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Immature teratoma of the ovary
GYNECOLOGIC
34, 46-49 (1989)
ONCOLOGY
Immature Teratoma of the Ovary JOHN *Division
P. KOULOS,M.D., *.’ JAMES S. HOFFMAN, M.D.,* AND MARGARET M. STEINHOFF, M.D.?
of Gynecologic
Oncology,
Department
of Obstetrics and Gynecology, TDepartment Center, Farmington, Connecticut 06032
of Pathology,
University
of Connecticut
Health
Received February 4, 1988
mature neural elements. These tumors are generally radioresistant. However, with the usage of triple-agent chemotherapy, the prognosis for patients with malignant germ cell tumors has improved considerably. In this study we examined the clinical management and therapy of Twenty-oneof the twenty-threepatients were treated with some cases of immature teratoma of the ovary as recorded by form of unilateral adnexal surgery with or without adjuvant com- a population-based cancer registry.
Twenty-five casesof patients with pure immature teratoma of the ovary, accrued from the Connecticut Tumor Registry from 1969 to 1984, were reviewed. Two patients had grade 1 tumors, twelve had grade 2 tumors, and eleven had grade 3 tumors. The majority of patients (23) were stage I at the time of initial surgery.
bination chemotherapy (VAC). Two of the twenty-three patients weretreatedwith total abdominalhysterectomy/bilateralsalpingooophorectomy (TAH/BSO) with the addition of either VAC chemotherapy or radiation therapy. Recurrence occurred in two patients, both of whom had grade3 tumors and weresubsequentlytreated
with surgicalresectionplus VAC chemotherapy.Onepatient, who recurred after initial therapy with unilateral salpingo-oophorectomy (USO) plus VAC chemotherapy, was successfully treated with surgical resectionand further chemotherapy.Two patients were
stageIII at the time of initial surgery, one of whom was treated with US0 plus adjuvant combination chemotherapy and radiotherapy. The other patient was treated with TAH/BSO plus VAC chemotherapy. In our series, no patient died from immature teratoma (one patient died from advanced breast carcinoma). It is reasonableto withhold chemotherapyfrom patients with stage I, grade 1 and 2, immature teratoma which may be treated initially with conservative surgery. The risk of recurrence in patients with grade 3 tumors warrants the addition of further chemotherapy. 8 1989 Academic
F’ress, Inc.
INTRODUCTION
Germ cell tumors of the ovary account for approximately U-20% of all ovarian neoplasms. The immature teratoma is the third most common germ cell tumor of the ovary and is composed of tissues derived from the three germ cell layers which contain immature or embryonal structures. The grading is based upon the distribution of im-
MATERIALS
AND METHODS
Case histories of female patients with pure immature teratoma diagnosed between 1969and 1984were reviewed from the Connecticut Tumor Registry (CTR) records. The CTR is a population-based registry that accrues data primarily from hospital and clinic records throughout the State of Connecticut, with a small number of casesreported from death certificates and private physicians’ offices. Only cases of pure immature teratoma, 25 patients, were included in this study. Histopathological review of all slides was done at the Department of Pathology, University of Connecticut Health Center, by one pathologist (M.S.). Immature teratoma was graded using the criteria of Thurlbeck and Scully [I], as modified by Norris et al. [2]. The histologic grade of the tumor was based on three factors: degree of immaturity, presence of neuroepithelial component, and quantity of the latter. Teratomas containing elements of other malignant germ cell tumors, such as dysgerminomas, endodermal sinus tumor, or choriocarcinoma were excluded from this study. Clinical data were collected from CTR records, hospital medical records, and correspondence with patients’ physicians. Follow-up information was obtained on all cases. RESULTS
’ To whom reprint requests should be addressed at Division of Gynecologic Oncology, College of Physicians and Surgeons, ColumbiaPresbyterian Medical Center, 161 Fort Washington Avenue, AP-447, New York, NY 10032. 46 0090-8258189$1SO Copyright 0 1989 by Academic Press, Inc. All rightsof reproduction in any form reserved.
