PURPOSE: The study goal was to improve outcome in children with rhabdomyosarcoma by comparing risk-based regimens of surgery, radiotherapy (RT) and chemotherapy. PATIENTS AND METHODS: Eight hundred eighty-three previously untreated eligible patients with nonmetastatic rhabdomyosarcoma entered the Intergroup Rhabdomyosarcoma Study-IV (IRS-IV) (1991 to 1997) after surgery and were randomized treatment by primary tumor site, group (1 to 3), and stage (I to III). Failure-free survival (FFS) rates and survival were the end points used in comparisons between randomized groups and between patient subgroups treated on IRS-III and IRS-IV. Most patients were randomized to receive vincristine and dactinomycin (VA) and cyclophosphamide (VAC, n = 235), or VA and ifosfamide (VAI, n = 222), or vincristine, ifosfamide, and etoposide (VIE, n = 236). Patients with group 3 tumors were randomized to receive conventional RT (C-RT) versus hyperfractionated RT (HF-RT). RESULTS: Overall 3-year FFS and survival were 77% and 86%, ...

Intergroup Rhabdomyosarcoma Study-IV: Results for Patients With Nonmetastatic Disease

PURPOSEThe ultimate goal of the Third Intergroup Rhabdomyosarcoma Study (IRS-III, 1984 to 1991) was to improve treatment outcome in children with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irradiation.PATIENTS AND METHODSOne thousand sixty-two previously untreated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tumor. Initial responses, progression-free survival (PFS), and survival (S) were the end points used in comparisons between randomized groups and between patients treated in IRS-III and IRS-II (1978 to 1984).RESULTSThe overall outcome of therapy in IRS-III was significantly better than in IRS-II (5-year PFS, 65% +/- 2% v 55% +/- 2%; P < .001 by stratified testing). Patients with group I favorable-histology tumors fared as well on a 1-year regimen of vincristine an...

The Third Intergroup Rhabdomyosarcoma Study.

Progress in immunology: Syndromes of diminished resistance to infection

Background. There is a need to develop a single prognostically significant classification of rhabdomyosarcomas (RMS) and other related tumors of children, adolescents, and young adults which would be a current guide for their diagnosis, allow valid comparison of outcomes between protocols carried out anywhere in the world, and should enhance recognition of prognostic subsets.



Method. Sixteen pathologists from eight pathology groups, representing six countries and several cooperative groups, classified by four histopathologic classification schemes 800 representative tumors of the 999 eligible cases treated on Intergroup Rhabdomyosarcoma Study II. Each tumor was classified according to each of the four systems by each of the pathologists. In addition, two independent subsamples of 200 of the 800 patients were reviewed according to the new system, so that 343 distinct patients were reviewed once, and 57 of these twice.



Results. A study of the survival rates of all subtypes in the sample of 800 patients led to the formation of a new system. This was tested on two independent subsets of 200 of the original cases and found to be reproducible and predictive of outcome by univariate analysis. A multivariate analysis of the 343 patients classified according to the new system indicated that a survival model including pathologic classification and known prognostic factors of primary site, clinical group, and tumor size was significantly better at predicting survival than a model with only the known prognostic factors.



Conclusion. This new classification, termed International Classification of Rhabdomyosarcoma (ICR) by the authors, was reproducible and predictive of outcome among patients with differing histologies treated uniformly on the Intergroup Rhabdomyosarcoma II protocols. We believe it should be utilized by all pathologists and cooperative groups to classify rhabdomyosarcomas in order to provide comparability among and within multi-institutional studies. Cancer 1995;76:1073-85.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819950915%2976%3A6%3C1073%3A%3AAID-CNCR2820760624%3E3.0.CO%3B2-L

Classification of rhabdomyosarcomas and related sarcomas. Pathologic aspects and proposal for a new classification‐an intergroup rhabdomyosarcoma study

