Survival improvement in anaplastic astrocytoma, combining external radiation with halogenated pyrimidines: final report of RTOG 86-12, Phase I-II study.

PURPOSE: This study evaluated the toxicity and tumor efficacy of the halopyrimidine IUdR as a chemical modifier of radiation response in patients with malignant glioma. The preliminary results published in 1993 demonstrated no real advantage in the group of patients with glioblastoma. However, a benefit appeared to be evolving in the group of patients with Anaplastic Astrocytoma (AA). We are now presenting the results on the long-term follow-up of patients with AA. METHODS AND MATERIALS: Between August 1987 and October 1991, 79 patients were entered in a prospective study with newly diagnosed malignant glioma. Twenty-one of 79 were AA. The study was designed to have a fixed dose of radiation consisting of 60.16 Gy in 32 fractions in 6.5 weeks but varying the dose schedule of IUdR, delivered in a continuous intravenous infusion of long (96 h) or short (48 and 24 h) duration, every week for the 6.5 weeks of radiation treatment. RESULTS: The last AA patient was entered in March 1991. Ninety-five percent of the AA patients were under 59 years of age and 86% had a Karnofsky score 80. Thirty-eight percent had a tumor diameter of less than 5 cm and 52% had a tumor diameter between 5-10 cm. Seventy-six percent had partial or total tumor resection. The toxicity of this treatment was acceptable and has already been published elsewhere. At the time of this report, 14 out of 21 patients with AA are dead. The median survival, calculated from the Kaplan-Meier, is 3.2 years. Thirty-three percent of the patients have survived 5 years. These results compare favorably with the best results reported in the literature with postoperative external radiation plus chemotherapy, median survival time (MST) of 3 years, and previous Radiation Therapy Oncology Group (RTOG) experience with radiation alone, MST of 2 years. CONCLUSIONS: Our findings in patients with AA corroborate the improved therapeutic results published recently when combining external radiation with "long" infusion of i.v. BUdR and indicate the need to proceed with randomized Phase III studies utilizing halogenated pyrimidines and radiation. One such study has already been activated, RTOG # 94-04.

Brain metastases and testicular tumors: long-term survival.

In this updated and expanded retrospective analysis, the treatment records of 24 patients with brain metastases from nonseminomatous germ cell testicular tumors (NSGCT's) treated at the Indiana University Department of Radiation Oncology from 1975 through 1988 were reviewed. All patients received standard cisplatin-based induction chemotherapy. These patients were divided into three groups. Group 1 (n = 10) consisted of patients who presented initially with brain metastases and had no prior systemic treatment. Group 2 (n = 4) consisted of those patients who, after achieving a complete response (CR) with cisplatin, vinblastine, and bleomycin (PVB) +/- doxorubicin, developed a relapse confined to the brain. Group 3 (n = 10) consisted of those patients who were initially treated with PVB +/- doxorubicin or bleomycin, etoposide, and cisplatin (BEP) and eventually developed progressive disease and brain metastases. Group 1 was treated with whole brain irradiation (WBRT) and PVB +/- doxorubicin or BEP. Group 2 was treated with WBRT, cisplatin-based chemotherapy +/- surgical excision. Group 3 was usually treated with WBRT palliatively. Six patients, three in Group 1 and three in Group 2, are alive and disease-free with follow-up of 5+ years from beginning WBRT. Two additional patients in Group 1 survived 5+ years from beginning WBRT before dying with disease. No patient in Group 3 survived. Patients with brain metastases who have potentially controllable systemic disease should be treated curatively with WBRT (5000 cGy/25 fractions) +/- surgical excision and concomitant chemotherapy.

Radiation therapy in colorectal carcinoma.

In spite of advances in surgical technique and patient management, there continues to be a high rate of local recurrence for the advanced stages of rectal and colon carcinomas. The addition of radiotherapy to the treatment of colorectal carcinoma, however, has diminished the local recurrence rate; the acute and chronic toxicity is tolerable, and the patients with higher stages benefit from the combined modality. It is recommended that modified Astler-Coller stages B2 or greater receive some form of adjuvant radiotherapy. The ideal sequencing and the benefit of combining radiation with chemotherapy has not yet been determined. The use of intraoperative radiotherapy is very promising and continues to be investigated for initially unresectable lesions and recurrent lesions.

