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15030 Background: To assess the role of pelvic radiotherapy (RT) in the outcome of patients treated with chemotherapy (CT) with or without surgery in the management of metastatic rectal cancer. Met...

15098 Background: To report a single-center experience treating patients with squamous-cell carcinoma of the anal canal using helical tomotherapy (HT) and concurrent chemotherapy, and compare the dosimetric results with 3D conformal radiotherapy (RT) or intensity modulated RT (IMRT). Methods: From May 2007 to December 2007, 8 patients were treated with HT and concurrent chemotherapy (5-fluorouracil and mitomycin) for anal squamous-cell carcinoma. All patients underwent computed-tomography-based treatment planning, with pelvic regions and inguinal nodes receiving 36 Gy in 1.8 Gy per fraction. Following a planned one-week break, primary tumor site and involved nodes were boosted to a total dose of 59.4 Gy. DVHs of several organs at risk (OAR; bladder, small intestin, rectum, femoral heads, penile bulb, external genitalia) were assessed in terms of conformal avoidance. All toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. HT plans and treatment were implemented...

2041 Background: While new brain cancer therapies may help extend survival, both the disease and its treatment can have substantial impact on HRQoL. In this analysis we evaluated the psychometric properties of the EORTC QLQ-BN20, a brain cancer specific HRQoL questionnaire. Methods: Data were derived from two completed phase III EORTC / NCIC clinical trials including 891 brain cancer patients from 119 centers in 15 countries. Experimental treatments were surgery followed by radiotherapy and adjuvant PCV chemotherapy for highly anaplastic oligodendroglioma; and surgery followed by concomitant radiotherapy plus temozolomide (TMZ) chemotherapy and adjuvant TMZ chemotherapy for glioblastoma multiforme. Standard treatment consisted of surgery and postoperative radiotherapy alone. HRQoL assessments were performed before randomization, 1 month after ending radiation, and every 3 months after the start of chemotherapy. The BN20 scoring transforms 20 questions into 11 scales to assess neurological deficits (visual...

2026 Background: VEGF is an essential mediator of angiogenesis. PTK/ZK is an orally available tyrosine kinase inhibitor of all known VEGF receptors. The EORTC has initiated a randomized phase I/II study in which PTK/ZK is being investigated in combination with standard RT and concomitant TMZ. The results of the safety and dose-finding run-in of the triple combination are reported here. Methods: Escalating doses of PTK/ZK QD continuously (using classical 3+3 design) and concomitant RT (60 Gy) and TMZ (75 mg/m2/day) during 6–7 weeks were to be administered. During the adjuvant/maintenance part, PTK/ZK was prescribed at a fixed standard dose of 750mg bid until progression. Dose limiting toxicities (DLT) were defined as >G3 toxicity occurring during RT + 2 weeks. Results: 18 GBM pts (M/F: 11/7, median age: 53 years, PS 0/1) have been enrolled and complete data for 15 pts are currently available. DL1 (500 mg): 4 pts; no DLT; DL2 (1000 mg): 6 pts: 1 DLT: G3, liver enzyme (ALAT) elevation and hyponatremia DL3 (1250 mg); 8 pts: 3 DLTs: G3 hepatic toxicity (2 pts) and G3 platelets and G4 neutrophil (1 pt). In a 4th patient a G3 diarrhea and hepatic DLT leading to PTK/ZK interruption was doubtful therefore it was decided to extend DL3. Frequently observed possibly related non-dose limiting drug adverse events of all grades included: abdominal pain/cramping (2 pts), ALAT/ASAT elevation (10 pts), creatinine elevation (2 pts), allergic reaction (2 pts), constipation (4 pts), diarrhea (5 pts), fatigue (11 pts), hypertension (6 pts), nausea (8 pts), vomiting (3 pts), and weight loss (4 pts). All toxicities were reversible. Conclusions: MTD has been reached at 1250 mg and the recommended dose of PTK/ZK in combination with RT and TMZ is 1000 mg/day. A randomized 3-arm phase II will start accrual in January 2007. Patients will receive standard TMZ/RT alone or with PTK/ZK starting at the beginning of radiotherapy or at the beginning of adjuvant therapy 4 weeks after the end of radiotherapy. [Table: see text]

S. Cherix1, M. Speiser2, M. Matter3, L. Guillou4, D. Lienard5, F. Lejeune5, R. Mirimanoff6, S. Leyvraz5, P. Leyvraz1. 1University Hospital, Orthopaedics and Traumatology, Lausanne, Switzerland; 2Universty of Lausanne, Medecine, Lausanne, Switzerland; 3University Hospital, General Surgery, Lausanne, Switzerland; 4University Hospital, Pathology, Lausanne, Switzerland; 5University Hospital, Medical Oncology, Lausanne, Switzerland; 6University Hospital, Radiation Oncology, Lausanne, Switzerland

5516 Background: The concept of expecting radiosensitive tumors in patients genetically hypersensitive to radiation is not widely accepted. Here, we aim to assess whether the tumors of patients with increased lymphocyte apoptotic response with head and neck cancer have a better outcome than their normoresponsive counterparts. Methods: Seventy-five patients with head and neck cancer treated with curative radiation therapy (RT) were included in the KFS 00539–9-1997/SKL 00778–2-1999 prospective study aiming at assessing the value of CD8 T-lymphocyte apoptosis in predicting intrinsic radiosensitivity. Male to female ratio was 60/15, and median age was 59 years (35–85). Median radiation dose was 66 Gy (60–74.4) administered in median 41 days (37–58). Dose per fraction was 2 Gy in the majority of the patients (n = 70). Prior to RT, all patients were tested using a rapid (48 h) apoptosis assay where fresh blood samples were irradiated with 8-Gy X rays. Lymphocytes were collected and prepared for flow cytometric ...

