Unusual Metastatic Pattern in Testicular Malignant Teratoma

ONCOLOGY AND CHEMOTHE':tAPY

Survival for with stages I and II ncnseminornatous germ cell tumors is now ~90 per cent and for those with stage II tumors it is ~60 per cent. This finding is owing to improved chemotherapy and tumor monitoring, made possible by radioimmunoassay for a-fetoprotein and human chorionic gonadotropin. In contrast, cure rates for metastatic seminoma, once considered the most curable type of testicular tumor, are now <40 per cent. a- Fetoprotein is never elevated in patients with pure seminoma, whereas human chorionic gonadotropin is elevated in only 15 to 20 per cent of the cases. A tumor marker that is associated more frequently with seminoma would be useful for monitoring the treatment of these patients. The current study uses a recently described enzyme-linked immunoabsorbent assay for serum levels of placental alkaline phosphatase. Placental alkaline phosphatase levels were normal in all control patients and in 33 men who apparently were cured of the testicular cancer. Of 28 men with active seminoma 16 had elevated placental alkaline phosphatase levels. In 68 per cent of these patients either human chorionic gonadotropin or placental alkaline phosphatase was elevated. These observations suggest that seminoma may have useful clinical markers more often than was thought previously. It is suggested that the simultaneous measurement of human chorionic gonadotropin and placental alkaline phosphatase should be performed in all patients with seminoma and that these measurements should be used to monitor progress during treatment. D. K. M. 4 figures, 23 references

Radiotherapy in Seminoma: More is Not Better L. H. EINHORN, Department of Urology, Indiana University Medical Center, Indianapolis, Indiana Into J. Rad. Oncol. Biol. Phys., 8: 309-310 (Feb.) 1982 The author comments on a report of 444 patients with seminoma treated with radiotherapy from 1958 to 1976. Overall, there was an 87 per cent 5-year survival rate, including 87 per cent for patients with stage HA and 62 per cent with stage IIB disease. These results are as good as those in other series but what is unique about this stage II patient population is that prophylactic mediastinal irradiation was not used. There were no mediastinal recurrences in 40 patients with stage IIA disease, while 22 per cent of those with stage HB cancer had mediastinal recurrences. However, 7 of these 10 patients were cured with subsequent radiatioR The author has demonstrated clearly that prophylactic mediastinal irradiation is unnecessary to ensure optimal cure rates in patients with stage H disease. Furthermore, such radioprophylaxis may well be deleterious, since Ytredal and Bradfield describe marrow hypoplasia and second malignancies with supradiaphragmatic and infradiaphragmatic irradiation compared to abdominal irradiation alone. Also, 2 of 20 patients with stage I disease treated with prophylactic mediastinal irradiation at M. D. Anderson Hospital died of acute leukemia. In addition, there is considerably more severe and prolonged myelosuppression, and an increased incidence of pulmonary fibrosis in patients treated with combination chemotherapy following radiation therapy. Einhorn believes that all patients with stages III and IV seminoma should receive cisplatin, vinblastine and bleomycin as initial therapy. It is difficult to be dogmatic concerning the management of patients with stage IIB disease, a clinical stage accounting for 10 per cent of seminoma presentations. At Indiana University such patients are treated initially with

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vinblastine and and all 7 !'"~•,c~e,ou ya,~c,;•'f""'rl achieved response and remain free of disease ·with a minimum followup of 1 year. H. D. P. 6 references

Radiation Therapy of Testicular Non-Seminomas B.

