Disease sites : Others

CLINICAL/DISEASE SITES

and overall survival (OS). Kaplan-Meier method was used to calculate survival rates. Univariate and multivariate analyses of prognostic factors were performed using log rank test and Cox's proporti onal hazard method. Patients were treated by means of different treatment modalhles: surgery followed by radiotherapy (52%), radiotherapy alone (13%), chemoradiotherapy alone (15%), surgery followed by chemoradiotherapy (5%), surgery alone (5%) and others. Results: The to -year LRRFS was 79 %, DFS was 57% and OS was 57%. Masaoka stage was the only independent prognostic factor for LRRFS. Masaoka stage and method of radiotherapy delivery (higher photon energies), were independent prognostic factors for OS. For DFS, the independent prognostic factors were age, type of treatm ent (favoured surgery followed by radiotherapy or chemoradioth erapy), Masaoka stage and year of start of treatment. Most common reactions were lung fibrosis in 36% of patients (mainly asymptomatic in most patients), pneumonitis (9%) and oesophagitis (4%). Conclusions : Surgery combined with radiotherapy and chemoradiotherapy and modern radiotherapy techniques are correlated with improvement of survival in patients with early stage thymoma . Anyway, in patients with very early stage thymoma the complete surgical excision seems to be sufficient method of treatment. 932 poster TOTAL SKIN ELECTRON IRRADIATION (TSEI) FOR MYCOSIS FUNGOIDES ? CLINICAL RESULTS . RETREATMENT POSSIBLE? M. Doleckova " P. Berkovsky " A. Studynkova 1 1 NEMOCNICE CESKE BUDEJOVICE A.S., ONO, Ceske Budejovice, Czech RepUblic

Purpose: TSEltherapy is a complex method for delivering superficial irradiation to entire skin surface for patients with cutaneous T-cell lymphoma especially with mycosis fungoides (MF). The majority of patiens has recurrence after TSEI eventually. Some patients may be candidates for a second course of TSEI. The purpose of this report is to evaluate short and long-term clinical results of TSEI and using this metod for retreatment. Materials: Thirty six patients (p.) with MF received TSEI in Department of Oncology, Reg. Hospital C. Budejovice, Czech Republik (1993- 2007). There were 26 male, 10 female, the average age 62. Diferent treatments modalities have been used prior to TSEI for 24 patients. TSEI technique developed at McGill University, Montreal (Freeman C.A. , 1992) was modified to our condi tions. The patient standing in position ballet dancer" rotates on a carrousel. Two oblique fields produce a uniform treatment field" over the total length patient for SSD 355 ern, 6 MeV electrons. By rotational radiotherapy technique (n=26) maximal dose is achieved on the surface of Ihe skin. By stationary radiotherapy technique (n=10) is on the surface 88% (max. dose in 9 mm) with plexi, without plexi 77% (max. dose in 14 mm). A total dose was 30-40 Gy (l O Gy / week). Dose distribution was monitored with set of TLD dosimetres with subseq uent patch" (n=36) and boost" treatments (n=22). Some patiens with relaps were candidates for second course of TSEI after other failed treatment. Seven patiens had TSEI retreatment with average dose 23 Gy (6-30 Gy), average total dose (inicial plus repeated TSEI) was 64 Gy (46-88 Gy). A second complete course of intense TSEI was administered to 2 p. Average time for repeating TSEI was 35 months. Third course TSEI was offered to 2 patients, total dose 70 Gy and 88 Gy. Results : Response to initial TSEI was in 100% (n=36). Complete response has been seen in 95% (34/36), 15 p. (42%) are alive (10 p. without MF, 5 p. with MF), 21 p. (58%) died (l Op. died from progressive MF, 11 p. from other cause). Overall survival (n=36) (by Kaplan-Meier): 3-survival rate was 6872%, 5-surv ival rate was 52%, 10-survival rate was 11%. Results achieved are not statistically significant, the group of patients is too small. Relaps: 61% p. (21/36). Good paliation effect has been achieved for all patients with repeating TSEI, relief of symptoms, for someon es only for short time, average was 10,5 months (1-29). Conclusions: Most patiens with MF have benefit from TSEI. Some patients achieved long-standing remission, patients with advance disease effective palliation. The repeating TSEI offers next posibility for paliative treatment. TSEI retreatment improves quality of life for all patients.

Clinical/Disease sites . Others 933 poster BE XXAR PROTOCOL CP 98 -0 20 : RESULTS WITH 1-131 LABELED ANTIBODY IN PATIENTS WITH NON-HODKIN 'S LYMPHOMA RE FRACTORY TO CHEMOTHERAP Y AND RITUXAN : A REPORT OF 50

CASES D. Quick " A. Mark

2,

P. Anderson

2,

S 297

OTHERS

T. Neumann

2,

M. Nair

2,

R. Akins

3

JOE ARRINGTON CANCER CENTER, Department of Medical Oncology, Lubbock, USA 2 JOE ARRINGTON CANCER CENTER, Department of Radiation Oncology, Lubbock, USA 3 UNIVERSITY OF MIAMI, Department of Radiation Oncology, Miami, USA 1

