Potential Benefit of Radiation Therapy in Resectable Anorectal Melanoma

I. J. Radiation Oncology d Biology d Physics

S274

2207

Volume 75, Number 3, Supplement, 2009

Preoperative, Moderately Hypofractionated Radiotherapy with Image-guided Tomotherapy Concomitant to Chemotherapy in Rectal Adenocarcinoma: Early Results of a Phase II Study

P. Passoni1, M. Ronzoni2, C. Fiorino3, N. Slim1, K. Bencardino2, S. Di Palo4, A. Tamburini4, R. Calandrino3, C. Staudacher4, N. Di Muzio1 1 Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy, 2Medical Oncology, San Raffaele Scientific Institute, Milan, Italy, 3Medical Physics, San Raffaele Scientific Institute, Milan, Italy, 4Surgical Department, San Raffaele Scientific Institute, Milan, Italy

Purpose/Objective(s): To evaluate efficacy and toxicity of preoperative, moderately hypofractionated radiotherapy (RT) with Tomotherapy (TT) in combination with concomitant oxaliplatin (Oxa) and 5-FU continuous infusion (c.i.). Materials/Methods: From 5/2007 to 1/2009, 20 patients (pts), median age 66 years, median ECOG PS 0 (0-1) with rectal adenocarcinoma were enrolled (Stage IIA: 1 pt, IIIA: 1 pt, IIIB: 14 pts, IIIC 4 pts). Three pts had anal sphincter infiltration and 4/ 20 had disease\6 cm from anal verge. Pre-treatment examination included colonoscopy with biopsy, EUS, pelvis MR and CT scanning of thorax and abdomen. After positioning in an immobilization device, a simulation contrast-enhanced CT was performed. CTV encompassed mesorectum, obturator, internal iliac and common iliac lymph nodes. The perineum was included in case of disease # 6 cm from anal margin. A margin of 0.5 cm was added from CTV to PTV. Chemotherapy consisted of Oxa 100 mg/m2 day -14, 0, and + 14, and 5-FU 200 mg/m2/day c.i. from day -14 to the end of RT. RT started on day 0 and was delivered with TT. A daily check of rectal and bladder filling as well as set up errors was performed by megavoltage-CT. The prescribed dose was 41.4 Gy in 18 fractions (2.3 Gy/day). Surgery was performed 6-8 weeks after completion of chemo-radiation (CTRT). Results: Median treatment duration was 25 days in 16/20 pts (range 21-28 days); 2 pts had treatment interruptions due to gastrointestinal toxicity (G2: 1; G3: 1) and completed the treatment in 28 and 35 days. Two pts did not complete the treatment due to toxicity and received 37.5 Gy and 22.5 Gy. Acute toxicity was as follows: diarrhoea G1: 7 (35%); G2: 5 (25%), G3: 1 (5%); cystitis G1-G2: 2 (10%); skin burning G1: 3 (15%); anemia G1: 2 (10%). Two consecutive pts (10%) had G3 diarrhoea probably Clostridium Difficile related. All pts but one underwent surgery. Laparoscopic anterior resection (LAR): 17/19 (89%). Laparoscopic abdominal-perineal resection (LAPR): 2/19 (11%). Of the 3 pts with anal infiltration, 1 pt had complete pathologic response (pCR) and LAR, 1 pt had pCR but LAPR for local complication, 1 pt had LAPR for residual disease. Types of resection were: R0 17/19 (89%), R1 2/19 (10.5%). Nineteen/20 (95%) pts obtained downstaging with 5/19 (26%) pCR. The pt who was not operated on was still disease free 14.4 months after the end of CTRT. Postoperative complications consisted of anastomotic leakage (2 pts) and sepsis (1 pt). Conclusions: This regimen of moderately hypofractionated RT with concurrent CT seems to be effective and has an acceptable rate of acute toxicity. A phase III study comparing this schedule with our conventionally delivered bi-fractionated regimen is warranted. Author Disclosure: P. Passoni, None; M. Ronzoni, None; C. Fiorino, None; N. Slim, None; K. Bencardino, None; S. Di Palo, None; A. Tamburini, None; R. Calandrino, None; C. Staudacher, None; N. Di Muzio, None.

2208

Does Chemotherapy Intensity in Pre-operative Chemoradiation for Rectal Cancer affect Pathologic Response?

