- Email: [email protected]
Preoperative chemoradiation by infusional 5FU and bolus platinum for extraperitoneal rectal cancer: Acute toxicity, tumor response, sphincter reservation
I. J. R a d i a t i o n O n c o l o g y • B i o l o g y • Physics
278
V o l u m e 42, N u m b e r 1 S u p p l e m e n t , 1998
2101 FIVE FRACTIONS OF PREOPERATIVE RADIOTHERAPY FOR SELECTED CASES OF RECTAL CARCINOMA: LONG TERM TUMOR CONTROL AND TOLERANCE R. Myerson*, D. Genovesi**, M. Locketl*, E. Birnbaum*, J. Fleshman*, R. Fry*, 1. Kodner*, J. Pious*, T. Read*, B. Walz*
*Washington University School of Medicine, St. Louis Mo. and **Catholic University of S.Heart, A.Gemelli Hospital, Rome, Italy
Background/Objective: Randomized Swedish studies demonstrate the efficacy of a five fraction course of preoperative radiotherapy for rectal carcinoma. The present study evaluates the results in a single U.S. institution over a 20 year period with a similar regimen. Methods and Materials: During the period 1975-1995 eighty four patients received pelvic radiotherapy 20 Gy/5 fx followed by immediate surgery for rectal cancer. These patients represented 16% of cases receiving preoperative treatment, the remainder received 45-50 Gy preoperatively. The five fraction course was used for lesions deemed resectable but too bulky for conservative endocavitary treatment. Since 1990 it has been our policy to administer postoperative chemotherapy to medically fit patients with stage I1 or 11I. Patient characteristics including age (mean 65 years, range 23-90), gender (45% male) and location within the rectum (30% within 5 cm of the anal verge) were comparable to our overall cohort. However the group selected for 5 fractions preoperatively had relatively fewer lesions that were tethered (23% vs. 65%), circumferential (11% vs. 24%), or near obstructing (0 vs. 13%) than the overall cohort. Results: With a post treatment follow up of 1-15 years (mean 4.7 years) there have been two local failures and l 1 distant failures, with an actuarial local control 0f97% and disease free survival of 77% at 5 and 10 years. Grade > 3 perioperative or late toxicity occurred in 11 cases (13%) including 3 (3.5%) late bowel obstructions. Stage II or II1 disease was found in 58% of the cases, 77% of which were free of disease at last follow up. Sphincter preserving surgery was possible in 62% of the patients. In recent years, postoperative chemotherapy has been administered to 17 patients with stage II or III disease; this has been well tolerated with only one late toxicity (cystitis managed medically). Conclusion: Patients with resectable rectal cancer who received 20 Gy/5 fx preoperative radiotherapy to the pelvis had excellent local and distant control of disease. These patients were able to tolerate sphincter preserving surgery and postoperative chemotherapy well. It would be of interest to conduct a randomized trial comparing short course with longer course (45 or 50 Gy) preoperative radiotherapy for resectable T3 lesions. The results of this study suggest, however, that differences in toxicity, local control, and disease free survival would probably be < 10%.
2102 P R E O P E R A T I V E C H E M O R A D I A T I O N BY I N F U S I O N A L 5FU A N D B O L U S P L A T I N U M F O R E x T R A P E R I T O N E A L R E C T A L C A N C E R : A C U T E TOXICITY, T U M O R R E S P O N S E , S P H I N C T E R P R E S E R V A T I O N M.E.Rosetto*, V.Valentini*, C.Coco#, N.Cellini*, A.Picciocchi#, B.Barbaro ~,
C.Fares*, G , N u z z o # ,
F.Ambesi-Impiombato§,
M.Cosimelli§ * Divisione di R a d i o t e r a p i a - Universit~ Cattolica S.Cuore - Rome - Italy Istituto di Radiologia- Universit~ Cattolica S.Cuore - Rome - Italy # Istituto di Patologia C h i r u r g i c a - Universita Cattolica S.Cuore - R o m e - Italy § Istituto N a z i o n a l e Regina Elena - R o m e - Italy .Purpose: To e v a l u a t e w h e t h e r p r e o p e r a t i v e external r a d i a t i o n t h e r a p y intensified b y systemic c h e m o t h e r a p y c o u l d i m p r o v e t u m o r response, sphincter p r e s e r v a t i o n a n d t u m o r control. M a t e r i a l s & M e t h o d s : Between J a n u a r y 1996 a n d December 1997, 32 consecutive patients w i t h resectable extraperitoneal a d e n o c a r c i n o m a of the rectum w e r e treated w i t h p r e o p e r a t i v e c h e m o r a d i a t i o n : bolus iv C i s p a l t i n u m (CDDP), 60 m g / m 2 d a y 1,28 p l u s 24h c o n t i n u o u s infusion iv 5 Fluorouracil (5FU) 1,000 m g / m 2, d a y s 1-4, 28-31 a n d c o n c u r r e n t external b e a m r a d i o t h e r a p y (50.4 Gy). All b u t 3 patients h a d T3 disease. S u r g e r y w a s p e r f o r m e d 4-6 w e e k s after the e n d of c h e m o r a d i a t i o n . N o a d j u v a n t chemotherapy was administered. Results: Total hematological g r a d e 3 acute toxicity d u r i n g c h e m o r a d i a t i o n w a s o b s e r v e d in 2 (7%) patients. N o p a t i e n t h a d m a j o r