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Background. An International Pathology study was conducted to measure the agreement demonstrated among and within groups of pathologists involved in the categorization of childhood rhabdomyosarcoma according to four pathology classifications. Data concerning agreement and survival experience according to pathonew subtypes were used as a basis for selection of a proposed new pathologic classification. Methods. A random sample of 800 eligible patients was chosen from the Intergroup Rhabdomyosarcoma Study II (IRS-II) and was reviewed by pathologists representing eight institutions. A 20% sample of the 800 patients was then rereviewed by the pathologists to determine the level of agreement with their original classification. In each instance the patients were classified according to four pathology systems: the conventional system, the International Society for Pediatric Oncology system (SIOP), the National Cancer Institute (NCI) system, and the cytohistologic system. Results. Among the groups of pathologists, the highest measure of agreement was a Kappa value of K = 0.451 for the conventional system, followed by K = 0.406 for the SIOP system, K = 0.384 for the NCI system, and K = 0.328 for the cytohistologic system. For reproducibility within the groups of pathologists, the highest measure of agreement was K = 0.605 for the conventional system, followed by K = 0.579 for the NCI system, K = 0.573 for the SIOP system, and K = 0.508 for the cytohistologic system. Conclusions. There was a general similarity between the agreement reached within the modified conventional, SIOP, and NCI systems, with the modified conventional system having the highest Kappa values, and thus the highest measure of agreement, both among and within the groups of pathologists. Also, the subtypes of the conventional system demonstrated a highly significant relationship to survival time. Hence, based on criteria of reproducibility and prognostic significance, the proposed classification will essentially be a modification of the conventional system with elements of the SIOP and NCI systems. Cancer 1994;74:2579-88.

Background: Recent reports have documented the occurrence of treatment-related acute myeloid leukemia (AML) following therapy with epipodophyllotoxins. These reports have led to growing concern among oncologists, which could lead to premature abandonment of these agents at a time when the relationship between cumulative dose of epipodophyllotoxin and risk of treatment-related AML has not been determined. Purpose: Because of the increasingly important role of epipodophyllotoxins in the treatment of several types of adult and pediatric tumors, the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan to obtain reliable estimates of the risk of treatment-related AML following epipodophyllotoxin treatment. Methods: We identified 12 NCI-supported Cooperative Group clinical trials in which patients with solid tumors are being treated with epipodophyllotoxins at different cumulative doses. One trial is using a moderate dose of teniposide (900 mg/[m.sup.2]), and 11 trials are using etoposide at a low dose (

Background. As increasing numbers of young patients with cancer survive, interest in the late effects of therapy is rising. Methods. The sequelae of treatment were reviewed after a minimum of 5 years of observation in 109 surviving patients with sarcoma of the bladder or prostate who were enrolled in the Intergroup Rhabdomyosarcoma Studies I and II (1972-1984). The 82 male and 27 female patients were 3 weeks to 19 years of age when the diagnosis was made (median, 2 years) and were 5-29 years of age at last contact (median, 11 years). Treatment consisted of chemotherapy with vincristine, dactinomycin, and cyclophosphamide and bladder irradiation in nearly all patients. Results. Fifty-four patients underwent total cystectomy, and 10 had a partial cystectomy. Of the 55 patients with bladder preservation, 1 had a urinary conduit with a nonfunctioning bladder. Thus, 54 bladders (50% of the total) remained in place as part of the urinary tract. There was no information regarding bladder function in two patients. Satisfactory bladder function was found in 38 patients (73%), 9 were incontinent, and 5 had urinary frequency with or without nocturia. Posttherapy hematuria was detected in 29% of patients. Nine of the 31 patients (29%) with follow-up renal imaging studies had a structural abnormality, chiefly hydronephrosis, which was more frequent in those with urinary diversion. Positive urine cultures were found mainly among those with enteric urinary conduits, but only two cases of pyelonephritis were documented. Abnormalities of irradiated bone and bowel were observed infrequently. Only one patient had a significantly elevated blood urea nitrogen or serum creatinine value, and only one patient was hypertensive. Most patients were still prepubertal at last follow-up. Of 24 patients who were intrapubertal or post-pubertal, 7 (29%) were receiving sex hormone replacement because of delayed pubertal development. Height was decreased by 25% or more in 11 patients, as confirmed by growth chart analysis. Secondary surgical procedures other than repeat biopsy or cystectomy consisted primarily of urinary conduit revisions and repair of bowel adhesions or fistulous tracts. Information about psychosocial status was limited. Conclusions. Overall, 50% of the patients retained their bladders, and 73% of them had satisfactory bladder function. Renal function was preserved in nearly every patient. Cancer 1993; 71:2387-94.

