Clear cell sarcoma: the Roswell Park experience

BACKGROUND AND OBJECTIVES: Clear cell sarcoma of the tendons and aponeuroses (CCSTA) is an aggressive, rare soft-tissue tumor with approximately 300 reported cases. Although it appears to be histogenetically related to melanoma, its clinical behavior resembles soft tissue sarcoma with a propensity for lymph node metastases. We report our experience at a tertiary cancer center. METHODS: Eight cases of CCSTA evaluated at Roswell Park Cancer Institute between 1970 and 1998 were reviewed retrospectively. Patient data analyzed included patient age, gender, anatomic location, size of tumor, development of local, regional and distant recurrence, and patient status at last follow up. RESULTS: Six of eight patients were alive at 2 years, while three of seven patients were alive at 5 years. Of the patients alive with no evidence of recurrence, two had tumors of less than 2 cm, and the remaining patient had incomplete information regarding tumor size. Five patients recurred within 2 years of definitive surgical management. Four had tumors > 5 cm. All five patients progressed to metastatic disease at a median follow up of 20 months (range 1-108 months) following definitive surgical management and all eventually died of their disease at a median of 3 months (range 0-24 months) from presentation with metastatic disease. Four of five patients with lesions > 5 cm received adjuvant chemotherapy with intent to cure, but all eventually died of disease at 4, 22, 34, and 41 months from initial presentation. CONCLUSIONS: CCSTA is an aggressive tumor of the soft tissues. Early recognition and management are associated with an excellent long-term prognosis. Tumors greater than 5 cm warrant aggressive surgical management and treatment, and are at high risk of the development of distant disease. Aggressive multiagent chemotherapy appeared to have no impact on outcome. Other adjuvant therapeutic options including immunotherapy should be investigated.     

Malignant melanoma brain metastases. Review of Roswell Park Memorial Institute experience

One-hundred twenty five of 700 patients with malignant melanoma treated at Roswell Park Memorial Institute from 1972 to 1978 were found to have brain metastases. Seventy-three percent of the patients had multiple brain metastases. Male to female ratio was 1.9:1. The median survival of the untreated group of patients was 3 weeks as compared with that of 6 weeks for the patients maintained on steroids only, 9 weeks for those who received radiotherapy, 11 weeks for the patients treated with intraarterial chemotherapy, and 26 weeks for the patients who underwent successful surgical excision of a solitary lesion.     

Fallopian tube cancer: The role of radiation therapy

Thirty-four patients with fallopian tube cancer were evaluated at the Mayo Clinic between 1964 and 1985and received radiation therapy postoperatively. Employing a system analogous to FIGO ovarian cancer staging, there were 9 patients with stage I disease, 13 with stage II, and 12 with stage III/IV. Residual disease was present in 15 patients and absent in 19. Nodal metastases were documented in 12 patients or 35% (10 at presentation, two at relapse), with para-aortic nodes most commonly involved (67%) and 7 of the 12 having disease otherwise limited to the pelvis at presentation. Fifteen of 34 (44%) patients survived disease-free until intercurrent death or to a median follow-up of 70 months. Seven patients were treated with palliative intent for massive disease, and 27 patients were treated with curative intent (21 radiation alone, six radiation plus chemotherapy). Of those treated with curative intent, 15 patients received pelvic irradiation (with or without para-aortic nodal irradiation), 10 received whole abdominal irradiation, and 2 received intraperitoneal radiophosphorus. In the potentially curative group, seven of nine (78%) patients with stage I disease, five of 12 (42%) with stage II, and 2 of 6 (33%) with stage III have remained disease-free. Among the 21 patients with stage I or II disease, only four of the 11 (36%) patients who received pelvic irradiation alone were disease-free, but four patients had an isolated upper abdominal failure. In contrast, eight of 10 (80%) patients receiving treatment to the entire abdomen (including two patients who received ³²P) were disease-free. In potentially curative cases, 83% (29/35) of irradiated sites were controlled. Among 19 patients with persistent or recurrent disease, 15 (79%) had disease restricted to the abdomen/pelvis. Fallopian tube and epithelial ovarian cancers have similar natural histories, including abdominal failures in early disease, and whole abdominal irradiation appears to be an effective treatment modality.     

