Aly Razek

Intergroup Ewing's Sarcoma Study Local Control Related to Radiation Dose, Volume, and Site of Primary Lesion in Ewing's Sarcoma

One hundred ninety‐three patients with localized Ewings sarcoma treated at participating institutions of the Intergroup Ewings Sarcoma Study form the basis for this report. All patients received radiation therapy to the primary lesion and were randomized to receive vincristine, actinomycin‐D, and cyclophosphamide (VAC) plus adriamycin (Regimen I); VAC alone (Regimen II); or VAC and bilateral pulmonary irradiation (Regimen III). Local control was achieved in 96% of the patients in Regimen I, and 86% of the patients in both Regimens II and III. The median duration of follow up was 83 weeks and median survival time was 172 weeks. Incremental doses of irradiation did not result in significant changes in the rate of local control of primary lesions. The local control rate was the same (92%) for tumors treated by means of whole‐bone irradiation or with at least 5 cm of free margin around the lesion. The local control rate decreased to 79% for lesions treated with less than a 5‐cm margin. Excellent control was obtained for lesions involving the skull or spine (100%), and distal bones (fibula, 96% and tibia, 91%). Less favorable control rates were noted for pelvic and humeral lesions (84% and 79%, respectively). Bilateral pulmonary irradiation for subclinical disease played a role in lowering the incidence of lung metastases from 38% to 20% for patients treated with VAC. Lung metastases were similarly decreased (10%) when adriamycin was added to VAC chemotherapy. Cancer 46:516–521, 1980.

Analysis of local tumor control in ewing's sarcoma. Preliminary results of a cooperative intergroup study

This report is a preliminary analysis of the local tumor control in 187 patients treated with multi‐agent chemotherapy and local radiation therapy for non‐metastatic Ewings sarcoma. Patients were treated according to three different regimens, all of which included irradiation of the primary tumor and involved bone (5000‐6000 rads in 5‐6 weeks). The first group was treated with a combination of cyclophosphamide, vincristine, adriamycin and actinomycin‐D. The second group received cyclophosphamide, vincristine and actinomycin‐D. The third group was treated with cyclophosphamide, vincristine and actinomycin‐D in addition to bilateral pulmonary irradiation. The present results, after a median follow‐up of 24‐30 months in the various groups combined, indicate that the local control is 87%. Twenty‐two of 25 local failures appeared within 24 months (88% of recurrences). No difference in time of appearance of local recurrence was noted in the three treatment regimens. The highest incidence of local recurrence has been noted in the humerus (22%), the pelvis (19%), the tibia (14%) and the femur (11%). Sixty‐seven of the 187 patients (35.8%) have developed distant metastases, mostly to the lungs and to other skeletal sites. Of the patients with pelvic primaries, 62% have developed distant metastases followed by the humerus (41%), the femur (36%) and the tibia (24%). A detailed analysis of radiation therapy technical factors was done in 110 patients with complete dosimetry data at the time of this report. There is a trend indicating that patients who received doses over 6000 rads (20/20) or with lower doses combined with chemotherapy containing adriamycin (9/9) have a higher local control. However, the difference with the other groups (67/81‐83%) was not statistically significant. Radiation therapy in combination with multiple chemotherapy is an effective treatment method to control Ewings sarcoma locally. The late effects of this intensive combined therapy must be assessed in long term survivals. Future studies in Ewings sarcoma should attempt to elucidate crucial issues such as the optimal volume of bone that should be irradiated, the potential value of limited surgical resection of gross tumor and the determination of optimal multi‐agent regimens which will enhance local tumor control and diminish distant metastases. Because of the rarity of this tumor, the need for cooperative controlled clinical trials is emphasized. Cancer 40:2864‐2873, 1977.

Local control and survival related to radiation dose and volume and to chemotherapy in non-metastatic Ewing's sarcoma of pelvic bones.

Abstract This manuscript reviews 25 patients with non-metastatic Ewings sarcoma of the pelvis. In 4/25 (16%) the disease recurred locally and then metastasized. In addition, 15/25 patients have shown widespread metastases without local recurrence. Thus, only 10/25 (40%) remain with no evidence of disease at this writing. Patients who received VAC

An analysis of neuroblastoma at a single institution.

and Adriamycin (Regimen I) seemed to have a lower incidence of local recurrence than those who received VAC alone, even when radiation dose and/or volume were not optimum. Further study including isotope bone scanning and lymphangiograms are recommended for future clinical study to evaluate the natural history of disease for this site. More intensive chemotherapy has been instituted by reducing the “rest” period to 3 weeks instead of 6 weeks chemotherapeutic courses.

Combined treatment modalities of rhabdomyosarcoma in children

Between 1949 and 1978, 119 children with the diagnosis of neuroblastoma or ganglioneuroblastoma were treated at the Washington University Medical Center. Of these, 50 (41%) were alive and disease‐free 3 or more years after diagnosis. Important prognostic variables included stage of tumor (Evans staging), histology, age at diagnosis, and site of primary tumor. A stepwise logistic regression analysis of these data has shown that, in order of significance, stage, histology and age at diagnosis are independent prognostic variables. Sex of the patient and nodal status at diagnosis (where known) were not significant prognostic variables. No effects of individual treatment modalities could be detected. This study confirms the overwhelming influence of factors unrelated to treatment in determining the prognosis of neuroblastoma.

Optimum Time Sequence for the Administration of Vincristine and Cyclophosphamide in Vivo

Thirty‐nine previously untreated children with rhabdomyosarcoma were managed by a coordinated program of surgery, radiation therapy, and chemotherapy during the years 1960 to 1973. The primary tumor was located in the head and neck (24), chest wall (1), abdomen (1), pelvis (10), and lower extremity (3). Radiation therapy consisted of tumor doses of 5000 to 6000 rads delivered in five to six weeks. Combination chemotherapy with actinomycin‐D, vincristine and cyclophosphamide was used after 1968. Seventeen of 25 cases (68%) treated after 1968 are alive two to five years following treatment. Only four of 14 cases (29%) who received less radical therapy before 1968 are alive. A relatively high incidence of local failure (23%) was noted in spite of adequate doses of radiotherapy. None of the four cases with metastatic disease at the time of diagnosis survived. Major complications were mainly noted in patients with orbital rhabdomyosarcoma. Correlation of absolute survival with dose of irradiation, primary site, extent of disease and histologic subtypes of the tumor are discussed.