Background. Intergroup Rhabdomyosarcoma Study (IRS)-II, (1978-1984) had the general goals of improving the survival and treatment of children with rhabdomyosarcoma (RMS). Methods. Nine hundred ninety-nine previously untreated eligible patients entered the study after surgery and were randomized or assigned to therapy by IRS Clinical Group (I-IV), tumor site, and histologic type. Outcomes were compared between treatments and with results of IRS-I (1972-1978). Results. Patients in Group I, excluding extremity alveolar (EA) RMS, were randomized to standard vincristine (V), dactinomycin (A), and cyclophosphamide (C) or standard VA. At 5 years, disease-free survival (DFS) and survival (S) rates were similar between VAC and VA (DFS: 80%, 70%, P = 0.47;S: 85%, 84%, P = 0.73). Patients in Group II, excluding EA RMS, received radiation and were randomized to intensive VA or repetitive-pulse VAC. Outcomes were similar for rates of DFS (69%, 74%, P = 0.83) and S (88%, 79%, P = 0.17). Patients in Group III, excluding certain pelvic tumors, received radiation and were randomized to repetitive-pulse VAC or repetitive-pulse VAdrC-VAC (Adr, Adriamycin [doxorubicini]). Complete remission (CR) rates were close at 74%, 78%, respectively (P = 0.32), as were percentages in CR (73%) and S (66%) rates; the latter outcomes were significantly better than IRS-I (CR: 56%, P < 0.001; S: 50%, P < 0.001). Central nervous system prophylaxis for Group III patients with cranial parameningeal sarcoma increased S rate to 67% from 45% in IRS-I (P < 0.001). Patients in Group IV received the same regimens as Group III; the CR rate was 53%, 38% remained in CR and S rate was 27% with and 26% without Adr (P = 0.90). At 5 years, S rate for IRS-II, including EA and all pelvic tumors, was 63%: an 8% increase over IRS-I (P < 0.001). Outcomes by primary site were as good as, or better than, the IRS-I experience. Conclusions. Combining all Groups and treatments in IRS-II, the major improvement in S rate at 5 years between studies was in nonmetastatic patients (71% for IRS-II versus 63% for IRS-I, P = 0.01). Cancer 1993; 71:1904-22.

A review of cases of children with cancer in or near the bladder revealed that children with complete surgical resection of the surrounding area enjoyed only a marginal increase in survival over those who received chemotherapy as a primary treatment. Only a quarter of the surgically treated patients who were alive at the end of two years still had their bladder, however. Since the loss of the urinary bladder has significant physical and psychosocial effects, an attempt was made to determine if more aggressive chemotherapy might permit a greater number of children to retain at least a portion of their bladder. A total of 109 children with genitourinary sarcomas were treated in an uncontrolled study in which the individual physician made the therapeutic choice for each patient with the objective of saving the bladder, if possible. The chemotherapeutic regimen consisted of vincristine, dactinomycin, and cyclophosphamide. Radiation and/or surgery was used to treat residual or recurrent tumor. While the three-year survival rate was comparable to a previous study in which the treatment was primarily surgical, the disease-free survival was worse (52 percent compared with 70 percent for the surgically treated patients). After three years, only 22 percent of the surviving patients with bladder or prostate cancer still retained their bladders, which is not significantly different from the 23 percent who retained their bladders with surgery as the primary treatment. The evidence, therefore, suggests that present chemotherapeutic techniques are not effective in permitting the preservation of bladder function in children with genitourinary sarcomas. This does not preclude the possibility that improved chemotherapeutic regimens may make bladder preservation possible. (Consumer Summary produced by Reliance Medical Information, Inc.)