- Email: [email protected]
Effective salvage radiation therapy in advanced and recurrent ovarian carcinoma
Proceedings
2 105 L. Incrocci.’
Sexual functioning J. B. Madalinska,’
317
of the 42nd Annual ASTRO Meeting
in patients with prostate cancer prior to radical prostatectomy M. L. Essink-Bat.’
‘Drrniel Den Hoed Cmcer Center, Rotterdom. Hocpittrl Rotterdmn, Rotterdmn, Netherlands
Purpose: To evaluate sexual functioning radiation (RT).
W. L. van Putten,’ P. C. Koper,’
Netherlnnds,
‘Ertwnus
Univrrsip,
or radiation
therapy
F. H. Schriider’
Rotterdam,
Netherlands,
in patients with prostate cancer prior to radical prostatectomy
‘University
(RP) or external beam
Materials and Methods: a total of 158 patients awaiting primary treatment for prostate cancer filled out a lS-item questionnaire regarding sexual functioning. 77 subjects were to be treated with RP and Xl with RT. Results: Median age of the RP patients was 63 years, of the RT patients was 69 years (p < 0.0001). There was no difference in clinical stage between the two groups. The median prostate specific antigen was 4 ug/l in the RP group versus 8 ug/l in the RT group (p
2 106
Treatment
of ovarian cancer with intraperitoneal
chromic phosphate
P32
K. R. Stevens. Jr., S. C. Hoffelt
Purpose: To determine and evaluate the long-term therapeutic effectiveness of intraperitoneal chromic phosphate P32 (with or without external pelvic irradiation) as treatment for cancer of the ovary. The acute and chronic toxicities, which are primarily intestinal, of this treatment will also be determined. Materials and Methods: From 1964 to 1998. 215 women with carcinoma of the ovary have been treated at Oregon Health Sciences University with postoperative intraperitoneal 15 mCi chromic phosphate P32. lntraperitoneal air (200 ml) was used at the time of the P32 procedure to confirm intraperitoneal placement of the catheter used to instill the P32, and to improve the intraperitoneal distribution of the radioisotope. Nuclear imaging was obtained on each patient to document distribution of the P32. Ninety-two women also received 40 Gy external beam pelvic irradiation in addition to the P32. Results: The Kaplan-Meier overall and cause-specific IO-year survival by AJCC stage are(# of patients): IA 91% (31/34), 97% (3 l/32); IB 67% (IO/IS). 79% (10/13); IC 67% (45/69), 73% (45164): IIA 50% for both (3/6); IIB 50% for both (6/12). IIC 22% for both (2/c)): IIIA 100% (I), IIIB 24% (6/25), 32% (6/23); IIIC 0% (29). IV 0% (6); recurrent tumor 50% for both (l/2). Of the 122 patients who did not receive external pelvic irradiation, 6 (5%) had bowel surgery for tumor recurrence and 3 (2.5%) had surgery for radiation-related small bowel obstruction. Of the 93 patients who received 40 Gy external pelvic irradiation in addition to P32, 8 (9%) had bowel surgery for tumor recurrence, 2 had bowel surgery for second carcinoma of the colon, and 12( 13%) had surgery for radiation-related bowel obstruction. Conclusion: lntraperitoneal chromic phosphate P32 (IS mCi) is an effective treatment. with low incidence of intestinal toxicity, for patients with stage IA to stage IIIB ovarian carcinoma. The addition of 40 Gy external pelvic irradiation to intraperitoneal chromic phosphate P32 increases the ri\k of small bowel injury requiring surgical intervention.
2107
Eff ec t’tve salvage radiation
therapy in advanced
and recurrent
A. Tinger,‘.’ T. Waldron,‘.’ N. Peluso,‘.’ M. J. Katin,‘.’ D. E. Dosoretz,‘.’ Patrice,‘.’ G. R. Carton.‘. B. A. Nakfoor.‘,” L. Chuang.’ J. W. Orr, Jr.’
ovarian
carcinoma
P. R. Blitzer,‘,* J. H. Rubenstein,‘.’
‘Rtrdirrtion Tlwrtrpy Srr-+e.r, Ycmkrrs, NY, ‘Rndiatiml Thrrtrp Servicw, Vrrlhtrlln. NY, JF/oridrr ~~~rwcologir~ Onco10,py. Fort Meverv. FI.
