Borderline epithelial ovarian tumors: a review of 81 cases with an assessment of the impact of treatment.

Optimal management of borderline epithelial ovarian tumors remains controversial because of the lack of clear, universally accepted pathologic criteria for diagnosis, the lack of complete understanding of the significance of intraperitoneal implants, and the desire to employ more limited surgery in young women. We reviewed the experience with borderline epithelial ovarian tumors at Princess Margaret Hospital in order to assess the natural history of the disease, to determine prognostic factors that would aid in management decisions, and to determine if adjuvant therapy influenced outcome. Eighty-one patients were analyzed. The mean age was 48 years. Seventy-two percent of tumors were of the serous histologic sub-type and 28% were mucinous. Seventy-eight percent were Stage I, 11% Stage II, and 11% Stage III. Peritoneal washings contained malignant cells in 14 of 32 patients (not recorded or obtained in 49), cyst rupture occurred in 25%, surface excrescences in 40%, and adhesions in 46%. None of these factors had a significant effect on recurrence rate or survival. Eleven patients received adjuvant radiation therapy (10 abdomino-pelvic and 1 pelvic alone), four adjuvant chemotherapy, and one both radiation therapy and chemotherapy. The rest (65) received no adjuvant therapy. Due to the small numbers and infrequent events, it was not possible to analyze and thus draw valid conclusions regarding the effect of adjuvant therapy on survival or recurrence. The overall survival (OS) and cause specific survival (CSS) were 85% and 96% at 10 years, respectively. No Stage I patient died of tumor. OS for Stage I patients was 90% at 10 years, the majority of whom (61 of 63) received no adjuvant therapy, and is thus unnecessary in Stage I disease. The adequacy of unilateral oophorectomy or ovarian cystectomy could not be confirmed because of small numbers. The 10 year OS and disease-free survival in Stage II and III were 75% and 50%, respectively, despite the use of adjuvant radiation therapy, chemotherapy, or both. It is necessary to create a multi-center tumor registry in order to acquire a prospective data base from which to develop sound therapeutic decisions.     

Transitional cell carcinoma in high-grade high-stage ovarian carcinoma. An indicator of favorable response to chemotherapy

We reviewed 53 high-grade carcinomas of the ovary in order to define pathologic features that correlate with prognosis. All tumors were Stage III with comparable amounts of residual tumor left after the primary resection. Similar postoperative chemotherapeutic regimens were given to each patient, and there was a clinical followup of at least four years in each case. The tumors were classified according to their predominant (greater than 50%) histology as transitional cell carcinoma (TCC) (18 tumors), papillary serous (18), undifferentiated (8), or endometrioid (3). There were six mixed carcinomas without predominant histology. In 17 of 18 patients, TCC predominant tumors responded completely to chemotherapy and 15 of 18 patients (83%) are alive without disease 4 to 10 years after presentation (average 6.8 years). In comparison, tumor progression/recurrence developed in 31 of 35 non-TCC tumors (18 serous, eight undifferentiated, one endometrioid predominant, and four mixed carcinomas). Of these 35 patients, 27 (77%) died of disease from 6 months to 7 years after presentation (average 2.5 yrs.). Flow cytometric determination of DNA content and immunoperoxidase studies did not allow discrimination between the histologic types of high-grade ovarian carcinomas. We conclude that TCC should be recognized as a distinct histologic type of ovarian carcinoma because of the favorable response to chemotherapy and improved patient survival.     

Patterns of failure after the multimodality treatment of uterine papillary serous carcinoma

