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Abdominopelvic irradiation for stage II–IV ovarian carcinoma patients with limited or no residual disease at second-look laparotomy after completion of cisplatinum-based combination chemotherapy
GYNECOLOGIC
ONCOLOGY
24, 149-154 (1986)
Abdominopelvic Irradiation for Stage II-IV Ovarian Carcinoma Patients with Limited or No Residual Disease at Second-Look Laparotomy after Completion of Cisplatinum-Based Combination Chemotherapy J. MENCZER,
M. MODAN,*
J. BRENNER,? G. BEN-BARUCH,
AND H. BRENNER?
Departments of Obstetrics and Gynecology, ‘Clinical Epidemiology and iOncology, The Shebu Medical Center Tel-Hashomer, Tel-Aviv University School of Medicine, Isruel Received January 28, 1985 Abdominopelvic irradiation was given to 18 stage II-IV ovarian carcinoma patients who completed cisplatinum-based combination chemotherapy, were in complete clinical remission, and who underwent second-look laparotomy. The survival as well as the progression-free interval (PFI) was significantly longer in patients with a negative second-look laparotomy than in those with limited residual disease at this operation. Abdominopelvic irradiation was not effective in patients with limited residual disease at second-look laparotomy (3 year survival-34.3% and median PFI from second-look laparotomy-4.8 months). Even in patients with a negative second-look laparotomy the median PFI was only 13 months from this operation and the 3-year survival was 87.5%. The results were similar to other comparable series in which no treatment was administered to patients with a negative second-look laparotomy. 0 1986 Academic Press, Inc.
INTRODUCTION The treatment of advanced ovarian carcinoma of epithelial origin remains unsatisfactory. With adjuvant postoperative chemotherapy and especially with cisplatin-based combination chemotherapy, a considerable proportion of patients have no evidence of disease at second-look laparotomy, yet among these patients a variably high percentage may eventually develop recurrence [l-13]. The purpose of this report is to present the results of abdominopelvic irradiation given to patients with advanced ovarian cancer who completed postoperative cisplatinum-based combination chemotherapy and to compare the outcome in those without residual disease and those with limited residual diseases at secondlook laparotomy. MATERIALS AND METHODS The study group comprises 18 consecutive patients with histologically confirmed stage II-IV ovarian carcinoma of epithelial origin who completed IO-12 courses (about 1 year) of postoperative cisplatinum-based combination chemotherapy and who had no residual or limited residual disease at second-look laparotomy. All patients received abdominopelvic irradiation immediately following the secondlook operation. 149 0090-8258186 $1.50 Copyright D 1986 by Academic Press, Inc. All rights of reproductmn m any form reserved.
150
MENCZER
ET AL.
The adjuvant chemotherapy after the initial operation consisted of cyclophosphamide 600 mg/m2, adriamycin 40 mg/m2, and cisplatinum 60 mg/m’ iv every 3-4 weeks, The dose of cisplatinum was 120 mg/m2 during the first l-5 courses in seven of the patients. At the end of chemotherapy all patients had no clinical or radiological evidence of disease. Clinical characteristics of these patients are presented in Table 1. Second-look laparotomy was performed through a midline vertical incision extending above the umbilicus. At least 3 peritoneal washings (from the pelvic cul-de-sac, the left and right paracolic gutters) were submitted separately for cytologic examination. Macroscopic residual tumour nodules were biopsied. When after careful exploration of the entire abdominal cavity no macroscopic residual disease was found, multiple biopsies (12-20) were obtained. Biopsies from the diaphragms were not performed and lymph nodes were not sampled. No serious postoperative morbidity was encountered. At second-look laparotomy, 10 patients had neither macroscopic nor histological or cytological evidence of disease. The remaining 8 patients had limited residual disease: 4 had histologically proven minimal macroscopic disease (diameter of largest mass < 2 cm) and 4 had only microscopic residual disease. Abdominopelvic irradiation was given to all patients by the moving strip and pelvic boost technique at 120 SSD using a Co6’ Picker machine. The tumor dose was 2500 rad given over eight treatments to each strip. The fields included the pelvis and dome of the diaphragm. The liver was not shielded and the kidneys were shielded only posteriorly. A pelvic boost of 3000 rad was subsequently added. Duration of progression-free interval (PFI) was defined as the time in months from second-look operation to the time of (1) renewed appearance of a clinically palpable or radiologically demonstrable tumor mass; (2) appearance of ascites TABLE PATIENT
