344 poster Interstitial brachytherapy supplemented with external radiotherapy in carcinoma tongue

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induced xer0stomia will be provided after final analysis at the time of presentation. 341

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Population-based and individual survival probability estimation in medullary thyroid cancer O. E-sik1,2 G. Tusnady3, Z. Szentirmay 4, L. Tr6n5, J. Fodot2, J. Szekely 2 1Semmelweis University, Dept. of Radiotherapy, Budapest, Hungary 2National Institute of Oncology, Dept. of Radiotherapy, Budapest, Hungary 3Hungarian Academy of Sciences, Renyi Alfred Mathematical Institute, Bu dapest, Hungary 4National Institute of Oncology, Dept. of Molecular Pathology, Budapest, Hungary 5University of Debrecen, PET Center, Debrecen, Hungary Purpose: The typically indolent, but occasionally rapidly fatal clinical course of medullary thyroid cancer (MTC) has raised the need for individual survival probability estimation. Patients and methods: A retrospective study on 91 MTC patients with a mean follow-up of 6 years indicated incidences of local, regional and distant residual tumor on primary care completion of 23%, 54% and 54%, respectively. Local, regional and new distant relapses occurred in 8%, 23% and 26% of the cases, and 26% of the patients died from cause-specific death. Prognostic factors statistically significantly influencing on the survival were selected by uni- and multivariate analysis. A Markov methodbased model was developed for estimation of individual time-dependent survival probability functions with parameters numerically determined via a maximum likelihood procedure. Results: In multivariate studies, the patient's age and gender, the genetic basis of the disease, lymph node involvement, general symptoms (diarrhea/flush) at presentation, and the adequacy of the external irradiation dose proved to be prognostic factors. The population averages of the cause-specific survival functions indicated 69%, 62% and 58% for the mean 5, 10 and 15-year survival probabilities. Cause-specific survival probabilities can be predicted for extrastudy cases if the new patients' clinical events undergo in the same manner and with similar probability as within the study population ("MEDUPRED" software on the home page of the National Institute of Oncology, Budapest: www.oncol.hu). Conclusions: Individual survival probability prediction for extrastudy cases affords a rationale for individualization of MTC patient treatment. 342

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Early laryngeal carcinoma in non smokers R.:Smee 1, G.P. Bridget 2, J. Williams 1 1prince of Wales Hospital, Radiation Oncology, Sydney, Australia 2prince of Wales Hospital, Otolaryngology, Sydney, Australia Aim: Larynx carcinoma is typically regarded as a smoking induced malignancy. The purpose of this review is to establish the natural history of early glottic carcinoma in life long non smokers for whom definitive treatment was radiotherapy. Materials and Methods: Amongst 380 patients with early glottic carcinoma treated within this department between 1967 and 1995 25 were documented as life long non smokers. There were 20 males and 5 females, the mean age was 61 years. The carcinoma was T1 in 19 and T2 in 6 with restricted cord movement in 4 of these patients. The median dose delivered was 65Gy, and median of 30 fractions. Alcohol was not able to be reliably assessed for this group of patients. A history'of passive smoking was not able to be documented in the patient, notes. Results: The proportion of females in this population (20%) was statistically significantly different to that for the proportion in the smoking and ex smoking group (4%). Otherwise the two groups were comparabl e . Local failure occurred in 8/25 patients:(32%) compared to 18% (65/355) of the remaining population, a non statistical significant difference. Salvage surgery took place in all those patients, with no nodal failures and only one patient dying due t O larynx cancer. Three patients (12%) developed second malignancies compared to 14% for the remaining group. While cancer-specific survival (96%) was comparable to the remainder (89%) at 10 years, 80% of non smokers were alive compared to only 50% of the current or ex smokers (P=0.0092). Conclusion: Although infrequent, early glottic carcinoma does occur in non smokers with females more iikely to be effected. Treatment is very likely to be curative, and although second malignancies do occur death from othe r non smoking disease is much less likely.