PURPOSE: Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial carcinoma. The majority of patients with clinical Stage I UPSC are found to have extrauterine disease at the time of surgery. Most authors report survival rates of 35-50% for Stage I-II and 0-15% for Stage III and IV UPSC. Surgical treatment as the sole therapy for patients with Stage I-IV UPSC is unacceptable because of high recurrence rates. Chemotherapy, radiotherapy, or both have been added after surgery in an attempt to improve survival. However, the survival benefit to patients from such multimodality therapy remains uncertain. This study analyzes the patterns of failure in patients with FIGO Stages I-IV UPSC treated by multimodality therapy. METHODS AND MATERIALS: Forty-two women with FIGO Stages I-IV UPSC who were treated by multimodality therapy were analyzed retrospectively between 1988 and 1998. Data were obtained from tumor registry, hospital, and radiotherapy chart reviews, operative notes, pathology, and chemotherapy flow sheets. All the patients underwent staging laparotomy, peritoneal cytology, total abdominal hysterectomy and salpingo oophorectomy, pelvic and para-aortic lymph node sampling, omentectomy, and cytoreductive surgery, when indicated followed by radiotherapy and/or chemotherapy. Therapy consisted of external beam radiation therapy in 11 patients (26%), systemic chemotherapy in 20 (48%), and both radiotherapy and chemotherapy in 11 (26%). The treatments were not assigned in a randomized fashion. The dose of external beam radiation therapy ranged from 45-50.40 Gy (median 45). Of the 31 patients (74%) who received chemotherapy, 18 received single-agent (58%), whereas 13 received multiagent chemotherapy (42%). RESULTS: Median follow-up for all patients was 19 months (range 4-72). Median follow-up for the surviving patients was 36 months (range 21-72). Their median age was 65 years. Six patients (14%) had Stage I, 8 patients (19%) had Stage II, 10 (24%) had Stage III, and 18 (43%) had Stage IV disease. Twenty-nine patients (69%) had suffered recurrence at the time of last follow-up. The actuarial failure rate at 2 and 5 years was 58% and 67%, respectively. The majority of the patients (19/29) recurred in the abdomen, vagina, or pelvis (66%). Metastases outside the abdomen were much less common as the first site of failure (17%). Twenty-five patients (60%) had died at the time of reporting; the observed survival rate at 2 years and 5 years was 52% and 43%, respectively. CONCLUSIONS: Our data suggest that, after multimodality therapy of FIGO Stage I-IV UPSC, most patients developed abdominopelvic (locoregional) failure, and the great majority of the failures occurred in the abdomen, vagina, and pelvis (66%). Abdominopelvic failure as a component of distant failure occurred in an additional 5 patients (17%). Distant failure alone occurred in 17% of the patients.We propose that future studies should combine whole abdominal radiotherapy (WART) with pelvic and vaginal boosts, in addition to chemotherapy for FIGO Stage I-IV UPSC, especially in patients with minimal residual disease, to attempt to improve the dismal prognosis of patients with UPSC.     

Pathology of ovarian carcinoma

Serous carcinoma is the most common type of ovarian cancer and usually is associated with peritoneal metastases and poor survival except for meticulously staged patients with tumors confined to the ovaries. Endometrioid and clear cell carcinomas account for most nonserous carcinomas and more often present with low-stage disease; survival for the various cell types is similar when stratified by stage. Borderline ovarian tumors can be subdivided into benign and malignant neoplasms, and in the view of some experts, this renders the borderline category obsolete. Women with typical serous borderline tumors (atypical proliferative serous tumors) constitute most of these patients and have virtually 100% survival, unless invasive peritoneal implants are present. Micropapillary serous carcinomas (a less common variant, also called serous borderline tumor with a micropapillary pattern) and tumors with invasive implants behave similar to low-grade invasive carcinomas.     

Combined modality treatment for stage III ovarian carcinoma

Thirty-eight Stage III ovarian carcinoma patients were treated with a combined modality protocol consisting of sequential initial surgery with a maximal tumor reduction, CHAD combination chemotherapy, second look reductive surgery and whole abdominal irradiation. Sixteen patients (42%) had minimal residual tumors (less than 2 cm) after initial surgery (Stage IIIA) and 22 (58%) had large residual tumors (greater than 2 cm) (Stage IIIB). The patients received 3-14 courses of CHAD combination chemotherapy, with a response rate (CR + PR) in the evaluable (Stage IIIB) patients of 91%. Twenty-eight patients had a second attempt of cytoreductive operation (10 Stage IIIA patients and 18 Stage IIIB patients). In 10 patients no residual tumor was found. In another 12 patients residual tumor (less than 2 cm) was found and completely resected, whereas in six patients a complete resection of large residual tumors (greater than 2 cm) was not possible. Twenty-one of the patients also completed a course of whole abdominal radiotherapy. Radiation was well-tolerated with the usual expected amounts of nausea, vomiting, diarrhea and transient leukopenia and thrombocytopenia. 11/21 (52%) of the patients relapsed within the first 18 months after completion of radiotherapy. The actuarial relapse-free survival at 36 months from completions of radiotherapy was 44%. The actuarial survival for the whole group from diagnosis was 43% at 3 years (70% for Stage IIIA and 41% for Stage IIIB). The data indicated that this combined modality protocol is both feasible and well-tolerated but its curative potential for patients with advanced ovarian carcinoma is as yet unknown.     