Fort A4yrr.y. FL, -‘Westchester
Purpose: To review our experience
in ovarian carcinoma
using radiation
as salvage treatment
Medico1
S. J Center,
Materials and Methods: The records of 80 patients who received radiation therapy for ovarian carcinoma between 1983 and 1998 at Radiation Therapy Services were reviewed. Only 8 patients received radiation therapy that was intended to be curative. The remainder were treated for palliation when their symptoms became unmanageable and/or the other available chemotherapy options were exhausted. All patients had pathological documentation of carcinoma of the ovary. Care was taken to obtain all prior surgical and chemotherapy treatment information. The indications, radiation therapy techniques, details, tolerance, and response were recorded. A complete response required complete resolution of the patients symptoms, radiographic findings, palpable mass, and/or CA- I25 level. A partial response required at least 50% resolution of these parameters. The actuarial survival rates from diagnosis and from the completion of radiation therapy were calculated. The median follow-up from the date of diagnosis until death or last follow-up was 36 months (range 33216 months). The median follow-up rom the completion of radiation therapy was seven months (range O-151 months). Results: The median age of the patients was 67 years (range 26 to 90). A median of one prior laparotomy was performed prior to irradiation with a range from 0 to four (mean = 12). Zero to 20 cycles of a platinum-based chemotherapy regimen were delivered prior to irradiation (median = 6 cycles). The reasons for palliative treatment were: pain (n = 22), mass (n = 23).
I. J. Radiation
318
Oncology
l Biology
l Physics
Volume 48, Number 3, Supplement,
2000
obstruction of ureter, rectum, esophagus, or stomach (n = 12), a positive second look laparotomy (n = 9), ascites (n = 8), vaginal bleeding (n = 6), rectal bleeding (n = I), lymphedema (n = 3), skin involvement (n = l), or brain metastases with symptoms (n = 11). Some patients received treatment for more than one indication. Treatment was directed to the abdomen or pelvis in 64 patients, to the brain in 11, and to other sites in five. The overall response rate was 73%. Twenty-eight percent of the patients experienced a complete response of their symptoms, palpable mass, and/or CA- 125 level. Forty-five percent had a partial response. Only 1 I % suffered progressive disease during therapy that required discontinuation of the treatment. Sixteen percent had stable disease. The duration of the responses and stable disease lasted until death except in ten patients who experienced recurrence of their symptoms between one and 21 months (median = 9 months). The one- two-, three-, and five-year actuarial survival rates from diagnosis were 89%, 73%, 42%, and 33% respectively. The same survival rates calculated from the completion of radiotherapy were 39%, 278, 13%, and 10% respectively. Five percent of patients experienced grade 3 diarrhea, vomiting, myelosuppression, or fatigue. Fourteen percent of patients experienced grade 1 or 2 diarrhea: 19% experienced grade 1 or 2 nausea and vomiting, and 11% had grade 1 or 2 myelosuppression. Conclusion: In this large series of radiation therapy for ovarian carcinoma, the response, survival, and tolerance rates compare favorably to those reported for current salvage chemotherapy regimens. Cooperative groups should consider evaluating prospectively the use of radiation therapy prior to non-platinum and/or non-paclitaxel salvage chemotherapy in these patients.
