Faculty Bibliography

Purpose: This study was a prospective phase I/II trial performed by the Radiation Therapy Oncology Group (RTOG) to test the tolerance and efficacy of preirradiation cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD) chemotherapy followed by large-volume, high-dose brain radiation therapy (Ri) for patients with primary CNS lymphoma (PCNSL). Patients and Methods: Fifty-four (52 assessable) human immunodeficiency virus (HIV)-negative patients with PCNSL were entered on study and received two (n = 20) or three (n = 32) cycles of CHOD (six patients with positive CSF cytology received intrathecal methotrexate in addition to CHOD). Whole-brain RT to 41.4 Gy and tumor boost to 18 Gy (total dose, 59.4 Gy) followed chemotherapy. Results: As of July 1994, with a minimum potential follow-up time of 20 months, 12 of 52 assessable patients remain alive without evidence of progression. The median survival time for the entire group is 16.1 months, with a 2-year survival rate of 42%. By univariate analysis, patient age was found to be a significant prognostic factor with respect to survival (P =.005) in favor of age less than 60 years, Karnofsky performance status (KPS) was of borderline significance (P =.057). Survival for patients treated on RTOG 88-06 was compared with that of patients treated on RTOG 83-15, which tested RT alone. No difference in overall survival was found (P =.53). Grade 4 neutropenia developed in 29 of 51 patients during chemotherapy, There were two deaths during chemotherapy: one as a result of sepsis and one of a pulmonary embolus. The worst toxicity during RT was less than or equal to grade 2 in 50 of 52 patients. Conclusion: preirradiation CHOD chemotherapy does not significantly improve survival over RT alone for patients with PCNSL. Age remains a powerful prognostic factor independent of therapy and must be considered in testing alternative combined approaches. (C) 1996 by American Society of Clinical Oncology

Discrimination in the delivery of health care, based on the age of the patient, is attracting increased attention. We investigated this problem by studying possible age-related delay in diagnosis in patients treated for glioblastoma multiforme (GBM). A total of 213 charts of patients with GBM seen from 1972 to 1992 were evaluated for type and duration of symptom, with 204 charts having sufficient data to be analyzed. The mean and median duration of symptoms for the entire group was 48.9 and 28 days, respectively. No age-related difference in duration of symptoms was noted. In light of the increasing incidence of GBM in patients above 60 years of age, further investigation of other possible areas of age discrimination in patients with GBM is warranted

BACKGROUND. In light of the steadily improving capability to treat opportunistic infections, the authors reviewed their recent experience with short course empiric radiotherapy for the treatment of human immunodeficiency virus (HIV)-associated presumed central nervous system (CNS) lymphoma. METHODS. Medical records were reviewed of 32 previously unreported HIV-infected patients who had computed tomography and/or magnetic resonance imaging findings consistent with lymphoma, whose lesions had failed to respond to antitoxoplasmosis therapy and therefore subsequently treated with empiric radiotherapy to the cranium and meninges, nearly always 3000 cGy in 10 fractions. RESULTS. The majority of patients were in poor general condition (median Karnofsky score = 50) when radiotherapy was initiated. Fifty percent improved during or after radiation. Median survival was 2.1 months. CONCLUSIONS. Despite progress made in the past several years in the treatment of opportunistic infections and brief clinical response to radiotherapy, patients with acquired immunodeficiency syndrome who have a presumed diagnosis of CNS lymphoma continue to have extremely poor survival. Early biopsy in patients with lesions that fail to respond to empiric antitoxoplasmosis treatment or with lesions radiographically most consistent with lymphoma may improve outcome

PURPOSE: To examine the effects of lomustine (CCNU), a commonly used nitrosourea, and craniospinal radiation therapy on the subsequent development of restrictive lung disease (RLD) following treatment for malignant brain tumors. PATIENTS AND METHODS: Pulmonary function testing with measurement of lung volume, spirometry, and diffusion capacity was performed in 28 patients who had received CCNU and/or radiation therapy as treatment for a malignant brain tumor. The median age at the time of treatment was 11.4 years (range, 3.9 to 36.7) and radiation therapy was completed 6 months to 11.6 years (median, 2.6 years) before testing. Patients were divided into four groups based on prior therapy. Group 1 received involved-field irradiation and a CCNU-containing chemotherapy regimen (n = 7); group 2, craniospinal irradiation with a boost to the primary tumor site and a CCNU-containing chemotherapy regimen (n = 6); group 3, craniospinal irradiation with a boost to the primary tumor site and a non-CCNU-containing chemotherapy regimen (n = 7); and group 4, craniospinal irradiation with a boost to the primary tumor site without chemotherapy (n = 8). RESULTS: Fourteen patients (50%) had findings consistent with RLD. One of seven patients (14.3%) who received CCNU without spinal irradiation had RLD, whereas 13 of 21 (61.9%) who received spinal irradiation with or without CCNU had RLD (P = .038), including four of eight patients treated with craniospinal irradiation alone. Logistic regression analysis showed that only spinal irradiation was a significant predictor for RLD. Patients who received spinal irradiation were 4.3 times more likely to have RLD than those who did not receive spinal irradiation. CONCLUSION: Spinal irradiation may be a risk factor for the development of RLD