Extraovarian peritoneal serous papillary carcinoma. A clinicopathologic study of 31 cases

The rate and clinical features of patients admitted to King George V Hospital with extraovarian peritoneal serous papillary carcinoma during a 9-year period were reviewed. In this time, 31 of 236 (13%) patients with an initial diagnosis of invasive serous ovarian carcinoma fulfilled the surgicopathologic criteria for this entity. All patients had disseminated tumor equivalent to ovarian Stage III and IV disease (International Federation of Gynecology and Obstetrics [FIGO]) and with predominantly high-grade neoplasms. They were managed by surgical exploration, tumor debulking where possible, and postoperative chemotherapy. A comparison with a contemporaneous series of 139 patients with primary epithelial ovarian carcinoma matched for stage and grade of disease and managed similarly showed no difference in actuarial survival. The median survival times were 11.3 months for patients with extraovarian serous papillary carcinomas and 13.5 months for patients with equivalent primary ovarian neoplasms. The features of the disease and the treatment regimens used are discussed.     

Treatment of advanced ovarian cancer with sequential combination chemotherapy

Fifty previously untreated patients with advanced or recurrent ovarian cancer (FIGO Stages III and IV) were treated with alternating combination chemotherapy. This consisted of high-dose doxorubicin (70 mg/m2) and cisplatin (100 mg/m2) alternated with CHF (cyclophosphamide, hexamethylmelamine, and 5-fluorouracil). Toxicity (myelosuppression, nephropathy, and neuropathy) was infrequent and mild. Clinical response rates were high (94% response, 62% complete clinical response), but the majority of patients had residual intraabdominal disease at second-look surgery (75%). Thirteen patients (26%) are alive after 4 years of observation (minimum follow-up). Survival was adversely influenced in patients who were older than 70, had Stage IV disease, residual tumor bulk greater than 2 cm, and who failed to achieve complete clinical remission. The median duration of survival (28 months) and percentage of long-term survivors appear similar to that in other platinum-based chemotherapy studies. Although the role of alternating combination chemotherapy in epithelial ovarian cancer remains undefined, it is likely that an alternate approach will be necessary to markedly improve survival rates for patients with this disease.     

Borderline ovarian tumour: pathological diagnostic dilemma and risk factors for invasive or lethal recurrence

By comparison with ovarian carcinomas, borderline ovarian tumours are characterised clinically by superior overall survival, even in women with peritoneal spread. In this Review, we aimed to clarify the histological and clinical factors potentially defining a high-risk group in whom disease is likely to evolve to invasive disease. Invasive peritoneal implants (in serous borderline ovarian tumours) and residual disease after surgery were the two factors clearly identified. Other factors are controversial owing to increased risk of invasive recurrence: micropapillary patterns in serous borderline ovarian tumour, intraepithelial carcinoma in mucinous lesions, stromal microinvasion in serous lesions, and use of cystectomy in mucinous borderline ovarian tumours. The pathologist has a pivotal role in assessment of the borderline nature of ovarian tumours and in identification of high-risk criteria, most of which are histological. But, reproducibility of the histological interpretation of some of these potential criteria--eg, classification of peritoneal implants (particularly in desmoplastic subtype), stromal microinvasion, micropapillary patterns, and intraepithelial carcinoma in mucinous borderline ovarian tumours--remains unclear, and should be investigated.     

Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy

BACKGROUND: A retrospective review of treatment results comparing women with clear cell carcinoma of the ovary (CCC) with a group with serous adenocarcinoma of the ovary (SAC) was conducted. METHODS: Between 1988-1998, 662 patients with epithelial ovarian carcinoma were identified through the medical records department and the tumor registry at 4 institutions. After the central pathologic review, 101 patients with pure or dominant (>/= 90%) CCC (15.3%) were entered into the current study. Two hundred thirty five patients with pure SAC were selected as a group for comparison. All patients underwent staging laparotomy followed by platinum-based chemotherapy. Distribution of the International Federation of Gynecology and Obstetrics (FIGO) disease stage, response to chemotherapy, and prognosis for patients with CCC were compared with the same values in patients with SAC. RESULTS: Patients with CCC were significantly more likely to have FIGO Stage I disease than were patients with SAC (48.5% vs. 16.6%). A high recurrence rate was noted in those patients with Stage IC CCC (37%). In those patients with Stage IC disease, the survival rates for patients with CCC were lower than those for patients with SAC. The 3-year and 5-year survival rates for Stage III CCC patients were significantly lower compared with Stage III SAC patients. The response rate to platinum-based chemotherapy in patients with CCC was significantly lower than that in patients with SAC. CONCLUSIONS: CCC is an intriguing histologic type of epithelial ovarian cancer that demonstrates a clinical behavior distinctly different from that of SAC.     

年轻妇女卵巢上皮细胞癌预后因素分析

目的　探讨年轻妇女卵巢上皮细胞癌的临床特点、生存率和影响预后的因素。方法回顾分析 1985～ 1997年收治的 4 5 5例卵巢上皮细胞癌患者的临床资料。生存率采用Kaplan Meier方法计算 ,利用Cox风险比例回归模型分析比较影响患者预后的独立因素。结果　≤ 4 0岁组92例 ,>4 0岁 36 3例。≤ 4 0岁组早期、高分化、黏液性癌所占比例明显高于 >4 0岁组 ,浆液性癌、腹水、肿瘤残存所占比例低于 >4 0岁患者 ,差异均有显著性 (P <0 .0 5 )。≤ 4 0岁组和 >4 0岁组的 5年生存率分别为 79.5 %和 2 8.2 % ,差异均有极显著性 (P <0 .0 0 1)。单因素分析两组间同一临床分期、组织类型、分级、肿瘤残存情况等显示 ,在相同情况下 ,≤ 4 0岁患者的生存率明显高于 >4 0岁者。多因素分析显示 ,临床分期、肿瘤残存情况和年龄为影响预后的独立因素。结论　≤ 4 0岁的卵巢上皮细胞癌患者 ,其早期、Ⅰ级、黏液性囊腺癌所占比例高 ,肿瘤残存小 ,腹水少 ,总的 5年生存率高。临床分期、肿瘤残存情况、年龄是影响卵巢上皮细胞癌预后的独立因素。     

Peritoneal implants of ovarian serous borderline tumors. Histologic features and prognosis

The clinicopathologic features of 56 cases of ovarian serous borderline tumors (SBT) associated with peritoneal implants were reviewed. Data from 368 person-years of follow-up (median follow-up, 6.0 years) were analyzed to investigate the possibility that the histologic features of implants of this type of tumor may correlate with the prognosis. Eighty-five percent of the 56 patients were clinically free of tumor at the time of death or at last contact. Thirteen percent of the patients died of tumor, and one patient (2%) was alive with widespread progressive tumor. The product-limit estimate of the probability of death from tumor (+/- standard error) was 4% (+/- 3%) at 5 years and 23% (+/- 9%) at 10 years. The following three histologic features of the implants correlated with an adverse prognosis: (1) invasion (P = 0.0004), (2) severe cytologic atypia in both invasive and noninvasive implants (P = 0.0008) and in noninvasive implants alone (P = 0.02), and (3) the presence of mitotic activity in both types of implants (P = 0.02) and in noninvasive implants alone (P = 0.02). The only other feature that correlated with the prognosis was the presence of residual tumor postoperatively as assessed by the surgeon (P = 0.01). The product-limit estimate of death of tumor in patients with at least one of these four adverse prognostic factors was 56% (+/- 20%) at 10 years. Whether or not the patients received radiation therapy, chemotherapy, or both had no statistically significant effect on the outcome. These data and the results of a stratified analysis suggest that patients may benefit from additional therapy if adverse prognostic factors are present, especially invasiveness or severe cytologic atypia. It is unlikely that additional therapy is necessary in patients without adverse prognostic features, because no deaths occurred in this group.     

Peritoneal papillary serous carcinoma with long-term survival

Three cases of peritoneal papillary serous carcinoma with a complete response to chemotherapy and long-term disease free survival are reported. All three patients presented with multifocal or diffuse peritoneal involvement. Microscopic ovarian serosal surface involvement was demonstrated in two cases. The ovaries were uninvolved in one case. All patients were treated with combination chemotherapy consisting of Adriamycin (doxorubicin) and cisplatin, with or without cytoxan. All three patients survived for 5 years or longer with no clinical evidence of persistent or recurrent tumor.     

