A randomized trial of radiotherapy versus radiotherapy plus CCNU for incompletely resected low-grade gliomas: a Southwest Oncology Group study.

Sixty adult patients with incompletely excised low-grade gliomas were randomly assigned to receive radiotherapy (55 Gy over a total of 6 1/2 to 7 weeks) either alone or with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; 100 mg/sq m every 6 weeks). Pathological review showed that six patients were ineligible for the study. Evaluation of patient age, extent of surgery, tumor grade, and performance status showed no significant differences between the treatment arms. The response rate, as judged by the disappearance or reduction in size of the tumor on computerized tomography scans, was 79% for radiation therapy alone versus 54% for irradiation plus CCNU. The median survival time was 4.45 years for all patients, with no significant difference between treatment arms (p = 0.7). For the group as a whole, patient age and performance status were the most important prognostic parameters. The majority of patients receiving chemotherapy experienced moderate hematological toxicity. This study demonstrates that CCNU chemotherapy does not improve the results of radiation therapy in the treatment of incompletely excised low-grade gliomas.

A phase II randomized study comparing sequential and combined intraarterial cisplatin and radiation therapy in primary brain tumors. A Southwest Oncology Group study.

The Southwest Oncology Group conducted a trial of intra-arterial cisplatin (150 mg intravenously every 21 days for 2 doses) administered concomitant with or before radiation therapy. Because of technical difficulties cannulating the artery, 27 of 33 eligible patients were able to receive the cisplatin by arterial injection. Five patients died before completion of the study, and 11 patients in each treatment arm were evaluable for response. Three patients (27%) had an objective tumor regression in each treatment arm. Thromboembolic problems complicated 8 of 57 (14%) chemotherapeutic courses. The median survival for the 33 eligible patients was comparable for both groups: 10.8 months in the concomitant treatment arm and 9.6 months with sequential therapy. Problems related to drug administration and toxicity made it impossible to determine the role of intraarterial cisplatin in the initial management of primary high-grade gliomas.

Randomized comparisons of radiotherapy and carmustine versus procarbazine versus dacarbazine for the treatment of malignant gliomas following surgery: a Southwest Oncology Group Study.

Between 1977 and 1981, the Southwest Oncology Group entered 278 patients on a randomized study (SWOG 7703) to compare the effect of three different chemotherapeutic agents given in combination with radiotherapy (6000 rads over 7 weeks) following surgery for malignant gliomas. The chemotherapy regimens were: carmustine (BCNU)--80 mg/m2 iv daily X 3 every 6 weeks; procarbazine (PCB)--100 mg/m2 orally; or dacarbazine (DTIC)--175 mg/m2 iv daily X 5 every 4 weeks. Patients were stratified according to age, and degree of resection, with no differences identified between groups. The response rates (complete plus partial) for BCNU and DTIC were significantly better than for PCB [BCNU, 39%; PCB, 13%; and DTIC, 38% (P less than 0.01)]. The response duration and survival were somewhat better in patients treated with BCNU and DTIC, but compared to patients treated with PCB, the difference was not statistically significant. Median survival times were: BCNU, 45 weeks; PCB, 31 weeks; and DTIC, 49 weeks (P greater than 0.3). There were six toxic deaths with BCNU and four with PCB, most of which were due to infection associated with leukopenia. The high toxicity and minimal benefit of chemotherapy added to radiotherapy compared to historical results with radiotherapy alone suggest that combined treatment may not be indicated for some patients.

A comparison of deep regional hyperthermia from an annular array and a concentric coil in the same patients.

Twenty-two patients with advanced pelvic or abdominal malignancy (or both) were treated on successive occasions with hyperthermia produced by an annular array (AA) (60-80 MHz, 500-1800 W forward power) and a concentric coil (CC) (13.56 MHz, 350-1000 W forward power). Both devices were compared with respect to acute toxicity and power limitations. There was no power limiting factor in pelvic heating in 7/14 patients treated with the AA, however 13/14 experienced power limiting sacrococcygeal pain with the CC. The 9 patients who underwent abdominal heating had a variety of power limitations with both devices. Thermal mapping was performed in 23 treatments with the AA and in 19 with the CC. Composite thermal maps of patients with similar thermometry sites show that heating patterns produced by the CC were predictable from theory and static phantom measurements. The AA achieved broader regional heating, particularly at depth, but heating patterns were less predictable. Spatial thermal dose (TD) analysis revealed higher minimum tumor TDs and more favorable mean tumor/normal tissue TD ratios with the AA than with the CC. We conclude that the AA is superior to the CC for pelvic treatment and that both devices have limitations in abdominal treatment.