1
CHARACTERISTICS
No. of patients
18
Median age at diagnosis
(range) Stage at diagnosis II III IV Residual disease after initial operation > 2 cm < 2 cm Histologic category Serous cystadenocarcinoma Mutinous cystadenocarcinoma Anaplastic carcinoma
55 (41-67) 11 4 14 4 12 1 5
RADIOTHERAPY
AFTER
SECOND-LOOK
151
LAPAROTOMY
or new metastases, or (3) death. The follow-up period from second-look laparotomy ranged from 2 to 42 months with a median of 8.5 months, and from the diagnosis it ranged from 12 to 56 months with a median of 23 months. The duration of the PFI and survival probability were calculated by KaplanMeier survival analysis. Differences between patients with and without residual tumor were calculated by the log-rank method [ 141. RESULTS
The 3-year survival probability from diagnosis of the total group of patients was 64.1% (median survival 43 months) (Fig. 1). The 3-year survival of patients without residual diseases at second-look laparotomy (negative group) was 87.5% (median survival more than 56 months), while 3 year survival in patients with limited residual disease (positive group) was 34.3% (median survival 22 months). This difference was statistically significant (P < 0.01). The median PFI from the time of the second look operation in the total group was 7.7 months (Fig. 2). In patients with a positive second look laparotomy the median PFI from this operation
1;
i4 MONTHS
36
4s
60
FIG. 1. Survival of patients in months from diagnosis.
I
2
3
4
6
6
7
6
9 IO II MONTHS
FIG. 2. Duration of progression-free
I2
13 I4
IS
IS
I7
IS
interval from second-look laparotomy.
42
152
MENCZER
ET AL.
was 4.8 months. In all eight of these patients the disease progressed within 17 months from the second-look laparotomy and in two of them (one stage II and one stage III at diagnosis) metastases appeared in the lungs after abdominopelvic irradiation. In patients with a negative second-look laparotomy the median PFI was 13 months longer than median PFI in patients with limited residual disease at this operation. The difference between the two groups was highly significant (P -=I 0.001). Interruption of irradiation for 3 to 14 days was necessary in one patient because of transient myelosuppression and in six because of severe diarrhea. No other complications of postchemotherapy irradiation were observed. DISCUSSION
Our data indicate that the survival and PFI are significantly longer in patients with a negative second-look laparotomy than in patients with limited residual disease at this operation, when abdominopelvic irradiation is administered after reexploration. Similarly unfavorable results of abdominopelvic irradiation given to patients with a positive second-look laparotomy following single-agent and combination chemotherapy have been reported by others [ 1,3,15,16]. While immediate postoperative abdominopelvic irradiation in ovarian cancer patients with limited disease after the initial operation, is an effective mode of treatment [ 17,181, it is of limited value in such patients after chemotherapy. The reason for this difference is not clear. It has been suggested that after chemotherapy the biology of the cancer cells is altered and that they are resistant to radiotherapy. In addition, as observed in our series, recurrence may appear outside the field of irradiation. For patients with microscopically negative second-look laparotomy, there is no commonly accepted protocol. In most reports [ 1,3,4,6,8,9,11,12] no treatment was given, while in some, including our own, radiotherapy [10,13] or chemotherapy [2,7] was administered. Our rationale for giving radiotherapy was based on the reported unsatisfactorily high recurrence rate. In our series the PFI ended within 13 months after secondlook laparotomy in 50% of the patients with 95% confidence limits ranging from 15.4 to 84.6%. Available reports did not present this rate in terms of life table analysis of the PFI, nor gave the appropriate confidence limits. Thus comparison had to be based on approximate evaluation of the data as presented. When so assessed it seems that the rate of patients still in their PFI after about 12 to 16 months is approximately 90% in most series [3-6,9,10,13], between 70 and 80% in two [3,12], and 50% in one [8]. As the number of cases in all series is small it is not possible to evaluate to what extent these differences are real. Although in our series the rate of patients in the PFI after 13 months is 50%, the confidence limits indicate that they are consistent even with the best reported results. It is important to note that there was no apparent effect of radiotherapy on the PFI. The reports with the better results comprise both those without treatment [46,9] as well as the two with radiotherapy [10,13]. Similarly, shorter PFI was observed in three reported series without therapy [1,8,12] and in ours with radiotherapy.
