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502Combined hyperfractionated radiotherapy and protracted infusion chemotherapy in bladder cancer for organ preservation. A pilot study
S129 502
503 RADICAL RADIOTHERAPY AS AN ORGAN-SPARING TREATMENT FOR INVASIVE BLADDER CANCER
COMBINED HYPERFRACTIONATED RADIOTHERAPY AND PROTRACTED INFUSION CHEMOTHERAPY IN BLADDER CANCER FOR ORGAN PRESERVATION. A PILOT STUDY B Saracino ( I ). G Arcangeli (1), D Tirindelli Danesi (2), A.Mecozzi (2), E Cruciani (3). Istituto Medico e di Rieerca S¢ientifiea (1), ENEA Casaccia (2), and Ospedale Fatebenefratelli-lsolaTiberina (3), Roma The aim of this study is to define the optimal schedule of chemoradiotherapy in selective bladder preservation From November 1992 34 patients with muscle invading bladder tumors underwent an aggressive TURB followed by 2 MCV chemotherapy cycles and, then, by XRT and concomitant PVI CDDP/SFU Dose levels ranging from 180 to 220 mg/m2/day 5FU and from 4 to 6 mg/m2/day CDDP were tested XRT was delivered as three 100 cGy fractions per day to a dose of 50 Gy to the pelvis plus a boost of 20 Gy to the bladder in 4 5 weeks Grade Ill-IV rectal tenesmus and dysuria, and grade III hematological toxicity were observed in 6/6 and in 4/6 patients, respectively, in the highest dose level, while only I case in the lowest dose-level showed a grade IV bone marrow depletion Therefore, 5 mg/m2/day CDDP plus 220 mg/m2/day 5FU appeared to be the maximum tolerated dose when given for 4 5 weeks concomitantly to XRT Of the 31 evaluable patients, CR was observed in 28 (90 3%) and PR in 3 0 f t h e s e latter, I with a disease limited to the mucosa was successfully treated with intravesical therapy and 2 developped distant metastases and died at 12 and 24 months from the start of treatment Ad~er a median follow-up of 26 months, 23 of the 28 CR patients are alive and free of tumor Two of these 23 patients had a superficial local failure and were successfully treated with intravescical therapy Five patients died. all with functioning tumor-free bladder, 2 for intercurrent disease and 3 for distant metastases No patients underwent total cistectomy These results deserve further attention and need to be evaluated by a controlled clinical study
504
I . H~NOV~, P. tDUPEK, R. SOUMAROV~ Masaryk Memorial Cancer I n s t i t u t e Brno, Czech Republic 8ackqround Over the l a s t decade, multimodality organ-sparing t r e a t m e n t has b e c o m e the s t a n d a r d of c a r e for m a n y tely, b l a d d e r Purpose The o b j e c t i v e assessing the t h e r a p y for 62
common cancer
malignancies. is a d i s t i n c t
Unfortunaexception.
of the s t u d y p r e s e n t e d has o e e n effectiveness of r a d i c a l r a d i o patients with invasive bladder cancel treated f r o m 1986 t i l l 1990. Materials and Methods
Retrospective a n a l y s i s o f 62 p a t i e n t s (47 men and 15 women) has bee p e r f o r m e d . T o t a l doses f r o m 50 6y ,to 62 Gy (mean: 56 + 3 Gy) were g i v e n w i t h 20 MV p h o t o n s f r o m l i n e a r acceller a t o r or w i t h c o b a l t u n i t . Results The c o m p l e t e r e s p o n s e was a c h i e v e d i n 28 p a tients (45 ~ ) . Tumour r e c u r r e n c e d e v e l o p e d i n 6 o u t o f 28 c o m p l e t e r e s p o n d e r s (21 ~) as a superficial b l a d d e r c a n c e r and i n 3 f r o m 28 p a t i e n t s ( 1 1 % ) as an i n v a s i v e t u m o u r . Survival a t 5 y e a r s was 36 %. D i s t a n t m e t a s t a s e s o c c u r r e d in 17 c a s e s (27 %). Conclusion The r e s u l t s p r e s e n t e d are c o n s i s t e n t with t h o s e r e p o r t e d for r a d i a t i o n t h e r a p y as the sole treatment modality. To i m p r o v e the outc o m e of treatment, it is n e c e s s a r y to use c o m bined chemo-radiotherapy for s e l e c t e d g r o u p of p a t i e n t s .
505
RAPIDLY ALTERNATING CHEMO-RADIOTHERAPY RATHER THAN CYSTECTOMY FOR MUSCLE-INVADING CANCERS OF THE URINARY BLADDER
PULMONARY IN MICE
B.Vikram, M.Chadha, S.Malarnud, H.Grabstald. Albert Einstein College of Medicine, New York, New York, USA.
