The aim of this review is to present the specificities of clinical research in radiation oncology. Objectives are similar to all research in oncology: to improve the efficacy and to decrease toxic effects. Phase III trials remain the main methodology to demonstrate an improvement in efficiency, but phase I-II and registers are also important tools to validate an improvement in the therapeutic index with new technologies. In this article we discuss the special features of end-points, selection of population, and design for radiation oncology clinical trials. Quality control of delivered treatments is an important component of these protocols. Financial issues are also discussed, in the particular context of France.

Results of acute and 1-year toxicities of a Phase 3 randomized trial evaluating the impact of dose escalation (10 Gy) in combination with 3-year androgen deprivation treatment on 5-year biochemical or clinical control in high-risk prostate cancer patients. Inclusion criteria: cT3 or T4 or a PSA of ≥20 ng/mL or a Gleason score of ≥ 8–10; N0 on CT scan or MRI or pelvic lymph node dissection (PLND). Eligible patients were randomized between 70 Gy or 80 Gy prostate radiation therapy (RT; 3-dimensional conformal RT [3D-CRT] or intensity modulated RT [IMRT]). Pelvic nodal irradiation (46 Gy) was performed for all patients except in the case of negative PLND. LH-RH agonists were given for 3 years in both arms and could be started within 6 months before RT. Randomization (1:1) was stratified on PLND (yes or no) and institution. Primary endpoint is biochemical or clinical control (bPFS; cPFS); secondary endpoints are overall survival, disease-specific survival, acute and late toxicity (CTCAE V3.0), and quality of life (QLQ-C30 and PR25). To improve bPFS or cPFS from 65% to 75% (HR = 0.67), 500 patients were required (a = 5% and 1-b = 80%), with 197 events at 5 years. A total of 505 patients were included between June 2009 and January 2013, 250 in the 80-Gy arm and 255 in the 70-Gy arm. Main characteristics were well balanced: Mean age: 70.6 years (range, 52–80); Gleason score ≥ 8: 77 (15.3%); median PSA value at diagnosis: 13.8 ng/mL (0.35–109.93); cT3-4: 56.5%; PLND: 16.4%. A transurethral prostate resection (TURP) was performed before RT in 7.5% of the patients. In terms of treatment, 68.4% of patients were treated with IMRT (with 57.3% in the 80-Gy arm, P < .001), and 59.6% were treated by image guided RT (with 55.1% in the 80-Gy arm, P = .004). Acute (during and 1-month post-RT) and 1-year (6 months and 1 year) toxicities were described for Grade ≥3 (G≥3). Acute toxicity was 15.8% and 20.6% in the 80-Gy and 70-Gy arms, respectively (NS). One-year toxicities were 18.1% and 20.5% in the 80-Gy and 70-Gy arms, respectively (NS). No difference in acute or 1-year toxicity was observed between 3D-CRT and IMRT. One-year toxicity was 26.4% and 18.1% (P = .106) for patients with or without pelvic irradiation, respectively; TURP does not increase the incidence of 1-year toxicities (29.4%).Oral Scientific Abstracts 98; Table 1.G≥3 ToxicitiesAcute1-yr80 Gy70 Gy80 Gy70 GyBladder/ urethra4.0%7.4%0.9%2.8%Rectum/anus0.4%0.4%0.9%0.9%Sexual6.8%6.2%10.0%9.3%Endocrine0.4%0.4%01.4%Dermatological disorders0.4%0.4%00Cardiac disorders5.2%8.1%5.0%5.6%Osteo-articular muscle diseases1.2%1.6%0.5%1.4% Open table in a new tab No significant difference was observed between acute and 1-year toxicities between the 2 arms. The experimental arm seems well tolerated in the first year, probably due to the RT technique used (IMRT was more frequently used in the 80-Gy arm). The 2-year late toxicity results are planned for 2016, and the primary endpoint analysis is planned for 2017

