality of life (QoL), The effects of GM-CSF on QoL were studied within the framework of an open randomised phase-Ill-study. A total of 45 patients from two of the participating centres were included in the QoL-study. They completed the EORTC Quality of Life Questionnaire (QLQ C-30) and the EORTC Head & Neck module (EORTC-H&N35) six times once a week during RT, The first questionnaire was completed before randomisation, Differences between the two randomisation arms are analysed, using ANOVA repeated measurement, with respect to the five functional QLQ-30 variables, "global health status" , the fatigue scale, and H&N-variables "weight loss", "pain", "swallowing", "speech problems", "teeth", "opening mouth", "dry mouth", "felt ill" and "pain killers", The data are currently being analysed and will be presented at the conference. Preliminary analyses suggest differences between the two randomisation arms in the head- and neck cancer specific symptom scales.
811
Poster
The role of radiotherapy for the treatment of etmoidal cancer: a retrospective analysis of 100 cases treated in Brescia (19702000) S.M. Maerini. A. Somensari, A. Scheda, B. La Face, S, Tonoli Istituto del Radio Ofindo Alberti, Radiation Oncology, Brescia, Italy Purpose: This study aims at a definition of the results of radiotherapy for the treatment of ethmoid cancer, mainly in the context of a combined radlo-surgical approach. Methods and Materials: A relatively large series of t00 consecutive ptS treated at our Institution has been retrospectively analysed, also according to the accrual period (Group 1, 1970-88; Group 2, 1989-00). The vast majority of the pts had T3 or T4 disease (79%) and 21% had undlfferentiated (G3) tumours. Radical surgery was more common in Group 2 pts (81% vs 52%). Average ICRU dose varied according to the extent (~f p0stsurgical residual disease (Group 1 : R0, 58 Gy; R1, 66 Gy (1 pts); R2, 62 Gy; Rx, 61 Gy; Group 2: R0, 55 Gy; R1, 58 Gy; R2, 66 Gy; Rx, 57 Gy), ReSults:The 5-year actuarial overall survival of the entire series was 43% (39,4% versus 44,5%, respectively for Group 1 and 2), 5°year disease-specific survival (DSS) 52% (Group 1: 43,3% versus Group 2: 57,7%) and 5year relapse free survival (RFS) 46% (Group 1: 38,8%; Group 2: 50,4%). DSS and RFS were significantly better (Log-rank) for early stage pts (T1T2), and for those with low-grade disease; RFS was also better for pts who had radical Surgery and for those with less extended post-sUrgical residue. Higher cumulative doses (> 60 Gy) are related to a not significantly lower recurrence probability in R1-R2 cases (54% vs 62%). Conclusions: The relevance of radical surgery is evident but radiotherapy has an important role for loco regional Control and for survival, being able by itself to cure 20% of the negatively selected biopsy-only cases. The prognostic relevance of the different clinical therapeutic features will be discussed in detail, along with the possible interatton betwean surgery and radiotherapy. 812
Poster
HDR hyperfractionated interstitial brachytherapy for m o b i l e tongue cancer at the Osaka University Hospital T. /noue 1, T. /noue 1, E. Tanaka2, K. Shimizutani2, N. Kaklmoto 3, S. Furukawa3 1OsakaUniversity Graduate School of Medicine, Division of Mu/tidiscip/inary Radiotherapy, Suita, Osaka, Japan 2Osaka University Graduate School of Medicine, Department of Radiology, Suit& Osaka, Japan 3Osaka University Graduate School of Dentistry, Department of Oral & Maxillofacial Radiology, Suita, Osaka, Japan Purpose: To present 11-year experience of HDR hyperfractionated intersti° tial brachytherapy for early mobile tongue cancer through phase I/ii study for oral cancer, and phase Ill study of HDR versus LDR brachytherapy for T1-2N0 carcinoma of the mobile tongue. In July 1991, we began HDR interstitial brachytherapy using microSelectron-HDR with plastic tube technique for tongue cancer through submandibular approach, At that time, there was no standardized dose schedule for HDR interstitial brachytherapy for oral cancer. Methods: From July to December 1991, 9 patients with oral cancer entered phase 1/11study, We performed dose escalation study of 20% intervals from starting dose of 35 Gy using hyperfractionated interstitial brachytherapy. From April 1992 to October 1996, a total of 59 patients entered phase III study. Twenty4ive patients in HDR group and 26 patients in LDR group were eligible for the final assessment, There were no differences of patient and treatment characteristics between two groups, except for the thickness of the tumor. HDR group included more patients with thicker tumor. In LDR arm (70 Gy/4-9 days) we used guide gutter technique with intraoral handltng, while in HDR arm (60 Gy/10 fractions/5-7 days) we treated patients with linked double-button technique through submandibular approach. This technique resulted in more correct