Testicular seminoma: analysis of treatment results and failures.

Pure testicular seminoma has historically been treated primarily with radiation therapy, and excellent results have been achieved. Recently, several aspects of the treatment of seminoma have been questioned; namely, the value of mediastinal irradiation in Stage II disease, and whether a dose response curve existed for seminoma. Because these questions have remained unanswered, we undertook a retrospective review of all patients with pure testicular seminoma treated in the Department of Radiation Oncology at Indiana University Medical Center. From 1961-1981, 54 patients with pure testicular seminoma were given megavoltage irradiation with curative intent. Thirty three patients were Stage I, with tumor confined to the testicle with no evidence of nodal spread. Fifteen patients were Stage IIA, with metastases less than 5 cm in size in the retroperitoneal nodes. Four patients were Stage IIB, with metastases greater than 5 cm in size in the retroperitoneal nodes. One patient was Stage III, with supradiaphragmatic metastases confined to the mediastinum and supraclavicular area. One patient was Stage IV, with evidence of extralymphatic metastases. The crude survival rate (corrected for intercurrent death, except for treatment toxicity) for the entire group was 87%. For Stage I, it was 91%, Stage IIA-80%, Stage IIB-75%, Stage III-100%, and Stage IV-0%. All patients had a minimum follow-up of 2 years with a range of 2 to 21 years. Evaluation of the Stage I patients reveals that 2500 rad in 3 weeks appears to be adequate in controlling microscopic disease, as there were no in-field recurrences when this dose was given. Those patients with Stage IIA and IIB disease who received greater than or equal to 3500 rad to macroscopic disease had 100% (7/7) survival and local control, while those receiving less than or equal to 3000 rad had a 66.6% (8/12) survival with three of four demonstrating persistent or recurrent abdominal disease. Thus, we feel that macroscopic disease requires 3500 rad to 4000 rad for control. All Stage II and III patients had planned mediastinal irradiation. No patients who received mediastinal irradiation recurred in the mediastinum. Whether this is because of our treatments or the natural disease process remains unanswered. Overall, we were able to salvage 12.5% (1/8) of our recurrences, while 37.5% (3/8) died from toxicity of their salvage therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain metastases and testicular tumors: need for aggressive therapy.

In late 1974, the combination of cisplatin, vinblastine, and bleomycin (PVB) became the standard chemotherapeutic regimen for treatment of disseminated nonseminomatous germ cell testicular tumors (NSGCT) at Indiana University Hospital. A retrospective analysis of the treatment records of all patients with brain metastases from NSGCTs treated at the Indiana University Radiation Oncology Department from 1975 through 1982 was undertaken. These 22 patients were divided into four groups. Group 1 (n = 5) consisted of those patients who presented initially with brain metastases and had no prior systemic treatment. Group 2 (n = 4) were referred to Indiana University after failing systemic therapy other than PVB chemotherapy. Group 3 (n = 5) consisted of those patients who after achieving a complete response with PVB developed a relapse confined to the brain. Group 4 (n = 8) consisted of those patients who were initially treated with PVB and eventually developed progressive disease and brain metastases. The survival by group is 80%, 0%, 60%, and 0%, respectively, with the overall survival for the entire group being 31.8%. All patients currently alive have a range of follow-up of 22 to 96 months from diagnosis and 12 to 83 months from whole brain irradiation (WBRT). Group 1 was treated with PVB +/- doxorubicin plus WBRT. Group 3 was treated with surgical excision, when feasible, followed by WBRT and platinum-containing chemotherapy. Group 2 and 4 were usually treated with palliative intent WBRT. The CNS is a site of sanctuary from PVB. Patients with brain metastases who may achieve a complete response should be treated with curative intent and receive aggressive WBRT (5,000 rad/25 fractions) with concomitant chemotherapy.