Purpose: Non-Hodgkin's Lymphoma (NHL) B-Cell subtype, is generally very sensitive to Chemotherapy and Rituxan. In patients who have developed refractory disease, the course of disease is usually rapidly fatal. Many NHL B-Cells express CD-20 Antigen. Such patients may be cand idates for Radioimmunolherapy (RIT) with tositumomab murine monoclonal antibody conjugated with 1-131, which can bind to CD-20 expressing cells with potentially lethal effects. We present results in 50 patients treated according to the Bexxar CP98-020 Protocol. Materials: Initially, candidates for Bexxar CP98-020 Protocol, were patients with NHL expressing CD-20 which had become refractory to Chemotherapy and Rituxan. Since 2006, four patients have received primary treatment for NHL with RIT. Eligibility criteria included Platelet count> 100,000, less than 25% involved bone marrow, and no kidney dysfunction. In addition, the patients could not be pregnant or breast feeding. Between 2001 and 2008, 50 patients received 1-131 labeled Antibody. The total body dose was 75 cGy for Platelet counts> 150,000 and 65 cGy for Pit 100-150,000. Activity ranged from 60 mCi to 120 mCL Results: Median follow-up was 48 months (range 6-84 months ). The response rate was 72.0% (36/50), with complete response achieved in 28.0% (14/50) of the patients. Median progression free survival was 14 months. All four patients treated with primary RIT remain free of recurrence , with followup periods ranging from 8-36 months. Toxicity was moderate, with 10.0 % (5/50) ot patients experiencing profound (Platelets < 10,000) thrombocytopenia, which was prolonged , lasting more than 20 weeks. There were no bleeding complications, and no patient required a transfusion. For the remaining 45 patients, Pit counts decreased mildly for 4-6 weeks following RIT, and then returned to normal values by 10-20 weeks. Conclusions: RIT has yielded promising results in NHL patients refractory to Chemothe rapy and Rituxan. Toxicity has been acceptable. While follow-up is short, RIT may be considered for first line treatment in some cases of NHL. 934 poster DETERMINATION OF THE DOSE ·RESPONSE RELATIONS OF ACOUSTIC NEUROMAS AFTER TREATM ENT WITH GAMMA KNIFE E. Koutsouveli " P. Mavroidis 2 . P. Karaiskos 3 , P. Sandilos 4 , C. Slergiou 1 , M. Torrens 1 1 HYGEIA HOSPITA L, Department of Radiosurgery and Medical Physics, Athens, Greece 2 KAROLINSKA INST. AND STOCKHOLM UNIVER SITY, Department of Medical Radiation Physics, Stockholm , Sweden 3 UNIVERSITY OF ATHENS, Department of Medical Physics, Medical School, Athens, Greece 4 ARETEION UNIVERSITY HOSPITAL, Department of Radiology, Athens, Greece Purpose: The purpose of this work is to examine factors that are related with the response of acoustic neuromas after Gamma Knife radiosurgery. This is accomplished by associating dosimetric measures and other treatment related parameters with the clinical follow-up results. Materials: This study examines 25 patients who were treated for acoustic neuromas with the Leksell Gamma Knife (model C) unit, which is equipped with an automated positioning system (APS). The treatment outcome and the dose distribution delivered to the target were available for each patient. The dedicated GammaPlan treatment planning system was used for the development of the treatment plans based on CT and MRI images using the stereotactic frame in position. Clinical and radiological findings were used for assessing target response, which is express as a significant size reduction of the target voiume (response group). All the patients had at least 2 years of follow-up. Results: The mean age of the patients in the response group is 60.3 y, whereas in the non-response group it is 54.2 y. The corresponding prescribed doses range between 11-12 Gy with a mean reference isodose of 49% (45-54%) and 11-14 Gy with isodose 47% (40-50%), respec1ively. The initial target volume in the response group is 5.5 ee (0.7-12.1 ee), whereas in the non-response group it is 5.0 CC (0.2-19.3 cc). For the two groups of patients the mean and minimum doses (Dmean, Dmin) are 15.8 and 8.5 Gy and 16.4 and 8.1 Gy, respectively. The average volume receiving 10 and 12 Gy is 6.3 and 4.4 cc for the response group and 6.5 and 3.8 cc for the nonresponse group, respectively. Finally, the average conformity index was 0.8 (0.5-0.9) in the response group and 0.8 (0.7-0.9) in the non-response group, respectively. A positive association of target response with Dmin was found (odds ratio (OR) = 4.3) at the cutoff dose of 8.7 Gy. Furthermore, the Dmin seems to differentiate well the two patient groups since in a ROC analysis it gives the area under the ROC curve = 0.69. Finally, it is found that documented target response rate increases with minimum target dose.

S 298

CLINICAL/DISEASE SITES

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Conclusions: It is shown that the response group receives larger average minimum dose than the non-response group. The minimum dose of 8.7 Gy can be considered as a primary threshold above which the probability of having target response increases considerably. In the future, a maximum likelihood fitting will be used to determine the parameters characterizing the doseresponse relation of acoustic neuromas.

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935 poster DOES THYROID STUNNING OCCUR IN PATIENTS TREATED WITH 1-131 FOR HYPERTHYROIDISM? E. Forssell-Aronsson ", C. Lundh ", U. Lindencrona ", J. Himmelman ", A. Lundstrom ", G. Berg 2 1 GOTEBORG UNIVERSITY, SAHLGRENSKA UNIVERSITY HOSPITAL,Radiation Physics, Gothenburg, Sweden 2 GOTEBORG UNIVERSITY, SAHLGRENSKA UNIVERSITY HOSPITAL, Oncology, Gothenburg, Sweden

Purpose: Thyroid stunning is discussed mainly regarding thyroid carcinoma patients undergoing radioiodine treatment. The extent of the effect varies among published studies. Attempts have been made to identify the highest absorbed dose that does not cause stunning. Previously, we showed that stunning was evident in primary cultured porcine thyrocytes exposed to 0.15 Gy from 1311. If this result is applicable in vivo, stunning would be found also in hyperthyroid patients receiving 131 1therapy, since the absorbed dose from the diagnostic amount of 131 1is typically 0.1-0.3 Gy. Therefore, we investigated whether thyroid stunning could be identified in patients receiving radioiodine treatment for benign thyroid disease. Materials: Nineteen Batients diagnosed with Graves' disease or toxic nodular goiter who received 31 I treatment were included in the study. Uptake measurements were performed one and six days after administration of both diag131 nostic (0.45-0.62 MBq) and therapeutic (200-620 MBq) amounts of 1was determined. The ratio between the percentage uptake of therapeutic and di131 agnostic amounts of 1was calculated. The estimated effective half-life and the absorbed dose delivered per unit activity administered were determined for both administrations of 1311. Serum levels of antibodies against thyroperoxidase and TSH receptor were determined. Results: Large individual variations in 131 1 uptake after therapy compared to after diagnostics were evident. In 26% (day 1) and 47% (day 6) of the patients, the percentage uptake was lower at therapy than at diagnostics, indicating possible stunning. Uptake was higher at therapy in 37% (day 1) and 26% (day 6) of the patients. No correlations between the change in uptake and absorbed dose at diagnostics or at therapy were observed. There was a statistically significant correlation between the absorbed dose from diagnostic 131 1and the change in estimated effective half-life from diagnostics to therapy and also the change in absorbed dose per unit activity administered at therapy compared to at diagnostics. No overall changes in effective half-life or uptake 131 for diagnostic or therapeutic administration of 1were detected. Conclusions: The statistically significant negative correlation between absorbed dose from diagnostic 131 1and the change in estimated effective halflife as well as the change in absorbed dose delivered per unit activity suggest thyroid stunning. Further studies are needed to establish a connection between absorbed dose, time, and stunning, for low absorbed doses such as those administered for hyperthyroidism.