BACKGROUND. Central nervous system (CNS) germinomas respond readily to both radiotherapy and chemotherapy. This study was designed to selectively reduce the dose of radiotherapy in those patients expressing a complete response (CR) to neoadjuvant carboplatin. METHODS. A Phase II trial with carboplatin was conducted in 11 newly diagnosed patients with histologically confirmed, radiologically evaluable CNS germinomas before they received radiotherapy. All patients had normal cerebrospinal fluid and serum tumor markers (i.e., human chorionic gonadotropin [HCG] and alpha fetoprotein [AFP]). Seven patients had localized tumors (three pineal, three suprasellar, and one thalamus), and four had multifocal disease. Their median age at diagnosis was 13 years (range, 7-31). One course of carboplatin consisted of 150 mg/m2 weekly for 4 consecutive weeks followed by a 2-week break. Response was evaluated after two courses. If a patient had a CR to chemotherapy, the radiotherapy doses to the involved field and the craniospinal axis were lowered from 50 Gy to 30 Gy and from 36 Gy to 21 Gy, respectively. If less than a CR was observed, two additional courses of chemotherapy were administered, after which the patient's response was reevaluated. Less than a CR required full radiotherapy doses. The radiotherapy volume was determined by the extent of disease at diagnosis (i.e., localized disease was treated with an involved field and craniospinal therapy was used for disseminated disease). RESULTS. Seven patients had a CR to carboplatin (five patients after two courses and two patients after four courses). Three patients had a partial response (one after four courses and two after two courses). The investigators of the latter two patients chose not to give additional chemotherapy. Another patient opted for radiotherapy after receiving only one course of chemotherapy and was not evaluable for response. Ten of 11 patients remain in continuous remission for a median of 25 months. One patient had a recurrence. He presented with a localized pineal germinoma and had a CR after two courses of carboplatin. He received 30 Gy of involved field radiotherapy and suffered a relapse 5 months later in multiple CNS sites. He died 23 months after diagnosis with diffuse CNS and peritoneal metastases. His serum AFP and HCG levels were elevated, consistent with a nongerminoma germ cell tumor. CONCLUSIONS. Carboplatin was highly active in treating newly diagnosed CNS germinomas. Further chemotherapy studies eventually may permit additional dose reductions and/or elimination of radiotherapy for patients with CNS germinomas

Brain tumors are the second most common malignancy of childhood after acute lymphocytic leukemia. Improvements in therapy have led to increased survival. It is estimated that by the year 2000 there will be approximately 200,000 survivors of childhood cancer. A proportion of these will have survived a central nervous system malignancy. As more children survive, complications of treatment are increasingly recognized. This paper reviews the spectrum of radiation-induced complications, both short- and long-term. Their frequency and characteristics will be reviewed as well as suggestions made to decrease their incidence

The ability of surgery or bromocriptine to produce endocrine control of a prolactin macroadenoma decreases as the prolactin level increases. Guidelines for the use of multimodality therapy have not been developed for tumors associated with markedly elevated prolactin levels. We reviewed the records of 21 patients with prolactin levels greater than 200 ng/ml treated by transsphenoidal surgery and postoperative radiotherapy with or without a dopamine agonist. Values before and after treatment were available for 19 patients (13 men and 6 women). The mean basal prolactin level before treatment for the entire group was 2410 ng/ml. Surgery and radiotherapy resulted in a 90% reduction and serum prolactin levels within normal limits in 0 of 7 patients, versus the combination of surgery, radiotherapy, and dopamine agonist, which resulted in a 99.5% reduction and values within the normal range in 12 of 12 patients. Spontaneous physiological improvement was not often observed. One woman and two men were able subsequently to have children. A plan for these patients is discussed.

The optimal treatment of prostatic carcinoma limited to the gland remains controversial. Treatment has included implantation of Iodine-125 seeds via both a suprapubic approach and, more recently, a transperineal technique utilizing ultrasound guidance. We recently have noted a heretofore unreported complication with this latter technique, namely, embolization of seeds to the lungs. Review of the chest x-ray films of 31 patients who underwent suprapubic implants showed no evidence of this phenomenon. One of 5 patients undergoing transperineal implant was found to have seeds lodged in the lung. Complications surrounding the various treatments of localized prostate carcinoma are reviewed