Central nervous system (CNS) metastasis was noted in 309 patients of 1044 autopsy cases of breast carcinoma. The brain was involved in 193 cases, and cranial dura in 167 cases. In 82 cases, the cranial dura was the sole site of CNS involvement. Metastasis to the leptomeninges was found in 59 cases, and to the spinal cord and dura in 32 cases. Metastases to the infratentorial portion of the brain was almost as frequent as to the cerebrum. Forty‐two percent of the brain metastasis were single lesions, which is similar to the frequency of solitary metastasis to the brain from malignant tumors as a whole. CNS metastasis occurred more frequently in younger patients than older patients, and the clinical course of these patients was shorter than for those patients without CNS metastasis. CNS metastasis developed in the late stage of the disease, and often was not recognized clinically. Only 31% of the cases were clinically diagnosed or suspected before death. A median survival of these patients after clinical diagnosis of CNS metastasis was 33 days. However, a significant improvement was noted in the clinical diagnosis and median survival in the latter half of the study period. Eleven patients lived for more than 1 year after diagnosis of CNS metastasis. Only 14% of the 309 patients died from CNS failure. Cancer 52:2349‐2354, 1983.

Recently, the RTOG and ECOG concluded a joint randomized study on malignant gliomas that was in progress for the past five years. A total of 626 patients entered this protocol. Sixty‐seven percent of the 535 evaluable patients have died and thus this represents a preliminary report of a major joint clinical trial. The objective of this study was to evaluate the efficacy after neurosurgery of three new treatment options as compared with control treatment of radiotherapy alone. The four options were: (1) control radiation; 6000 rad/6–7 weeks to whole brain; (2) a higher radiation dose; Control dose plus a booster dose of 1000 rad/1–2 weeks to the tumor; (3) control radiation dose plus BCNU (80 mg/m2/day IV X 3 and repeat BCNU every 8 weeks); (4) Control radiation dose plus combination methyl‐CCNU (125 mg/m2/day orally X 1 and repeat methyl‐CCNU every 8 weeks), and DTIC (150 mg/m2/day IV X 5 and repeat DTIC every 4 weeks). All pertinent patient characteristics were studied and several important prognostic factors have been identified. Notably, age, histologic type (Astrocytoma with anaplastic foci, versus glioblastoma multiforme), initial performance status, time since first symptoms and presence or absence of seizure. At this time, it appeared that there was no treatment option which was significantly better than the control. The study identified that age was the most important prognostic factor. Patients who were younger than age 40 years had an 18‐month survival of 64%, patients who were age 40–60 years had an 18‐month survival of 20%, and patients who were older than age 60 had an 18‐month survival of 8%. The study also demonstrated that a modified histologic classification of anaplastic astrocytoma versus glioblastoma provided better prognostic information than the astrocytoma grading system of Kernohan. Patients with anaplastic astrocytoma had a median survival of 27 months as compared to 8 months for patients with glioblastoma. In further evaluation of any beneficial effect of chemotherapy, it was identified that only among the 40–60‐year‐old groups, BCNU treated patients appeared to have significantly increased survival than patients in the control groups (P = 0.01, one‐sided). Similarly, methyl‐CCNU + DTIC was suggestively better than the control (P = 0.08, one‐sided). The higher radiation dose, 7000 rad/8–9 weeks appeared to give no significantly better survival over the control dose option. Both BCNU and methyl‐CCNU + DTIC produced some toxicity. The combination of methyl‐CCNU + DTIC was more toxic than BCNU, producing severe or worse thrombocytopenia in 23% of the patients as compared to 6% on BCNU.

The autopsy findings of 428 patients with various histologic types of ovarian cancer were studied to determine if metastatic patterns were different. Epithelial tumors were the most frequent (89%), followed by sarcomas (7.2%). Germ cell and stromal tumors each occurred in 1.9% of cases. Sites of metastasis were nearly identical, with no statistical difference among histologic types. The peritoneum was most frequently involved (83% to 100% of cases), but lymph node metastasis was common (50% to 60% of cases). Metastasis was more common to the paraaortic lymph nodes than to the pelvic lymph nodes. In seven of eight stromal tumors, hepatic metastasis was present but did not cause the patient's death. For epithelial tumors, metastasis to distant sites was dependent on nodal and intraperitoneal disease. However, this was not true in the 31 ovarian sarcomas or the series of germ cell or stromal tumors. This finding supports a hematogenous route of metastasis for ovarian sarcomas. Understanding the metastatic potential of ovarian cancer is important in designing effective treatment regimens.