e20521 Background: Abdominal tumors involving retroperitoneal vessels are rare but often constitute a terminal condition because of the presumed inextirpability of the tumor. In order to address these technical difficulties, a surgical task group was formed by experienced oncological and vascular surgeons. Methods: 69 patients with abdominal or retroperitoneal tumors involving vessels presumed on preoperative imaging data, have been retrospectively reviewed from June 2000 to December 2009. A systematic assessment of the resecability had been done for every case preoperatively with both the oncologic and the vascular surgeon to plan an operative strategy. Median age was 50,5 years old. Major histologic subtypes were retroperitoneal sarcoma (n = 26; 38%), lymph node metastasis of testicular germ cell tumor, (n = 17; 25%), endocrine tumors (n = 10; 14%), renal cell carcinoma (n = 5; 7%), adrenal tumors (n = 3; 4%). Results: 60 patients underwent a resection of their tumor. In 9 cases, the tumor was considered inextirpable at laparotomy. Complete resection was performed to guarantee clear margins: R0 in 45 patients (75%), R1 in 12 (20%). A gross residual tumor was left behind in 3 cases R2 (5%). The main vessels involved were the inferior vena cava (n = 35; 50%), iliac axis (n = 11; 16%), abdominal aorta (n = 12; 17%) and superior mesenteric artery (n = 4; 6%). The conservation of these vessels was possible in 21 (30%) cases. In 31 (45%) other cases a graft replacement was required. There was no operative mortality and one patient died postoperatively because of pulmonary embolism. The global morbidity rate was 27%. The overall survival rate at 24 months was 76.5%, 95%CI (58.51-87.43). Conclusions: This particular approach of four hands surgery should constitute a new paradigm in the field of surgical resection of tumors with retroperitoneal vascular involvement. The synergies provided by a joint oncological and vascular approach have a positive impact on local control of the disease, improving the resecability rate and the operative safety in association with a low morbidity rate. No significant financial relationships to disclose.

Abstract Introduction: The status of the surgical margin is an important factor associated with local recurrence after lumpectomy in breast cancer patients. Standard surgical practice is to obtain clear margins even if this requires a second surgical procedure. The aim of the present study was to identify factors predicting a positive histological re-excision specimen and to propose a score to evaluate the risk of residual disease (RRD).Material and Methods: A retrospective search of our Database from 2000 to 2005 was conducted to identify patients with the following inclusion criteria: invasive carcinoma, pT1-2 with positive margins or cavity margin shavings, pN0 to pN2, second surgery for re-excision. The exclusion criteria were multi-centric or multifocal carcinomas; pT3-4; extensive intraductal carcinoma with micro-invasive tumor, pre-operative treatments. A negative margin was defined by the absence of tumor cells at the inked margin. Positive margins were defined as tumor cells directly at the cut edge of the specimen, and close margins as tumor cells ≤ 2 mm from the cut edge. For cavity margin shavings, positivity was defined by the presence of tumor cells anywhere in the cavity shaving. A multivariate logistic regression model was used on the basis of the prior univariate analysis results to assess the independent relative risk on the presence of residual tumor and to establish a score to predict the RRD.Results: 1611 patients benefited from breast conservative surgery, and 186 met our selection criteria. Median age was 56 years, and post-menopausal status was 67%. Tumor size was pT1 in 75% (pT1a 11%, pT1b 27%, pT1c 37%) and pT2 in 24%. Node status was pN0 in 70% patients. Histotype at first surgery was invasive ductal in 77%, invasive lobular in 19% and both in 4%. An extensive intraductal component was associated in 25%. Cavity margin shavings were performed for 96% of the patients, and all had at least one positive shaving. Lumpectomy margins were positive in 51%, close in 25% and negative in 24%. Margin status was unknown in 11%. Residual disease was found in 66% of the re-excision. The second surgery consisted in conservative surgery for 56% of patients. The median time interval between primary surgery and re-excision was 32 days (range: 6-86). Histotype at re-excision could be mixed and was intraductal in 72%, invasive ductal in 27%, invasive lobular in 15%. In univariate analysis, the following factors were associated with a higher rate of residual disease: age < 55 (p =0.004), pre-menopaused status (p=0.006), presence of an extensive intraductal component (p=0.03), positive and close margins (p=0.005), number of positive cavity margin shavings (p=0.005). Multivariate analysis identified 3 independent prognostic factors for residual disease: age, margin status and number of positive cavity margin shavings. The score established a RRD of 37%, 60%, 69% and 100% if none, 1, 2 or 3 factors were present, respectively.Conclusion: In this highly selected population, the RRD is high, even when the score =0. Further study will compare the score groups with local relapse and survival. Meanwhile, re-excision should be considered for all patients with positive margins or cavity margin shavings involved. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3116.