RADIOTHERAPY
AFTER
SECOND-LOOK
LAPAROTOMY
153
In all series, including our own, regardless of PFI or treatment after secondlook laparotomy, 3-year survival was close to 90%. Again only few series [ 1,3,7,10,1 I] included life table analysis of survival and in the rest an approximate estimate had to be made to enable comparison. The above presented data show that describing the patient’s status, the rate of PFI as well as of survival provides a more meaningful picture than survival rate alone. To enable comparison between patient groups, both rates should be calculated in the context of life table analysis. Finally an overall evaluation of the reviewed reports and our data lead to the conclusion that in patients in complete clinical remission currently available treatment after second-look laparotomy is ineffective whether microscopically positive or negative. This conclusion raises the question of the clinical value of second-look laparotomy in such patients. Indeed recently identical survival has been reported for patients who were eligible for second-look laparotomy but did not undergo it and those who were eligible and did have it performed [I 11. New drugs or novel therapeutic approaches are needed to improve survival of patients following the completion of postoperative chemotherapy, even when they are in complete clinical remission. REFERENCES 1. Smith, J. P., Delgado, Cl., and Rutledge, E. Second-look operation in ovarian cancer, Cancer 38, 1438-1442
(1976).
Phillips, B. D., Buchsbaum, H. J.. and Lifshitz, S. Re-exploration after treatment for ovarian carcinoma, Gynecol. Oncol. 8, 339-345 (1979). 3. Schwarts, P. E., and Smith, J. P. Second-look operation in ovarian cancer, Amer. J. Ohsler. 2.
Gynecol.
138, 1124-I
130
(1980).
4. Curry, S. L., Zembo, M. M., Nahhas, W. A., Jahshan, A. E., Whitnney, C. W., and Motel, R. Second-look laparotomy for ovarian cancer, Gynecol. Oncol. 11, 114-l 18 (1981). 5. Greco, F. A., Julian, C. G., Richardson, R. L., Burnett, L., Hande, K. R., and Oldham, R. K. Advanced ovarian cancer: Brief intensive combination chemotherapy and second-look operation, Obstet. Gynecol. 58, 199-205 (1981). 6. Webb, M. J., Snyder, J. A., Williams, T. J., and Decker. D. J. Second-look laparotomy in ovarian cancer, Gynecol. Oncol. 14, 285-293 (1982). 7. Raju, K. S., McKinna, J. A., Barker, G. H., Wiltshaw, E.. and Jones, J. M. Second-look laparotomy in the planned management of advanced ovarian cancer, Amer. J. Obstet. Gynecol. 144, 650-654
(1982).
8. Roberts, W. S.. Hodel, K., Rich, W. M., and DiSaia, Ph.J. Second-look laparotomy in the management of gynecologic malignancy, Gynecol. Oncol. 13, 345-355 (1982). 9. Stuart, G. C. E., Jefries, M., and Anderson, R. J. Changing role of “second-look” laparotomy in the management of epithelial carcinoma of the ovary, Amer. J. Obsrer. Gynecol. 142, 612616 (1982). 10. Fuks, Z., Rizel, Sh., Anteby, Sh.O., and Biran, Sh. The multimode1 approach to the treatment of stage III ovarian carcinoma, Inr. J. Radiat. Oncol. Eiol. Phys. 8, 903-908 (1982). 11. Cohen, C. J., Goldberg, J. D., Holland, J. F., Bruckner, H. W., Deppe, G., Gusberg, S. B., Wallach, R. C., Kabakow, B., and Rodin, J. Improved therapy with cisplatin regimens for patients with ovarian carcinoma. (FIG0 stage III and IV) as measured by surgical end-staging (second-look operation), Amer. J. Obstet. Gynecol. 145, 955-967 (1983). 12. Berek, J. S., Hacker, N. F., Lagasse, L. D., Poth, T., Resnick, B., and Nieberg, R. K. Secondlook laparotomy in stage III epithelial ovarian cancer: Clinical variables associated with disease status,
13.