Twenty-five patients with pure immature teratoma were accessioned from the CTR over the 15year study period 1969 to 1984. The patients ranged from 7 to 32 years of
IMMATURE
TERATOMA
TABLE 1 Treatment of Immature Teratoma-Connecticut Stage
Treatment”
47
OF THE OVARY
Tumor Registry (1969-1984) Grade 1
Grade 2
Grade 3
IA (20)b 1 UC 1 uo 2 UO + VAC 4 us0 10 US0 + VAC 1 TAH/BSO + VAC 1 TAH/BSO + WA/P-RT
1 1
1 1 2 5 1
2d 5 1
IC (3) 1 UC 1 uo 1 US0 + VAC
1 1 1
III (2) 1 US0 + VAC + P-RT + Bleo/CCNU 1 TAH/BSO + VAC
1 1
Note. UC, unilateral cystectomy; UO, unilateral oophorectomy; USO, unilateral salpingo-oophorectomy; TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy; VAC, vincristine, actinomycin D, Cytoxan; WA/P-RT= whole abdomen/pelvic radiotherapy. y No patiets died from immature teratoma. b Number of patients. ’ Death secondary to breast cancer. d Two patients developed recurrence-both subsequently treated with TAH/BSO + VAC; both NED (109-l 12 months). ’ Recurrence-subsequently treated with debulking + VAB/DTIC; NED (111 months).
age, with a median age of 21 years. Twenty-four patients were white; one patient was black. Table 1 depicts the stage, treatment (surgery, chemotherapy, radiation therapy), grade, and outcome for all 25 patients. The majority of patients were stage I at the time of initial surgery (20 patients were stage IA; 3 patients were stage IC). With the exception of two patients in the stage I group, the patients were initially treated with some form of unilateral adnexal surgery (cystectomy, oophorectomy, or salpingo-oophorectomy) with or without the addition of postoperative adjuvant combination chemotherapy (VAC). The two remaining patients underwent total abdominal hysterectomy and bilateral salpingooophorectomy (TAH/BSO) with the addition of either postoperative VAC chemotherapy or whole abdominal pelvic radiation therapy. In the stage I group, 22 out of 23 patients are alive with no evidence of disease (NED) at 13-152 months. One patient remained NED for 5 years but subsequently died from a secondary breast carcinoma. Eight patients in the stage I category were treated initially with conservative surgery only. One patient had a grade 1 tumor; four patients, grade 2; and three patients, grade 3. Recurrences occurred in two patients, both of whom had grade 3 tumors. Both patients were subsequently treated with TAH/BSO and VAC and were NED at 109 and 112 months. Fourteen of the remaining fifteen patients in the stage I category were given VAC chemotherapy after initial surgery. One patient had a grade 1 tumor; eight patients, grade 2; and five patients, grade 3. Recurrence occurred
in one patient, who had a stage IC, grade 2 tumor initially treated with unilateral salpingo-oophorectomy and VAC chemotherapy. This patient was subsequently successfully treated with laparotomy with debulking, followed by VAB/DTIC chemotherapy. All fourteen patients are NED. The remaining patient, who had a grade 3 tumor, was intially treated with TAH/BSO followed by pelvic abdominal radiation therapy and was NED at 152 months. Eight patients in the stage I category underwent secondlook laparotomy following completion of therapy. All eight patients were NED at operation. Of interest, three of the eight patients had presence of implants compatible with mature teratoma, grade 0. Two patients were stage III, grade 3, at the time of initial surgery. One patient was treated with unilateral salpingo-oophorectomy with subsequent adjuvant combination chemotherapy and pelvic radiation therapy. The other patient was treated with TAH/BSO and postoperative adjunctive VAC chemotherapy. These two patients remained NED at 149 and 81 months, respectively. DISCUSSION In the past, especially before the use of combination chemotherapy, the prognosis of patients with a diagnosis of immature teratoma was poor. Norris er af. [21 studied 58 immature ovarian teratomas. Although his group found that size and stage of teratomas were correlated to survival, it was the grade of the primary tumor that best determined the likelihood of metastatic spread and it was the grade
48
KOULOS, HOFFMAN, AND STEINHOFF