arrangement with equal spacing by suturing these buttons, and sufficient dosage to the dorsal end of thetongue by means of one additional buttons attached to the upper end of catheter. Dose optimization was able to perform in HDR. Results: According to the phase 1/11study, HDR interstitial brachytherapy of 60 Gy in 10 fractions Over one week had the same effect to LDR of 70 Gy over one week for the mobile tongUe cancer, as to the early mucosal reaction and local tumor control. From the phase III study, 5-year cause specific survivals of HDR and LDR groups were 88% and 87%, respectively. Corresponding 5-year local control rates were 88% and 84%, and 5-year nodal recurrence free survivals were 76% and 77%. Adverse effects including the
$242 Friday/Saturday, 20-21 September 2002
late tongue atrophy of HDR were the same to that of LDR brachytherapy, Conclusions: Treatment results of HDR hyperfractionated interstitial brachytherapy for tongue cancer were higher or the same as that of LDR continuous one through 11-year experience at the Osaka University Hospital. 813
Poster
Hemoglobin as an independent prognostic factor in the radiotherapy of head and neck tumors U. Sch&fer 1, O. Micke 1, C. RObe2, P. SchOIler I, N. Willich 1 1University of MOnster, Department of Radiotherapy, MOnster, Germany 2University-Hospital of the Saarland, Department of Radiotherapy, Homburg, Germany Purpose: The purpose of this study was to analyze the prognostic value of pre-treatment hemoglobin prior to radiotherapy in patients with head and neck tumors. Material and methods: In a retrospective study with a median follow-up of 33 months, we analyzed the results of 228 patients irradiated for head and neck cancer between 1-1-1990 and 1-1-1998 (197 men and 31 women with a median age of 58 years). The treatment concept was adjuvant radiotherapy in 67 patients, 77 patients received definitive radiochemotherapy (RCT), 38 patients definitive radiotherapy (RT), and 46 patients re-irradiation for in-field recurrence (re-RT). Several known prognostic factors like sex, age (< median vs. > median), tumor stage (AJCC stage I-IV), tumor grade (G1-G4), general condition (AJCC 0-1 vs. 2-3), and treatment concept were analyzed for their influence on overall survival and correlated with pre-treatment hemoglobin values (< 12 g/100 ml vs. > 12 g/100 ml). Results: Median survival of all patients amounted to 13 months (adjuvant treatment: 49 months, RCT 13 months, RT 8 months, re-RT 4 months). In univariate analysis, the following variables were significant prognostic factors for overall survival: treatment concept (p<0.0001), tumor stage (p=0:004), general condition (p<0.0001), and pre-treatment hemoglobin (p=0.039). Multivariate analysis (Cox) showed all these parameters to be independent from each other (treatment concept p=0.01, tumor stage p=0.0001, general condition p=0.001, pre-treatment hemoglobin p=0.024). Conclusion: In this retrospective analysis, pre-treatment hemoglobin proved to be an independent significant prognostic factor in the radiotherapy of head and neck cancer patients. Therefore there might be a sensible indication for the use of erythropoietin in patients treated for malignancies of the head and neck region, 814
Poster
Repopulation and tumour response to postoperative irradiation with or without adjuvant chemotherapy in head and neck c a n c e r patients V. Pedraza Murie/1, M. Guerrero Tejada 2, J. Luna de/Castil/o 3 1University Hospital, Radiation Oncology, Granada, Spain 2University Hospital, Radiation Oncology, Granada, Spain 3Faculty of Medicine, Biostatistics, Granada, Spain Background and purpose: Based on the radiobiological data relating to accelerated tumour repopulation following radiotherapy, it is rational to expect that the same kinetic changes would occur in residual tumour cells after surgery. Recent results from series of head and neck Cancer patients suggest that postoperative irradiation should not be unduly prolonged in order to minimize the amount of tumour cell proliferation: That this phenomenon is not specifically related to irradiation but it also occurs after effective chemotherapy is shown by the lack of improvement in local control rates from adding pretreatment chemotherapy to radiation therapy for head and neck cancers. The aim of the present study is to demonstrate that a similar effect can occur in such patients if adjuvant chemotherapy is given after surgery prior to postoperative irradiation, Methods and materials: From 1985 to 1995, 214 patients with head and neck squamous cell carcinomas were irradiated after radical surgical or single tumour resection. The total doses given ranged between 50 and 75 Gy to the primary bed and between 42 to 56 Gy to the neck with fraction sizes of 1.7-2Gy/day. A subgroup of 61 patients (28% of the total) were treated with adjuvant chemotherapy prior to irradiation, generally with cis-platinum+5-fluouracil (x3). The end-point analized was the local-regional tumour control rate at the primary tumour bed and the neck for 5 years from the begining of radiotherapy, Results: The actuarial 5-year tumour control rate for the entire group was 72%. Tumour control was inversely related to T stage and N status. Patients who received chemotherapy had a lower index of local control than those who did not (63% vs 75%, p= 0.0342). In contrast, the multivariate analysis