2108
L oss of heterozygosity on chromosome after radiotherapy of cervical cancer
Y. Harima.
K. Nagata,
Kansai Medical
K. Harima,
Univemity,
6~212 plus 17~13.1 as a potential marker for relapse-free
survival
S. Sawada
Moriguchi,
Jqxm
Purpose: Cervical carcinomas develop as a result of multiple genetic alterations, and specitic alterations lead to specific clinical behavior. However, the effect of such alterations on the recurrence of cervical cancer after radiotherapy remains unknown. Chromosome arm 6p and 17p are one of those most frequently involved in a loss of heterorygosity (LOH) in patients with cervical carcinoma. Our study explored whether LOH on chromosome 6~2 12 plus 17~ 13.1 is associated with treatment outcome in patients with cervical cancer after radiotherapy. Materials and Methods: A total of 64 patients with cervical cancer (stage 1, 5 patients: stage II, 9 patients; stage III, 38 patients; and stage IV, 12 patients) who underwent definitive radiotherapy between 1995 and 1999 were included in this study. We analyzed specimens from the tumor and venous blood of all patients. Tumors and normal DNA were analyzed by polymerase chain reaction for genetic losses at six polymorphic microsatellite loci (D6S276, D6S1624, D6S1583 (6~211) and D17S796, Dl7Sl353, Dl7SlX81 (17~13. I)). Actuarial methods were used to calculate overall survival and disease-free survival. Results: A total of 26 patients (40.6%) had cancer recurrence: 8 patients had a local recurrence, six had distant metastases, and 12 had both local recurrence and distant metastases after radiotherapy. The mean tumor diameter of all patients was 5.6 cm. We divided the patients into two groups, those with tumors smaller than 5.6 cm in diameter (n = 35) and those with tumors equal to or greater than 5.6 cm in diameter (n = 29). There was a signiticant difference in overall survival (P = 0.004) and disease-free survival (P = 0.02) between these groups: the former group survived signiticantly longer than the latter group. Chromosome 6~212 and 17~13.1 is involved in the LOH in 46.9% (30 of 64), and 40.6 % (26 of 64) of the informative carcinomas. Both LOH on chromosome 6~212 and 17~13.1 are shown in 17 patients (26.6%) and no LOH on same region are revealed in 25 patients (39. I %).There was a significant difference in overall survival (P = 0.02) and disease-free survival between patients with LOH on 6p and those without (P = 0.001). The latter group survived significantly longer than the former. In addition, there was a significant difference in overall survival (P = 0.006) and disease-free survival between patients with LOH on 17~ and those without (P = 0.01). The latter group survived significantly longer than the former. The patients with LOH on chromosome 6~2 I? plus 17~13. I survived significantly shorter than the those without in overall survival (P = 0.003). Relapse-free survival were significantly worst for the patients with LOH on chromosome 6~212 plus 17~13. I as compared to those without LOH (P = 0.0004). Conclusion: The results of this study suggest that LOH on 6~212 plus 17~13. relapse-free survival in patients with cervical carcinoma after radiotherapy.
2 109
I are the most important determinant
Prognostic factors in patients with cervical cancer treated with surgery and adjuvant
D. Utzig,’ J. Dunst,’ C. Richter.’
H. Methfessel,’
‘Dept. of Radiotherapy, Martin-Luther-Uni~,er.siry University Halle- Wittenberg. Halle, Germmy
H. Koelbl,’
of
radiotherapy
G. Haensgenr
H&e- Wittenberg,
Hulk,
Germmy,
‘Dept.
qf Gynecology, Martin-Luther-
Background: We have retrospectively evaluated the treatment results and prognostic factors in patients with high risk stage IB/IIB cervical cancers treated with radical hysterectomy and lymphadenectomy followed by adjuvant radiotherapy. Materials & Methods: From 198 1 through 1993, a total number of 289 patients with stage IB or IIB cervical cancers received adjuvant radiotherapy in our department. Radiotherapy was administered in surgically treated patients only in case of high risk for local failure. Indications for radiotherapy were pathologically proven lymph node involvement or unfavorable histological features for pNO-patients (G3 + histological lymphangiosis, no pelvic lymphadenectomy, involved/small vaginal margins. adenocarcinoma). Radiotherapy was administered via opposing ap/pa-portals with telecobalt or 9MV- or ISMV-photons in daily doses of I&2Gy up to a total dose of 50Gy with a parametrial boost up to 54Gy in selected cases. Additional vaginal cuff boost irradiation with HDR-brachytherapy was given if the vaginal margin was less than 1 cm. The age ranged from 25 through 81 years (mean 46 ? 12 years). All patients were followed regularly for at least 5 years in our department. Results: The overall 5.year survival was 70%. 5.year survival according to stage was 75% for IB and 58% for stage IIB. The most important single prognostic factor was lymph node involvement with a 5-year-survival of 75% for pN0 and 52% for pN + (p = 0.0003). The prognosis decreased with increasing number of involved lymph nodes (5.year survival 58% for I-2
2 105 L. Incrocci.’