Obsret.
Gynecol.
64,
207-212
(1984).
Greiner, R., Goldhirsh, A., Davis, B. W., Dreher, E., Peyer, T., Lecher, G., Neuenschwander,
154
MENCZER
ET
AL.
H., Joss, R., Brunner, K., and Veraguth, P. Whole-abdomen radiation with advanced carcinoma after surgery, chemotherapy and second-look laparotomy, J. C/in. Res. Oncol. 107, 94-98 (1984). 14. Peto, R., Pike, M. C., Armitage, P., Breskow, N. E., Cox, D. R., Howard, S. V., Mantel, N., McPherson, K., Peto, J., and Smith, P. G. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. &it. J. Cancer 35, l-39 (1977). 15. Hainsworth, J. D., Malcolm, A., Johnson, D. H., Burnett, L. S., Jones, H. W., and Greco, F. A. Advanced minimal residual ovarian carcinoma: Abdominopelvic irradiation following combination chemotherapy. Obstet. Gynecol. 61, 619-623 (1983). 16. Piver, M. S., Barlow, J. J., and Lee, F. T. Sequential therapy for advanced ovarian adenocarcinoma. Operation, chemotherapy, second-look laparotomy and radiation therapy, Amer. J. Obstet. Gynecol.
122, 355-357
(1975).
17. Dembo, A. J., Bush, R. S., Beale, F. A., Bean, M. A., Pringle, J. F., Sturgeon, J., and Reid, J. G. Improved survival following abdominopelvic irradiation in patients with a completed pelvic operation. Amer. J. Obsret. Gynecol. 134, 793-800 (1979). 18. Menczer, J., Ben-Baruch, G., Modan, M., Brenner, J., and Brenner, H. A comparison of postoperative radiotherapy with postoperative chemotherapy in stage II-IV ovarian cancer patients, Gynecol. Oncol. 17, 207-212 (1984).
ONCOLOGY
24, 149-154 (1986)
Abdominopelvic Irradiation for Stage II-IV Ovarian Carcinoma Patients with Limited or No Residual Disease at Second-Look Laparotomy after Completion of Cisplatinum-Based Combination Chemotherapy J. MENCZER,
M. MODAN,*
J. BRENNER,? G. BEN-BARUCH,
AND H. BRENNER?
Departments of Obstetrics and Gynecology, ‘Clinical Epidemiology and iOncology, The Shebu Medical Center Tel-Hashomer, Tel-Aviv University School of Medicine, Isruel Received January 28, 1985 Abdominopelvic irradiation was given to 18 stage II-IV ovarian carcinoma patients who completed cisplatinum-based combination chemotherapy, were in complete clinical remission, and who underwent second-look laparotomy. The survival as well as the progression-free interval (PFI) was significantly longer in patients with a negative second-look laparotomy than in those with limited residual disease at this operation. Abdominopelvic irradiation was not effective in patients with limited residual disease at second-look laparotomy (3 year survival-34.3% and median PFI from second-look laparotomy-4.8 months). Even in patients with a negative second-look laparotomy the median PFI was only 13 months from this operation and the 3-year survival was 87.5%. The results were similar to other comparable series in which no treatment was administered to patients with a negative second-look laparotomy. 0 1986 Academic Press, Inc.
INTRODUCTION The treatment of advanced ovarian carcinoma of epithelial origin remains unsatisfactory. With adjuvant postoperative chemotherapy and especially with cisplatin-based combination chemotherapy, a considerable proportion of patients have no evidence of disease at second-look laparotomy, yet among these patients a variably high percentage may eventually develop recurrence [l-13]. The purpose of this report is to present the results of abdominopelvic irradiation given to patients with advanced ovarian cancer who completed postoperative cisplatinum-based combination chemotherapy and to compare the outcome in those without residual disease and those with limited residual diseases at secondlook laparotomy. MATERIALS AND METHODS The study group comprises 18 consecutive patients with histologically confirmed stage II-IV ovarian carcinoma of epithelial origin who completed IO-12 courses (about 1 year) of postoperative cisplatinum-based combination chemotherapy and who had no residual or limited residual disease at second-look laparotomy. All patients received abdominopelvic irradiation immediately following the secondlook operation. 149 0090-8258186 $1.50 Copyright D 1986 by Academic Press, Inc. All rights of reproductmn m any form reserved.