Background. According to previous reports, primary peritoneal carcinoma indistinguishable from primary ovarian adenocarcinoma had developed in five women with a history of familial ovarian cancer who had undergone prophylactic oophorectomy. Methods. The records from the Gilda Radner Familial Ovarian Cancer Registry were reviewed for instances of prophylactic oophorectomy and cases of primary peritoneal carcinoma occurring after prophylactic oophorectomy. Results. From 1981 through July 1992, the Gilda Radner Familial Ovarian Cancer Registry accessioned 931 families (a total of 2221 cases of familial ovarian cancer). Currently, 324 women in these families have undergone prophylactic oophorectomy as a preventive measure against the subsequent development of ovarian cancer. Primary peritoneal carcinoma indistinguishable histologically from primary ovarian adenocarcinoma has developed in six of these women 1‐27 years after prophylactic oophorectomy. Conclusions. Based on this finding and other reports of such primary peritoneal carcinoma, a prospective international study is planned. This study will compare the incidence of peritoneal carcinoma in first‐ or second‐degree relatives who underwent prophylactic oophorectomy because of a family history of ovarian cancer with that of those who did not undergo prophylactic oophorectomy.

Surgical specimens of malignant, supratentorial, astrocytic gliomas from 503 patients randomized on an RTOG‐ECOG treatment protocol were examined by central pathologic review. The diagnosis of glioblastoma multiforme (GBM) was made only when one or more foci of coagulation necrosis involving astrocytic tumor cells were identified histologically. Malignant astrocytic neoplasms without necrosis were classified as astrocytoma with atypical or anaplastic features (AAF). The median survival stratifying for treatment for patients with GBM was eight months compared to 28 months for patients with AAF. In most cases the specimens were received with a Kernohan grade. On the basis of these grades, patients with astrocytoma Grade 3 had a median survival of ten months as compared to a median survival of nine months for those with astrocytoma Grade 4. Observations demonstrate that necrosis is a reliable, decisive prognostic factor associated with malignant, supratentorial, astrocytic gliomas. The Kernohan system is of limited value in assessing prognosis for this group of tumors.

The autopsy findings of 73 patients with uterine sarcoma were studied to determine the sites and possible modes of metastasis. Homologous mixed mesodermal tumors were the most frequent (41%) followed by leiomyosarcoma (26%), heterologous mixed mesodermal tumor (18.3%), stromal sarcoma (12%), and endolymphatic stromal myosis (3%). The peritoneal cavity and omentum were the most frequently involved sites (59%), followed by the lung (52%), pelvic lymph nodes (41%), paraaortic lymph nodes (38%), and liver parenchyma (34%). The presence of lung metastasis was not associated with pelvic or paraaortic node metastasis or intraperitoneal disease. Metastasis to other distant sites including the brain, heart, kidney, and bone were independent of pelvic and paraaortic nodal metastasis or intraperitoneal disease. Metastatic sites were not different among various histologic types. Distant metastatic sites were statistically associated with lung metastasis. Hematogenous metastasis best explains this metastatic pattern and adjuvant systemic therapy seems indicated.

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Forty consecutive patients with stage III and IV invasive ovarian carcinoma were treated on a phase II protocol consisting of optimal debulking surgery, induction cisplatin, cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy, 6-month interval laparoscopy, reinduction cisplatin, PAC chemotherapy, and second-look procedure. All 40 patients have either disease progression or have completed the 12-month protocol. Eighty-seven percent of the patients (35) underwent optimal (less than or equal to 2 cm residual) debulking surgery before chemotherapy, in spite of the fact that 50% (20) were referred to Roswell Park Memorial Institute (RPMI) as inoperable after initial surgery elsewhere. There were no postoperative deaths and chemotherapy was started in less than or equal to 14 days in 97% of the patients. Of the 40 patients, 30% (12) achieved a pathologic complete remission (11) or a clinical complete remission (one patient refused second-look surgery). The estimated 3-year survival rate was 62%, but the 3-year progression-free survival rate was only 29%. The median survival time was 48 months. The estimated 3-year progression-free survival rate was 31% for residual disease less than or equal to 2 cm. For the five patients with residual disease greater than 2 cm, four died within 3 years. The median survival time of patients with less than or equal to 2 cm residual disease was 48 months, as compared with 21 months for those with greater than 2 cm residual disease. Although the estimated 3-year survival rate of 62% is noteworthy, the 3-year progression-free survival rate of only 29% is probably indicative that in spite of extensive debulking surgery and cisplatin-based chemotherapy as used in this protocol, the long range proportion of patients "cured" will remain small.