A total of 342 previously untreated eligible children were entered into the first Intergroup Ewing's Sarcoma Study (IESS) between May 1973 and November 1978. In group I institutions, patients were randomized between treatment 1 (radiotherapy to primary lesion plus cyclophosphamide, vincristine, dactinomycin, and Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] [VAC plus ADR]) or treatment 2 (same as treatment 1 without ADR), and group II institutions randomized patients between treatment 2 or treatment 3 (same as treatment 2 plus bilateral pulmonary radiotherapy [VAC plus BPR]). The percentages of patients relapse-free and surviving (RFS) at 5 years for treatments 1, 2, and 3 were 60%, 24%, and 44%, respectively. There was strong statistical evidence of a significant advantage in RFS for treatment 1 (VAC plus ADR) versus 2 (VAC alone) (P less than .001) and 3 (P less than .05) and also of treatment 3 versus 2 (P less than .001). Similar significant results were observed with respect to overall survival. Patients with disease at pelvic sites have significantly poorer survival at 5 years than those with disease at nonpelvic sites (34% v 57%; P less than .001). Among pelvic cases, there was no evidence of differing survival by treatment (P = .81), but among nonpelvic cases, there was strong evidence of differing survival by treatment (P less than .001). The overall percentage of patients developing metastatic disease was 44%; the percentages by treatments 1, 2, and 3 were 30%, 72%, and 42%, respectively. The overall incidence of local recurrence was 15%, and there was no evidence that local recurrence rate differed by treatment. Patient characteristics related to prognosis, both with respect to RFS and overall survival experience, were primary site (nonpelvic patients were most favorable) and patient age (younger patients were more favorable).

Thirty-six patients underwent curative resection of a primary pancreatic carcinoma from January 1977 to September 1987; 26 had Whipple resections, seven had total pancreatectomies, and three had distal pancreatectomies. Twenty-six patients manifested recurrent disease, four died of intercurrent disease, and six were apparently cured. Median survival was 11.5 months with actuarial survival at 2 and 5 years of 32% and 17%, respectively. Of the eventual recurrences, 19% were local only (pancreatic bed, regional nodes, adjacent organs, and immediately adjacent peritoneum) and 73% had a component of local failure. All patients failing did so with a component in the intraabdominal cavity. Peritoneal (42%) and hepatic failures (62%) were common. Extraabdominal metastases were documented in only 27%, but never as a sole site. Fourteen patient and tumor characteristics were evaluated for any relationships with failure or survival. No single variable independently predicted for local failure. However, a group of three (age > 60 years, T2 or T3 stage, and location of tumor in the body or tail) was associated with a substantial local failure risk (85% of all patients with local failure). Multivariate analysis showed that low tumor grade (P = O.oOZ), female sex (P = 0.002), and adjuvant radiation (P = 0.02) were all independent predictors of prolonged survival. Ten patients were treated in an adjacent setting. Those given 55 Gy or greater had improved local control (50% versus 25%) and cure (33% versus none) when compared with patients treated to lower doses. The authors conclude that local failure after curative resection remains a significant problem and further efforts to improve local control are warranted. However, peritoneal and hepatic relapses occur frequently. Thus, adjuvant treatment strategies using wide-field radiation techniques or intraperitoneal therapy, in combination with local tumor bed irradiation and chemotherapy, should be explored. Cancer 66:56-61,1990. ANCREATIC CARCINOMA remains a devastating P problem for the patient as well as those charged with its management. By recent estimates, this malignancy will account for 3% of the total cancer incidence in adults and 5% of the total deaths, taking 24,500 lives in the US in 1988.' Moreover, the incidence has risen over the last 40 years.2 Even in the highly selected subgroup that undergoes "curative" resection, the expected 5-year survival is in the range of 0% to 18%,3 with median survivals of 10 to 14 month^.^,^ For the remainder of patients, approximately one third will have unresectable locoregional disease only and the rest will have metastases at pre~entation.~ In patients who have undergone complete resection, a previous randomized study from the Gastrointestinal Tumor Study Group (GITSG) as well as a follow-up non-randomized registration study have shown a survival advantage for patients treated with postoperative combined radiation and 5-fluorouracil (5-FU).637 In light of this 56

Two hundred fourteen eligible patients with previously untreated, localized Ewing's sarcoma of bone were randomized on IESS-II to receive Adriamycin (ADR; doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, vincristine, and dactinomycin by either a high-dose intermittent method (treatment [trt] 1) or a moderate-dose continuous method (trt 2) similar to the four-drug arm of IESS-I. Patient characteristics (sex, primary site, type of surgery) were stratified at the time of registration; these and other patient characteristics (age, time from symptoms to diagnosis, race) were distributed similarly between treatments. Surgical resection was encouraged, but not mandatory. Local radiation therapy was the same as for IESS-I. The median follow-up time is 5.6 years. The overall outcome was significantly better on trt 1 than on trt 2. At 5 years, the estimated percentages of patients who were disease-free, relapse-free, and surviving were 68%, 73%, and 77% for trt 1 and 48%, 56%, and 63% for trt 2 (P = .02, .03, and .05, respectively). The major reason for treatment failure for both treatment groups was the development of metastatic disease. The lung was the most common site of metastases followed by bone sites. The combined incidence of severe or worse toxicity (67%) was comparable between the treatments; however, severe or worse cardiovascular toxicity was significantly greater on trt 1. Tne only treatment-associated deaths (N = 3) were on trt 1 and were cardiac-related.

A total of 422 patients with malignant lymphoma of bone who were seen at the Mayo Clinic from 1907 through 1982 were placed into four major groups based on stage of disease. There was one group with primary lymphoma of bone, one group with multifocal osseous lymphoma, and two groups with lymphoma of bone and nodal or soft tissue (or both) disease. The last-mentioned two groups were separated on the basis of time of onset of osseous lymphoma in relation to the nonosseous disease. The stage of disease was the single most important prognostic indicator of overall survival in malignant lymphoma of bone. The 5- and 10-year survival rates were, respectively, 58% and 53% for patients with primary bone lymphoma, 22% and 12.5% for patients with bone and nodal or soft tissue (or both) disease, and 42% and 35% for patients with multifocal osseous disease. Features having no significant prognostic value were sex of the patient, histologic grade of the lymphoma (according to the Working Formulation and the Kiel system), and presence of T-cell features or cleaved cells (or both). This study is not able to adequately address efficacy of treatment. In fact, treatment may be very important in outcome.

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