Four hundred and twenty-three children with newly diagnosed rhabdomyosarcoma have been entered to date in the Intergroup Rhabdomyosarcoma Study (IRS), which began in 1972. Patients were classified into Clinical Disease Groups (Stages) I-IV, based on disease extent and resectability, and treatment regimens were randomly assigned according to group. Two hundred and seventy-eight of 423 patients are evaluable for this analysis. Thus far, for Group I disease (localized/completely resected), disease control achieved by vincristine, dactinomycin, and cyclophosphamide (VAC) given in combination for 2 years has not been enhanced by the administration of postoperative radiation to the tumor bed. To date, 92% of patients in both irradiated and nonirradiated groups exhibit no evidence of disease, and 92-96% are still alive, with the median time of follow-up being 72 weeks. For Group II disease (microscopic residual/nodal involvement), VAC given for 2 years has not been found to be more effective than vincristine plus dactinomycin given for 1 year, both groups also having received postoperative irradiation. Thus far, over 85% of patients on either treatment have no evidence of disease and 90% are still alive. Survival and complete remission durations range from 1+ to 143+ weeks and the median duration of follow-up is 45 weeks. Chemotherapy as initial treatment has been studied in Group III (localized sarcoma not treated initially by gross total resection) and Group IV (metastases present at diagnosis) patients. They have received either intensive “pulse” VAC or “pulse” VAC plus Adriamycin, and radiation has been administered after 6 weeks. Eighty-one percent of patients in Group III and 81-83% in Group IV have responded favorably, with complete regression of disease having been observed in over one-fourth of patients even before the start of radiation and in approximately one-half of all the patients after receiving radiation therapy. There is no indication as yet that one treatment regimen is superior to the other. Seventy-nine percent of patients in Group III are still alive (0+ to 154+ weeks) and 69% remain in continuous response (0+ to 139+ weeks) with the median duration of follow-up being 41-44 weeks. Fifty percent of patients in Group IV are still alive (0+ to 127+ weeks) with a median time of follow-up of 41-44 weeks. Tumors arising either from genitourinary sites or the extremities have had a higher incidence of lymphatic spread than tumors in all other primary sites of origin.

The intergroup rhabdomyosarcoma study. A preliminary report

Current therapy of rhabdomyosarcoma involves the use of several modalities of treatment: surgery, radiotherapy, and chemotherapy. The present controlled study was designed to evaluate the role of chemotherapy in the control of occult residual disease following surgery and radiotherapy. The results of this study support the adjunctive use of combined chemotherapy with actinomycin D and vincristine sulfate for 1 year in preventing growth of metastatic or recurrent disease when children are made grossly tumor free by surgery and radiotherapy. Twenty-four (85.7%) of 28 children in this category are disease free for periods greater than 2 years after initial treatment and a year of chemotherapy. Initial staging and the degree to which a patient can be made tumor free with primary definitive therapy are the most significant variables in prognosis. Vinblastine was not useful in the treatment of metastatic rhabdomyosarcoma.

https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/1097-0142%28197412%2934%3A6%3C2128%3A%3AAID-CNCR2820340638%3E3.0.CO%3B2-M

The role of combined chemotherapy in the treatment of rhabdomyosarcoma in children.

One hundred twenty-five cases of sarcoma of the bladder and prostate in children have been reviewed from the literature. Eighty-seven arose in the bladder and 37 in the prostate. One arose in an unknown site. Seventy percent of patients with rhabdomyosarcoma of the bladder survived following total cystectomy; no patient survived following more limited surgical resection. Five of 25 patients with rhabdomyosarcoma of the prostate survived following limited or radical surgery, irradiation in 3 patients, and chemotherapy in all cases. No patient survived without chemotherapy. Review of our own experience revealed a survival of 78% (seven of nine patients) for rhabdomyosarcoma of the bladder following radical surgery. Four of these patients had chemotherapy and two had irradiation also.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28197311%2932%3A5%3C1161%3A%3AAID-CNCR2820320525%3E3.0.CO%3B2-V

Sarcoma of the bladder and prostate in children. Rationale for the role of radiation therapy based on a review of the literature and a report of fourteen additional patients

Unsuspected lymphosarcoma of the kidneys diagnosed as bilateral Wilms tumor.

The one boy and two of three girls in a consanguineous kindred have exhibited undue susceptibility to invasive infections with Hemophilus influenzae and pneumococci. One of the affected siblings died of overwhelming H. influenzae type B sepsis and was found at autopsy to have a minute spleen. No other anatomic abnormalities were present. The two affected live siblings were each shown to have no demonstrable splenic tissue by scintillation scanning of the abdomen following intravenous injection of colloidal Au198. Normal splenic tissue was demonstrable in both parents by this tecnique. Examination of the peripheral blood of affected offspring revealed the presence of Heinz and Howell-Jolly bodies. The antibody response to subcutaneous injection of tetanus and diphtheria toxoids and typhoid bacilli was normal. Their red cell survival and response to intravenous particulate antigens are under investigation and the results will be reported. (SPR)

/pdf/62-hereditary-splenic-hypoplasia-14q92a89z6.pdf

Melvin Tefft

Papers

The role of combined chemotherapy in the treatment of rhabdomyosarcoma in children.

Sarcoma of the bladder and prostate in children. Rationale for the role of radiation therapy based on a review of the literature and a report of fourteen additional patients

Unsuspected lymphosarcoma of the kidneys diagnosed as bilateral Wilms tumor.

62 Hereditary Splenic Hypoplasia