150
MENCZER
ET AL.
The adjuvant chemotherapy after the initial operation consisted of cyclophosphamide 600 mg/m2, adriamycin 40 mg/m2, and cisplatinum 60 mg/m’ iv every 3-4 weeks, The dose of cisplatinum was 120 mg/m2 during the first l-5 courses in seven of the patients. At the end of chemotherapy all patients had no clinical or radiological evidence of disease. Clinical characteristics of these patients are presented in Table 1. Second-look laparotomy was performed through a midline vertical incision extending above the umbilicus. At least 3 peritoneal washings (from the pelvic cul-de-sac, the left and right paracolic gutters) were submitted separately for cytologic examination. Macroscopic residual tumour nodules were biopsied. When after careful exploration of the entire abdominal cavity no macroscopic residual disease was found, multiple biopsies (12-20) were obtained. Biopsies from the diaphragms were not performed and lymph nodes were not sampled. No serious postoperative morbidity was encountered. At second-look laparotomy, 10 patients had neither macroscopic nor histological or cytological evidence of disease. The remaining 8 patients had limited residual disease: 4 had histologically proven minimal macroscopic disease (diameter of largest mass < 2 cm) and 4 had only microscopic residual disease. Abdominopelvic irradiation was given to all patients by the moving strip and pelvic boost technique at 120 SSD using a Co6’ Picker machine. The tumor dose was 2500 rad given over eight treatments to each strip. The fields included the pelvis and dome of the diaphragm. The liver was not shielded and the kidneys were shielded only posteriorly. A pelvic boost of 3000 rad was subsequently added. Duration of progression-free interval (PFI) was defined as the time in months from second-look operation to the time of (1) renewed appearance of a clinically palpable or radiologically demonstrable tumor mass; (2) appearance of ascites TABLE PATIENT
1
CHARACTERISTICS
No. of patients
18
Median age at diagnosis
(range) Stage at diagnosis II III IV Residual disease after initial operation > 2 cm < 2 cm Histologic category Serous cystadenocarcinoma Mutinous cystadenocarcinoma Anaplastic carcinoma
55 (41-67) 11 4 14 4 12 1 5
RADIOTHERAPY
AFTER
SECOND-LOOK
151
LAPAROTOMY
or new metastases, or (3) death. The follow-up period from second-look laparotomy ranged from 2 to 42 months with a median of 8.5 months, and from the diagnosis it ranged from 12 to 56 months with a median of 23 months. The duration of the PFI and survival probability were calculated by KaplanMeier survival analysis. Differences between patients with and without residual tumor were calculated by the log-rank method [ 141. RESULTS
The 3-year survival probability from diagnosis of the total group of patients was 64.1% (median survival 43 months) (Fig. 1). The 3-year survival of patients without residual diseases at second-look laparotomy (negative group) was 87.5% (median survival more than 56 months), while 3 year survival in patients with limited residual disease (positive group) was 34.3% (median survival 22 months). This difference was statistically significant (P < 0.01). The median PFI from the time of the second look operation in the total group was 7.7 months (Fig. 2). In patients with a positive second look laparotomy the median PFI from this operation
1;
i4 MONTHS
36
4s
60
FIG. 1. Survival of patients in months from diagnosis.
I
2
3
4
6
6
7
6
9 IO II MONTHS
FIG. 2. Duration of progression-free
I2
13 I4
IS
IS
I7
IS
interval from second-look laparotomy.