936 poster FIRST TOXICITY REPORT OF THE BC2001 TRIAL; A MULTICENTRE PHASE III RANDOMISED TRIAL OF RADIOTHERAPY WITH AND WITHOUT SYNCHRONOUS CHEMOTHERAPY IN MUSCLE INVASIVE BLADDER CANCER ISCRTN NO. 68324339, EUDRACT NO.

2004-000164-26. N. James 1, S. Hussain 1, C. Rawlings 2, P. Jenkins 3, J. Tremlett 4, M. Crundwell 5, R. Huddart 6, E. Hall 7, S. Rogers 7 1 UNIVERSITY OF BIRMINGHAM, CRUK Institute for Cancer Studies, Birmingham, United Kingdom 2 SOUTH DEVON HEALTHCARE NHS TRUST, Department of Radiotherapy, Torquay, United Kingdom 3 CHELTENHAM GENERAL HOSPITAL, Giocestershire Oncology Centre, Cheltenham, United Kingdom 4 SUSSEX CANCER CENTRE, Department of Radiotherapy, Brighton, United Kingdom 5 ROYAL DEVON & EXETER HOSPITAL NHS FOUNDATION TRUST, Department of Urology, Exeter, United Kingdom 6 THE INSTITUTE OF CANCER RESEARCH, Clinical Academic Radiotherapy, Sutton, United Kingdom 7 THE INSTITUTE OF CANCER RESEARCH, Clinical Trials and Statistics Unit, Sutton, United Kingdom

Purpose: The BC2001 trial was set up to address whether the use of concomitant chemotherapy could improve loco regional control and whether radiotherapy volume modification could reduce late toxicity without detriment to tumour control. The trial was designed to assess initial toxicity, toxicity during treatment, and then at six months, twelve months and annually thereafter according to the CTC, RTOG and Lent/Som scales. The trial closed to accrual on 30/04/2008. This is the first report of this trial focusing on acute toxicity. Materials: BC2001 was a multi-centre phase randomised phase III trial utilising a 2x2 design. Patients were randomised to one or both of two randomisations: 1. radiotherapy alone (RT) or with 5-fluoruracil (5FU) (500mg/m2 daily for 5 days as continuous infusion weeks 1 and 4) and mitomycin C (MMC) day 1 (chemoRT); 2. radiotherapy to the tumour and whole bladder or a 2-stage technique reducing dose to uninvolved bladder to 85%. Results: The initial summary analyses have been made for the purposes of this abstract; a full clinical trial analysis will be presented at the meeting. At the time of trial closure 352 patients had been recruited to the chemoradiotherapy comparison , with 175 patients randomised to chemoRT. Median age was 73 (lOR 54-84) years, 80% male, WHO performance status (0) 57%, (1) 37%, (2) 6%. Patients were well balanced with respect to age, stage and performance status. Haematological toxicity during treatment: 12 chemoRT patients suffered grade 3 or 4 haemotological toxicities versus 7 RT patients. Non-haematologicaltoxicity: there were 15 grade 3 toxicities in the chemoRT arm compared with 12 grade 3 and two grade 4 toxicities in the RT only arm. We have 6 month follow up data on 197/352 patients: 9% of chemoRT patients have grade 3/4 toxicity versus 3% of RT only patients. The remaining patients in both arms had maximum toxicity grade 0-2. Conclusions: In keeping with our previous phase I and II trials, chemoRT with 5FU/MMC was well tolerated with modest increases in reported toxicity compared to RT only. We will present a fuller analysis at the meeting including delivered dose intensity and a detailed breakdown of patterns and duration of toxicity.

937 poster FRACTIONATED CYBERKNIFE RADIOSURGERY MELANOMA U. Selek ", F. Zorlu ", H. Kyratly 2, A. Dogan 1

FOR

UVEAL

1 HACETTEPE UNIVERSITY, FACULTY OF MEDICINE, Radiation Oncology, Ankara, Turkey 2 HACETTEPE UNIVERSITY, FACULTY OF MEDICINE, Department of Ophtalmology, Ankara, Turkey

Purpose: To evaluate prospectively local tumor control and morbidity after fractionated Cyberknife radiosurgery for uveai meianoma, unsuitable for ruthenium-106 brachytherapy or local resection. Materials: Cyberknife radiosurgery was offered only to patients with uveal melanoma who were deemed unsuitable for ruthenium-1 06 brachytherapy or local resection. This study includes: (1), melanoma of '2,7 mm in initial height; or (2), juxtapapillary and/or juxtamacular tumors (height, '2,3 mm; posterior tumor magrin extending to 3 mm of optic disk rim and/or fovea). In these cases, episcleral ruthenium-1 06 brachytherapy is complicated by a increased rate of local tumor control failures and radiation-induced side-effects. Patients were excluded if they presented evidence of echographic extrascleral tumor extension, neovascular glaucoma, or any form of pretreatment or metastases at baseline. The eye was stabilized by peribulbar injection of 5 cc 2% lidocaine while the patient is staring. CT-scans with a 1 mm slice thickness were obtained for planning. Cyberknife radiosurgery is performed to a total dose of 60 Gy to 70% or 85% isodose line in 3 fractions (20 Gy/fraction). PTV for Cyberknife is the contrast-enhancing lesion demonstrated on MRI plus a 1 mm margin. Results: Four patients with uveai melanoma were treated in this protocol. All patients had serous retinal detachment accompanied with the tumor. None of the potential grade '2,2 acute toxicities were observed. One month follow up revealed no progression of disease with stabile mass in all patients and improvement of retinal detachment in three patients and increment in one. Longer follow up is required for further recommendations.

