336 poster A clinical trial in improving external irradiation technique for nasopharyngeal carcinoma

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Despite this, by whatever treatment modality in this series overall survival and local control rates remain statistically unchanged. AStage shift& relating to results in this series was not a significant feature• 332 poster A low dose of elective neck irradiation could reduce 10 %

later regional relapse of stage II tongue cancer. Y. Akagi 1, Y. Hirokawa 1, M. Fujita 1, S. Hamamoto 2, H. Shibuya 3, A. Yorozu 4, N. Shikama 5, N. Kunitake 6, K. Ito 1 1Hiroshima University, Dept. of Radiology, Hiroshima, Japan 2yamagata Uni, Dept. of Radiology, Yamagata, Japan 3Tokyo Medical and Dental University, Dept. of Radiology, Tokyo, Japan 4National Tokyo Medical Center, Dept. of Radiology, Tokyo, Japan 5Shinshuu University, Dept. of Radiology, Matsumoto, Japan Purpose: Multi institutional retrospective questionnaire was conducted and done to evaluate the efficacy of elective neck irradiation (ENI) with a dose of 10 to 40 Gy to prevent later regional relapse of stage II tongue cancer. Method: Six hundred forty five patients treated with brachytherapy (BT) from 1980 to 1994 were evaluated. Events free survivors whose follow up periods less than 2 years were excluded for analysis. There were 454 patients treated with BT only, and 191 with external beam irradiation (EBI) + BT. Median BT and EBI dose was 70 Gy and 30 Gy, respectively. Cause specific survival (CSSR), local controls (LCR), regional relapse rates (RRR) were calculated by Kaplan Meier method, significance was tested by Cox Mantel method• Late complications were evaluated by RTOG/EORTC criteria• Results: Median follow up periods of survivors was 87 months• There were 54 patients who had only local relapse, 192 had only regional relapse and 60 had both. CSSR, LCR and RRR of patients treated with BT and EBI + BT was 77, 85, 43 and 81, 78, 33mts, respectively. RRR of patients treated with EBI + BT was significantly lower than that of BT (p < 0.01). There were no significance of CSSR, LCR and late complications between BT and EBI + BT. RRR of radiation field including mid jugular node was significantly lower than that of smaller field (p < 0.0001). Conclusions: ENI significantly reduced later regional relapse without increasing late complications for Stage II tongue cancer patients. Radiation field including mid jugular node and EBI dose of 30 Gy was recommended for brachytherapy of Stage II tongue cancer• 333

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The significance of hemoglobin level during postoperative radiotherapy in patients with larynx carcinoma G. Stryczynska, P. Milecki, S. Nawrocki GreatPoland Cancer Centre, Radiation Oncology, Poznan, Poland Aim: to assess an influence of a low Hgb level on the Iocoregional control in patients with advanced cancer of the larynx treated with surgery and postoperative radiotherapy. Material and methods: A retrospective analysis of two hundred and fifty four patients with larynx carcinoma in the III or IV stage squamous cell carcinoma of the larynx who were treated between Jan 1993 and Dec 1996 was done. Postoperative radiotherapy was performed in a coventional way to the total dose of 60 Gy, 5 times a week. Of 254 patients, 86 patients (34%) were considered to have a low level of hemoglobin (below 13 g/dl) prior the beginning of radiotherapy and 56 patients (22%) at the end of treatment. We have also noted in 38 (15%) out of 254 patients a decreasing hemoglobin level higher than 1 g/all during the treatment• Results: No impact on the outcome of treatment was observed in the group of patients with low level of Hgb before irradiation. An increase in Iocoregional failure rates after postoperative radiotherapy was noted in the group of patients with Hgb level below 13 g/dl ( p=0,004 ) at the end of irradiation and also in the group of patients with decreasing Hgb level during treatment ( p= 0,038 ). Conclusions: Low Hgb levels at the end of postoperative irradiation and the decrease during irradiation are associated with a statistically significant increase in Iocoregional failure rates in patients with advanced carcinoma of the larynx. 334

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Shenlongye herbs in combination with radiation-chemotherapy for advanced nasopharyngeal carcinoma S.F. Wanq, A. Wang, R.S. Wang The First Affiliated Hospital, Guangxi Medical University, Nanning, China Purpose: to evaluate the effect of using shenlongye herbs (SLY) in combination with radiation-chemotherapy (RT-CT) for advanced nasopharyngeal carcinoma (NPC).