42
152
MENCZER
ET AL.
was 4.8 months. In all eight of these patients the disease progressed within 17 months from the second-look laparotomy and in two of them (one stage II and one stage III at diagnosis) metastases appeared in the lungs after abdominopelvic irradiation. In patients with a negative second-look laparotomy the median PFI was 13 months longer than median PFI in patients with limited residual disease at this operation. The difference between the two groups was highly significant (P -=I 0.001). Interruption of irradiation for 3 to 14 days was necessary in one patient because of transient myelosuppression and in six because of severe diarrhea. No other complications of postchemotherapy irradiation were observed. DISCUSSION
Our data indicate that the survival and PFI are significantly longer in patients with a negative second-look laparotomy than in patients with limited residual disease at this operation, when abdominopelvic irradiation is administered after reexploration. Similarly unfavorable results of abdominopelvic irradiation given to patients with a positive second-look laparotomy following single-agent and combination chemotherapy have been reported by others [ 1,3,15,16]. While immediate postoperative abdominopelvic irradiation in ovarian cancer patients with limited disease after the initial operation, is an effective mode of treatment [ 17,181, it is of limited value in such patients after chemotherapy. The reason for this difference is not clear. It has been suggested that after chemotherapy the biology of the cancer cells is altered and that they are resistant to radiotherapy. In addition, as observed in our series, recurrence may appear outside the field of irradiation. For patients with microscopically negative second-look laparotomy, there is no commonly accepted protocol. In most reports [ 1,3,4,6,8,9,11,12] no treatment was given, while in some, including our own, radiotherapy [10,13] or chemotherapy [2,7] was administered. Our rationale for giving radiotherapy was based on the reported unsatisfactorily high recurrence rate. In our series the PFI ended within 13 months after secondlook laparotomy in 50% of the patients with 95% confidence limits ranging from 15.4 to 84.6%. Available reports did not present this rate in terms of life table analysis of the PFI, nor gave the appropriate confidence limits. Thus comparison had to be based on approximate evaluation of the data as presented. When so assessed it seems that the rate of patients still in their PFI after about 12 to 16 months is approximately 90% in most series [3-6,9,10,13], between 70 and 80% in two [3,12], and 50% in one [8]. As the number of cases in all series is small it is not possible to evaluate to what extent these differences are real. Although in our series the rate of patients in the PFI after 13 months is 50%, the confidence limits indicate that they are consistent even with the best reported results. It is important to note that there was no apparent effect of radiotherapy on the PFI. The reports with the better results comprise both those without treatment [46,9] as well as the two with radiotherapy [10,13]. Similarly, shorter PFI was observed in three reported series without therapy [1,8,12] and in ours with radiotherapy.
RADIOTHERAPY
AFTER
SECOND-LOOK
LAPAROTOMY
153
In all series, including our own, regardless of PFI or treatment after secondlook laparotomy, 3-year survival was close to 90%. Again only few series [ 1,3,7,10,1 I] included life table analysis of survival and in the rest an approximate estimate had to be made to enable comparison. The above presented data show that describing the patient’s status, the rate of PFI as well as of survival provides a more meaningful picture than survival rate alone. To enable comparison between patient groups, both rates should be calculated in the context of life table analysis. Finally an overall evaluation of the reviewed reports and our data lead to the conclusion that in patients in complete clinical remission currently available treatment after second-look laparotomy is ineffective whether microscopically positive or negative. This conclusion raises the question of the clinical value of second-look laparotomy in such patients. Indeed recently identical survival has been reported for patients who were eligible for second-look laparotomy but did not undergo it and those who were eligible and did have it performed [I 11. New drugs or novel therapeutic approaches are needed to improve survival of patients following the completion of postoperative chemotherapy, even when they are in complete clinical remission. REFERENCES 1. Smith, J. P., Delgado, Cl., and Rutledge, E. Second-look operation in ovarian cancer, Cancer 38, 1438-1442
(1976).
Phillips, B. D., Buchsbaum, H. J.. and Lifshitz, S. Re-exploration after treatment for ovarian carcinoma, Gynecol. Oncol. 8, 339-345 (1979). 3. Schwarts, P. E., and Smith, J. P. Second-look operation in ovarian cancer, Amer. J. Ohsler. 2.
Gynecol.
138, 1124-I
130
(1980).