Ot6n L.F.; Rodriguez F; Pefiate G; Gallego R; Ot6n C. DEPARTMENT OF RADIATION ONCOLOGY. HOSPITAL UNIVERSITARIO DE CANARIAS. FACULTAD DE MEDICINA. TENERIFE, SPAIN
Purpose: To study alternating chemo-radiotherapy as an alternative to cystectomy in muscle-invading carcinoma of the urinary bladder. The toxicity and preliminary results have been published previously (J. Urol. 151:602-604, 1994).
induced by r a d i a t i o n can enhance the number o f subsequent metastases. Experimental previous studies
Patients & Methods: Twenty patients with T2-4 NX MO transitional cell carcinomas of the bladder underwent transurethral resection (TURB), followed by 3 cycles of chemotherapy during weeks I, 4 and 7 (methotrexate, vinblastine, doxorubicin & cisplatin), with pelvic irradiation during weeks 2, 5 and 8 (1.8-2 Gy b.i.d for l0 fractions, total 54-60 Gy). The median follow-up is 3.5 years, the longest 8 years. Results: All patients had a complete response cystoscopically. After 5 years, 94% of the patients have remained free of invasive cancer in the pelvis, 69% remained free of distant metastases; the cause-specific survival was 60%, and the overall survival was 39%. Four patients required further TURB for carcinoma in-situ. Bladder function remained normal in 84%. Conclusions: Rapidly alternating chemo-radiotherapy resulted in a 5-year survival rate comparable to cystectomy, but with normal bladder function in most of the patients.
METASTASES
BACKGROUND.-
AFTER
Morphological
SINGLE
and
LUNG IRRADIATION~
functional
changes
show from none to a marked increase of metastases in irradiated organs. PURPOSE.- To establish the influence of lung preirradiation on development of artificial pulmonary metastases. MATERIAL AND METHODS.Ten-Weeks old C57-BL6 male mice were asigned to receive single lun£ (half right, half left lung) irradiation doses from 5 to 15 Gy. Subsequently, they were intravenously injected whith melanoma BI6~FIO cells at tines varying from 2 to 42 days. Three weeks after injection, animals were sacrificed and pulmonary metastases counted and measured. Ratio: number of metastases in irradiated lung/number of metastases in control lung, was obtained in each mouse for statistical survey as coupled series. Correction for right/left lung size was done. RESULTS.Fifty-six mice were evaluable. Mean of ratios radiated/unradiated lung was 1.12 (p=O.O25).Sho[ ter interval radiation-inoculation and higher doses produced more metastatic enhancement. Pleural metastases were correlated with number of pulmonary metastases. Microphotographs are shown and clinical implication discussed. CGNCLUSION.Prior lung irradiation increase the incidence of pulmonary metastases after intravenous inj,rction of melanoma cells.
503 RADICAL RADIOTHERAPY AS AN ORGAN-SPARING TREATMENT FOR INVASIVE BLADDER CANCER
COMBINED HYPERFRACTIONATED RADIOTHERAPY AND PROTRACTED INFUSION CHEMOTHERAPY IN BLADDER CANCER FOR ORGAN PRESERVATION. A PILOT STUDY B Saracino ( I ). G Arcangeli (1), D Tirindelli Danesi (2), A.Mecozzi (2), E Cruciani (3). Istituto Medico e di Rieerca S¢ientifiea (1), ENEA Casaccia (2), and Ospedale Fatebenefratelli-lsolaTiberina (3), Roma The aim of this study is to define the optimal schedule of chemoradiotherapy in selective bladder preservation From November 1992 34 patients with muscle invading bladder tumors underwent an aggressive TURB followed by 2 MCV chemotherapy cycles and, then, by XRT and concomitant PVI CDDP/SFU Dose levels ranging from 180 to 220 mg/m2/day 5FU and from 4 to 6 mg/m2/day CDDP were tested XRT was delivered as three 100 cGy fractions per day to a dose of 50 Gy to the pelvis plus a boost of 20 Gy to the bladder in 4 5 weeks Grade Ill-IV rectal tenesmus and dysuria, and grade III hematological toxicity were observed in 6/6 and in 4/6 patients, respectively, in the highest dose level, while only I case in the lowest dose-level showed a grade IV bone marrow depletion Therefore, 5 mg/m2/day CDDP plus 220 mg/m2/day 5FU appeared to be the maximum tolerated dose when given for 4 5 weeks concomitantly to XRT Of the 31 evaluable patients, CR was observed in 28 (90 3%) and PR in 3 0 f t h e s e latter, I with a disease limited to the mucosa was successfully treated with intravesical therapy and 2 developped distant metastases and died at 12 and 24 months from the start of treatment Ad~er a median follow-up of 26 months, 23 of the 28 CR patients are alive and free of tumor Two of these 23 patients had a superficial local failure and were successfully treated with intravescical therapy Five patients died. all with functioning tumor-free bladder, 2 for intercurrent disease and 3 for distant metastases No patients underwent total cistectomy These results deserve further attention and need to be evaluated by a controlled clinical study
504
I . H~NOV~, P. tDUPEK, R. SOUMAROV~ Masaryk Memorial Cancer I n s t i t u t e Brno, Czech Republic 8ackqround Over the l a s t decade, multimodality organ-sparing t r e a t m e n t has b e c o m e the s t a n d a r d of c a r e for m a n y tely, b l a d d e r Purpose The o b j e c t i v e assessing the t h e r a p y for 62
common cancer
malignancies. is a d i s t i n c t
Unfortunaexception.