343 poster Clinical u s e f u l n e s s o f twice-a-day fractionated radiotherapy

for laryngeal cancer K. Karasawa T. Kusaura, K. Seki, K. Katui, M. Kohno, N. Hanyuu, M. Isobe Tokyo Women's Medival University, Radiology, Tokyo, Japan Purpose / objective : To improve the local control and laryngeal preservation rate in the treatment of laryngeal cancer, we conducted a Phase II trial of Twice-a-day fractionated radiotherapy (TDFR). Materials & Methods : Since April 1986, we began TDFR for laryngeal cancer with the stages of T2 or higher with no distant metastases. In principle, TDFR group was irradiated with a fraction dose of 1.5 Gy twice a day at least 6 hours apart, 10 times a week to a total dose of 72 Gy within 6 weeks. For cases of large radiation field, we reduced the fraction dose to 1.2 Gy. Control group treated with CRT was irradiated with a fraction dose of 2 Gy to a total dose of 66Gy within 7 weeks. Results: As of May 2000, 107 cases were treated as TDFR group and 125 cases were treated as the control group. All cases in both group were squamous cell carcinoma. Patient characteristics did not differ between the two groups. In TDFR group there were 75 glottic, 27 supraglottic and 5 subglottic cases. In the control group there were 85 glottic, 33 supraglottic and 7 subglottic cases. In TFDT group there were 75 T2N0 cases, 15 T3-4N0 cases and 17 N(+) cases and In the control group there were 80 T2N0 cases, 25 T3-4N0 cases and 20 N(+) cases. As for acute reactions TDFR group got severer reactions than control group without statistical significance, and for late reactions there was no difference between the two groups, Five year actuarial local control rate (5yLCR) was 70.8% for TDFR group and 60.3 % for the control group (n.s.). 5yLCRs for supraglottic cancers were 78.6% and 40.4% for TDFR group and the control group (p<0.10). And for larger tumors such as T2B (cases with reduced vocal cord motility), T3, T4, and N(+) TDFR group got the better results. Conclusions: From these data we may conclude that TDFR tended to increase the local control rate especially for large tumors and was useful in preserving laryngeal function. 344

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Interstitial brachytherapy supplemented with external radiotherapy in carcinoma tongue R. Vashistha 1, N. Jain 1, H. Singh 1, P, Kaur 1, N. Verma2, R. Arora 3, K. Passi 1, S. Jain4 1M.D.Oswal Cancer Treatment & Research Foundation, Ludhiana, Radiation Oncology, Ludhiana, India 2M. D.Oswal Cancer Treatment & Research Foundation, Ludhiana, Head & Neck Oncology, Ludhiana, India 3M.D.Oswal Cancer Treatment & Research Foundation, Ludhiana, Medical Oncology, Ludhiana, India 4M.D.Oswal Cancer Treatment & Research Foundation, Ludhiana, Surgical Oncology, Ludhiana, India Introduction: In this era aim of treatment is to improve the quality of life and the emphasis is on organ preservation. Radiation therapy in combination of teletherapy with brachytherapy has proved to be successful in this approach and after breast ,anorectum and larynx, the oral cavity lesions now can effectively be managed without surgery. Materials and methods: From 1991 - 1999, 40 patients with early stage carcinoma of tongue were treated with external radiotherapy and interstitial implant. Out of these 36 had disease at anterior tongue and 4 at base tongue. 26 were male and 14 female in the age group of 25-70 years. 13 patients had T1, 21 had T2 and 6 had Tx disease. 32 patients were node -ve and 8 patients were node +ve. Pre-treatment evaluation included complete blood counts~ liver function tests, chest x-ray, CT scan oropharynx and neck. 4 patients had excision of primary tumour and 7 patients received adjuvant chemotherapy. Dose given was 45-55 Gy depending upon size of lesion and nodal status. For T1 or NO 45 - 50 Gy was given for T2, Tx or node +ve 50 to 55 Gy was given. Brachytherapy was given with interstitial iddium implant, based on Paris system. Earlier we gave a dose of 25-30 Gy(Till 1995) but now a days we give 20-25 Gy. Results: Patients who followed for 6 months after completion of treatment were evaluated for response.. Out of 40 patients 33 (83%) achieved complete response as assessed one month after completion of treatment. 7(17%) patients had partial response. Out of these one was advised chemotherapy, two underwent glossectomy, two patient absconded and two expired. Acute complications noted during or immediately after the implant were haematoma of tongue in 5 patients and acute mucosal reaction in approximately all the patients which were managed with conserva-