Fallopian tube carcinoma

Twenty-one patients with fallopian tube carcinoma from Yale-New Haven Medical Center are reviewed. Most patients who died of disease did so in the first two years after diagnosis, even following complete resection, clearly indicating the need for adjuvant therapy. Negative second-look surgery did not provide assurance of permanent remission. There was a high recurrence rate with Stage I and completely resected Stage II and III disease (8 of 14 patients). Some recurrences occurred late, up to nine years after initial diagnosis. We recommend whole abdomino-pelvic radiation if no disease greater than 2 cm3 bulk exists after surgery. Chemotherapy may be an alternative to radiation as primary adjuvant treatment in early stage disease. Chemotherapy for unresectable disease or recurrent disease has shown palliation with occasional prolonged survival but no patient with recurrent disease survived longer than two years.     

Fallopian tube carcinoma: a review

PURPOSE: Primary fallopian tube carcinoma (PFTC) is a rare tumor that histologically and clinically resembles epithelial ovarian cancer (EOC). The purpose of this study is to review the current available literature data on PFTC. PATIENTS AND RESULTS: Early clinical manifestation and prompt investigation often lead to diagnosis at an early stage of disease. However, the diagnosis of PFTC is rarely considered preoperatively and is usually first appreciated by the pathologist. Surgical staging/management and the use of chemotherapy follow the concepts used in epithelial ovarian cancer (EOC). In contrast to EOC is the importance of early lymphatic spread in this disease. The earlier diagnosis of PFTC leads to an apparent better survival compared with EOC. However, as with EOC, stage and residual tumor are the most important prognostic variables. CONCLUSION: Until more extensive clinical research has been performed, ovarian carcinoma management principles should be used in clinical practice.     

Seminoma at Roswell Park, 1970 to 1979. An analysis of treatment failures

A retrospective study of all cases of seminoma treated at Roswell Park Memorial Institute from 1970 through 1979 was conducted. Fifty-six evaluable patients treated initially with radiation therapy were seen during this period, and the overall survival rate at an average follow-up period of 52 months was 82%. The survival rate in patients with bulky abdominal or supradiaphragmatic metastases was only 33% (4 of 12 patients). Treatment failures were analyzed to determine their apparent causes and the implication of such failures to the future management of seminoma. The use of combination chemotherapy as the initial treatment modality in advanced seminoma is discussed in light of these results.     

Purified Roswell Park cultured antilymphocytic globulin RPMI-CALG: preparation and clinical trial

Purified human antilymphocytic globulin (RPMI-CALG) has been prepared in bulk quantities by immunization of horses with purified normal lymphocytes maintained in continuous cell culture at the Roswell Park Cell Plant. The characterization studies herein described reveal RPMI-CALG to be purified, nontoxic, and nonpyrogenic with specific in vitro immunosuppressive activity. Contamination with hemolysins and hemagglutinins is minimal and in marked contrast to other available preparations. Initial clinical trials with a lyophilized preparation reveal that it can be safely administered intravenously to humans without untoward effects. Comparison of hematological data was made on patients receiving RPMI-CALG pretransplant without other immunosuppressive agents to the same patients post-transplant receiving RPMI-CALG plus azathioprine and prednisone. No significant depressive hematological effect was apparent. Platelets were not depressed. Eosinophilia was not seen acutely or on follow-up examination. Urticaria was not evident. Follow-up studies up to 6 months after allografting failed to reveal any specific toxicity in the measured hematological parameters. This purified preparation merits further clinical trial.     