of the s t u d y p r e s e n t e d has o e e n effectiveness of r a d i c a l r a d i o patients with invasive bladder cancel treated f r o m 1986 t i l l 1990. Materials and Methods
Retrospective a n a l y s i s o f 62 p a t i e n t s (47 men and 15 women) has bee p e r f o r m e d . T o t a l doses f r o m 50 6y ,to 62 Gy (mean: 56 + 3 Gy) were g i v e n w i t h 20 MV p h o t o n s f r o m l i n e a r acceller a t o r or w i t h c o b a l t u n i t . Results The c o m p l e t e r e s p o n s e was a c h i e v e d i n 28 p a tients (45 ~ ) . Tumour r e c u r r e n c e d e v e l o p e d i n 6 o u t o f 28 c o m p l e t e r e s p o n d e r s (21 ~) as a superficial b l a d d e r c a n c e r and i n 3 f r o m 28 p a t i e n t s ( 1 1 % ) as an i n v a s i v e t u m o u r . Survival a t 5 y e a r s was 36 %. D i s t a n t m e t a s t a s e s o c c u r r e d in 17 c a s e s (27 %). Conclusion The r e s u l t s p r e s e n t e d are c o n s i s t e n t with t h o s e r e p o r t e d for r a d i a t i o n t h e r a p y as the sole treatment modality. To i m p r o v e the outc o m e of treatment, it is n e c e s s a r y to use c o m bined chemo-radiotherapy for s e l e c t e d g r o u p of p a t i e n t s .
505
RAPIDLY ALTERNATING CHEMO-RADIOTHERAPY RATHER THAN CYSTECTOMY FOR MUSCLE-INVADING CANCERS OF THE URINARY BLADDER
PULMONARY IN MICE
B.Vikram, M.Chadha, S.Malarnud, H.Grabstald. Albert Einstein College of Medicine, New York, New York, USA.
Ot6n L.F.; Rodriguez F; Pefiate G; Gallego R; Ot6n C. DEPARTMENT OF RADIATION ONCOLOGY. HOSPITAL UNIVERSITARIO DE CANARIAS. FACULTAD DE MEDICINA. TENERIFE, SPAIN
Purpose: To study alternating chemo-radiotherapy as an alternative to cystectomy in muscle-invading carcinoma of the urinary bladder. The toxicity and preliminary results have been published previously (J. Urol. 151:602-604, 1994).
induced by r a d i a t i o n can enhance the number o f subsequent metastases. Experimental previous studies
Patients & Methods: Twenty patients with T2-4 NX MO transitional cell carcinomas of the bladder underwent transurethral resection (TURB), followed by 3 cycles of chemotherapy during weeks I, 4 and 7 (methotrexate, vinblastine, doxorubicin & cisplatin), with pelvic irradiation during weeks 2, 5 and 8 (1.8-2 Gy b.i.d for l0 fractions, total 54-60 Gy). The median follow-up is 3.5 years, the longest 8 years. Results: All patients had a complete response cystoscopically. After 5 years, 94% of the patients have remained free of invasive cancer in the pelvis, 69% remained free of distant metastases; the cause-specific survival was 60%, and the overall survival was 39%. Four patients required further TURB for carcinoma in-situ. Bladder function remained normal in 84%. Conclusions: Rapidly alternating chemo-radiotherapy resulted in a 5-year survival rate comparable to cystectomy, but with normal bladder function in most of the patients.
METASTASES
BACKGROUND.-
AFTER
Morphological
SINGLE
and
LUNG IRRADIATION~
functional
changes
show from none to a marked increase of metastases in irradiated organs. PURPOSE.- To establish the influence of lung preirradiation on development of artificial pulmonary metastases. MATERIAL AND METHODS.Ten-Weeks old C57-BL6 male mice were asigned to receive single lun£ (half right, half left lung) irradiation doses from 5 to 15 Gy. Subsequently, they were intravenously injected whith melanoma BI6~FIO cells at tines varying from 2 to 42 days. Three weeks after injection, animals were sacrificed and pulmonary metastases counted and measured. Ratio: number of metastases in irradiated lung/number of metastases in control lung, was obtained in each mouse for statistical survey as coupled series. Correction for right/left lung size was done. RESULTS.Fifty-six mice were evaluable. Mean of ratios radiated/unradiated lung was 1.12 (p=O.O25).Sho[ ter interval radiation-inoculation and higher doses produced more metastatic enhancement. Pleural metastases were correlated with number of pulmonary metastases. Microphotographs are shown and clinical implication discussed. CGNCLUSION.Prior lung irradiation increase the incidence of pulmonary metastases after intravenous inj,rction of melanoma cells.