CLiNICALIOISEASE SITES

Conclusions: Cyberknife fractionated radiosurgery appears to be an effective local treatment in uveal melanoma with no serious acute side effects. 938 poster INFLUENCE OF I.V. CONTRAST AGENT ON DOSE CALCULATION IN 3D-TREATMENT PLANNING FOR RADIOSURGERY OF CEREBRAL ARTERIOVENOUS MALFORMATIONS A. Zabel-du Bois 1, B. Ackermann 1, S. Milker-Zabel 1, H. Hauswald 1, O. Schramm 1, G. Sroka-Perez 1, P.Huber 2, J. Debus 1 1 UNIVERSITY OF HEIDELBERG, Radiooncology and Radiotherapy, Heidelberg, Germany 2 GERMAN CANCER RESEARCH CENTER (DKFZ), Radiation Therapy, Heidelberg, Germany Purpose: For radiosurgery (RS) in cerebral arteriovenous malformations (AVM) accurate contouring of the target volume is recommended. Therefore, the application of l.v, contrast agent is needed to outline the nidus during the computed tomography (CT) scans. In order to calculate the dose from CT scans the Hounsfield units (HU) are converted into the corresponding eiectron densities. Due to the high atomic number of contrast agent a certain overdosage is expected. We investigate the influence of local density increase by i.v contrast agent on dose calcuiation in three-dimensional (3D)treatment pianning for RS of cerebral AVM. Materials: For 3D-treatment planning all CT images were transferred to the STP 3.0 software (Stryker-Leibinger, Freiburg, Germany). Linac-based RS was performed using a total number of 9 to 14 isocentrlc, non-coplanar, irregulary shaped beams. An estimation of dose deviation was calculated from the data sets of 30 patients using the published equation for 6 MeV photons. Additionally, we used the enhanced and unenhanced data sets of 10 patients for exact analysation of dose deviation. Dose calculation was performed using the same RS treatment plan on both data sets. Both plans were standardized to 1 Gy at isocenter with the same dose weight for all beams. Results: Mean target volume was 5.3 cc (range, 0.1-41.2 cc). Mean maximum diameter of target was 23.2 mm (range, 8-51 mm). Mean difference of HU (dHU) between enhanced and unenhanced CT was 152 HU (range, 50-350 HU). The estimated dose deviation was <1% in 80% of cases with a mean deviation of 0.67% and a maximum dose deviation of 1.8%. Dose deviation was dependent on max. diameter and dHU. With increasing dHU and increasing max. diameter dose deviation increased as well resulting in an overdosage. We generated a diagramm with iso-dHU-lines in order to estimate the overdosage for known dHU and different target sizes. The calculated overdosage in the 10 data sets of enhanced and unenhanced CT scans was 0.66% mean (range 0.2-1.2%) whereas the estimated overdosage was 0.65% (range 0.1-1.1%). Conclusions: The use of i.v, contrast agent in 3D-treatment pianning for RS of cerebral AVM may iead to an underestimation of actual applied dose. The effect on dose calculation is rather low with dose deviations below + 1% in most of the cases. However, there are cases especially in large AVM with high dHU in which an additionai unenhanced CT scan is recommended for exact dose calculation. This may be of special importance in AVM located next to radiosensitive structures like the chiasm or cranial nerves. 939 poster MANAGEMENT OF THE PREGNANT PATIENTS WITH LYMPHOMA FROM SINGLE INSTITUTION E. Wojciechowska - Lampka 1, J. Tajer 1, W. Osiadacz 1, B. Brzeska 1, M. Kania 2, J. Rostkowska 2, J. Meder 1 1 MSC MEMORIAL CANCER CENTRE AND INSTITUTE, Department of Lymphoma, Warsaw, Poland 2 MSC MEMORIAL CANCER CENTRE AND INSTITUTE, Departement of Radiotherapy, Warsaw, Poland

Purpose: 44 patients with Hodgkin Lymphoma (HL) and 5 patients with NonHodgkin Lymphoma (NHL were treated at the MSCMCC Warsaw between 1986 and 2007. Materials: Hodgkin Lymphoma:Age :mean(range):17-38(28); CSI-7,:CSII32,CSIII-5; Trimester of the pregnant: 1-9,11-23,111-12; B symptoms-14(32%), Tumor mass-18(41%); MMR>1/3 -15(34%); Histology: NSI-33,NSII-9,MC-2 Non Hodgkin Lymphoma: Age:mean(range)-20-32 (26) ;2-breast DLBCL,1brain DLBCL 2-mediastinal DLBCL; Treatment: Hodgkin Lymphoma I trimester: therapeutic abortion-6, radiotherapy(IF)-2, miscarriage(7Hbd)-1 ; II trimester: radiotherapy (IF-total dose 30-35 Gy) and chemotherapy regimen EVA(2cycles)before delivery-2; chemotherapy EVA(3-4 cycles)before delivery and radiotherapy after delivery-16 radiotherapy(IF-total dose between 20-44 Gy)before delivery and chemotherapy LOPP,MOPP,MOPP/ABV after delivery -5; In vivo dosimetry of testes during radiation treatment by irregular fields- supradiaphragmatic lymph node. Thermoluminescent dosimetry and indiVidually blocks of the abdomen were used. The dose to the fetus was estimated individually in all. III trimester-method "watch and wait"-12 patients NHL-individual therapy Results: Hodgkin Lymphoma: Live with CR/CRu-37 (20-206 months after