Current report on the interferon program at Roswell Park Memorial Institute

An overview of the interferon program at Roswell Park Memorial Institute (RPMI), is presented. This program encompasses three interrelated areas of research and new drug development: (a) basic research on purification and characterization of animal and human interferons (leukocyte, fibroblast, and immune); (b) large scale manufacture and preclinical testing of human fibroblast interferon (HFIF); and (c) clinical trials with HFIF to determine its safety of administration as well as antiviral, antitumor, and immunomodulatory activities in patients with neoplastic or viral disease. The antitumor effect of HFIF produced at RPMI as assessed by intralesional injection of various metastatic nodules resulted in an overall 71% local response. Phase I studies in 13 patients demonstrated that HFIF can be administered safely by the subcutaneous, intramuscular, and intravenous routes in doses up to 25 million units per day without any serious untoward effects. Intrathecal administration of HFIF into patients with CNS leukemia was also well tolerated. Pharmacokinetic studies indicated significant levels of HFIF in serum and cerebrospinal fluid after intravenous and intrathecal administration, respectively. Coincidental with the HFIF systemic administration during the Phase I trials, favorable responses in several laboratory, immune, and clinical parameters were observed. These results provide the rationale for conducting phase II and phase III clinical trials with HFIF produced at RPMI.     

The treatment of Stage III nonseminomatous testicular tumors. Roswell Park Memorial Institute results (1970-1979)

A review of 92 patients with Stage III nonseminomatous tumors treated at Roswell Park Memorial Institute between 1970-1979 was undertaken to verify changes in concepts as related to multiple agent chemotherapy and cytoreductive surgery. Each patient had a minimal follow-up of 18 months. Fifty-three patients were seen before 1975. Eighteen had metastasis to the lungs only. These were treated with a variety of single chemotherapeutic agents and cytoreductive surgery. The survival of this group was 38%. Among 35 patients with lung and visceral involvement seen at the same time, only one patient is alive. Thirty-nine patients were seen after 1975 and treated with multi-drug chemotherapy and cytoreductive surgery. The current survival rate of 23 patients with lung metastasis only is 69%. Among 16 patients with lung and visceral involvement, the present survival rate is 31%. This report confirms the effectiveness of multi-drug therapy in conjunction with cytoreductive surgery in the treatment of disseminated testicular tumors.     

Fallopian tube and primary peritoneal carcinomas associated with BRCA mutations.

PURPOSE: The aims of this study were to determine the incidence of BRCA mutations among Ashkenazi Jewish patients with fallopian tube carcinoma (FTC) or primary peritoneal carcinoma (PPC), to study the clinicopathologic features of these cancers, and to estimate the risks of these cancers in association with a BRCA mutation. PATIENTS AND METHODS: A retrospective review at two institutions identified 29 Jewish patients with FTC and 22 Jewish patients with PPC. These patients were genotyped for the three Ashkenazi Jewish BRCA founder mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2). Surgical and pathologic information, family history, and survival data were obtained from hospital records. All statistical tests were two sided. RESULTS: Germline BRCA mutations were identified in five of 29 patients with FTC (17%) and nine of 22 patients with PPC (41%). Mutation carriers had a younger mean age at diagnosis than patients without a mutation (60 v 70 years; P =.002). The overall median survival was 148 months for mutation carriers and 41 months for patients without a mutation (P =.04). For BRCA mutation carriers, the lifetime risks of FTC and PPC were 0.6% and 1.3%, respectively. CONCLUSION: Substantial proportions of Ashkenazi Jewish patients with FTC or PPC are BRCA mutation carriers. Patients with BRCA-associated FTC or PPC are younger at diagnosis and have improved survival compared with patients without a BRCA mutation. Although the lifetime risks of FTC or PPC for patients with BRCA heterozygotes are greater than those for the general population, the absolute risks seem relatively low.     