Sexual functioning J. B. Madalinska,’
317
of the 42nd Annual ASTRO Meeting
in patients with prostate cancer prior to radical prostatectomy M. L. Essink-Bat.’
‘Drrniel Den Hoed Cmcer Center, Rotterdom. Hocpittrl Rotterdmn, Rotterdmn, Netherlands
Purpose: To evaluate sexual functioning radiation (RT).
W. L. van Putten,’ P. C. Koper,’
Netherlnnds,
‘Ertwnus
Univrrsip,
or radiation
therapy
F. H. Schriider’
Rotterdam,
Netherlands,
in patients with prostate cancer prior to radical prostatectomy
‘University
(RP) or external beam
Materials and Methods: a total of 158 patients awaiting primary treatment for prostate cancer filled out a lS-item questionnaire regarding sexual functioning. 77 subjects were to be treated with RP and Xl with RT. Results: Median age of the RP patients was 63 years, of the RT patients was 69 years (p < 0.0001). There was no difference in clinical stage between the two groups. The median prostate specific antigen was 4 ug/l in the RP group versus 8 ug/l in the RT group (p
2 106
Treatment
of ovarian cancer with intraperitoneal
chromic phosphate
P32
K. R. Stevens. Jr., S. C. Hoffelt
Purpose: To determine and evaluate the long-term therapeutic effectiveness of intraperitoneal chromic phosphate P32 (with or without external pelvic irradiation) as treatment for cancer of the ovary. The acute and chronic toxicities, which are primarily intestinal, of this treatment will also be determined. Materials and Methods: From 1964 to 1998. 215 women with carcinoma of the ovary have been treated at Oregon Health Sciences University with postoperative intraperitoneal 15 mCi chromic phosphate P32. lntraperitoneal air (200 ml) was used at the time of the P32 procedure to confirm intraperitoneal placement of the catheter used to instill the P32, and to improve the intraperitoneal distribution of the radioisotope. Nuclear imaging was obtained on each patient to document distribution of the P32. Ninety-two women also received 40 Gy external beam pelvic irradiation in addition to the P32. Results: The Kaplan-Meier overall and cause-specific IO-year survival by AJCC stage are(# of patients): IA 91% (31/34), 97% (3 l/32); IB 67% (IO/IS). 79% (10/13); IC 67% (45/69), 73% (45164): IIA 50% for both (3/6); IIB 50% for both (6/12). IIC 22% for both (2/c)): IIIA 100% (I), IIIB 24% (6/25), 32% (6/23); IIIC 0% (29). IV 0% (6); recurrent tumor 50% for both (l/2). Of the 122 patients who did not receive external pelvic irradiation, 6 (5%) had bowel surgery for tumor recurrence and 3 (2.5%) had surgery for radiation-related small bowel obstruction. Of the 93 patients who received 40 Gy external pelvic irradiation in addition to P32, 8 (9%) had bowel surgery for tumor recurrence, 2 had bowel surgery for second carcinoma of the colon, and 12( 13%) had surgery for radiation-related bowel obstruction. Conclusion: lntraperitoneal chromic phosphate P32 (IS mCi) is an effective treatment. with low incidence of intestinal toxicity, for patients with stage IA to stage IIIB ovarian carcinoma. The addition of 40 Gy external pelvic irradiation to intraperitoneal chromic phosphate P32 increases the ri\k of small bowel injury requiring surgical intervention.
2107
Eff ec t’tve salvage radiation
therapy in advanced
and recurrent
A. Tinger,‘.’ T. Waldron,‘.’ N. Peluso,‘.’ M. J. Katin,‘.’ D. E. Dosoretz,‘.’ Patrice,‘.’ G. R. Carton.‘. B. A. Nakfoor.‘,” L. Chuang.’ J. W. Orr, Jr.’
ovarian
carcinoma
P. R. Blitzer,‘,* J. H. Rubenstein,‘.’
‘Rtrdirrtion Tlwrtrpy Srr-+e.r, Ycmkrrs, NY, ‘Rndiatiml Thrrtrp Servicw, Vrrlhtrlln. NY, JF/oridrr ~~~rwcologir~ Onco10,py. Fort Meverv. FI.
