Karen Benezery

Depending on its location or stage, rectal cancer may differ significantly. Before any treatment decision a careful work up is mandatory relying mainly on endoscopy and imaging (MRI). Surgery according to the TME principle is the cornerstone of treatment. Most of the time surgery is associated with external beam radiotherapy often combined with concurrent chemotherapy (capecitabine) according to the neoadjuvant regimen CAP 50 (5 weeks long). It is sometimes possible to escalate safely the dose of irradiation using contact X-ray brachytherapy 50 Kv or Iridium 192 interstitial brachytherapy. Adjuvant chemotherapy may be given in case of pejorative pathological findings but its benefit is not yet proven in contrast with colon cancer. Local recurrences are becoming unusual as is permanent APE surgery with permanent stoma. To reduce the risk of distant metastasis clinical trials are testing first line chemotherapy in T3-4 lesions. For early stage (T2-"small" T3) clinical trials try to achieve organ preservation. Intensification of CAP 50 either with more chemotherapy or radiation dose escalation using contact X-ray aim at achieving a clinical complete response followed by local excision or close surveillance.

676 Background: Organ preservation (avoiding TME surgery) for T2 T3 a-b rectal cancer is a field of active clinical research. Contact X Ray CXB combined with external beam radiotherapy (EBRT) ± concurrent chemotherapy (CRT) is an attractive method to achieve clinical complete response (cCR) and consequently rectal preservation. We report an overview of 120 patients treated with CXB+EBRT over a 25 year period in Lyon since 1986 and then in Nice until 2012. Methods: Between 1986 and 2012, 120 patients presenting rectal adenocarcinoma T2 T3a-b (distal rectum: 87; middle rectum: 33) were treated with CXB +EBRT with conservative intent. In Lyon (1986-2001), 80 patients median age: 73y; T2:52; T3:28) risk were treated using CXB (80-110 Gy/3-4 fr/4-6 weeks) followed by EBRT (39 Gy/13 fr/18 days) and 192 Iridium implant boost (20 Gy). When cCR was achieved, close surveillance was proposed. In Nice (2002-2012), 40 patients (median age 81y; T2:22; T3:18) received CXB same regimen as in Lyon (using new Papillon 50 machine since 2009) + EBRT (45-50 Gy/5weeks) with concurrent chemotherapy (5-FU or Capecitabine). When cCR was achieved close surveillance was proposed or local excision (13 pts). Results: Median follow-up time 58 months in both groups. Local relapse occurred mainly in the 2 first years. Isolated lymph node recurrence

To assess clinical outcomes of patients treated with a high-dose rate brachytherapy boost for anal canal cancer (ACC). From August 2005 to February 2013, 28 patients presenting an ACC treated by split-course external beam radiotherapy (EBRT) and HDR brachytherapy with or without chemotherapy in a French regional cancer center in Nice were retrospectively analyzed. Median age was 60.6 years [34 - 83], 25 patients presented a squamous cell carcinoma and 3 an adenocarcinoma; 21 received chemotherapy. Median dose of EBRT was 45 Gy [43.2 - 52]. Median dose of HDR brachytherapy was 12 Gy [10 - 15] with a median duration of 2 days. Median overall treatment time was 63 days and median delay between EBRT and brachytherapy was 20 days. Two-year local relapse free, metastatic free, disease free and overall survivals were 83%, 81.9%, 71.8% and 87.7% respectively. Acute toxicities were frequent but not severe with mostly grade 1 toxicities: 37% of genito-urinary, 40.7% of gastro-intestinal and 3.7% of cutaneous toxicities. Late toxicities were mainly G1 (43.1%) and G2 (22%). Two-year colostomy-free survival was 75.1%, one patient had a definitive sphincter amputation. High-dose rate brachytherapy for anal canal carcinoma as boost represents a feasible technique compared to low or pulsed-dose rate brachytherapy. This technique remains an excellent approach to precisely boost the tumor in reducing the overall treatment time.

The treatment of anal cancer is based on concomitant radiotherapy and chemotherapy and is associated with a nonnegligible rate of local severe toxicities that can strongly impair the quality of life. A retrospective analysis was performed to screen the following factors as potential predictive factors for local skin and digestive toxicities, and as potential prognostic factors for cumulative colostomy incidence: sex, age, tumor size, clinical T and N stage, circumferential extension, invasion of anal margin, HIV status, type of chemotherapy, and type of radiotherapy and dose delivered. One hundred five patients in our database treated between January 2000 and February 2010 met the eligibility criteria. Median follow-up was 54.1 months (range, 1-133). Early and late severe local toxicities occurred in 33 patients (31.4%) and 18 patients (17.1%). The 5-year cumulative rate of colostomy was 26.6%. Predictive factors for local severe early toxicities were as follows: clinical stage III/IV (p = 0.01), no brachytherapy boost (p = 0.003), and use of chemotherapy (p = 0.01). Only brachytherapy retained its independence in multivariate analysis (OR = 4.8 (1.4-16.3), p = 0.01). Human immunodeficiency virus positivity (p = 0.04) was the only predictive factor for late toxicities in univariate analysis; it was linked independently to the occurrence of ulcer (OR = 0.1 (0.01-0.66), p = 0.01). Tumor size ≥4 cm (p < 0.001) and occurrence of grade 2 to 3 ulcers (p < 0.001) were correlated with greater cumulative colostomy incidence. In this cohort, nonuse of brachytherapy was an independent predictive factor for local acute toxicity. Human immunodeficiency virus positivity was the only predictive factor for local late toxicities and strongly influenced the onset of ulcer.

667 Background: Treatment of anal cancer is based on combined radiotherapy and chemotherapy (CT). Some patients present early (2 months) toxicities of grade 3 or greater which can strongly impair quality of life. We aimed to identify predictive factors of toxicities in 106 patients treated in a single center between January 2000 and February 2010. Methods: Retrospective analysis of our databases reported severe local toxicities (grade 3 or higher) during treatment of proven localized epidermoid carcinoma of the anal cancer. The following factors were screened as potential predictive factors: gender, age, irradiation dose, HIV status, type of boost (external vs brachytherapy), circumferential extension, type of chemotherapy, invasion of anal margin, clinical T and N stage, and clinical stage. Results: With a median follow-up of 54.1 months (46.8-61.4) early severe local toxicities occurred in 42 patients (pts) (39.6%) whereas late severe toxicities happened in 21 pts (19.8%). Both early and late toxicities were dominated by proctitis (diarrhea and/or rectal bleeding) (7 pts, 6.6% and 6 pts, 5.6% respectively) and recto-anal epithelial toxicities (27 pts, 25.4% and 17 pts, 16% respectively). Two patients got colostomia because of treatment toxicities (1,8%). Predictive factors of increased early toxicities were as follows: clinical stage III/IV (p=0.04), no brachytherapy boost (p=0.008) and type of CT (no CT, 5.9%, CT, 48.8% p=0.001). Brachytherapy boost and presence of CT retained their independency in multivariate analysis (respectively, p=0.001 and p=0.05). Only HIV positivity (p=0.02) was identified as a predictive factor of late toxicities. HIV positivity (p=0.02), invasion of anal margin (p=0.01) and circumferential extension > 33% (p=0.007) correlated with epithelial ulcer. Invasion of anal margin (p Conclusions: In this cohort absence of brachytherapy boost and CT correlated with more severe early local toxicities whereas HIV positivity was the only predictor of local late toxicities.