Methods: Ninety patients were divided randomly into three groups, 30 for each group. Group A was treated by combined therapy of SLY herbs with RT-CT, group B with combined therapy of RT-CT and group C with radiation alone. The clinical conditions of the three groups were similar before treatment. Patients in the three groups were treated with RT using the same technique and method; patients in groups A and B were treated with CT using the same schedule; patients in the group A, SLY herbs to be taken till the end of RT. Results: at the end of the treatment, the immediate regression rates of cervical lymph nodes were 83.33 (25/30), 70% (21/30), 56.66% (17/30) in groups A, B and C, respectively, the 3-year survival rates were 53.33 (16/30), 46.67% (14/30) and 36.67% (11/30), the effect of group A was the best, in comparison of group A and C, the difference was significant (p<0.05), but the comparison of group B with A or B with C was insignificant (p>0.05). Conclusions: the combination therapy of SLY herbs with RT-CT was preferable in treating advanced NPC, SLY herbs plus CT may increase the sensitivity of tumor to RT, and control the distant mierometastatic disease, SLY herbs reduce side-effect of RT-CT. 335

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Endogenously targeted 211 at alpha-radiation therapy of iodo-refractory metastatic differentiated thyroid cancer /. Brown Sidney Sussex College, University of Cambridge, Cambridge, UK +/nstitut f(Jr Medizin, Forschungszentrum JE~/ichGmbH, Germany Metastatic differentiated thyroid carcinoma (DTC) refractory to radioiodine (131-0 poses a significant therapeutic challenge. Uniquely, the highest radiohalogen astatine-211 (211 At) has been found to concentrate in many of these tumours such that it may be possible to achieve a tumorcidal highLET quality radiation absorbed dose. Studies have been undertaken on two human DTC xenografts that negligibly concentrate radioidine but exhibit a significant and sustained affinity for ionic 211 AT. 211 At was produced by the 208 Bi (alpha, 2n) 211 At nuclear reaction, and prepared as a sterile buffered Na-211 at solution. Therapy was carried out in thyroid-blocked male nu/nu mice 7 days after SC implantation of 10-6 tumour cells. Single IV dose aliquots of 5-75 kBq 211 At/g body weight were administered. A significant therapeutic effect was observed, for which a dose-response relationship has been defined. Tumour growth was not evident following 211 At doses > 60 kBq/g. Internalised alpha-radiations from targeted 211 At proved effective in controlling the growth of poorly iodo-affinie DTC xenografts. Results have indicated a possible therapeutic role for 211 At in the management of metastatic DTC refractory to 131 I. A clinical trial has been initiated. 336 poster A c l i n i c a l trial in improving external irradiation technique for

nasepharyngeal carcinoma w. Luo, E.P. Zhang, J. Y. Qian, N.J. Cui, T.X. Lu, Y.F. Xia, Y.H. Hu Cancer Center, Sun-yat-sen University of Medical Sciences, Radiation Therapy, Guangzhou, P.R.China Purpose: To improve the external irradiation technique for nasopharyngeal carcinoma• Methods: From Mar. 1992 to Jun. 1995, 124 patients with pathologically confirmed nasopharyngeal carcinoma(stage ll~lVa) and without any kind of anti-tumor treatment previously were divided into the investigation group(initially using two lateral faciocervial photon fields to 40~45Gy/20-22 fractions in 4~4.5 weeks, then followed by two lateral facial photon fields or plus a anterior facial field to 26~30Gy/13~15 fractions in 2~3 weeks, utilizing cerrobend block) and conventional group (using two or three facial fields and anterior-posterior and opposal lateral cervical fields to same dose), and the short, long*term clinical outcome and acute, late radiation sequelae were observed by clinical trial. Results: After 2~3 months of radiation therapy, the results of CT scans revealed that complete remission rate (58•06%) of primary lesion in inves: tigation group was higher than that(30.64%) in conventional group (P=0.002), and the acute radiation react=on of oral cavity and GI in idvesti: gation group was milder than in conventional group (P<0.05). The 1~, 3and 5-years overall survival rates in investigation group and conventional group were 96.88%, 77,59%,70.84% and 87.50%,59.43%,55.47% , respectively (P=0.025), the 1-,3- and 5- years disease-free survival rates in investigation group and conventional group were 83.87%,67.10%,60.03% and 74.19%,50.69% ,46.47% , respectively (P=0.045), the 1-,3- and 5years Ioceregional failure free rates in investigation group and conventional group were 90.32%,79.45%,71.08% and 83.06%, 61.14%, 56.05% respectively (P=0.037), the 1-, 3- and 5-years free distant metastasis for •