Fort A4yrr.y. FL, -‘Westchester
Purpose: To review our experience
in ovarian carcinoma
using radiation
as salvage treatment
Medico1
S. J Center,
Materials and Methods: The records of 80 patients who received radiation therapy for ovarian carcinoma between 1983 and 1998 at Radiation Therapy Services were reviewed. Only 8 patients received radiation therapy that was intended to be curative. The remainder were treated for palliation when their symptoms became unmanageable and/or the other available chemotherapy options were exhausted. All patients had pathological documentation of carcinoma of the ovary. Care was taken to obtain all prior surgical and chemotherapy treatment information. The indications, radiation therapy techniques, details, tolerance, and response were recorded. A complete response required complete resolution of the patients symptoms, radiographic findings, palpable mass, and/or CA- I25 level. A partial response required at least 50% resolution of these parameters. The actuarial survival rates from diagnosis and from the completion of radiation therapy were calculated. The median follow-up from the date of diagnosis until death or last follow-up was 36 months (range 33216 months). The median follow-up rom the completion of radiation therapy was seven months (range O-151 months). Results: The median age of the patients was 67 years (range 26 to 90). A median of one prior laparotomy was performed prior to irradiation with a range from 0 to four (mean = 12). Zero to 20 cycles of a platinum-based chemotherapy regimen were delivered prior to irradiation (median = 6 cycles). The reasons for palliative treatment were: pain (n = 22), mass (n = 23).
I. J. Radiation
318
Oncology
l Biology
l Physics
Volume 48, Number 3, Supplement,
2000
obstruction of ureter, rectum, esophagus, or stomach (n = 12), a positive second look laparotomy (n = 9), ascites (n = 8), vaginal bleeding (n = 6), rectal bleeding (n = I), lymphedema (n = 3), skin involvement (n = l), or brain metastases with symptoms (n = 11). Some patients received treatment for more than one indication. Treatment was directed to the abdomen or pelvis in 64 patients, to the brain in 11, and to other sites in five. The overall response rate was 73%. Twenty-eight percent of the patients experienced a complete response of their symptoms, palpable mass, and/or CA- 125 level. Forty-five percent had a partial response. Only 1 I % suffered progressive disease during therapy that required discontinuation of the treatment. Sixteen percent had stable disease. The duration of the responses and stable disease lasted until death except in ten patients who experienced recurrence of their symptoms between one and 21 months (median = 9 months). The one- two-, three-, and five-year actuarial survival rates from diagnosis were 89%, 73%, 42%, and 33% respectively. The same survival rates calculated from the completion of radiotherapy were 39%, 278, 13%, and 10% respectively. Five percent of patients experienced grade 3 diarrhea, vomiting, myelosuppression, or fatigue. Fourteen percent of patients experienced grade 1 or 2 diarrhea: 19% experienced grade 1 or 2 nausea and vomiting, and 11% had grade 1 or 2 myelosuppression. Conclusion: In this large series of radiation therapy for ovarian carcinoma, the response, survival, and tolerance rates compare favorably to those reported for current salvage chemotherapy regimens. Cooperative groups should consider evaluating prospectively the use of radiation therapy prior to non-platinum and/or non-paclitaxel salvage chemotherapy in these patients.