VAN DER WERF-MESSING AND W. C. J. HOP, Departments of Radiotherapy and Statistics, Rotterdam Radiotherapy Institute, and Department of Radiotherapy, Erasmus University, Rotterdam, The Netherlands

Int. J. Rad. Oncol. Biol. Phys., 8: 175-178 (Feb.) 1982 The treatment and prognosis of 121 patients with nonseminomatous germ cell tumors of the testis treated between 1967 and 1977 are reviewed. Staging diagnostic studies consisted of physical examination, chest x-ray, chest tomography, excretory urography, pedal lymphangiography and a-fetoprotein but not /3-human chorionic gonadotropin. In the case of no demonstrable distant metastatic disease radiotherapy was delivered to the periaortic lymph nodes and to the homolateral iliac nodes to a dose of 4,000 rad during 4 weeks. If pulmonary metastases became evident total lung irradiation was given up to 1974 and, after that, chemotherapy was given, usually followed by a booster dose of irradiation of about 3,000 rad to the initially visible pulmonary lesions. Of the 121 patients 50 had clinical stage Tl-4,NO,MO and 41 had clinical stage Tl-4,Nl-2,MO disease. Actuarial survival figures are given and the authors conclude that the risk of pulmonary relapse is considerably higher in patients with undifferentiated malignant teratoma than in those with intermediate malignant teratoma, and all pulmonary recurrences were noted ;:;i2 years after radiation therapy. The patients with undifferentiated malignant teratoma were more likely to present with advanced stage and the prognosis for intermediate malignant teratoma was better, even if comparison was made in the same stage categories" Fifteen patients in the intermediate malignant teratoma category had pulmonary relapse and 7 (42 per cent) were cured, while 23 in the undifferentiated malignant teratoma category had pulmonary relapse and 5 (22 per cent) were cured. The authors conclude that "With positive lymphangiography, the question is whether chemotherapy should be given first, followed by radiation therapy, or whether radiotherapy should be given first and chemotherapy reserved for those cases with persistent markers" The value of lymphadenectomy in of radiation therapy still must be assessed in prospective clinical trialso,,

Abstracter's comment. This series of patients treated between 1967 and 1977 is in contrast to the present approach to nonseminomatous germ cell tumors of the testis in this country" No direct reference is made to the status of the post-radiotherapy abdomen in these patients, and the over-all cure rate in patients with positive retroperitoneal nodes is not as good as that using combination chemotherapy and retroperitoneal lymphadenectomy. H. D. P. 1 figure, 5 tables, 4 references

Unusual Metastatic Pattern in Testicular Malignant Teratoma H. A. WASSENAAR, R. A. C. Roos, P. J. SPAANDER AND A. T. VAN OOSTEROM, Departments of Clinical Oncology,

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ONCOLOGY AND CHEMOTHERAPY

Neurology, and Pathology, University Hospital, Leiden, The Netherlands Med. Ped. Oncol., 11: 8-11, 1983 The authors present a 25-year-old white man with a malignant teratoma of the right testicle who suffered massive bone marrow involvement with bleeding tendency and hypercalcemic nephropathy. The response to chemotherapy was excellent but the patient suffered carcinomatous leptomeningitis, which was confirmed at autopsy as the cause of death. P. R. R. 4 figures, 14 references

Editorial comment. The authors described malignant teratoma of the right testicle, which metastasized to the bone without any evidence of disease in the retroperitoneal lymph nodes or lungs, the usual sites of primary metastasis. M. M. Computed Tomography in Definitive Radiotherapy of Prostatic Carcinoma, Part 2: Definition of Target Volume V. PILEPRICH, S. C. PRASAD AND C. A. PEREZ, Division of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri

M.

Int. J. Rad. Oncol. Biol. Phys., 8: 235-239 (Feb.) 1982 Pre-treatment computerized tomography (CT) scanning of the pelvis was performed in 100 consecutive patients with carcinoma of the prostate (82 treated with external irradiation and 18 treated with interstitial 125iodine implantation). Treatment plan modifications prompted by CT scan findings were more frequent in patients with involvement of the seminal vesicles, in whom the conventional treatment plan often resulted in an underestimate of tumor volume. With skeletal landmarks as a reference the dimensions of the prostate, seminal vesicles and detectable tumor, and their topographic relationships were tabulated systematically. These measurements provided a basis for definition of the target volume in patients with carcinoma of the prostate. Conventional treatment planning would have resulted in inadequate coverage of tumor volume in 7 per cent of the patients with stages B and C disease without seminal vesicle involvement, 53 per cent with stage C disease and sem1nal vesicle involvement, and 50 per cent with stage Dl cancer. H. D. P. 5 figures, 1 table, 3 references

Advanced Carcinoma of the Prostate: Treatment With a Gonadotrophin Releasing Hormone Agonist J.