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investigation group and conventional group were 87.10%, 73.55%, 73.55% and 87.10%, 74.63%, 74.63% respectively (P=0.988).The radiation injury rates of IX, X, XI and/or XII cranial nerves were lower in investigation group (4.8%) than in conventional group (16.1%) (P=0.04). Conclusions: Compared with conventional irradiation technique, the improving external irradiation technique comprehensively elevated the Iocoregional control rate, the survival rate and life quality in patients with nasopharyngeal carcinoma. 337

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Amitotic cell divisions and tumour growth: An alternative model for cell kinetic compartments in solid tumours V.N. Bhattathiri Dept. of Radiotherapy, Regional Cancer Centre, Trivandrum, India Purpose: Amitotic changes such as micronucieation/nuclear budding (due to akaryokinesis), and multinucleation (due to acytokinesis) during radiotherapy (Bhattathiri RadiotherOncol 1998;41:139-142; ActaCytol 1998;42:1084-1090) reflect tumour radiosensitivity and repopulation attempts. The present study examined how their pre-treatment frequency is related to clinical tumour growth. Methods: The frequency of micronucleated/nuclear budded, binucleated and multinucieated cells taken as the akaryokinesis index (AKI) , mitotic index (MI) and acytokinesis index (ACI) respectively were evaluated in smears from 121 untreated oral cancers. The tumours were categorised to three size-groups (<2cm ; 2-4cm and >4cm) and two clinical durationgroups (<4 months; >4 months). The relation of the above indices, as well as the amitotic index (AMI ie AKI+ACI) and cell division index (CDI ie AKI+ACI+MI) to size-groups was analysed by KruskalI-Wallis and to duration-groups by Mann-Whitney tests. Results: All the indices were higher in larger tumours, the median frequencies being 1.2%, 2.29% and 3.28% in the three size groups (pvalue=0.0025) and 1.0%, 6.3% and 10.05% (pvalue=0.0015) in the case of CDI and AMI respectively. The increase was not significant for MI, the frequency being 0.69%, 0.99% and 1.32% respectively. AKI and ACI also showed significant increase. Tumours which reached larger size in shorter duration had higher frequency of MI; those remaining small in spite of longer clinical duration had significantly higher AKI; those reaching 2-4cm in shorter duration had significantly higher ACI. Conclusion: Evaluation of mitoses and amitoses can identify proliferation characteristics of solid tumours. Amitoses ileads to cell loss as tumours enlarge, particularly in fast growing tumours. Akaryokinesis starts earlier than acytokinesis. An alternative model of tumour cell kinetic compartments, which also includes a sub-clonogenic compartment consisting amitotically dividing cells, is presented. Since amitotic cells are clonogenically but not physically dead, proliferation parameters measured by flowcytometry, BrdUrd labelling, etc., (which measure DNA synthesis and nuclear cycling) may be wrong. 338

infection of Ad-LacZ to thyroid cancer celIS(NPA, ARC, FRO) and 293 cells showed 100% of infection rate in FRO, ARC and infection rate of NPA cells was about 70%. According to these results we infected Ad-hNIS to ARC cells and measured 1-125 uptake. When ARC cells were infected with the adenovirus, 1-125 uptake was increased over 5.2 fold. Conclusions: Overexpression of hNIS gone in thyroid cancer cells elicited over 5.2 fold increase in 1-125 uptake, suggesting that the Ad-hNIS infection to the thyroid cancer cells may improve the efficiency of radio-iodine therapy.