of metastasis that best correlated to outcome. Norris et al. observed progression of disease in 18% of patients with grade 1 disease, in 37% with grade 2 disease, and in 70% of patients with grade 3 disease. It is evident that the majority of patients with immature teratoma in the study had been successfully treated with some form of surgery with or without the addition of adjuvant chemotherapy. The use of VAC chemotherapy has been shown to be highly successful in selective patients with immature teratoma. This result has been demonstrated in several other series. Curry et al. [3] performed a retrospective study of 25 patients with pure malignant teratoma of the ovary. Radiation therapy and/or singleagent chemotherapy were used in eight advanced-stage cases. All of those cases died of progressive disease. However, survival was observed in 10 of 12 patients treated postoperatively with combination chemotherapy using VAC. Gershenson et al. [4] reviewed 41 patients with pure immature teratoma of the ovary treated at M.D. Anderson Hospital and Tumor Institute from 1944 to 1985. Twentyone patients received combination VAC chemotherapy postoperatively, and 18 patients were cured. Schwartz [5] treated 24 patients with ovarian germ cell malignancies with combination chemotherapy. Of 9 patients who had pure immature teratoma, adjuvant VAC chemotherapy was administered postoperatively with courses ranging from 6 to 18 cycles. There were no failures, with follow-up ranging from 14 to 82 months. Of these 9 patients, one had grade 1 disease, 3 had grade 2 disease, and 5 had grade 3 disease. Eight of Schwartz’ patients have been included in our study. In the final report of the Gynecologic Oncology Group study of the use of adjuvant VAC chemotherapy in the treatment of malignant germ cell tumors, Slayton et al. [6] analyzed 76 patients treated postoperatively. Of 28 patients with grade 2 and 3 immature teratoma, 5 (18%) failed during or after treatment with VAC, including 1 of 20 patients (5%) with completely resected immature teratoma (recurrent disease) and 4 of 8 patients (50%) with incompletely resected immature teratoma. Furthermore, in their analysis, unilateral salpingo-oophorectomy appeared to be just as effective as TAH/BSO in patients with stage I disease, thereby preserving fertility. In our series, 18 of the 23 patients with stage I disease were able to undergo conservative surgery with preservation of the uterus and contralateral adnexa. The Gynecologic Oncology Group is currently undergoing a phase II adjuvant chemotherapy study with BEP (bleomycin/VP16/c&platinum), in patients with totally resected choriocarcinoma, endodermal sinus tumor, embryonal carcinoma, or grade 3 immature teratoma of the ovary. In our series, one patient who recurred after the use of VAC chemotherapy was subsequently successfully
treated with VAB/DTIC chemotherapy. Over the past decade, two very active cytotoxic drugs, &-platinum and etoposide (VP-16), have been utilized in the treatment of malignant germ cell tumors. Alternative regimens to VAC, in immature teratoma and other malignant germ cell tumors, included such agents as &-platinum, bleomycin, vinblastine, and etoposide (VP-16). In contrast to VAC chemotherapy, the use of alternative therapy such as PVB has allowed reduced treatment cycles because of improved effectiveness, but this is coupled with potential side effects. Most significant is the onset of pulmonary toxicity secondary to bleomycin. Carlson et al. [7] reported on nine women with malignant germ cell tumors of the ovary who were treated with PVB chemotherapy after cytoreductive operations. All nine patients are NED with median follow-up of 27 months since completion of PVB. Of these nine patients, four had immature teratoma (one had grade 2 and three had grade 3). At Charing Cross Hospital, Newlands et al [8] has stressed the importance of combination chemotherapy, including cisplatin and etoposide, in the treatment of advanced malignant ovarian germ cell tumors. The use of sequential combination chemotherapy with reduced intervals between courses carries the possibility of reducing the opportunity for tumor recovery and the potential development of drug resistance. Our review confirms the efficacy of VAC as therapy for immature teratoma. Only one of 16 treated cases had recurrence of immature teratoma after the use of VAC chemotherapy. She was one of 14 stage I patients. Both stage III patients had durable responses to VAC although one had simultaneous use of other treatments. There were insufficient advanced-staged cases to evaluate Dr. Slayton’s concern that the efficacy of VAC might be reduced in advanced stage. Eight patients were not given adjuvant therapy following resection of stage I immature teratoma. Two of three patients with grade 3 tumors recurred, while none of the five patients with grade 1 and 2 tumors recurred. Both of the recurrent grade 3 tumors responded well to surgical resection plus VAC following recurrence. Thus, our series suggests the reasonableness of withholding chemotherapy therapy from patients with stage I, grade 1 and 2, immature teratomas if they can be carefully followed for possible recurrence. Despite the success of salvage therapy in patients with grade 3 teratomas, their risk of recurrence in this group warrants therapy. REFERENCES 1. Thurlbeck, W. M., and Scully, R. E. Solid teratoma of the ovary: A clinico-pathologic analysis of 9 cases, Cancer 13, 801 (1960). 2. Norris, H. J., Zirkin, H. J., and Benson, W. L. Immature (malignant) teratoma of the ovary, Cancer 37, 2359-2372 (1976).