OTHERS

S299

therapy),PR 2 patient PD-7(3-72 months after CR), Live with PD-1 after PBSCT, Death with PD -4 Children(age)-35 (3 month-20 years); Non-Hodgkin Lymphoma: Live with CR/CRu-2(39-58 months after therapy); Death with PD-2 (12-94 months after delivery); Live after abortion and chemotherapy protocol GMALL before radiotherapy -1; Children(age)4 -(2-9 years); In all cases of studied children ,physical, neurological psychological, hematological functions are normal. One infant developed acute respiratory distress syndrome and died 6 days after delivery Conclusions: Treatment requires individualization to insure that the patient will be cured and fetus protected. The group of pregnant woman with NHL had a poorer overall prognosis compared with the group with HL. 940 poster PROGNOSTIC FACTORS IN PATIENTS WITH ENDOMETRIAL CANCER TREATED WITH SURGERY AND POSTOPERATIVE RADIOTHERAPY B. Lindner 1, R. Krynicki 1, W. Michalschi 2, J. Jonska-Gmyrek 1, J. Staniaszek 1, M. Niemec 1 1 MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTER, Radiotherapy , Warsaw, Poland 2 MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTER, Biostatistic, Warsaw, Poland

Purpose: To assess the prognostic factors in endometrial cancer. Materials: Material consisted of 880 patients with FIGO stage I-III endometrial cancer treated between 1992-1998 with total hysterectomy and adjuvant radiotherapy. The median follow-up time for leaving patients was 9 years, range 0,5-13 years. The multivariate Cox's analysis of prognostic factors for overall survival was carried out. The following variables were analyzed: stage of the disease; histopatological type of the tumor; grade; depth of the invasion of myometrium (:'050% vs, > 50%); WHO performance status (0 vs ~1); the hormonal activity status (pre- or postmenopausal); coexistence of Obesity, hypertension and diabetes; interval between hysterectomy and radiotherapy (:'0 74 vs > 74 days). Results: The following variables were negatively associated with overall survival: long time interval between surgery and radiotherapy, hazard ratio (HR) 1,33 (95 % confidence interval (CI) 1,01;1,75 (p=0.040); advanced stage of disease HR 2,8 CI 2,05;3,81 p<0.001; deeper myometriai infiltration HR 1,52, CI 1,16;1,98 (p=0.002), performance status ~ 1 HR 2,54 CI 1,92; 3,36 (p<0.001), diabetes mellitus HR 1,56 CI 1,12 ; 2,17 (p=0.008). Conclusions: Apart from well known prognostic factors as stage of disease and age, delay of postoperative radiation and diabetes were associated with lower survival. 941 poster RADIATION DOSE-BENEFIT ANALYSIS OF HEMATOPOIETIC STEM CELL GRAFTING FOR TOLERENCE INDUCTION ACROSS MHC BARRIERS IN LIVING RELATED DONOR RENAL ALLOGRAFT RECIPIENTS H. Chiramana 1, V. Shankar 2, H. L. Trivedi 3, A. Vanikar 3, P. R. Shah 3, P. R. Modi 4, V. Shah 3 1 M.S.PATELCANCER CENTER, Medical Oncology, Karamsad, Gujarat, India 2 M.S.PATEL CANCER CENTER, Radiation Oncology, Karamsad, Gujarat, India 3 INSTITUTE OF KIDNEY DISEASES & RESEARCH CENTER, Department of Nephrology, Ahmedabad, Gujarat, India 4 INSTITUTE OF KIDNEY DISEASES & RESEARCH CENTER, Department of Urosurgery, Ahmedabad, Gujarat, India Purpose: Transplantation biology has accumulated evidence of persistent Mixed Iymphohematopoietic chimerism after allogeneic hematopoietic stem cell (HSC) grafting, resulting in donor-specific tolerance to solid organ alloantigens. Ahmedabad-Tolerance induction protocol (A-TIP) allows grafting in living related donor renal allograft (LRD-RA) recipients with persistent lowlevel MLHC & donor-specific tolerance across MHC barriers. The study aims to evaluate the ideal radiation dose needed for tolerance induction in patients undergoing A-TIP in LRD-RA recipients. Materials: 210 consecutive end stage renal disease patients recruited between May 2004 through Mar.2007 underwent renal transplantation (RTx) following A-TIP and negative Lymphocytotoxicity cross match (LCM). A-TIP included (a) 2 donor lymphocyte transfusions (b) low intensity conditioning & (c) HSC grafting. The conditioning regimen included fractionated low dose target specific irradiation, Cyclosporine, Cyclophosphamide, anti T-cell antibody & Treosulfan. All Patients underwent subtotal lymphoid irradiation (STU) targeting spleen, abdominai, iliac & inguinal Lymph nodes, thoracolumbar vertebra & 75% of pelvis. Patients were randomized into 3 groups of 70 each: STU 600, STU BOO, STU 1000, corresponding to doses of 600cgy, BOOcgy & 1000cgy delivered conventionally using 6MVI15MV photons by 3-D CRT Technique. Patients in 3 groups were comparable for demographic features, ESRD etiology & donor HLA match profiles.Unfractionated HSC procured from donor BM was administered into portal circulation, within 24 hours

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of ach ieving CD4+/CD8+ T cell count ::; 10% of baseline. Donor specific cyto toxic antibodies were eliminated with i.v immunoglobulins & plasmapharesis before RTx. Immunosuppression was withdrawn 3-6months after RTx for patients with consistently positive chimerism . Robust tolerance was def ined as stable allograft func tion for> 100 days without immunosuppression. Prope tolerance was defined as early adequate, stable grafts func tion with no rejection episodes on minimum immunosuppression . Metastable tolerance was adequate graft function on immunosuppression with single episode of steroid responsive acute rejection. Results :