Posters
showed that the time interval between surgery and radiotherapy (<50/>50 days) had an independent significant impact on local control [hazard ratio, 2.43; CI (95%), 1.01-5.83] and the univariate analysis showed that the total time of treatment (<150/"150 days) also significantly influenced the local control rate (77% vs 63%, p= 0.015). Conclusions: It therefore seems likely that adjuvant chemotherapy not only afforded no tangible benefit to the patients but may also have worsened the prognosis. This paradoxical effect can be explained assuming that the cell kill produced by the cytotoxic systemic therapy was offset by the tumour celt regeneration occurring during the prolonged overall course of treatment. 815
Poster
Moderately accelerated radiotherapy w i t h w e e k l y Carboplatin for stage Ill-IV head and neck carcinoma: the experience o f the district of Le Havre Normandy L. Martin 1, A. Moran2, E. Sevin 3, M. Richard4, M. Damour 5, S. Durand 3, P. Oudinot 1, G. Plot 5, P. Pie 4 1Centre Guillaume Le Conquerant, Oncologie, Le Havre, France 2petit Colmoulins, Oncologie, Harfleur, France 3HOpital Monod, Oncologie, Montivilfiers, France 4H5pital-Clinique Val de Seine, Oncologie, Lillebonne, France 50rmeaux, Oncologie, Le Havre, France As a regional group, we present a retrospective study of a moderately accelerated radiotherapy with concomitant chemotherapy protocol that we routinely perform for every patient with advanced head and neck tumor. Material and method: between March 98 and September 2001, 63 censecutive patients, OMS < 2, mean age= 51 (31-75). non previously treated stage Ill-IV non metastatic advanced head and neck squamous carcinoma were treated as follow: Radiotherapy was: 70 G y / 6 weeks/40 fractions with 30 Gy, 1,5 Gy/f twice daily, 3 Gy/d during the first 2 weeks and then 40 Gy 2 Gy/d in 4 weeks. Chemotherapy was carboplatin: 100 mg/m 2 every week. Tumors sites were: 30 hypopharyngeal (47%), 27 oropharyngeal (43%), 6 oral cavity (10%). Acute and late toxicities were assessed using RTOG scales. Disease free survival and overall survival were calculated using the Kaplan-Meier product limit estimator and were controlled by independent observator. Results: Median follow-up is 22 months (7-48).. Mucositis grade Ill-IV were reported in 72% of the patients (median duration = 70 days). Median loss of weight was 15% (2-32). feeding tube was necessary in 55% of the patients (median duration =131 days (18-624)). 53% of the patients were concerned by toxicity-related hospitalisation. Median duration of hospitalisation was 22 days (4-102). 9 patients (14%) interrupted radiotherapy for a 17 days median duration: 8 for mucositis and 1 for symptoms linked to progressive disease. All completed the treatment. 8% of the carboplatin infusions (32) were cancelled in 12 patients for haematologic toxicity (14) or other acute toxicities (18). Grade Ill-IV neutropenia occurred for six (10%) patients (2% of the cycles) and thrombopenia occurred for five (8%) patients (1%/cycles). 2 deaths could be linked to acute to acute toxicity and 3 deaths to late toxicities (necrosis). Complete remission (CR) rate was 66%. 3 years disease free survival (DFS) rate was 31% (median=9,4 months). 3 years overall survival (OS) rate was 33% (median=21months). Among CR patients, 10 local-regional failure (median delay = 7,5 months), 8 metastasis failure (median delay = 7,5 months) were noted. 25 patients were evaluable for late reaction at one year: 3 (12%) patients developed a grade 4 mucositis (necrosis). 2 patients were still alimented by feeding tube (8%). 2 patients got a full-time job. Conclusion: this scheme of treatment is feasible as routine treatment if intensive background is provided. 816
Poster
The patterns of taste loss after radiotherapy for head and neck cancer A. Maes 1, I. Huygh 2, C. We~tens1, G. Vandeve/de 1, P. De/aere 3, G. Evers 4, W. Van den Bogaert 1 1UZ Gasthuisberg, Radiotherapy, Leuven, Belgium 2AIgemeen Ziekenhuis Heilig Hart, Asse, Belgium 3UZ Gasthuisberg, Otorhinolaryngology, Leuven, Belgium 4Catholic University Leuven, Centre for Health Services and Nursing Research, Leuven, Belgium Background and purpose: Taste loss is a frequent complaint of head and neck cancer patients during and after radiotherapy (RT). The aim of the study was to quantify the prevalence of taste loss at different time periods