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Development of radioactive iodine therapy using Adenovirus-human Sodium Iodide Symporter (Ad-hNIS) gene in thyroid cancer H. ChanQ 1, I. Ahn2, D. Moon 3, J. Jin4, K. Park4 1Asan Medical Center, College of Medicine, Ulsan University, Radiation Oncology, Seoul, Korea 2Asan Medical Center, College of Medicine, Ulsan University, Endocrinology, Seoul, Korea 3Asan Medical Center, College of Medicne, Ulsan University, Nuclear Medi cine, Seoul, Korea 4Asan Institute for Life Sciences, Molecular Genetics, Seoul, Korea Purpose: hNIS is an intrinsic transmembrane protein that mediates the transport of iodide, cDNA of hNIS was cloned and characterized recently. To develope the gene therapy for thyroid cancer utilizing hNIS gene, we investigated the intrinsic hNIS expression in the thyroid cancer cell lines and we measured the uptake of 1-131 in thyroid cancer cells infected with adenovirus that expressed hNIS. Methods:The 2.4 kb fragment of hNIS cDNA was isolated and ligated into Swa I site of adenoviral vector(pAxCAwt). The adenoviral cosmid was prepared from E-coli(JM109) after infection of ¥~packaged cosmid. We have produced adenovirus particle after transfection of the cosmid to 293 cell line. We also performed RT-PCR to measure intrinsic hNIS expression in NPA, FRO, ARC cell lines. Adenovirus particle that express b-Galactosidase after transfection of pAxCAiLacZ also prepared and infection efficiency was measured in three thyroid cancer cells. Results: RT-PCR confirmed that the endogenous hNIS was expressed only in FRO ceils but not in NPA, ARC and Hela cells. B-Gal staining after

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Investigation of the protective effect of pilocarpine hydrochlorid (Salagen) during radiotherapy on patients with head and neck cancer Z. Takacsi-Nagy, A. Somogyi, L. Mangel, J. Vfzkeleti, G. Nemeth National Institute of Oncology, Radiotherapy, Budapest, Hungary Purpose: To compare subjective postirradiation xerostomia scores of patients who received concomitant oral pilocarpine during radiotherapy for head and neck cancer with a similar cohort who did not. Methods: Between January 1998 and February 2000 thirty patients received 5 mg Salagen three times per day from the beginning of radiotherapy (mean dose was 56 Gy) till 3 months after treatment. The other thirty patients were not treated with Salagen. Comparison of the radiation induced xerostomia and its consequences (difficulties with swallowing, eating, speech and sleep, worsening of oral comfort) was carried out by means of subjective questionnaires after 3 months from the end of the irradiation. Results: In treated patients total xerostomia did not occur. Initial symptoms of partial form developed 1 week later compared to the control patients. The same observation applied to the mucositis. The rate of grade 3 mucositis was higher without than with pilocarpine (73 % and 40 % respectively, p = 0.0091). Evaluation of the parameters of questionnaires showed two times better results in the Salagen group. Side effects of the drug were mild and temporary. Conclusions: This study demonstrates that Salagen is a very effective compound in the prevention of the irradiation caused xerostomia. 340 poster A r a n d o m i z e d , d o u b l e - b l i n d , placebo-controlled trial of con-

comitant pilocarpine with head and neck irradiation for prevention of radiation-induced xerostomia P. Haddad 1, A. Fard-Esfahani 2, M. Karimi 1 1Cancer Institute, Tehran University of Medical Sciences, Radiation Oncology Department, Tehran, Iran 2Tehran University of Medical Sciences, Nuclear Medicine Department, Tehran, Iran Introduction. Xerostomia is one of the disturbing side-effects of the radiotherapy to the head and neck region. Pilocarpine has been approved for the treatment of this condition in the chronic phase, but its use concurrent with radiation could also be beneficial for prevention or reducing the subsequent radiation-induced xerostomia. We undertook to test this hypothesis in a clinical trial. Methods. All 18-70 years old patients who were to be irradiated to the head and neck, with both parotid glands in the radiation fields of minimum 4,000 cGy, were eligible for this study. Patients with any medical contraindications for pilocarpine were excluded. After informed consent, randomization was performed at the start of radiotherapy to either pilocarpine 5 mg three times daily or placebo in a double-blind setting. The drug was started with irradiation and continued until 3 months after the end of radiotherapy. Serum pilocarpine levels were measured in a randomly selected number of patients (not violating the double-blind setting). Xerostomia was evaluated 6 months after the end of radiation by a subjective visual analog scale questionnaire. Also the objective scoring of xerostomia was recorded by two separate observers for comparison to the questionnaire results. In addition, some patients were evaluated by radioisotope scans of the salivary glands too. Patient, tumor and treatment details were gathered by file reviews. Xerostomia in the two groups was compared using the Student's t-test. Results. A total number of 60 patients were randomized into the trial, mostly with nasopharyngeal carcinomas. Details of the patients and tumors, radiotherapy fields and doses, patients' compliances with the prescribed drug, pilocarpine serum levels found, side-effects, and the xerostomia comparison results in the pilocarpine and placebo groups will be presented. Conclusion. A statement of conclusion regarding the use of pilocarpine concomitant with head and neck irradiation for prevention of radiation-