IMMATURE
TERATOMA
3. Curry, S. L., Smith, J. P., and Gallagher, H. S. Malignant teratoma of the ovary: Prognostic factors and treatment, Amer. J. Obstet. Gynecol. 131, 845-849 (1978). 4. Gershenson, D. M., DelJunco, G., Silva, E. G., Copeland, L. J., and Wharton, J. T. Immature teratoma of the ovary, Obstet. Gynecof. 68, 624-629 (1986). 5. Schwartz, P. E. Combination chemotherapy in the management of ovarian germ cell malignancies, Obstet. Gynecol. 64, W-572 (1984). 6. Slayton, R. E., Park, R. C., Silverberg, S. G., Shingleton, H., Creasman, W. T., and Blessing, J. A. Vincristine, dactinomycin,
OF THE OVARY
49
and cyclophosphamide in the treatment of mahgnant germ cell tumors of the ovary, Cancer 56, 243-248 (1985). 7. Carlson, R. W., Sikic, B. I., Turbow, M. M., and Ballon, S. C. Combination cisplatin, vinblastine, and bleomycin chemotherapy (PVB) for malignant germ-cell tumors of the ovary, .I. Clin. Oncof. 1, 645-651 (1983). 8. Newlands, E. S., Begent, R. H. J., Rustin, G. J. S., Parker, D., and Bagshawe, K. D. Further advances in the management of malignant teratomas of the testis and other sites, Lancet Vol. I 948951 (1983).
34, 46-49 (1989)
ONCOLOGY
Immature Teratoma of the Ovary JOHN *Division
P. KOULOS,M.D., *.’ JAMES S. HOFFMAN, M.D.,* AND MARGARET M. STEINHOFF, M.D.?
of Gynecologic
Oncology,
Department
of Obstetrics and Gynecology, TDepartment Center, Farmington, Connecticut 06032
of Pathology,
University
of Connecticut
Health
Received February 4, 1988
mature neural elements. These tumors are generally radioresistant. However, with the usage of triple-agent chemotherapy, the prognosis for patients with malignant germ cell tumors has improved considerably. In this study we examined the clinical management and therapy of Twenty-oneof the twenty-threepatients were treated with some cases of immature teratoma of the ovary as recorded by form of unilateral adnexal surgery with or without adjuvant com- a population-based cancer registry.
Twenty-five casesof patients with pure immature teratoma of the ovary, accrued from the Connecticut Tumor Registry from 1969 to 1984, were reviewed. Two patients had grade 1 tumors, twelve had grade 2 tumors, and eleven had grade 3 tumors. The majority of patients (23) were stage I at the time of initial surgery.
bination chemotherapy (VAC). Two of the twenty-three patients weretreatedwith total abdominalhysterectomy/bilateralsalpingooophorectomy (TAH/BSO) with the addition of either VAC chemotherapy or radiation therapy. Recurrence occurred in two patients, both of whom had grade3 tumors and weresubsequentlytreated
with surgicalresectionplus VAC chemotherapy.Onepatient, who recurred after initial therapy with unilateral salpingo-oophorectomy (USO) plus VAC chemotherapy, was successfully treated with surgical resectionand further chemotherapy.Two patients were
stageIII at the time of initial surgery, one of whom was treated with US0 plus adjuvant combination chemotherapy and radiotherapy. The other patient was treated with TAH/BSO plus VAC chemotherapy. In our series, no patient died from immature teratoma (one patient died from advanced breast carcinoma). It is reasonableto withhold chemotherapyfrom patients with stage I, grade 1 and 2, immature teratoma which may be treated initially with conservative surgery. The risk of recurrence in patients with grade 3 tumors warrants the addition of further chemotherapy. 8 1989 Academic
F’ress, Inc.