intestinal, skin or urological acute toxicity. All patients h a d radical s u r g e r y . T h e r e w a s no postoperative mortality, overall perioperative m o r b i d i t y rate w a s 16 %. Overall, 25% (8 of 32) of patients h a d a c o m p l e t e pathological response w h i l e three patients h a d r a r e isolated r e s i d u a l c a n c e r cells (Tmic). C o m p a r i n g the s t a g e at the d i a g n o s t i c w o r k - u p w i t h the p a t h o l o g i c a l stage, t u m o r d o w n s t a g i n g w a s o b s e r v e d in 19 (60%) patients. W e h a d 8 (25%) pT0, 3 (9%) pTmic, 2 (7%) pT1, 7 (22%) pT2 a n d 11 (34%) pT3. N o d a l status d o w n s t a g i n g w a s detected in 19 (60%) patients. No e v i d e n c e of n o d a l i n v o l v e m e n t w a s o b s e r v e d in 19 (60%) patients. The incidence of t u m o r r e s p o n s e w a s significantly affected b y the l e n g t h of the t u m o r (p=0.04). Both the n u m b e r of q u a r t e r s of rectal circumference i n v o l v e d a n d the distance b e t w e e n the l o w e r pole of the t u m o r a n d the anorectal r i n g h a d no influence. T w e n t y - s e v e n (84%) patients h a d a s p h i n c t e r saving surgical p r o c e d u r e . In 4 of 9 (45%) patients c a n d i d a t e for a n A P R the sphincter w a s p r e s e r v e d as w a s in all 8 p r o b a b l e candidates. L e n g t h e n i n g of the distance b e t w e e n the anorectal r i n g a n d the l o w e r pole of the t u m o r > 20 m m w a s o b s e r v e d in 5 (16%) patients. N o patients h a d m o d e r a t e soilage after the s p h i n c t e r saving p r o c e d u r e w i t h a m e d i a n f o l l o w - u p of 12 months. Conclusion: P r e o p e r a t i v e c o m b i n e d m o d a l i t y t h e r a p y seems to afford some potential a d v a n t a g e s in n o n r a n d o m i z e d trials: patients are able to tolerate h i g h e r c h e m o t h e r a p y doses a n d they experience a l o w e r acute toxicity; tumoi" d o w n s t a g i n g a n d resectability rates are high; s p h i n c t e r p r e s e r v a t i o n is feasible.
278
V o l u m e 42, N u m b e r 1 S u p p l e m e n t , 1998
2101 FIVE FRACTIONS OF PREOPERATIVE RADIOTHERAPY FOR SELECTED CASES OF RECTAL CARCINOMA: LONG TERM TUMOR CONTROL AND TOLERANCE R. Myerson*, D. Genovesi**, M. Locketl*, E. Birnbaum*, J. Fleshman*, R. Fry*, 1. Kodner*, J. Pious*, T. Read*, B. Walz*
*Washington University School of Medicine, St. Louis Mo. and **Catholic University of S.Heart, A.Gemelli Hospital, Rome, Italy
Background/Objective: Randomized Swedish studies demonstrate the efficacy of a five fraction course of preoperative radiotherapy for rectal carcinoma. The present study evaluates the results in a single U.S. institution over a 20 year period with a similar regimen. Methods and Materials: During the period 1975-1995 eighty four patients received pelvic radiotherapy 20 Gy/5 fx followed by immediate surgery for rectal cancer. These patients represented 16% of cases receiving preoperative treatment, the remainder received 45-50 Gy preoperatively. The five fraction course was used for lesions deemed resectable but too bulky for conservative endocavitary treatment. Since 1990 it has been our policy to administer postoperative chemotherapy to medically fit patients with stage I1 or 11I. Patient characteristics including age (mean 65 years, range 23-90), gender (45% male) and location within the rectum (30% within 5 cm of the anal verge) were comparable to our overall cohort. However the group selected for 5 fractions preoperatively had relatively fewer lesions that were tethered (23% vs. 65%), circumferential (11% vs. 24%), or near obstructing (0 vs. 13%) than the overall cohort. Results: With a post treatment follow up of 1-15 years (mean 4.7 years) there have been two local failures and l 1 distant failures, with an actuarial local control 0f97% and disease free survival of 77% at 5 and 10 years. Grade > 3 perioperative or late toxicity occurred in 11 cases (13%) including 3 (3.5%) late bowel obstructions. Stage II or II1 disease was found in 58% of the cases, 77% of which were free of disease at last follow up. Sphincter preserving surgery was possible in 62% of the patients. In recent years, postoperative chemotherapy has been administered to 17 patients with stage II or III disease; this has been well tolerated with only one late toxicity (cystitis managed medically). Conclusion: Patients with resectable rectal cancer who received 20 Gy/5 fx preoperative radiotherapy to the pelvis had excellent local and distant control of disease. These patients were able to tolerate sphincter preserving surgery and postoperative chemotherapy well. It would be of interest to conduct a randomized trial comparing short course with longer course (45 or 50 Gy) preoperative radiotherapy for resectable T3 lesions. The results of this study suggest, however, that differences in toxicity, local control, and disease free survival would probably be < 10%.