Prognosis of stage III or IV primary peritoneal serous papillary carcinoma.

AIMS: To study the prognosis of patients with stage IIIC/IV primary peritoneal serous papillary carcinoma (PSPC) (study group) compared with that of patients with epithelial ovarian carcinoma (EOC) (control group). METHODS: A retrospective case-control study including a study group of 37 patients who were matched with a control group of 37 patients. Patients were matched for the histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (initial or interval) and age (+/-5 years). RESULTS: Debulking surgery was performed initially or at interval surgery in respectively, 10 and 27 patients in the study group and 17 and 20 in the control group. All patients were treated with platinum-based chemotherapy (combined with paclitaxel in 33) in both groups. The overall survival rate at 3 years in the study and control groups was, respectively, 60% versus 55% (NS). However, event-free survival rates at 3 years (CI 95%) were statistically different (respectively, 29% in the study group versus 16% in the control group: p=0.008). CONCLUSIONS: Peritoneal disease is more bulky in patients with PSPC. Neoadjuvant chemotherapy is more often required to achieve optimal debulking surgery in PSPC. Overall survival of patients with PSPC is similar to that of their EOC counterparts. Thus, the management of PSPC should not be different from that of advanced stage EOC.     

Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma

PURPOSE: To determine the efficacy of adjuvant therapy in patients with early-stage uterine papillary serous carcinoma. METHODS AND MATERIALS: Data were collected on all surgically staged Stage I-II uterine papillary serous carcinoma patients. Statistical analyses were performed using the Kaplan-Meier and Cox proportional hazards regression methods. RESULTS: Of 68 patients, 50 had Stage I and 18 had Stage II disease; 35 underwent adjuvant treatment, including radiotherapy in 26, chemotherapy in 7, and combined RT and chemotherapy in 2. The remaining 33 were treated expectantly. The median follow-up was 56 months (range 1-173). The 5-year overall survival rate was 69%. Of 19 patients with disease limited to the endometrium, 10 received no additional therapy, 3 of whom developed recurrence. However, all 9 women who underwent adjuvant treatment remained free of disease. Patients receiving adjuvant therapy with chemotherapy or radiotherapy had a prolonged 5-year overall and disease-free survival compared with those who were treated expectantly (85% vs. 54%, p = 0.002 for overall survival and 85% vs. 49%, p = 0.01 for disease-free survival). In multivariate analysis, adjuvant therapy (p = 0.035) and the absence of lymphovascular space invasion (p = 0.001) remained as independent prognostic factors for improved survival. CONCLUSION: Adjuvant therapy with chemotherapy or radiotherapy improves the survival of women with early-stage uterine papillary serous carcinoma.     

Endometrioid epithelial ovarian cancer : 20 years of prospectively collected data from a single center

BACKGROUND: Clinicopathological features and outcome of women with endometrioid and serous ovarian adenocarcinoma were compared. METHODS: Between 1984 and 2004, baseline and follow-up data were prospectively recorded on 1545 patients with ovarian cancer. Of these, 270 had pure endometrioid tumors; 659 had pure serous adenocarcinoma of the ovary. Response to platinum-based chemotherapy (PBC) overall survival, stage-for-stage median progression-free survival (PFS), and cause-specific median survival were compared. Independent predictors of survival were examined by using multivariate analyses. RESULTS: Median age of diagnosis for patients with endometrioid tumors was younger than those with serous adenocarcinoma of the ovary (60 years vs 62 years; P = .013). They presented more often with early disease (stage I and II; 50% vs 17%; P < .001), had less ascites, and had better performance status both overall and for stage II and III disease. More endometrioid tumors were optimally debulked overall (71% vs 45%; P < .001), but there was no difference according to stage. Objective and CA125 PBC response rates were not significantly different, but median PFS was better for patients with endometrioid tumors (24 months vs 13 months; P < .0001) as was overall median survival (48 months vs 22 months; P < .0001). This relation remained for stage II and III disease and for moderately and poorly differentiated tumors. Patients with concurrent endometrioid ovarian and endometrial malignancies had a survival advantage compared with those with ovarian malignancies alone. Independent predictors of survival after PBC were histological type, debulking status, and disease stage. CONCLUSIONS: Despite similar PBC response rates, endometrioid histology is associated with better survival compared with serous adenocarcinoma of the ovary, even with stage III or poorly differentiated tumors.     