2 Background: Standard therapy of GBM after biopsy or resection is RT. TMZ, a novel methylating agent demonstrated some activity against recurrent glioma. In a phase II trial we observed a potential survival advantage by adding TMZ concomitantly and adjuvant to RT (Stupp et al. JCO 2002). In this randomized trial we tested this novel regimen against RT. Methods: Patients (pts) age 18–70 years with histologically proven newly diagnosed GBM (WHO grade IV) were eligible. Pts were randomized between standard RT (60 Gy in 30 daily fractions of 2 Gy) versus the same RT and concomitant (TMZ 75 mg/m2/d, daily up to 42 days) followed by up to 6 cycles of adjuvant TMZ (150–200 mg/m2, daily x 5d, q28 d). Survival (intent to treat) was the primary endpoint aiming at a 30% improvement (log-rank). Pathology was centrally reviewed. Results: Five hundred and seventy-three pts from 85 centers were randomized. Median follow-up is 2 years, 436 patients have died. Median time between histological diagnosis and treatment star...

B a c k g r o u n d : Ribonucleotide Reductase (RR) inhibitors such as Gemcitabline (dFdC) and Hydroxyurea (HUt are known to act as radiosensitizers both in vitro and in vivo. More recently, (E)-2'-Deoxy(Fluoromethylene) cytidine (FMdC) has been developed as an RR-inhibitor. It is a cytotoxic drug in vitro and in vivo. Purpose : To determine if at low doses of FMdC InM concentrations) a radiation sensitizing effect can be observed in human cancer cell lines of colon (WiDr) and cervix origin (SiHa, C4-1 and C33-A) and to investigate the cell cycle effects of FMdC after irradiation by flow cytometry. Material and methods : Postradiation surviving fraction has been evaluated by clonogenic assay. Postirradiation cell cycle distribution of WiDr has been evaluated by flow cytometry (double labelling with propidium iodine and bromodeoxy-uridine). Data were considered significantly different if a 0.05 p-value was reached (two-sided t-test). Results

The role of external beam radiation therapy (EBRT) in the management of choroidal metastases (CM) was evaluated retrospectively. From 1970 to 1993 58 patients with CM of 80 eyes underwent EBRT with doses ranging from 20 to 53 Gy. The female to male ratio was 2.9, median age 59 years. The results of treatment measured by complete response, visual acuity improvement, retinal reattachment and eye conservation was respectively 63%, 75%, 65% and 100%. Patient characteristics (primary tumor, histology, details of CM) will be presented. Post-irradiation complications and related technical characteristics of the treatment will be highlighted as well as the relationship between overall survival and primary site. From our data, EBRT is a very efficient and safe palliative treatment for CM and helps preserving a good vision, thus the quality of life in patients who have a poor overall prognosis.

Hodgkin's disease is one of the most curable cancers thanks to progress in radiotherapy and multi-drug chemotherapy regimens such as mechloretamine-vincristine-procarbazine-prednisone, best known as MOPP. However, long-term side-effects and treatment-induced second malignancies are of great concern. In our institution, 69 patients with nodular sclerosis Hodgkin's disease were treated over 10 years. Twenty-two per cent were stage I, 49% stage II, 23% stage III and 6% stage IV. Actuarial 10-year survival was 83% and actuarial relapse-free survival 61%. Six patients developed a second malignancy with a 10-year actuarial risk of 18%. All six cases occurred in the group treated with MOPP and extensive radiotherapy. Acute non-lymphoblastic leukemia occurred in three patients, preleukemia in two and non Hodgkin's lymphoma in one. In all of these patients, the results were quite poor. Overall survival was equally affected by Hodgkin's disease and by second malignancies. Since new multiple-drug chemotherapy regimens such as adriamycin-bleomycin-vinblastine-dacarbazine, known as ABVD, are equally effective and seem less likely to induce second hematologic malignancies, we suggest that MOPP should no longer be used as a first choice for the treatment of Hodgkin's disease, especially when in combination with radiation therapy.

The mamigement and prognosis of human chorionic gonadotropin-producing seminoma still are controversial issues. In a review of 210 patients irradiated between 1950 and 1982, 10 had elevated human chorionic gonadotropin values: 3 with stage I, 6 with stage II and 1 with stage IV disease. All human chorionic gonadotropin values became negative: 4 postoperatively and 6 following radiotherapy. All patients are well with a mean followup of 6 years. One patient who suffered liver metastases only was salvaged by chemotherapy. Based on these patients human chorionic gonadotropin production is not an unfavorable prognostic sign in cases of pure seminoma.