4. Curry, S. L., Zembo, M. M., Nahhas, W. A., Jahshan, A. E., Whitnney, C. W., and Motel, R. Second-look laparotomy for ovarian cancer, Gynecol. Oncol. 11, 114-l 18 (1981). 5. Greco, F. A., Julian, C. G., Richardson, R. L., Burnett, L., Hande, K. R., and Oldham, R. K. Advanced ovarian cancer: Brief intensive combination chemotherapy and second-look operation, Obstet. Gynecol. 58, 199-205 (1981). 6. Webb, M. J., Snyder, J. A., Williams, T. J., and Decker. D. J. Second-look laparotomy in ovarian cancer, Gynecol. Oncol. 14, 285-293 (1982). 7. Raju, K. S., McKinna, J. A., Barker, G. H., Wiltshaw, E.. and Jones, J. M. Second-look laparotomy in the planned management of advanced ovarian cancer, Amer. J. Obstet. Gynecol. 144, 650-654
(1982).
8. Roberts, W. S.. Hodel, K., Rich, W. M., and DiSaia, Ph.J. Second-look laparotomy in the management of gynecologic malignancy, Gynecol. Oncol. 13, 345-355 (1982). 9. Stuart, G. C. E., Jefries, M., and Anderson, R. J. Changing role of “second-look” laparotomy in the management of epithelial carcinoma of the ovary, Amer. J. Obsrer. Gynecol. 142, 612616 (1982). 10. Fuks, Z., Rizel, Sh., Anteby, Sh.O., and Biran, Sh. The multimode1 approach to the treatment of stage III ovarian carcinoma, Inr. J. Radiat. Oncol. Eiol. Phys. 8, 903-908 (1982). 11. Cohen, C. J., Goldberg, J. D., Holland, J. F., Bruckner, H. W., Deppe, G., Gusberg, S. B., Wallach, R. C., Kabakow, B., and Rodin, J. Improved therapy with cisplatin regimens for patients with ovarian carcinoma. (FIG0 stage III and IV) as measured by surgical end-staging (second-look operation), Amer. J. Obstet. Gynecol. 145, 955-967 (1983). 12. Berek, J. S., Hacker, N. F., Lagasse, L. D., Poth, T., Resnick, B., and Nieberg, R. K. Secondlook laparotomy in stage III epithelial ovarian cancer: Clinical variables associated with disease status,
13.
Obsret.
Gynecol.
64,
207-212
(1984).
Greiner, R., Goldhirsh, A., Davis, B. W., Dreher, E., Peyer, T., Lecher, G., Neuenschwander,
154
MENCZER
ET
AL.
H., Joss, R., Brunner, K., and Veraguth, P. Whole-abdomen radiation with advanced carcinoma after surgery, chemotherapy and second-look laparotomy, J. C/in. Res. Oncol. 107, 94-98 (1984). 14. Peto, R., Pike, M. C., Armitage, P., Breskow, N. E., Cox, D. R., Howard, S. V., Mantel, N., McPherson, K., Peto, J., and Smith, P. G. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. &it. J. Cancer 35, l-39 (1977). 15. Hainsworth, J. D., Malcolm, A., Johnson, D. H., Burnett, L. S., Jones, H. W., and Greco, F. A. Advanced minimal residual ovarian carcinoma: Abdominopelvic irradiation following combination chemotherapy. Obstet. Gynecol. 61, 619-623 (1983). 16. Piver, M. S., Barlow, J. J., and Lee, F. T. Sequential therapy for advanced ovarian adenocarcinoma. Operation, chemotherapy, second-look laparotomy and radiation therapy, Amer. J. Obstet. Gynecol.
122, 355-357
(1975).
17. Dembo, A. J., Bush, R. S., Beale, F. A., Bean, M. A., Pringle, J. F., Sturgeon, J., and Reid, J. G. Improved survival following abdominopelvic irradiation in patients with a completed pelvic operation. Amer. J. Obsret. Gynecol. 134, 793-800 (1979). 18. Menczer, J., Ben-Baruch, G., Modan, M., Brenner, J., and Brenner, H. A comparison of postoperative radiotherapy with postoperative chemotherapy in stage II-IV ovarian cancer patients, Gynecol. Oncol. 17, 207-212 (1984).