Long-term results of a cisplatin-containing combination chemotherapy regimen for the treatment of advanced ovarian carcinoma

Sixty-two patients with advanced ovarian adenocarcinoma (stages III and IV) and without prior chemotherapy or radiotherapy were treated with a four-drug combination consisting of cyclophosphamide, hexamethylmelamine, 5-fluorouracil (5-FU), and cisplatin (Chex-UP). All patients were evaluable for toxicity and response, and survivors have been observed for a minimum of 48 months. The overall response rate to Chex-UP chemotherapy was 69%, with 12 patients (19%) achieving a pathologically confirmed complete remission (CR) as documented by a negative second-look laparotomy. Seven of the twelve patients (58%) who achieved a surgically confirmed CR were randomized to six cycles of intraperitoneal (IP) 5-FU. There have been seven relapses in patients who had a negative second-look laparotomy, but only four of the patients died from recurrent ovarian cancer. The median duration of remission following a negative second-look laparotomy was 53 months, while the median duration of survival has not been reached and will exceed 7.5 years. Seventeen patients (27%) achieved a clinical CR with chemotherapy but were found to have residual disease at second-look laparotomy. The median survival for these patients was 29 months, which was statistically inferior to that achieved for those patients with a negative second-look laparotomy (P less than .002), and only one patient is alive after 4 years. All patients who either achieved a partial response (PR) to therapy (14 of 62; 23%) or did not respond to therapy (19 of 62; 31%) died of ovarian cancer by 24 months. Thus, prolonged survival is associated with a surgically confirmed CR to induction therapy with Chex-UP. However, only a minority of advanced-stage ovarian cancer patients (15%) are alive 4 years after initiation of treatment with this regimen.     

Is nuclear expression of Y box-binding protein-1 a new prognostic factor in ovarian serous adenocarcinoma?

BACKGROUND: Nuclear expression of Y box-binding protein (YB-1), a member of the DNA binding protein family, has been reported to be much more highly concentrated in cisplatin-resistant cell lines than in their parental counterparts, suggesting an ability to limit cisplatin sensitivity. Moreover, YB-1 plays a key role in P-glycoprotein expression. Because ovarian carcinoma traditionally has been treated with cisplatin-based chemotherapy, the sensitivity of the tumors to chemotherapy could reflect a particular prognosis in patients with ovarian carcinoma. The aim of the current study was to determine whether YB-1 expression correlated with prognosis in ovarian serous adenocarcinoma patients. METHODS: The expression of YB-1 in the nucleus was examined immunohistochemically in 42 paraffin embedded primary Stage III (International Federation of Gynecology and Obstetrics) serous ovarian carcinoma tumors extirpated by primary surgery at Kyushu University Hospital between 1985-1995. RESULTS: Of the 40 primary ovarian tumors examined, 12 (30%) were positive for YB-1 expression in the nucleus. There was no significant difference in intraperitoneal stage, histologic grade, or residual tumor size after primary surgery between patients with tumors with positive and those with negative nuclear expression of YB-1 protein. The disease free survival curve for patients whose tumors were positive for nuclear expression of YB-1 protein was significantly worse than that for patients whose tumors were negative (P = 0.0025). P-glycoprotein was overexpressed in 4 of 12 tumors with nuclear YB-1 expression (33%) but there was no statistical significance between the expression of nuclear YB-1 and P-glycoprotein. CONCLUSIONS: The expression of YB- 1 protein in the nucleus may be considered a useful prognostic marker and also may reflect the sensitivity of ovarian serous adenocarcinoma to chemotherapy.     

Treatment of childhood germ cell tumors. Review of the St. Jude experience from 1979 to 1988.

