Jean L. Grem

Clinical features and natural history of intramedullary spinal cord metastasis

Five cases of intramedullary spinal cord metastasis are presented and an additional 50 cases from the English language literature since 1960 are reviewed. Lung cancer and breast cancer were the most frequently occurring primary neoplasms, but a wide variety of solid tumors may cause intramedullary spinal cord metastasis. The presenting symptoms were pain and/or weakness. The neurologic status deteriorated rapidly in the majority of patients in a period to days to weeks. Progression to a cord hemisection syndrome or cord transection occurred in approximately half of the patients. The characteristic myelographic appearance of fusiform swelling of the cord was seen in one third of the patients, but the myelogram was normal in 42%. Plain radiographs of the spine showed no evidence of metastatic disease in three fourths of cases. The cerebrospinal fluid protein level was frequently elevated, but results of cytologic studies were usually negative. High‐resolution computer‐assisted tomographic scanning may show intramedullary metastases. Radiation therapy combined with corticosteroid administration offers the only effective palliation. The recognition of intramedullary spinal cord metastasis is an ominous finding. Intramedullary spinal cord metastasis generally occurred in the setting of widespread systemic and intracranial disease, but occasionally was the only site of relapse. More than 80% of patients died within 3 months. Heightened awareness of this entity may lead to early diagnosis at a stage when neurologic deficits are reversible and, it is hoped, more effective palliation can be achieved.

Metastatic Leydig cell tumor of the testis: report of three cases and review of the literature

Metastatic Leydig cell carcinomas account for less than 0.2% of all testicular cancers, and may be associated with sex hormone production. Leydig cell carcinoma is relatively refractory to radiotherapy and chemotherapy, and median survival of patients with metastatic disease is less than 2 years. Presented are three cases of metastatic Leydig cell cancer, and a review of the literature pertaining to this rare tumor.

Reversible increase in serum alpha-fetoprotein content associated with hepatic dysfunction during chemotherapy for seminoma.

Serial monitoring of the serum content of the beta subunit of human chorionic gonadotropin (beta hCG) and alpha-fetoprotein (alpha FP) is useful in the initial staging of germ cell tumors and assessing the response to treatment. An increase in either marker during or following treatment almost always heralds disease progression and indicates the need for additional therapy. We report two patients in whom substantial increases in the serum content of AFP occurred during chemotherapy for advanced seminoma. Hepatic dysfunction was present in both patients; in one patient, a chronic carrier of hepatitis B virus, the liver dysfunction was associated with reactivation of hepatitis B manifested by anicteric hepatitis and hepatitis B e antigen positivity. Marked tumor regression had occurred in both patients, and chemotherapy was discontinued in spite of the elevated alpha FP level. The alpha FP content in the serum gradually returned to normal, and hepatic dysfunction resolved. Both patients remain free of disease 15 and 17 months following the last chemotherapy treatment. These cases illustrate that hepatic dysfunction and alpha FP production may occur during chemotherapy and that increases in serum alpha FP content must be interpreted with caution since the elevated alpha FP level does not always indicate progression of germ cell tumors.

A phase II evaluation of combination chemotherapy plus aminoglutethimide in women with metastatic or recurrent breast carcinoma. An Eastern Cooperative Oncology Group pilot study

The Eastern Cooperative Oncology Group (ECOG) conducted a pilot study of combination chemotherapy with cy-clophosphamide, doxorubicin, and 5-fluorouracil plus aminoglutethimide (250 mg three times daily with hydrocortisone supplementation of 40 mg daily) as primary therapy for estrogen receptor-positive or unknown advanced breast carcinoma to assess whether these agents can be safely combined and to provide a preliminary estimate of response rate. A total of 47 patients, 45 with metastatic breast cancer and two with stage IV disease who were rendered clinically disease free following surgical resection of chest wall recurrence, were treated. Leukopenia and mucositis were the most frequent toxicities requiring dose reduction, but only five patients (10.6%; 95% confidence interval, 1.8–18.4%) experienced life-threatening leukopenia (<1000/mm3) at some point during their therapy. Neurologic side effects attributed to aminoglutethimide, predominantly lethargy, were reported in less than one-third of patients, and rarely required dose reduction. One elderly patient developed clinical hypothyroidism during the first 3 months on therapy and experienced a cardiac arrest at home while receiving supplemental thyroid hormones. The overall complete plus partial response rate in 45 patients was 55.5% (95% confidence interval, 41–70%). Among 16 patients with measurable disease, the complete plus partial response rate was 75% (95% confidence interval, 54–96%). The complete plus partial response rate in 29 patients with nonmeasurable but evaluable disease was 45% (95% confidence interval, 27–63%) and an additional 14% had improvement in bone pain. Eight patients electively discontinued chemotherapy after 7–24 months of therapy, but continued ami-noglutethimide. The median time to disease progression is 462 days (15.4 months); 25% of patients died by 552 days (18.4 months), and the median duration of survival is predicted to be 889 days (29.6 months). We conclude that aminoglutethimide can be combined with this doxorubicin-based regimen with acceptable toxicity and an overall response rate which is similar to that observed on prior ECOG trials with cyclophosphamide, doxorubicin, and 5-fluorouracil.

Review: Adjuvant hormonotherapy for breast cancer

ADEQUATE local therapy is available for primary brcast cancer in the form of surgery f radiotherapy. Unfortunately, the majority of women with breast cancer are destined to have disease recurrencc and ultimately die of their disease. The interest in adjuvant therapy for selected patients with primary breast cancer has been kindled by improvements in systemic therapy for advanced breast cancer and by increased appreciation for the biology of treatment of minima1 residual disease following primary therapy. The use of hormones as adjuvant therapy in the primary treatment of breast cancer is not a new concept. The roles of radiation-induced menopause and surgical castration as adjuvants to primary therapy were explored over the last three decades. Various non-controlled studies and randomized controllcd trials have yielded conflicting results; although several studies reported an effect of radiation-induced castration in delaying the appcarance of distant metastases in both preand postmenopausal patients, the overall survival has not been improvcd statistically with either surgical oophorcctomy or radiation to the ovaries. Mcakin el al. prospectivcly randomized premcnopausal patients over the age of 45 and postmcnopausal womcn following surgery and radiothcrapy to the chcst wal1 and regional lymph nodcs to obscrvation only, ovarian irradiation and ovarian irradiation plus prcdnisonc (7.5 mg po q day for up to 5 yr) [ 11. The combination of ovarian radiation plus smal1 doses of continuous prednisonc produccd a significant dclay in rccurrcncc and prolongation in survival in this subset of prcmcnopausal paticnts. NO differcncc in timc to rccurrcncc nor in survival was detccted in postmcnopausal paticnts among thc thrce arms. Thc bcncficial cf&cct of ovarian irradiation plus continuous prcdnisone in thc prcmcnopausal paticnts over thc age of 45 did not becomc statistically significant until aftcr 3 yr of follow up. It is important to notc that thc trial size was smal1 and thc duration of patient accrual was long.