INTRODUCTION
Germ cell tumors of the ovary account for approximately U-20% of all ovarian neoplasms. The immature teratoma is the third most common germ cell tumor of the ovary and is composed of tissues derived from the three germ cell layers which contain immature or embryonal structures. The grading is based upon the distribution of im-
MATERIALS
AND METHODS
Case histories of female patients with pure immature teratoma diagnosed between 1969and 1984were reviewed from the Connecticut Tumor Registry (CTR) records. The CTR is a population-based registry that accrues data primarily from hospital and clinic records throughout the State of Connecticut, with a small number of casesreported from death certificates and private physicians’ offices. Only cases of pure immature teratoma, 25 patients, were included in this study. Histopathological review of all slides was done at the Department of Pathology, University of Connecticut Health Center, by one pathologist (M.S.). Immature teratoma was graded using the criteria of Thurlbeck and Scully [I], as modified by Norris et al. [2]. The histologic grade of the tumor was based on three factors: degree of immaturity, presence of neuroepithelial component, and quantity of the latter. Teratomas containing elements of other malignant germ cell tumors, such as dysgerminomas, endodermal sinus tumor, or choriocarcinoma were excluded from this study. Clinical data were collected from CTR records, hospital medical records, and correspondence with patients’ physicians. Follow-up information was obtained on all cases. RESULTS
’ To whom reprint requests should be addressed at Division of Gynecologic Oncology, College of Physicians and Surgeons, ColumbiaPresbyterian Medical Center, 161 Fort Washington Avenue, AP-447, New York, NY 10032. 46 0090-8258189$1SO Copyright 0 1989 by Academic Press, Inc. All rightsof reproduction in any form reserved.
Twenty-five patients with pure immature teratoma were accessioned from the CTR over the 15year study period 1969 to 1984. The patients ranged from 7 to 32 years of
IMMATURE
TERATOMA
TABLE 1 Treatment of Immature Teratoma-Connecticut Stage
Treatment”
47
OF THE OVARY
Tumor Registry (1969-1984) Grade 1
Grade 2
Grade 3
IA (20)b 1 UC 1 uo 2 UO + VAC 4 us0 10 US0 + VAC 1 TAH/BSO + VAC 1 TAH/BSO + WA/P-RT
1 1
1 1 2 5 1
2d 5 1
IC (3) 1 UC 1 uo 1 US0 + VAC
1 1 1
III (2) 1 US0 + VAC + P-RT + Bleo/CCNU 1 TAH/BSO + VAC
1 1
Note. UC, unilateral cystectomy; UO, unilateral oophorectomy; USO, unilateral salpingo-oophorectomy; TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy; VAC, vincristine, actinomycin D, Cytoxan; WA/P-RT= whole abdomen/pelvic radiotherapy. y No patiets died from immature teratoma. b Number of patients. ’ Death secondary to breast cancer. d Two patients developed recurrence-both subsequently treated with TAH/BSO + VAC; both NED (109-l 12 months). ’ Recurrence-subsequently treated with debulking + VAB/DTIC; NED (111 months).