M. ALLEN, J. P. O'SHEA, K. MASHITER, G. WILLIAMS AND S. R. BLOOM, Departments of Medicine and Surgery,

Royal Postgraduate Medical School and Hammersmith Hospital, London, England Brit. Med. J., 286: 1607-1609 (May 21) 1983 Ten patients with stages T3 and T4 adenocarcinoma of the prostate were treated with a long-acting analogue of gonadotropin-releasing hormone. Of these patients 5 had failed previous hormonal treatment and 5 had not been treated previously. The patients received subcutaneous injections of 250 mg. ICI 118,630 twice daily for 1 week and then once weekly. Eight patients had relief of pain and regression of tumor. Serum gonadotropin and testosterone concentrations were suppressed significantly by the end of 2 weeks of treatment.

Use of these superactive agonists might well provide a safe and effective treatment for adenocarcinoma of the prostate. Further trials are required to establish long-term safety and efficacy. C. E. M. 2 figures, 12 references

Unusual Androgen Sensitivity of the Androgen-Independent Dunning R-3327-G Rat Prostatic Adenocarcinoma: Androgen Effect on Tumor Cell Loss J. E. HUMPHRIES AND J. T. ISAACS, The Johns Hopkins Oncology Center, Department of Urology, James Buchanan Brady Urological Institute and The Johns Hopkins School of Medicine, Baltimore, Maryland Cancer Res., 42: 3148-3156 (Aug.) 1982 Previous studies have indicated that the Dunning R-3327-G tumor subline continues to grow in a castrated host but grows at a slower rate than in an intact host. This study was done to investigate the mechanisms involved. The authors found that the G tumor subline did not require androgen stimulation for cell division but this subline was highly sensitive to androgens with respect to the rate of cell death. Thus, in castrated rats the rate of cell death was increased but cell growth still continued at a rate exceeding cell death and tumor growth slowed but continued. Additionally, testosterone and not dihydrotestosterone was the androgen found to be responsible for inhibiting a rate of tumor cell death. This probably was owing to the low level of 5 a-reductases present in these tumor cells. The authors suggest that while dihydrotestosterone normally is considered the intracellular androgen responsible for normal prostatic growth, this probably is owing to the fact that levels of dihydrotestosterone in the normal prostate are approximately 10 times higher than those of testosterone. According to this study testosterone may be as capable of affecting sensitive tissue (such as G tumor) as dihydrotestosterone. D. K. M. 3 figures, 5 tables, 15 references

m- and p-Halobenzoyl Derivatives of p-Halo-DL-Phenylalanine as Inhibitors in a Microbial Antitumor Prescreen

T. T. OTANI AND M. R. BRILEY, Laboratory of Pathophysiology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Res. Comm. Chem. Path. Pharm., 40: 325-328 (May) 1983 In previous studies the authors had shown that N-benzoyl derivatives of substituted phenylalanine showed considerable growth-inhibitory activity in a microbial antitumor prescreen. The derivatives of p-chloro-DL-phenylalanine, especially the p-chlorobenzoyl derivatives, exhibited the greatest degree of inhibition. In this study, the authors studied the p-chlorobenzoyl, p-bromobenzoyl, p-iodobenzoyl, m-chlorobenzoyl and pbromobenzoyl derivatives ofp-chloro, p-bromo and p-iodo-DLphenylalanine. Microbiological assays were done using Lactobacillus casei. Of these compounds 13 exhibited greater potency than any other acyl derivative of amino acid analogues studied to date. The medium infective dose values of these compounds ranged from 0.06 to 0.27 mM., some 4 to 20 times more potent than compounds studied earlier. These compounds are 2 to 8 times more active than 6-mercaptopurine. G. W. K. 1 table, 7 references