2102 P R E O P E R A T I V E C H E M O R A D I A T I O N BY I N F U S I O N A L 5FU A N D B O L U S P L A T I N U M F O R E x T R A P E R I T O N E A L R E C T A L C A N C E R : A C U T E TOXICITY, T U M O R R E S P O N S E , S P H I N C T E R P R E S E R V A T I O N M.E.Rosetto*, V.Valentini*, C.Coco#, N.Cellini*, A.Picciocchi#, B.Barbaro ~,
C.Fares*, G , N u z z o # ,
F.Ambesi-Impiombato§,
M.Cosimelli§ * Divisione di R a d i o t e r a p i a - Universit~ Cattolica S.Cuore - Rome - Italy Istituto di Radiologia- Universit~ Cattolica S.Cuore - Rome - Italy # Istituto di Patologia C h i r u r g i c a - Universita Cattolica S.Cuore - R o m e - Italy § Istituto N a z i o n a l e Regina Elena - R o m e - Italy .Purpose: To e v a l u a t e w h e t h e r p r e o p e r a t i v e external r a d i a t i o n t h e r a p y intensified b y systemic c h e m o t h e r a p y c o u l d i m p r o v e t u m o r response, sphincter p r e s e r v a t i o n a n d t u m o r control. M a t e r i a l s & M e t h o d s : Between J a n u a r y 1996 a n d December 1997, 32 consecutive patients w i t h resectable extraperitoneal a d e n o c a r c i n o m a of the rectum w e r e treated w i t h p r e o p e r a t i v e c h e m o r a d i a t i o n : bolus iv C i s p a l t i n u m (CDDP), 60 m g / m 2 d a y 1,28 p l u s 24h c o n t i n u o u s infusion iv 5 Fluorouracil (5FU) 1,000 m g / m 2, d a y s 1-4, 28-31 a n d c o n c u r r e n t external b e a m r a d i o t h e r a p y (50.4 Gy). All b u t 3 patients h a d T3 disease. S u r g e r y w a s p e r f o r m e d 4-6 w e e k s after the e n d of c h e m o r a d i a t i o n . N o a d j u v a n t chemotherapy was administered. Results: Total hematological g r a d e 3 acute toxicity d u r i n g c h e m o r a d i a t i o n w a s o b s e r v e d in 2 (7%) patients. N o p a t i e n t h a d m a j o r intestinal, skin or urological acute toxicity. All patients h a d radical s u r g e r y . T h e r e w a s no postoperative mortality, overall perioperative m o r b i d i t y rate w a s 16 %. Overall, 25% (8 of 32) of patients h a d a c o m p l e t e pathological response w h i l e three patients h a d r a r e isolated r e s i d u a l c a n c e r cells (Tmic). C o m p a r i n g the s t a g e at the d i a g n o s t i c w o r k - u p w i t h the p a t h o l o g i c a l stage, t u m o r d o w n s t a g i n g w a s o b s e r v e d in 19 (60%) patients. W e h a d 8 (25%) pT0, 3 (9%) pTmic, 2 (7%) pT1, 7 (22%) pT2 a n d 11 (34%) pT3. N o d a l status d o w n s t a g i n g w a s detected in 19 (60%) patients. No e v i d e n c e of n o d a l i n v o l v e m e n t w a s o b s e r v e d in 19 (60%) patients. The incidence of t u m o r r e s p o n s e w a s significantly affected b y the l e n g t h of the t u m o r (p=0.04). Both the n u m b e r of q u a r t e r s of rectal circumference i n v o l v e d a n d the distance b e t w e e n the l o w e r pole of the t u m o r a n d the anorectal r i n g h a d no influence. T w e n t y - s e v e n (84%) patients h a d a s p h i n c t e r saving surgical p r o c e d u r e . In 4 of 9 (45%) patients c a n d i d a t e for a n A P R the sphincter w a s p r e s e r v e d as w a s in all 8 p r o b a b l e candidates. L e n g t h e n i n g of the distance b e t w e e n the anorectal r i n g a n d the l o w e r pole of the t u m o r > 20 m m w a s o b s e r v e d in 5 (16%) patients. N o patients h a d m o d e r a t e soilage after the s p h i n c t e r saving p r o c e d u r e w i t h a m e d i a n f o l l o w - u p of 12 months. Conclusion: P r e o p e r a t i v e c o m b i n e d m o d a l i t y t h e r a p y seems to afford some potential a d v a n t a g e s in n o n r a n d o m i z e d trials: patients are able to tolerate h i g h e r c h e m o t h e r a p y doses a n d they experience a l o w e r acute toxicity; tumoi" d o w n s t a g i n g a n d resectability rates are high; s p h i n c t e r p r e s e r v a t i o n is feasible.