The Southwest Oncology Group experience: adjuvant therapy for stage IB and II non-seminomatous testicular cancer.

During a two year period, 65 patients with Stage II non-seminomatous testis cancer were randomized to receive adjuvant chemotherapy and radiation. Of the 52 evaluable patients, 23 received radiation followed by chemotherapy (sequential), and 29 received the same chemotherapy as initial treatment, but had drug treatment temporarily interrupted for radiation (sandwich). The combined treatment was well tolerated, but did not eliminate recurrence. With regard to duration of survival and disease-free survival, no statistically significant difference could be found between the sequential and sandwich approaches.

Randomized comparisons of radiotherapy and CCNU versus radiotherapy, CCNU plus procarbazine for the treatment of malignant gliomas following surgery. A Southwest Oncology Group Report.

One hundred and fifteen eligible patients with histologically verified malignant gliomas (astrocytoma grade III-IV) were randomized to receive either radiotherapy 6 000 rads/7 week plus CCNU 130 mg/M2 every 6 weeks (treatment 1) or radiotherapy 6 000 rads/7 weeks plus CCNU 75 mg/M2 day 1 plus procarbazine 100 Mg/m2 days 1-14 every 6 weeks (treatment 2) within 4 weeks following surgical resection. The response rates showed no statistically significant differences between treatment 1 CR/PR - 24/17% and treatment 2 CR/PR - 14/14% (P-value = 0.31). The median survival was also not significantly different: 55 and 50 weeks for treatments 1 and 2, respectively. The most important prognostic parameter identified was age with younger patients showing higher response rates and longer survival. Patients' performance status was also a useful prognostic parameter for response and survival. Neither the extent of surgical resection nor the tumor grade correlated significantly with the outcome. Further studies are needed to identify active chemotherapeutic agents for the treatment of brain tumors.

The effectiveness of prophylactic brain irradiation in small cell carcinoma of the lung: a Southwest Oncology Group study.

Brain involvement in small cell carcinoma of the lung is a common phenomenon occurring in from 29 to 45% of patients. Because of this, it was suggested that prophylactic brain irradiation be made a part of treatment plans for small cell carcinoma. In December 1974, the Southwest Oncology Group (SWOG) began treating patients with combination chemotherapy and irradiation of both the primary lesion and whole brain. In two years, there were 390 patients entered into the study. In patients with extensive disease only 6 of 152 prophylactically irradiated patients developed CNS signs or symptoms of CNS recurrence. In limited disease, 6 of 88 prophylactically treated patients had CNS recurrence and in only 4 was this the site of initial failure. We feel prophylactic brain irradiation in small cell carcinoma of the lung is of benefit.

Combined therapy for endometrial carcinoma preoperative intracavitary irradiation followed promptly by hysterectomy.

A group of 99 patients with endometrial cancer clinically confined to the uterus has been treated with preoperative adjunctive intracavitary irradiation followed within 72 hours by total abdominal hysterectomy and bilateral salpingoophorectomy. Those patients with poorly differentiated tumors, deep myometrial invasion, cervical involvement, or pelvic metastasis were then considered for external beam radiotherapy to the whole pelvis because of the increased risk of involvement of pelvic nodes or other pelvic structures. Only one of 16 patients so treated has failed in the pelvis. The overall Berkson-Gage actuarial survival at 3 years, uncorrected for death from intercurrent disease, is 85.8%. No vaginal recurrences have been identified. Although this series has not been randomized, it appears that there has been a reduction in vaginal and pelvic recurrences when compared with patients reported by others who have received no adjuvant radiotherapy. The low recurrent rate and favorable survival in this group of patients was achieved with low morbidity from this treatment technique.

Combined cardiotoxicity of adriamycin and x-radiation.