age, with a median age of 21 years. Twenty-four patients were white; one patient was black. Table 1 depicts the stage, treatment (surgery, chemotherapy, radiation therapy), grade, and outcome for all 25 patients. The majority of patients were stage I at the time of initial surgery (20 patients were stage IA; 3 patients were stage IC). With the exception of two patients in the stage I group, the patients were initially treated with some form of unilateral adnexal surgery (cystectomy, oophorectomy, or salpingo-oophorectomy) with or without the addition of postoperative adjuvant combination chemotherapy (VAC). The two remaining patients underwent total abdominal hysterectomy and bilateral salpingooophorectomy (TAH/BSO) with the addition of either postoperative VAC chemotherapy or whole abdominal pelvic radiation therapy. In the stage I group, 22 out of 23 patients are alive with no evidence of disease (NED) at 13-152 months. One patient remained NED for 5 years but subsequently died from a secondary breast carcinoma. Eight patients in the stage I category were treated initially with conservative surgery only. One patient had a grade 1 tumor; four patients, grade 2; and three patients, grade 3. Recurrences occurred in two patients, both of whom had grade 3 tumors. Both patients were subsequently treated with TAH/BSO and VAC and were NED at 109 and 112 months. Fourteen of the remaining fifteen patients in the stage I category were given VAC chemotherapy after initial surgery. One patient had a grade 1 tumor; eight patients, grade 2; and five patients, grade 3. Recurrence occurred
in one patient, who had a stage IC, grade 2 tumor initially treated with unilateral salpingo-oophorectomy and VAC chemotherapy. This patient was subsequently successfully treated with laparotomy with debulking, followed by VAB/DTIC chemotherapy. All fourteen patients are NED. The remaining patient, who had a grade 3 tumor, was intially treated with TAH/BSO followed by pelvic abdominal radiation therapy and was NED at 152 months. Eight patients in the stage I category underwent secondlook laparotomy following completion of therapy. All eight patients were NED at operation. Of interest, three of the eight patients had presence of implants compatible with mature teratoma, grade 0. Two patients were stage III, grade 3, at the time of initial surgery. One patient was treated with unilateral salpingo-oophorectomy with subsequent adjuvant combination chemotherapy and pelvic radiation therapy. The other patient was treated with TAH/BSO and postoperative adjunctive VAC chemotherapy. These two patients remained NED at 149 and 81 months, respectively. DISCUSSION In the past, especially before the use of combination chemotherapy, the prognosis of patients with a diagnosis of immature teratoma was poor. Norris er af. [21 studied 58 immature ovarian teratomas. Although his group found that size and stage of teratomas were correlated to survival, it was the grade of the primary tumor that best determined the likelihood of metastatic spread and it was the grade
48
KOULOS, HOFFMAN, AND STEINHOFF
of metastasis that best correlated to outcome. Norris et al. observed progression of disease in 18% of patients with grade 1 disease, in 37% with grade 2 disease, and in 70% of patients with grade 3 disease. It is evident that the majority of patients with immature teratoma in the study had been successfully treated with some form of surgery with or without the addition of adjuvant chemotherapy. The use of VAC chemotherapy has been shown to be highly successful in selective patients with immature teratoma. This result has been demonstrated in several other series. Curry et al. [3] performed a retrospective study of 25 patients with pure malignant teratoma of the ovary. Radiation therapy and/or singleagent chemotherapy were used in eight advanced-stage cases. All of those cases died of progressive disease. However, survival was observed in 10 of 12 patients treated postoperatively with combination chemotherapy using VAC. Gershenson et al. [4] reviewed 41 patients with pure immature teratoma of the ovary treated at M.D. Anderson Hospital and Tumor Institute from 1944 to 1985. Twentyone patients received combination VAC chemotherapy postoperatively, and 18 patients were cured. Schwartz [5] treated 24 patients with ovarian germ cell malignancies with combination chemotherapy. Of 9 patients who had pure immature teratoma, adjuvant VAC chemotherapy was administered postoperatively with courses ranging from 6 to 18 cycles. There were no failures, with follow-up ranging from 14 to 82 months. Of these 9 patients, one had grade 1 disease, 3 had grade 2 disease, and 5 had grade 3 disease. Eight of Schwartz’ patients have been included in our study. In the final report of the Gynecologic Oncology Group study of the use of adjuvant VAC chemotherapy in the treatment of malignant germ cell tumors, Slayton et