BACKGROUND. The outlook for patients with germ cell tumors was poor before the advent of effective chemotherapy. The authors assessed the outcome of treatment with multiagent chemotherapy (with or without radiation therapy) in children treated for germ cell tumors at St. Jude Children's Research Hospital (SJCRH). METHODS. Sixty children with germ cell tumors were treated between January 1979 and June 1988. Postsurgical treatment was based on tumor site, stage, and histology. Most patients received chemotherapy with vincristine, actinomycin-D, and cyclophosphamide (VAC), or a modified Einhorn regimen (cisplatin, bleomycin, and vinblastine [PVB]); in the absence of response to initial therapy, patients received alternating courses of VAC and PVB (VAC/PVB regimen). Exceptions were patients with Stage I testicular tumors (observation only) and ovarian germinomas (Stage I tumors measuring less than 10 cm, observation only; tumors larger than 10 cm or Stage II-III disease, radiation only; and Stage IV disease, VAC plus radiation). RESULTS. The estimated 5-year survival is 100% for patients with Stage I disease (n = 18), 87% for patients with Stage II (n = 8), 72% for Stage III (n = 25), and 56% for Stage IV (n = 9). Patients with testicular tumors of any stage or with Stage I-II ovarian tumors had 100% 5-year survival. Extragonadal tumors responded poorly to VAC alone with recurrent or progressive disease in eight of nine patients. Treatment for those tumors was changed to alternating courses of VAC and PVB, which failed in only one of seven patients. Nine of 19 patients with advanced ovarian tumors had disease recurrence with VAC; these patients then received PVB, which was effective in four cases. CONCLUSIONS. For patients with advanced germ cell cancers, intensification of therapy or the development of new approaches is necessary. In contrast, future trials in children with limited stage should focus on reducing acute and long-term toxicities.     

Long term results of cyclophosphamide, adriamycin and platinum chemotherapy in advanced epithelial ovarian cancer

Between January 1980 and December 1983, 57 consecutive patients with advanced epithelial ovarian cancer (FIGO Stage IIc n = 5; III n = 45; IV n = 7) were treated with 6 cycles of cyclophosphamide 600 mg/m2, adriamycin 30-45 mg/m2 and platinum 50 mg/m2 (CAP) at 3 weekly intervals. Pathological complete remission (CR) was documented in 10 (18%) and 4 with no residual disease after primary cytoreductive surgery were free from progression (FFP). There were 19 partial remissions (PR) giving a 51% overall response rate. The median duration of CR was 33 months from second look surgery. Median survival (MS) for all patients was 22 months. Multivariate analysis indicated that response to chemotherapy was the most important prognostic factor, with MS for CR of 53 months, PR 23 months and stable or progressive disease 11 months (p = 0.001). Most CR (8 of 10) occurred in patients with minimal residual disease (no single lesion greater than 2.0 cm), but extent of disease, though significant in univariate analysis of prognostic factors was not an independent predictor of survival. Six patients (11%) are alive and tumour free with a minimum follow-up of 7 years. All had FIGO Stage III disease at presentation and four had no residual tumour after primary surgery.     

Microscopic disease at second-look laparotomy in advanced ovarian cancer

During the 11-year interval from January 1971 to January 1982, 50 of 246 patients with advanced (Stage III and IV) epithelial ovarian carcinoma at second-look laparotomy had biopsy or cytologic evidence of persistent microscopic carcinoma. The stage and grade profile include 46 Stage III and 4 Stage IV patients: 4 borderline, 9 grade 1, 20 grade 2 and 17 grade 3 patients. Following second-look laparotomy, 4 patients received no further therapy, 45 received chemotherapy, and 1 received external radiation. No patient was lost to follow-up, and the median interval off therapy was 24 months. Progressive or recurrent disease has manifest in 12 (24%). No recurrences have developed either in patients younger than age 40 or in patients with grade 1 tumors. Two patients died of leukemia, 1 died of heart disease, and 35 (70%) are alive with no evidence of disease. In patients developing recurrence, the median progression-free interval was 17.5 months, with a range of 6 to 46 months. The median interval of survival following disease progression was 7 months. There was no evidence of progression at 2 years and 5 years in 81% and 70% of patients, respectively. The uncorrected 2- and 5-year survival rates were 96% and 71%, respectively. The 5-year survival rates for grades 1, 2, and 3 were 100%, 79%, and 36%, respectively. Other variables analyzed include number of positive foci, residual tumor volume at initial surgery, cytologic findings at second-look laparotomy, type of chemotherapy, and number of courses of chemotherapy before second-look laparotomy. In summary, patients with only microscopic evidence of disease at second-look surgery have a good probability for extended survival.