Our previous studies have shown that x-radiation produces cardiac lesions. Likewise, adriamycin, a useful antineoplastic agent, is known to be cardiotoxic. Maximal "safe" doses have been established for each of these forms of therapy. Since combined therapy with adriamycin and radiation is being used for malignancies involving the mediastinum, it is important to know whether the combination of both agents is more cardiotoxic than either agent alone. In this study young New Zealand White rabbits were divided into five groups and given: (1) a single dose of x-radiation of 1600 rads in the cardiac area; (2) 167 mg. per sq. m. of adriamycin; (3) both raddiation and adriamycin at the same doses; (4) 255 mg. per sq. m. of adriamycin; (5) no treatment. Animals in the third (combined) group developed radiation and adriamycin lesions, the frequency and severity of which were greater than those in the single therapy groups at the same (low) doses. These observations suggest a synergistic effect of the two agents. If so, patients receiving combined treatment are at risk of developing severe carditis from doses of adriamycin and cardiac x-radiation today regarded as safe. Although neither one is specific, the light and electron microscopic lesions caused by x-radiation (myocardial capillary damage, pericarditis) were easily distinguished from those caused by adriamycin (myocyte damage). Both agents led to diffuse myocardial fibrosis. These morphologic characteristics may have clinical applications.

Treatment of chromophobe adenmas with megavoltage tirradiation.

From 1956-1972, 62 previously untreated patients with chromophobe adenomas received high-dose (average equivalent dose: 5700rads in 6 weeks) megavoltage (4-4.8 MeV) irradiation at Stanford, 33 postoperatively and 29 as the only intended treatment. Initialtreatment failure rates were 18% and 41%, respectively; however, overall control was 85% and 90%, despite 2 uncontrolled "invasive" adenomas in each group. Nine of the 12 failures in the group treated by irradiation alone had cystic tumors, and 9 of the 12 "failed" in less than 3 months. Despite a considerably greater degree of abnormal vision initially in the postoperative irradiation group, improvement of vision with treatment in that group was 83% (19% returned to normal) compared to 46% (only 8% to normal) in the irradiation alone group. Based upon an evaluation of the extent of findings at diagnosis and our results, we recommend surgical decompression followed by 5000 rads in 5 weeks for patients with any one or more of the following findings: 1)more than minimal depression of peripheral visual fields; 2) corrected visual actuity of less than 20/30 in either eye; or 3)more than 1-cm suprasellar extension of tumor. We recommend irradiation alone, as specified, for smaller adenomas accompanied by less extensive or no visual abnormalities.

Adriamycin cardiomyopathy: enhanced cardiac damage in rabbits with combined drug and cardiac irradiation.

Rabbits received either (a) no treatment; (b) a single radiation dose; (c) protracted low-dose Adriamycin; (d) combined cardiac irradiation and low-dose Adriamycin; or (e) protracted high-dose Adriamycin. More severe myocardial lesions (similar to those in high-dose Adriamycin groups) developed in rabbits receiving combined treatment. Pericardial effusions and fibrosis were more common in the combined treatment group.

Results of postoperative megavoltage radiotherapy of malignant surface epithelial tumors of the ovary.

The results of postoperative radiotherapy in 151 patients with malignant epithelial tumors of the ovary are presented. Actuarial survival at five years for patients in FIGO Stage I was 76%; in Stage II, 56%; Stage III, 16%; and Stage IV, 0%. Survival also varied with histopathological type, the best prognoses occuring in the serous (malignant) and endometrioid types (NED survival of 35% and 50%, totalling all stages, respectively). The presence of ascites or intraperitoneal surgical spillage did not adversely affect survival. The role of lymphangiography in staging is discussed. New approaches to diagnosis, staging and treatment are required for improving the prognosis of patients with ovarian carcinoma.

Immunodeficiency in Hodgkin disease.

The immunodeficiency in Hodgkin disease is characterized by a defect in cell-mediated immunity. Recent studies have reported that delayed hypersensitivity responses (DHR) are normal in untreated patients with early disease. The present study evaluated the DHR of 218 untreated patients using 2,4-dinitrochlorobenzene and a battery of intradermal antigens. The results confirm an immune deficiency in early stages which is not an all-or-none phenomenon and may be unmasked by using lower concentrations of antigens.