J. Lee, E. Chie, H. Kim, G. Kang, D. Oh, S. Im, T. Kim, K. Park, J. Park, S. Ha Seoul National Univ. Hospital, Seoul, Republic Of Korea Purpose/Objective(s): To examine the relationship between chemotherapy intensity and outcome and factors affecting tumor response in patients who underwent preoperative chemoradiotherapy for rectal cancer. Materials/Methods: Medical records of 172 patients who received preoperative chemoradiotherapy followed by radical surgery for clinically staged T3 or 4 rectal cancer from July 2003 to November 2008 were retrospectively reviewed. Radiation dose ranged from 50.4 to 54 Gy. Thirty-four patients were treated with one cycle of bolus 5-FU (group A), 112 with two cycles of bolus 5-FU (group B) and 26 with oral capecitabine (group C). Interval from radiotherapy to surgery was 37 to 92 days (median 58). One hundred fifty eight patients underwent low anterior resection, while 3 patients underwent Hartmann’s operation and another 11 underwent abdominoperineal resection. Results: The complete pathologic response and overall downstaging rate were 18% and 72.1%, respectively. The pathologic response rate of grade 3 to 5 for group A, group B, and group C were 58.8%, 80.4% and 88.5% (group A vs. group B, p = 0.011, group A vs. group C, p = 0.012) The rate of sphincter saving surgery was higher in group B compared to group A in tumors located below 5cm from anal verge (96.2% vs. 76 %, p = 0.003). Pathologic response rate was correlated with overall downstaging. There was no statistically significant difference in overall downstaging and radial resection margin same or more than 2 mm between three groups. There was no grade 3 to 4 gastrointestinal or hematologic toxicity during treatment in all patients. Conclusions: Insufficient chemotherapy regimen showed inferior pathologic outcome and lower sphincter salvage rate in low lying tumor without difference in grade 3 or higher toxicity. Based on this result, patient should undergo sufficient chemotherapy in combination with radiotherapy to improve pathologic outcome and maximize the chance of sphincter preservation. Author Disclosure: J. Lee, None; E. Chie, None; H. Kim, None; G. Kang, None; D. Oh, None; S. Im, None; T. Kim, None; K. Park, None; J. Park, None; S. Ha, None.

2209

Potential Benefit of Radiation Therapy in Resectable Anorectal Melanoma 1

A. S. Reese , C. G. Willett1, D. S. Tyler1, H. F. Seigler2, R. W. Clough1, B. G. Czito1 Duke University Medical Center, Durham, NC, 2Duke University Medical Center/Durham Veterans Administration Medical Center, Durham, NC

1

Purpose/Objective(s): Anorectal melanoma is an uncommon malignancy with poor outcomes. The optimal treatment of patients with localized disease remains ill-defined, although surgical removal of disease is usually recommended. Rates of locoregional

Proceedings of the 51st Annual ASTRO Meeting recurrence following resection and the role of adjuvant radiation therapy are not well-established. This study examines the outcomes of patients undergoing resection of anorectal melanoma with or without radiation therapy. Materials/Methods: Fifty-nine patients (21 M: 38 F) with primary anorectal melanoma were treated at Duke University between 1975 and 2007. Median age was 60 (R 39-82). Of these, 42% underwent abdominoperineal resection (APR), 51% underwent local excision (LE) and 4 (7%) had no resection or incomplete surgical records. Twenty (34%) received either neoadjuvant or adjuvant radiation therapy to a median dose of 54 Gy (R 36-55.8 Gy). Results: At a median follow-up of 2.1 years, five-year overall survival (OS), local control (LC), disease-free survival (DFS) and metastasis-free survival (MFS) rates were 22%, 61%, 21% and 27%, respectively. Patients receiving radiation therapy had improved survival (OS 46% vs. 12%, p = 0.04) as well as local control rates (LC 77% vs. 47%, p = 0.09). Nodal involvement portended worse prognosis (OS 14% vs. 23%, p = 0.02, LC 40% vs. 90%, p = 0.03). Additionally, female patients showed a trend toward improved OS (26% vs. 14%, p = 0.17), DFS (26% vs. 9%, p = 0.09), and MFS (33% vs 18%, p = 0.13). Age, surgery type (LE vs. APR), margin status, lymphovascular invasion, perineural invasion, timing of radiation therapy (neoadjuvant vs. adjuvant) and the use of concurrent or sequential chemotherapy had no impact on disease-related outcomes. Conclusions: Anorectal melanoma is a lethal malignancy although long-term survival is achievable. Pelvic disease relapse is common following resection alone. Nodal involvement and male sex portend a worse prognosis. In this retrospective analysis, the use of (neo)adjuvant radiation therapy appears to improve local control and possibly survival outcomes. Distant disease relapse is the predominant mode of failure, indicating the need for improved systemic therapies. Author Disclosure: A.S. Reese, None; C.G. Willett, None; D.S. Tyler, None; H.F. Seigler, None; R.W. Clough, None; B.G. Czito, None.