I

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INS

Conclusions: The safe & effective dose for tole rance induction in LRD rena l transplantation is 1000 cGy. 942 poster RADIATION THERAPY ON lEFT THORACIC AN CHEMOTHERAPY ANTHRACYCLINE-CONTAINING : TRANSIENT ELECTROCARDIAGRAPHIC ABNORMALITIES AND PERSISTENT SCINTIGRAPHIC PERFUSION DEFECTS G. Gallucci " M. Coccaro 2 , A. Napp i 3 , S. Clemente 4 , V. Fusco 5 1 ONCOLOGICAL HOSPITAL, Department of Cardiology, Rionero in Vulture rz),ltaly ONCOLOGICAL HOSPITAL, Oncology Unit, Rionero in Vulture (Pz), Italy 3 ONCOLOGI CAL HOSPITAL, Neclear Med icine , Rionero in Vulture (Pz), Italy 4 ONCOLOGICAL HOSPITAL, Medical Physics, Rionero in Vulture (Pz) , Italy 5 ONCOLOGICAL HOSPITAL, Radioterapy Oncology, Rionero in Vulture (Pz), Italy

943 poster RADIATION-INDUCED PLEXOPATHY: SIGNIFICANT NEUROLOGICAL SYMPTOMS REGRESSION BY A PENTOClO COMBINATION IN A PHASE II TRIAL. S. Delanian " P. F. Pradat 2 , R. Porcher 3 , T. Maisonobe 4 , J. L. lefaix 5 1 HOP/TAL SAINT LOUIS, AHHP , Department of Onco logy-Radiotherapy, Paris , France 2 HOPITAL PITIE SALPETRIERE, APHP, Federation de Neurologie, Paris , France 3 HOPITAL SAINT LOUIS, APHP , Departernent d, Paris , France 4 HOPITAL PITIE SALPETRIERE , APHP , Federation de Neurophysiologie Clin ique , Paris, France 5 COMMISSARIAT A CENERGIEATOMIQUE, Caen , France

Purpose: Radiat ion-induced per ipheral neuropathy (RIP) is a rare and severe delayed complication of radiotherapy that is spontaneously irreversible, characterized by a triad combin ing demyelization, axonal degeneration and fibrosis. There is currently no medical treatment to limit or reduce symptoms [1J. We previously described a successful long term use of combined pentoxifylline -tocopherol (PE) in RI superficial fibrosis [2]; and PE- clodronate (pentoclo) in osteoradionecrosis [3J. In a series of patients treated with PE for superficial fibrosis including 8 patients who suffered with combined brachial plexopathy after breast cancer irradiation, we observed 4/8 neurological symptoms stabilisation but no improvement at 18 months. Materials: For last ten years , 93 pat ients were seen for RIP at Saint Lou is Hospital. Fifty assessable patients, with partial PRI of upper limb (32 cases ) or lower limbs (18 cases ) for mean seven years , 20 yrs after RT for breast cancer or Hodgkin disease (exclusion for analysis it complete motor def icit, 4 limbs, immediate lost of follow -up) were treated by a daily oral PENTOCLO combination using pentoxitylline (800mg)- tocopherol (1000mg)- intermittent clodronate (1600mg/d ; 5 daysl7) , alternated with predn isone (20 mg/d; 2 daysl7 ). The main endpoint was a neurological score/20 adapted from SOMA 95// CTAEv3.0 200311 NCI.CTC 9911 INCAT 2000 scales with pain/5 , sensory /5, motor/l0. Clinical assessment and EMG were done every 6 mont hs during 5 years: mean initial score Mo was 11 ± 3 [range 5-16]. Results: Treatment was well tolerated. Pentoclo was continuously effect ive over several years and resulted in a significant progressive neurological score improvement (p <0.00 1) with sensory and motor benef its: mean score reduction -14% at 6 months or M6 (sc 9.3 ± 3), -30% at M12 (sc 7.3 ± 3), -34% at M18 (sc 7.3 ± 4), -44% at M24 (sc 6.3 ± 3), -47% at M30 (sc 5.8 ± 3) ; w ith 80% (25 pts/31 ) partial responders and 6 stabilizations at 1 year . This symptomat ic regression during time was not linear, but rather exponential. Conclusions: PENTOCLO combination allowed , for the first time, half neurological symptoms reduction in 2·3 years for partial PRI patients. A randomized trial is on going to valid theses results . Ref : [1 J Delanian et al. Semin Radiat Oncol 2007 , 1: 99 ; [2] Delan ian et al. J Clin Oncol 2005 , 23: 8570 ; [3] De/anian et al. Head Neck 2005 , 27 : 114. 944 poster

Purpose: Radiation Therapy (RT) to the thorax and anthracycline-based chemotherapy (CHT) play an important role in the multimodality management of patients with breast cancer. Although modern RT techniques have reduced radiation exposure to the heart, they may not have eliminated cardiotoxicity. lt appears that contemporary RT methods to the left brest may still cause cardiovascular disease. Changes in myocardial perfusion, wall mot ion and ejection fraction have been demonstrated in pat ients undergoing rad iation treatment. To evaluate post-radiation reg ional heart changes from tangential photon beam RT, we have exam ined the surrogate endpoints 01 electrocardiographic (ECG) change and single photon em ission computed tomography (SPECT) cardiac perfusion after RT. Materials: 10 patients (mean age 44 affected by left side ductal infiltrating carcinoma of the breast) were treated with neoadjuvant CHT (epyrubicine 75 mg/m2 and taxol 175 mg/m2 ) every 3 weeks for 4 cycles, surgical rnastectomy, adyuvant CHT (CMF 1·8 given every 3 weeks for 6 cycles ) and RT (total dose of irradiation was 60Gy ). Results: Before surgery 12 lead ECG were normal. Six months after RT the ir 12 lead ECG showed marked abnormalities of ventricular repolar ization mimicking anterior myocardial ischemia with ST elevation in V2-V3 and negative T waves in 01 , a VL , V2-V6 wit hout both symptoms and echocardiographic abnormalities of left ventricle (l V) wall mot ion . SPECT myocardial perfusion SCintigraphy showed reversible perfus ion defects in distal anterolateral and anteroseptal region of the LV and a fixed perfusion defect in the apical reo gion poss ibly due to attenuation from breast prothesis. We put them on ASA and beta?lockers. After 3 months, the ir ECG was unchanged. After 1 year while their ECG are normal , myocardial perfusion defects in distal anterotateral and anteroseptal region of the lV are still present. The patiens are still asymptomatic and scheduled for a long follow-up. Conclusions: We recommend frequent cardiac monitoring of patients submitted to anthracycline-based CHT and to left side wall RT because recogni tion of the relationship between RT and CAD may lead to a better understanding of the clinical impact of these abnormalities, to a quantitative definition of the need for more intensive investigations and to an earlier intervention.