Lymphadenectomy in primary carcinoma of the Fallopian tube

OBJECTIVE: The bad prognosis of primary carcinoma of the Fallopian tube is ascribed to early lymphogenous metastasis. Due to the rarity of cases, there exist only few and divergent results on the importance of lymph node metastasis in the relevant literature. Thus, our study aimed at detecting the incidence of lymph node metastases and their influence on overall survival, as well as at evaluating the therapeutic effect of radical lymphadenectomy. METHODS: We studied 158 cases of primary carcinoma of the Fallopian tube in a retrospective multicenter analysis. Group I (n = 38) consisted of patients who were subjected to radical pelvic and para-aortic lymphadenectomy in addition to total abdominal hysterectomy, bilateral adenectomy and omentectomy. The control group II (n = 71) underwent the same surgical procedures but without radical lymphadenectomy. Patients who received post-operative irradiation (n = 49) were excluded from the study. RESULTS: On average, 38 lymph nodes (range 12-68) were extirpated. In group I 42.1% of the cases showed lymph node metastases. Lymphatic dissemination was observed only after the carcinoma had spread beyond the organ (intraabdominal stage II); the incidence of lymph node metastases rose significantly (P = 0.02) with growing intraperitoneal tumour masses. Pelvic and para-aortic metastases occur simultaneously. Overall survival with tumour of equal size is markedly, but not significantly reduced (P = 0.18) if the lymph nodes are involved. If, however, radical lymphadenectomy is performed (group I) the median survival time increases to 43 months (95% confidence-interval 20-66), compared with 21 months (95% confidence-interval 10-32) in group II (P = 0.095). CONCLUSION: Correct staging is obtained only on the basis of pelvic and para-aortic lymphadenectomy. Radical lymphadenectomy in tumours of equal size may markedly prolong survival.     

Results from treatment of Wilm's tumor at Roswell Park, 1927-1968

A retrospective study of forty-two of forty-nine cases of Wilm's tumors treated at the Roswell Park Memorial Institute over the past forty years is presented. Abdominal palpation to date remains the most important finding. Since over 20% demonstrated nonfunction on intravenous pyelogram, preoperative diagnosis and differentiation from neuroblastoma are therefore not always certain. Artereography may be helpful in selected instances. Metastases were present in 29 cases at the time they were first seen at the Institute. Modes of therapy were; nephrectomy, 41 cases; plus radiation therapy, 40 cases; and plus chemotherapy, 27 cases. The relationship of age of onset, stage of tumor, presence of metastasis, mode of therapy, and length of survival is presented. Current therapy includes nephrectomy, radiation therapy, and chemotherapy with actinomycin D or vincristine, or both, and monthly follow-up is advised. Further correlations of histopathological features with survival are made in 16 cases. The absence of undifferentiated sarcomatous components seems to be the best prognostic feature.     

Phase I and pharmacokinetic evaluation of floxuridine/leucovorin given on the Roswell Park weekly regimen

A phase I and pharmacokinetics study was carried out of floxuridine (FdUrd) modulated by leucovorin (LV) given on the Roswell Park regimen (LV given at 500 mg/m² by 2-h infusion and FdUrd given by i.v. push at 1 h after the start of LV infusion, treatment being given weekly×6). The dose-limiting toxicity was diarrhea; the MTD and recommended dose for phase II studies was 1,650 mg/m² per week of FdUrd. The dose-response curve was steep, with 3/3 patients treated at a dose of 1,750 mg/m² developing grade IV diarrhea. With this schedule there was no significant mucositis. Pharmacokinetic parameters showed very wide interpatient variability. Plasma decay was biphasic with at ^1/2 of approximately 2 h. Plasma clearance was high (>200 l h^–1). No correlation between pharmacokinetic parameters and toxicity could be identified.     

Screening for prostatic cancer. The German experience

The principles for screening for detection of early prostate cancer in the Federal Republic of Germany are described. Men are entitled from the beginning of their 45th year of life to an examination for early detection of cancerous diseases once annually and this examination is paid for by the insurance system. In the age group around 60 years about 15% of the men participate. Among 1,341,833 men participating in 1987, 1,638 new cases of prostate cancer were detected. The proportion of cases suitable for total prostatectomy has increased considerably since the screening program was introduced and now stands at about 25% in the author's department. The survival rate of this group is comparable to that of the general population, when adjusted for age distribution. It is suggested that screening for prostate cancer might reduce the mortality of this disease.     

Combination chemotherapy for mixed müllerian tumor of the Fallopian tube

A patient with mixed müllerian tumor of the fallopian tube was treated with cyclophosphamide and cisplatin. The regimen achieved a complete remission. No severe drug-related toxicity occurred.