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rive treatment. These reactions subsided after 2-6 months. Necrosis of tongue was seen in 1 patient. This was due to poor oral hygiene & poor dietary status. Conclusion: With the use of brachytherapy one can achieve good local control in early stage carcinoma oral tongue and all these patients should be given a chance of organ preservation. 345

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Hyperfractionated chemoradiotherapy with carbogen breathing,and with or without erythropoietin for head and neck cancer J. Martinez 1, M. Espineira 1, M. Cabezon 1, A. Villar 1, IV;. Perez 1, C. Borque 1, J. Serdio2, J. Git2, J. Artazkoz2, M. Suner 3 1Hospital NS Candelaria, Oncologia Radioterapica, Santa Cruz de Tener-

ife, Spain 2Hospital NS Candelaria, Otorinolaringologia, Santa Cruz de Tenerife,

Spain Purpose: To develop a new treatment schedule for head and neck cancer. Patients and methods: From March 1996 to March 2000, 46 patients were treated with a twice-a-day hyperfractienated schedule. Each fraction consisted of 10 mg of carboplatin + 115 cGy. Carbogen was breathed four minutes before and during irradiation. Treatment was given 5 days a week up to total doses of 700 mg of carboplatin + 8050 cGy in 7 weeks. In the first part of the protocol ( first 20 patients) transfusion was given when Hb levels reached the value of 11 gr/dl. In the second part of the protocol (up to 46 patients) erythropoeitin (10.000 U. 3 times a week) was given when Hb level decreased to 13 g/dl. There were 3 women and 43 men, 3 stage Ill and 43 stage IV, 4 nasopharynx, 9 oral cavity, 20 oropharynx, and 13 hypopharynx. Results : Forty-five patients tolerated the treatment as scheduled. One patient needed withdrawal of chemotherapy. All patients tolerated the planend radiation dose. Acute toxicity. Mucositis : 1 G2;45 G3. Leucopenia: 8 G.1 ;6 G2. Emesis : 6 G1 ; 3 G2. Anemia : 8 G1; 4 G2. Observed late toxicity is moderate up to now.Five transfusions were needed in the first part of the protocol while no transfusion the second one. Forty-six (100%) Complete Responses (CR) were achieved. After 24 of median follow-up thirty-two patients remain free of disease. At 2 years, actuarial Local Control (LC), Cause-specific Survival (CSS) and Overall Survival (OS) are 89, 72 and 70 % respectively. Estimated probability of LC, CSS and OS are 89,72 and 70% respectively at 4 years. With similar number of patients and follow-up period, our protocol consisting of the same chemoradiotherapy schedule without carbogen breathing showed 69, 55 and 50% of LC, CSS and OS respectively (Head&Neck 2 0 489496.-1998). Conclusions : The rates of LC, CSS and OS compare favourably with those of most reported pilot studies. The addition of carbogen breathing shows potential for improvement upon chemoradiotherapy alone. Erythropoietin avoided transfusions and, therefore, signifincantly contributed to the better tolerance of the protocol. 346

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Inverse planning by conventional beam optimization in 3-D conformal radiotherapy of NPC V: Wu_1, A. Mui 1, J. Sham2 lHong Kong Polytechnic University, Optometry & Radiography, Hong Kong , Hong Kong 2Hong Kong University, Clinical Oncology, Hong Kong, Hong Kong Purpose: To study the application of inverse planning by conventional beam optimization in 3-D conformal radiotherapy of NPC and compare the dosimetric details between the inverse and forward planning. Methods: Ten NPC patients with T2 and T3 primary tumours were conveniently recruited. CT images taken from the vertex to cervical region were transferred to the treatment planning system (FOCUS version 2.5.0). Routine 3-D conformal treatment plans were computed which consisted of 4 non-coplanar fields. Inverse planning by conventional beam optimization was performed for each patient with the same set of CT data including the planning target volume. The level of optimization in the inverse planning was on the field number, angles, weights with a specified margin for the conformal blocks. Two sets of plans, one coplanar and one non-coplanar, were produced by inverse planning. The dose to the planning target volume and organs at risks were studied through the dose volume histograms. The opera.rich time and dosimetric data between the inverse and forward plans were compared.