RADIOTHERAPY 5.0 - VOXEl CONTROL PROBABILITY GUIDED RADIOTHERAPY (VCP-GRT) : AN ATTEMPT TO INTEGRATE MOLECULAR IMAGING AND DOSE UNCERTAINTIES WITH MODERN RADIATION DOSE DELIVERY P. Lambin " S. Petit " W. van Elmpt " S. Fekkes " B. Wouters " A. Dekker I , D. De Ruysscher 1 1 UNIVERSITY HOSPITAL MAASTRICHT, MAASTRICHT UNIVERSITY, MAAS TRO CLINIC, GROW, Maas tr icht , Netherlands

Purpose: lt is now clear that both tumours and many dose-limiting organs are not homogeneous structures with respect to their biology, environment, and radia tion sensitivity. Importantly, new imaging modali ties are enabling the possibility of both assessing this heterogeneity and incorporating it into ther apeutic decisions. The use of margins in current rad iotherapy is requ ired to account for uncertainties in tumour del ineation, position and shape , as well as uncertainties in the delivery and planning phases of radiotherapy. However in the case of a heterogeneous treatment with multiple dose levels , anisotropic margins are needed that depend on local dose gradients. Consequently the ~se of margin is this situation is not stra ightforward. An alternative approach IS to Incorporate the uncertainties ot radiotherapy planning and delivery in a probabilistic manner. The goal of this study is to explore the concept of integrallng both dose uncertainties and tumour and normal tissue heterogeneity In voxel contro Vcomplicalion probab ility guided radiotherapy (VCP-G RT). This is a data-based approach independent of any a priori hypothesis for integrating clin ical and biological data with sys temic treatment. Materials: Results: We hypothesise that future processes of radiation oncology will be based on at least two probability maps and verification of the delivered dose (outlined below). Our group has submitted several abstracts with data supporting each of these hypotheses (see ref.) 1) Imaging-based VCP consisting of fused Images before and during treatment which will lead to information on the probability of relapse per voxel (Aerts et al. and Petit et al.). This al· lows optimization of the tumour dose distribution to minimize the probability

CLINICAL/DISEASE SITES

on residual disease. 2) Voxel dose probability, which describes the chance that a voxel actually receives a certain dose given a planned dose distribution. This is needed to adapt the multi-dose level treatment plan to make it robust to plann ing uncertainties without using marg ins...ln practice we will compute a Dynamic Probability with a confidence interval for each voxel of interest. Our simulations show that this is feasible (see Figure). 3) Verification of the actua l delivered cumulative dose using 3D in vivo dosimetry and taking advantage of non-rigid deformat ion models . (van Elmpt et al.: Fekkes et al.). Further refinements of this approach are possible by taking into account the effect of systemic treatments and other biological and genetic factors. We emphas ise, however, that a great deal of research and clinical studies are needed before this can be realised in clinical practice. Conclusions: Voxel Control! Complicat ion Probability is a quantitative, flexible model that may allow personalised radiation alone or combined with drugs and takes advantage of tumour and normal tissue heterogeneity. 945 poster SELECTION OF THYROID CANCER PATIENTS FOR THERAPEUTIC DOSES OF RADIOIODINE - CAN STIMULATED THYROGLOBULIN LEVELS AFTER IODINE 131 ABLATION PREDICT FOR THE NEED FOR SUBSEQUENT DOSES OF IODINE 131? S. Cherian " R. Benson " L. Tan " S. Jefferies 1 1 CAMBRIDGE UNIVERSITY HOSPITALS NHS FOUNDATION TRUST, Oncoiogy, Cambridge, United Kingdom

Purpose: In patients with differentiated thyroid cancer, British Thyroid Association guidelines recommend a diagnostic whole body iodine scan (WBS) 6 months atter 1 ablation. Patients with posit ive scans then proceed to a therapy dose of 1' 31. This policy avoids unnecessary treatment in some patients , thus minimising the risk of second malignancies . However, patien ts have to endure symptoms of hypothyroidism from thyroxine withdrawal twice (for WBS and subsequent therapy dose ). In selected high risk patients, there fore, our policy is to omit WBS and proceed directly to the therapy dose. This audit evaluates the use of stimulated thyroglobulin (sTg) levels at the time of initial ablation to improve patient selection for subsequen t therapy dose without diagnostic WBS. Materials: 58 consecut ive patients underwent 1' 31 ablation between June 04 and May 06 for differentiated thyroid cancer. sTg levels and WBS were obtained at the time of ablation. Patients considered low risk (based on age, sex and stage) proceeded to dia~nostic WBS at 6 months whilst high risk patients proceeded to therapy 1' 3 dose with WBS and sTg at the time of therapy. Resulls: 19 patients were excluded from the analysis with negative scan and sTg (2), anti Tg antibod ies (1) and missing sTg results (16). Of the remaining 39 patients, 29 were female and 10 male. 14 patients (35.9%) had diagnostic WBS at 6 months while 25 patients (64.1%) received therapy 1' 31. Of the 14 patients who had diagnostic WBS, WBS was negative in 12 patients (85.7%) and positive in 2 (14.3%). Of the 25 patients who had therapy 1 (64%) had positive scans or detectable sTg at the time of therapy. 9 patients (36%) had negative scans and undetectable sTg at the time of therapy and could be considered to have had unnecessary treatment. 7 patients had sTg > 50 mcg/I at the time of ablation, all of whom had positive scans and/or detectable sTg at the time of subsequent therapy 1'3' . 12 patients had sTg > 10 mcg/I at the time of ablation, 10 of them had detectable sTg at subsequent therapy 1' 31 . The sTg of the two that became undetectable was 18.8 and 40.9 mcg/1. Conclusions: Using a post ablation threshold sTg > 10 mcg/I to select patients for subseq uent 1'31 therapy could optimise patient selection for subsequent radtoiodlne. This would minimise the number thyroxine withdrawals for higher risk patients and decreas e the risk of over-treatment in lower risk patients.