2210

Role of Contact X-ray 50 Kv Therapy (CXRT) in the Treatment of Rectal Cancer for Patients of 80 Years or More

K. Benezery, J. Gerard, C. Ortholan, A. Ginot, E. Francois, S. Marcie, J. Hannoun-Levi Centre Antoine Lacassagne, Nice, France Purpose/Objective(s): Incidence of rectal cancer in elderly patients is increasing. Surgical trauma in this age group when comorbidity is present should be avoided as much as possible (Rutten HJ. Lancet Oncol. 2008 May;9(5):494-501). In order to achieve local control in rectal adenocarcinoma, a very high dose of radiation accurately targeted to the gross tumor is needed. CXRT is an appropriate technique to achieve this goal when radical surgery is contraindicated. Materials/Methods: In Centre Antoine Lacassagne, between 2002 and 2008, a total of 17 patients with rectal adenocarcinoma T23 (\5 cm diameter) N0-1 M0 aged 80 years or more were treated with curative intent with CXRT. CXRT delivered a dose between 90 and 120 Gy in 4 or 5 fractions over 4 to 6 weeks. External beam radiation therapy (EBRT) was always associated (45 to 50 Gy in 25 F/5 weeks). Concurrent chemotherapy (Capecitabine: 800 mg/m2/day during radiation days) was associated in 8 patients. Tolerance was good in all patients. Results: Local control (follow up 1 to 6 years) was achieved in 14/17 patients. There was no severe short or long term toxicity. Bowel function was considered as good or excellent in all the patients. Only 2 patients died from metastatic cancer. There was only one death within the first 6 months (Ge´rard JP. Int J Radiat Oncol, Biol, Phys 2008;72:665-70). Conclusions: In elderly patients with comorbidity CXRT provides an excellent rate of local control for T2 and early T3 rectal cancer in association with EBRT and concurrent chemotherapy when possible. This approach is most of the time very well tolerated in these fragile patients. The manufacturing of the new PapillonÔ 50 system should create a strong development of this technique. Author Disclosure: K. Benezery, None; J. Gerard, Medical Advisor, F. Consultant/Advisory Board; C. Ortholan, None; A. Ginot, None; E. Francois, None; S. Marcie, None; J. Hannoun-Levi, None.

2211

CYFRA21-1 and CEA - Useful Markers for Predicting Sensitivity to Chemoradiotherapy of Esophageal Carcinoma

Y. Yi, B. Li, Z. Wang, H. Sun, H. Gong, Z. Zhang Shangdong Tumor Hospital, Jinan, China Purpose/Objective(s): Esophageal cancer is a common malignant neoplasm throughout the world. Chemoradiotherapy(CRT) is currently performed for patients with advanced esophageal carcinoma. Sensitivity of tumors to CRT differs from one case to another and may be influenced by the expression of biological molecules. The aim of this study was to identify molecular markers which could predict the sensitivity of esophageal carcinoma to CRT. Materials/Methods: 91 patients with T1-4, N-any, and M-any esophageal carcinoma patients treated with CRT were evaluated. The regimen comprised protracted 5-fluorouracil infusion and a two-hour infusion of cisplatinum combined with radiation therapy at total radiation dose of 59.6Gy . The expressions of serum tumor markers cytokeratin 19 fragment antigen 21-1 (Cyfra21-1), carcino-embryonic antigen (CEA) and neuronspecific enolase (NSE) were measured in venous blood obtained before treatment from all 91 patients. The cutoff value of Cyfra21-1, CEA and NSE is defined as 3.4ng/ml, 3.3ng/ml, and17ng/ml, respectively. Levels above the cutoff value were defined as positive, and below the value as negative. The responsiveness to CRT was evaluated by WHO criteria in solid tumors. Chi-squared test and logistic regression analysis were used to evaluate the association between the response of primary lesions and clinical variables. Significance was defined as p \ 0.05. Results: The difference of the complete response (CR) rate between CYFRA21-1 or CEA positive and negative groups was significant (p = 0.001, 0.002, respectively). However, NSE did not show a significant correlation with the responsiveness of the

S275