2108
L oss of heterozygosity on chromosome after radiotherapy of cervical cancer
Y. Harima.
K. Nagata,
Kansai Medical
K. Harima,
Univemity,
6~212 plus 17~13.1 as a potential marker for relapse-free
survival
S. Sawada
Moriguchi,
Jqxm
Purpose: Cervical carcinomas develop as a result of multiple genetic alterations, and specitic alterations lead to specific clinical behavior. However, the effect of such alterations on the recurrence of cervical cancer after radiotherapy remains unknown. Chromosome arm 6p and 17p are one of those most frequently involved in a loss of heterorygosity (LOH) in patients with cervical carcinoma. Our study explored whether LOH on chromosome 6~2 12 plus 17~ 13.1 is associated with treatment outcome in patients with cervical cancer after radiotherapy. Materials and Methods: A total of 64 patients with cervical cancer (stage 1, 5 patients: stage II, 9 patients; stage III, 38 patients; and stage IV, 12 patients) who underwent definitive radiotherapy between 1995 and 1999 were included in this study. We analyzed specimens from the tumor and venous blood of all patients. Tumors and normal DNA were analyzed by polymerase chain reaction for genetic losses at six polymorphic microsatellite loci (D6S276, D6S1624, D6S1583 (6~211) and D17S796, Dl7Sl353, Dl7SlX81 (17~13. I)). Actuarial methods were used to calculate overall survival and disease-free survival. Results: A total of 26 patients (40.6%) had cancer recurrence: 8 patients had a local recurrence, six had distant metastases, and 12 had both local recurrence and distant metastases after radiotherapy. The mean tumor diameter of all patients was 5.6 cm. We divided the patients into two groups, those with tumors smaller than 5.6 cm in diameter (n = 35) and those with tumors equal to or greater than 5.6 cm in diameter (n = 29). There was a signiticant difference in overall survival (P = 0.004) and disease-free survival (P = 0.02) between these groups: the former group survived signiticantly longer than the latter group. Chromosome 6~212 and 17~13.1 is involved in the LOH in 46.9% (30 of 64), and 40.6 % (26 of 64) of the informative carcinomas. Both LOH on chromosome 6~212 and 17~13.1 are shown in 17 patients (26.6%) and no LOH on same region are revealed in 25 patients (39. I %).There was a significant difference in overall survival (P = 0.02) and disease-free survival between patients with LOH on 6p and those without (P = 0.001). The latter group survived significantly longer than the former. In addition, there was a significant difference in overall survival (P = 0.006) and disease-free survival between patients with LOH on 17~ and those without (P = 0.01). The latter group survived significantly longer than the former. The patients with LOH on chromosome 6~2 I? plus 17~13. I survived significantly shorter than the those without in overall survival (P = 0.003). Relapse-free survival were significantly worst for the patients with LOH on chromosome 6~212 plus 17~13. I as compared to those without LOH (P = 0.0004). Conclusion: The results of this study suggest that LOH on 6~212 plus 17~13. relapse-free survival in patients with cervical carcinoma after radiotherapy.
2 109
I are the most important determinant
Prognostic factors in patients with cervical cancer treated with surgery and adjuvant
D. Utzig,’ J. Dunst,’ C. Richter.’
H. Methfessel,’
‘Dept. of Radiotherapy, Martin-Luther-Uni~,er.siry University Halle- Wittenberg. Halle, Germmy
H. Koelbl,’
of
radiotherapy
G. Haensgenr
H&e- Wittenberg,
Hulk,
Germmy,
‘Dept.
qf Gynecology, Martin-Luther-
Background: We have retrospectively evaluated the treatment results and prognostic factors in patients with high risk stage IB/IIB cervical cancers treated with radical hysterectomy and lymphadenectomy followed by adjuvant radiotherapy. Materials & Methods: From 198 1 through 1993, a total number of 289 patients with stage IB or IIB cervical cancers received adjuvant radiotherapy in our department. Radiotherapy was administered in surgically treated patients only in case of high risk for local failure. Indications for radiotherapy were pathologically proven lymph node involvement or unfavorable histological features for pNO-patients (G3 + histological lymphangiosis, no pelvic lymphadenectomy, involved/small vaginal margins. adenocarcinoma). Radiotherapy was administered via opposing ap/pa-portals with telecobalt or 9MV- or ISMV-photons in daily doses of I&2Gy up to a total dose of 50Gy with a parametrial boost up to 54Gy in selected cases. Additional vaginal cuff boost irradiation with HDR-brachytherapy was given if the vaginal margin was less than 1 cm. The age ranged from 25 through 81 years (mean 46 ? 12 years). All patients were followed regularly for at least 5 years in our department. Results: The overall 5.year survival was 70%. 5.year survival according to stage was 75% for IB and 58% for stage IIB. The most important single prognostic factor was lymph node involvement with a 5-year-survival of 75% for pN0 and 52% for pN + (p = 0.0003). The prognosis decreased with increasing number of involved lymph nodes (5.year survival 58% for I-2