Results: The machine operation time for the inverse plans was 2-3 times longer than the forward plans, whereas the operator's time was 2-3 time less. The planning target volume doses between the inverse and forward plans were similar. The doses to the temporal lobe, pituitary gland and the optic nerve were significantly lower in the co-planar inverse plans while the other organs showed no significant differences. Conclusion: Inverse planning by conventional beam optimization offers reasonably good alternative plans to the traditional forward plans in 3-D conformal radiotherapy of NPC. Its dosimetric distributions are comparable to the forward plans while the opeiator's time is reduced. 347

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Quantitative assessment of salivary glands function by radioisotopic scanning in a randomized trial of pilocarpine for prevention of radiation-induced xerostomia A. Fard-Esfahani 1, P. Haddad2, IV/. Modarress-Mosalla 1 1Tehran University of Medical Sciences, Nuclear Medicine, Tehran, Iran 2Cancer Institute, Tehran University of Medical Sciences, Radiation OncoF ogy Department, Tehran, Iran Introduction. Radioisotope scanning is the best method for objective assessment of salivary glands function. Thus it was used in a randomized trial of concomitant pilocarpine for assessment of radiation-induced xerostomia, in addition to subjective evaluation by an approved questionnaire. The objective results found by radioisotope method was compared to the subjective questionnaire results for further validation. Methods. Patients randomized in a placebo-controlled trial of pilocarpine concurrent with irradiation for prevention of radiation-induced xerostomia were evaluated by salivary glands scintigraphy immediately before and 6 months after the end of head and neck radiotherapy. Salivary glands function was measured by the uptake and ejection fractions of Technetium99m pertechnetate. Post-radiotherapy scan findings in the two groups of pilocarpine and placebo were compared using the Student's t-test. Also the average differences of the pre- and post-radiotherapy scans in the two groups were calculated and compared. In addition, comparison was made between the radioisotopic and the subjective questionnaire findings. Results. A total number of 60 patients were .randomized into the trial, described with details separately. Most patients underwent the post-radiotherapy salivary scintigraphy, but the pre-radiotherapy scan was performed in only about half of them. Details Of the relevant salivary scintigraphy techniques and findings are presented here, with the comparison results between the two randomization groups and between the objective radioisotopic and subjective questionnaire findings provided. Conclusion. Salivary glands scintigraphy is a valuable method for the objective evaluation of xer0stomia. A statement of conclusion regarding the use of pilocarpine concomitant with head and :neck irradiation for prevention of radiation-induced xerostomiaby objective radioisotopic assessment will be provided after final analysis at the time of presentation, and these results will be compared with the subjective findings. 348

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Recovery salivary gland function/reflction salivary gland dose R. Bhalavat 1, S. Farzan 1, B. Malpani 2, R. Jaiswar 1, N. Arvind 1, A. Samuel 1 1Tara Memorial Centre, Radiation Oncology, Mumbai, India 2Radiation Medicine Centre, Nuclear Medicine, Mumbai, India Purpose: To quantify & correlate the recovery of kinetic activity of salivary glands (SG) in 98/550[I0ng survivors-(LS)] of h & n cancers (since1988) treated with brachytherapy Ext.RT. Methods: LS with differing levels of SG/Doses and at diff. times of follow up after completion of RT were subjected to quantitative analysis of parotid/Submandibular SG using 99Tc-pertechnetate(TCP) Sal. scintigraphy. Functions were compared with normal individual and with LS treated with standard radical Ext.RT.RTDose in text is SG dose. The % uptake of injected activity of previously counted 300MBq of TCP at 10mrs (%U10) & %excretion after a silogogue at 15minutes(%SE) were recorded for individual SG, from static images obtained through gamma camera.%SE is expressed as% of. %U10. Results: Mean %U10 and mean %SE was recorded for normal & for LS at different times (24-20mths) and at different doses (<40, >40 to<50, >50 Gy). %U10 and %SE with dose <40Gy is fair to good at 24 months. However for doses >55Gy, %U10 & %SE were significantly low and does not improve much with time but for doses inbetween %U10 & %SE value does improve with time although slowly, discretely and marginally. Conclusions: Recovery in SGF is dose/time dependent and is possible if at least one of the SG is prevented from