270 Radiation Oncology, Biology, Physics Voiume 32, Supplement 1

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RECTAL CANCER AND [NFLAMMAIt )RY BOWEl. DISEASE: NAFURAI. HISTORY AND IMPLICATIONS FOR RADIATION THERAPY

AUTHORS: Green. Sheryl. MBBCh: . Stock. Richard G.. M.D. and Greenstein. Adrian. MBBCh :

AFFILIATIONS: Departments of Radiatiun Oncoklgy and -'Surge W, The Mount Sinai Medical Center. One Gustave L L e v y Place. New Y{)rk. NY 10029

PURPOSES/OBJECTIVE: There exists little information concerning the natural history of rectal cancer in patients with inflammatory bowel disease In addition, the tolerance of pelvic irradiation in these patients is unknown. We analyzed the largest series of patients with inflammatory bowel disease and rectal cancer m order to determine the natural history' of the disease as well as the effect and tolerance of pelvic irradiation. M A T E R I A L AND METHODS: A retrospective analysis o f 47 patients with inflammatory, bowel disease and rectal cancer treated over a 34 year period (1960-19941 was performed. Thirty five patients had Ulcerative Colitis and 12 patients had Crohn's Disease. There were 31 male patients and 16 female patients. The stage (AJC) distribution was as follows: stage 0 in 5 patients, stage I in 13 patients, stage II in 7 patients , stage II1 in 13 patients and stage IV in 9 patients Surgical resection was performed in 44 patients. In 2 of these patients, preoperative pelvic irradiation was given followed by surgery. Twenty of these patients underwent post-operative adjuvant therapy ( 12 were treated with chemotherapy and pelvic irradiation and 8 with chemotherapy alone). Three patients were found to have unresectable disease and were treated with chemotherapy alone (2 patients) or chemotherapy and radiation therapy( I patient}. Radiation complications were graded using the RTOG acute and late effects scoring criteria. Follow up ranged from 4 to 250 months (median 24 months) RESULTS: The 5 year actuarial results revealed an overatl survival (OS) of 42%, a disease free survival (DFS) of 43%, a pelvic control rate (PC) of 67% and a freedom from distant failure (FFDF) of 47%. DFS decreased with increasing T stage with a 5 year rate of 86% for patients with Tis - T2 disease compared to 10~ for patients with T3-T,.I disease (p < 0 0 0 0 1 ) The presence of lymph node metastases also resulted in a decrease in DFS with a 5 year rate of 67 % for patients with NO disease compared to 0% for patients with N1 - N3 disease (P < 0.0001). An analysis of high risk patients (30) with T3 1"4 or N 1 N3 disease revealed at 5 years an OS of 9%, a DFS of 10%, a PC rate of 26 % and FFDF of 20%. In this subset of patients, there was a trend toward improved pelvic control in patients receiving radiation therapy (14) with a 5 year PC of 60% compared to a rate of 23% for those patients not irradiated (16) (p=0.59) . Acute complications (grade 3 or > ) were noted in 3 patients (20':;[) recmving radiation therapy and these included two cases of grade 3 skin reactions and one case of grade 4 gastro-intestinal toxicity. Two patients (13%) developed sinai[ bowel ohstcuctmn at 2 and 4 months, respectively, post-irradiation which were managed conservatively. There were no long term complications in patients irradiated CONCLUSION: Treatment results arc cnmparable to those historically reported t~w non inflammatory bowel disease related rectal cancer although the subset of high risk patients appeared to have a poorer ou tcome In light of this finding and the ability of patients with inflammatory bowel disease to tolerate pelvic irradiation, high risk patients should be treated aggressively with chemotherapy and radiation therapy.

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P R E - O P E R A T I V E R A D I O - C H E M O - T H E R M O T H E R A P Y F O R ADVANCED (T3-4) AND/OR R E C U R R E N T R E C T A L C A R C I N O - MAS

P. Wust 1. M. Gremmler I. B Rau 2. J L~llel;. J Gellermann I, H. Stahl I . T. Vogl I. H. Riess 3, P Schlag 2, R, Felix 1

Humboldt University of Berlin. V ircho~ Clinic. Departntents of Radiology I , Surgery '2 and Medical Oncology 3, 13344 Berlin, Germany

Objective: Recent studies suggest that pre operative radio chemotherapy in locally advanced rectal cancer can increase resectability and local control (T4 stages), and nught facilitate sphincter preserving surgery (T3 stages~. However, response rates are still unsatisfactory for radiotherapy alone, and are only slightly better for radio-chemotherapy. Radiofrequency hyperthermia has now achieved a technical stage already suitable for treating this tumor entity effectively in clinical practice Therefore, a trimodal pre-operative approach for T3-4 rectal carcinomas has been inve- stigated in a phase l/lI study.

Materials & Methods: A phase H I study was conducted on 30 pts with advanced and/or recurrent rectal cancer. 7130 pts had reeurrencies, 9/30 uT3, 14/30 T4-stage of the primary,. Initial tumor stage was assessed by endosonography, CT and occasionally MRI (Tl-w _+ Echovist, T2-w, proton density). Radiotherapy was delivered in prone position using a belly-board, three-field technique, standard blocks, 5xl .8 --+ 45 Gy in 5 weeks. In parallel, 5-FU (300-350 mg/kg, dose escalation) and folinic acid (50 rag) on days 1-5 and days 22-28. Regional hyperthermia was ad- ministered using the annular phased array applicator SIGMA-60 once a week. Index temperatures T x were deduced from thermal mapping scans in endocavitary/intratumoral catheters. Re-staging was done by endosonography and CT. Four weeks after radiotherapy, surgery was performed with preference to continence preserving operations. If the tumor remained unresectable, a boost to a total tumor dose of 60 Gy was claimed. Results: 7/30 pts (23%) did not undergo resection because their tumors remained technically non-resectable: 4 pts with persistent local control of 12-18 rots, 2 pts with progressive disease, I pt with too short observation time. 23/30 pts underwent surgery: only I R2-resection, 22 R0-resec- tions. The patho-histological analysis documented 4 CR (17%) at the primary tumor. 12 PR (downstaging compared with pre-therapeutic endoso- nography), 7 NC. Overall response rate was 70%. In 16/23 (70%) of surgical interventions, a continence preserving surgery was possible (full thickness resection, anterior resection, colon pouch). No severe postoperative side effects occured, only somewhat delayed healing after APR. 10/30 (33%) pts suffered from a RT-CHT induced acute toxicity of grade llI (skin or intestine), which in only 1 case caused treatment to be aban- doned. RHT-related toxicity was tolerable and mainly included myalgia or musculo-sceletal pain (acute or subacute in about 30%): 4 -10 ses-

sions in 26/30 pts, only 4 pts refused further RHT after 1-3 sessions. In 140 heat treatments mean Tma x at tumor contact was 41.5 °C, mean Tmin 39.6 °C. As yet, no significant correlation between thermal parameters and response or local control has been demonstrated. Conclusions: Pre-operative radio-chemo-thermotherapy (45 Gy, 5-FU - low dose folinic acid, RHT) is very practical and tolerable, causing an encouraging downstaging rate of 70% and local control. Toxicity is moderate and no complications were found during the pre-operative course or peri-operatively. The preliminary results suggest that RHT can improve local control for this particular indication. Now, a phase III-study has been started to compare bimodal radio-chemotherapy with trimodal radio-chemo-thermotherapy.