'3'

THE RELATIONSHIP BETWEEN RADIOTHERAPY DELAY AND LOCAL RECURRENCE D. Sutton i Z. Chen i W. Kong 1 , S. Keller 1 , J. P. Voroney I, W. MacKiliop

-1 ---

QUEEN 'S UNIVERSITY CANCER RESEARCH INSTITUTE, Cancer Care and Epidem iology, Kingston , Ontario, Canada 1

Purpose: There has been variation in the results of studies examining the effect of radiotherapy (RT) delay on clinical outcomes . The purpose of this study was to synthesize the most recent clinical evidence relating RT delay to the risk of local recurrence . MaterialS: We updated a systematic review of all papers published between 1975-2005 to include papers pUblished between 2005-2007 using PubMed, HealthStar, and the Cochrane Library databases. Only high quality (HQ) studies that properly controlled for confounding factors were included in our primary analysis. Results: Our combined search yielded 42 relevant papers, of which 22 met our HQ criteria. Meta-analyses of the 22 HQ papers on local recurrence showed evidence of increased risk from RT delay : RR local recurrence/month

S 301

= 1.12, 95%CI= 1.07, 1.18. For post-operat ive breast radiation , the RR local recurrence /month =1.09 , 95%CI= 1.02, 1.16. For definitive head and neck radiation , the RR local recurrence /month =1.15, 95%CI= 1.02, 1.29, and for post-operative head and neck radiation, the RR local recurrence/month =1.19, 95%CI=1 .08, 1.31. Meta·ana lyses of all 42 relevant papers produced similar findings to those in our primary analysis: RR local recurrence /month = 1.12, 95%CI= 1.07,1.16. Conclusions: RT delay is associated with an increased risk of local recurrence. This assoc iation is strongest in head and neck cancer patients. Waiting time for RT should be as short as reasonably achievable. 947 poster TREATMENT WITH GLUTAMINE DURING RADIOTHERAPY ON PELVIC AREA. INITIAL RESULTS I. Membrive Conejo I, A. Reig 1 , M. Algara I , P. Foro I, J. Sanz 1, N. Rodriguez I , J. Lozano I , J. L. Lopez 1 , J. Dengra 1 1 HOSPITAL DE L'ESPERANGA, Radiotherapy, Barcelona , Spain

Purpose: Diverse studies conclude that administration of glutamine during treatment with radiotherapy has a protective action on mucosa decreasing incidence of the inflammatory effect of the radiation or delaying toxicity. Mainly the benefit has been demonstrated in protection of esophageal mucosa and small bowel. The objective was to know if the administration of glutamine during radiotherapy treatment in pelvis has a good tolerance and if there are a decrease in the incidence of small bowel or rectum toxicity. Materials: Every patient received prophylactic glutamine powder in doses of 10 gl 8 h 10 days before the beginning of the treatment with pelv ic radiotherapy and up 10 10 days atter the end. We registered the G-I toxicity (enteritis and proctitis ) and the dose of radiation administered to the patient at the beginning of toxicity. RTOG toxicity criteria was used to evaluate the G-' toxicity. The toxicity was assessed only during the time of treatment on pelvic area , without including the toxicity during the boost treatment. Results: 27 patients were included in the study, mean age was 64.29 years. There were 10 (37 %) with cervix carcinoma , 11 (40.7 %) with endometrial carcinoma and 6 (22.3 %) with rectal carcinoma . In 11.5 % an abdominal surgery was performed and then chemotherapy , 29.6 % only with chemother apy, 44.4 only with surgery and in 7.5 % nor surgery nor chemotherapy. The type of chemotherapy was 5-Fluorouracil in 46.2 % of the patients and cisplatine in 53.8 'Yo. The average dose of radiotherapy administered on the pelvis was 45.29 Gy with 1.8-2 Gy/fraction. We excluded 1 patient because bad roterance to glutamine (nauseas and vomits atter the ingestion) The registered toxicity was (stratified in groups ):

Average Enteritis Enteritis Rectitis Rectitis dose at grade grade grade grade the start 0-1 0-1 of the 2-3 2-3 toxicity

'3',16

946 poster

OTHERS

~~:~?th:rapy 14 0% ~:e:~:a;y 37.5% 1

~U:~

IS,"10

N o surgery, no chemotherapy

Isw.

Chemotherapy

Iwvo 160% 14 0% 128 Gy 62. 5% 162.5% 137 .5% 117 .3 Gy

1

IS'"10 F}3Gy IsO% 1 FF 100%

1

10

0%

Conclusions: We conclude that acute gastrointestinal toxicity during treatment of pelvic radiotherapy with adminislration of gtutamine is similar to the habitual toxicity in our center. In our study the toxicity has been gathered during the pelvic treatment up to 45-46 Gy, in next studies we have to verify if the protective effect of glutam ine is demonstrated with higher doses of radiation. Glutamine was well tolerated , only 1 patient has been excluded from the study by adverse effects .