al. [6] analyzed 76 patients treated postoperatively. Of 28 patients with grade 2 and 3 immature teratoma, 5 (18%) failed during or after treatment with VAC, including 1 of 20 patients (5%) with completely resected immature teratoma (recurrent disease) and 4 of 8 patients (50%) with incompletely resected immature teratoma. Furthermore, in their analysis, unilateral salpingo-oophorectomy appeared to be just as effective as TAH/BSO in patients with stage I disease, thereby preserving fertility. In our series, 18 of the 23 patients with stage I disease were able to undergo conservative surgery with preservation of the uterus and contralateral adnexa. The Gynecologic Oncology Group is currently undergoing a phase II adjuvant chemotherapy study with BEP (bleomycin/VP16/c&platinum), in patients with totally resected choriocarcinoma, endodermal sinus tumor, embryonal carcinoma, or grade 3 immature teratoma of the ovary. In our series, one patient who recurred after the use of VAC chemotherapy was subsequently successfully
treated with VAB/DTIC chemotherapy. Over the past decade, two very active cytotoxic drugs, &-platinum and etoposide (VP-16), have been utilized in the treatment of malignant germ cell tumors. Alternative regimens to VAC, in immature teratoma and other malignant germ cell tumors, included such agents as &-platinum, bleomycin, vinblastine, and etoposide (VP-16). In contrast to VAC chemotherapy, the use of alternative therapy such as PVB has allowed reduced treatment cycles because of improved effectiveness, but this is coupled with potential side effects. Most significant is the onset of pulmonary toxicity secondary to bleomycin. Carlson et al. [7] reported on nine women with malignant germ cell tumors of the ovary who were treated with PVB chemotherapy after cytoreductive operations. All nine patients are NED with median follow-up of 27 months since completion of PVB. Of these nine patients, four had immature teratoma (one had grade 2 and three had grade 3). At Charing Cross Hospital, Newlands et al [8] has stressed the importance of combination chemotherapy, including cisplatin and etoposide, in the treatment of advanced malignant ovarian germ cell tumors. The use of sequential combination chemotherapy with reduced intervals between courses carries the possibility of reducing the opportunity for tumor recovery and the potential development of drug resistance. Our review confirms the efficacy of VAC as therapy for immature teratoma. Only one of 16 treated cases had recurrence of immature teratoma after the use of VAC chemotherapy. She was one of 14 stage I patients. Both stage III patients had durable responses to VAC although one had simultaneous use of other treatments. There were insufficient advanced-staged cases to evaluate Dr. Slayton’s concern that the efficacy of VAC might be reduced in advanced stage. Eight patients were not given adjuvant therapy following resection of stage I immature teratoma. Two of three patients with grade 3 tumors recurred, while none of the five patients with grade 1 and 2 tumors recurred. Both of the recurrent grade 3 tumors responded well to surgical resection plus VAC following recurrence. Thus, our series suggests the reasonableness of withholding chemotherapy therapy from patients with stage I, grade 1 and 2, immature teratomas if they can be carefully followed for possible recurrence. Despite the success of salvage therapy in patients with grade 3 teratomas, their risk of recurrence in this group warrants therapy. REFERENCES 1. Thurlbeck, W. M., and Scully, R. E. Solid teratoma of the ovary: A clinico-pathologic analysis of 9 cases, Cancer 13, 801 (1960). 2. Norris, H. J., Zirkin, H. J., and Benson, W. L. Immature (malignant) teratoma of the ovary, Cancer 37, 2359-2372 (1976).
IMMATURE
TERATOMA
3. Curry, S. L., Smith, J. P., and Gallagher, H. S. Malignant teratoma of the ovary: Prognostic factors and treatment, Amer. J. Obstet. Gynecol. 131, 845-849 (1978). 4. Gershenson, D. M., DelJunco, G., Silva, E. G., Copeland, L. J., and Wharton, J. T. Immature teratoma of the ovary, Obstet. Gynecof. 68, 624-629 (1986). 5. Schwartz, P. E. Combination chemotherapy in the management of ovarian germ cell malignancies, Obstet. Gynecol. 64, W-572 (1984). 6. Slayton, R. E., Park, R. C., Silverberg, S. G., Shingleton, H., Creasman, W. T., and Blessing, J. A. Vincristine, dactinomycin,
OF THE OVARY
49
and cyclophosphamide in the treatment of mahgnant germ cell tumors of the ovary, Cancer 56, 243-248 (1985). 7. Carlson, R. W., Sikic, B. I., Turbow, M. M., and Ballon, S. C. Combination cisplatin, vinblastine, and bleomycin chemotherapy (PVB) for malignant germ-cell tumors of the ovary, .I. Clin. Oncof. 1, 645-651 (1983). 8. Newlands, E. S., Begent, R. H. J., Rustin, G. J. S., Parker, D., and Bagshawe, K. D. Further advances in the management of malignant teratomas of the testis and other sites, Lancet Vol. I 948951 (1983).