Results of alternating chemotherapy and hyperfractionated radiation therapy in childhood rhabdomyosarcoma.

BACKGROUND: A regimen of multi-drug chemotherapy alternating with split course hyperfractionated radiation therapy (HFRT) was adopted for the treatment of patients with rhabdomyosarcoma (RMS). The purpose of this treatment regimen was to allow for the timely delivery of radiation and chemotherapy, reduce treatment-related toxicity, and improve compliance. PROCEDURE: Forty-four patients with stages II-IV RMS were treated with HFRT and received 5,400 cGy. The treatment was administered in two courses (3,000 and 2,400 cGy) and separated by a 4-week interval. HFRT consisted of 150 cGy delivered twice a day, 5 days a week with an interfraction interval of 4-6 hours. A limited comparison was made between the HFRT patients and 42 historical patients with comparable clinical characteristics who were treated with similar chemotherapy and conventionally fractionated radiation therapy (CFRT) (median 4,800 cGy, range 4,000-5,680 cGy). RESULTS: HFRT patients completed radiation therapy in 59.1 +/- 9.4 days (mean +/- SD) and CFRT patients completed treatment in 56.6 +/- 10.5 days compared to an expected 52 and 40 days, respectively. With a median follow-up of 55 months for the HFRT patients and 104 months for the CFRT patients, no differences in local control or survival were noted. Nine of 44 (21%) HFRT and 8/42 (19%) CFRT patients experienced local failure. The median time to local failure was 15 months for patients in the HFRT group and 11 months for patients in the CFRT group. CONCLUSIONS: The results of the HFRT regimen were acceptable in terms of toxicity and compliance. No improvement in local control was obtained by alternating radiation and chemotherapy. The lack of difference between patients treated with HFRT and CFRT may be related to the lengthened treatment time of the split course regimen, the small difference in total dose, and tumor repopulation.

High-dose induction chemoradiotherapy followed by autologous bone marrow transplantation as consolidation therapy in rhabdomyosarcoma, extraosseous Ewing's sarcoma, and undifferentiated sarcoma.

PURPOSE: To improve response and survival rates in patients with high-risk rhabdomyosarcoma (RMS), extraosseous Ewing's sarcoma, and undifferentiated sarcoma, we used a short course of induction with multi-agent chemotherapy, hyperfractionated radiotherapy, and surgery when possible. Consolidation was with intensive chemotherapy and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Twenty-six patients (21 with RMS, three with undifferentiated sarcoma, and two with extraosseous Ewing's sarcoma) were entered onto the protocol between June 1990 and March 1994. Induction consisted of ifosfamide, etoposide, doxorubicin, dactinomycin, cyclophosphomide, and vincristine, and a split course of hyperfractionated radiotherapy. Patients who attained a complete response (CR) or good partial response (GPR) received consolidation with high-dose melphalan and etoposide followed by ABMT. RESULTS: Of 26 previously untreated patients 19 (73%) achieved a CR (n=13) or GPR (n=6) at the completion of induction and underwent ABMT. Two-year overall survival (OS) was 56% (95% confidence interval [CI], 36% to 76%) and progression-free survival (PFS) was 53% for the whole group (95% CI, 33% to 73%). CONCLUSION: Consolidation of response by myeloablative chemotherapy was well tolerated. Split-course hyperfractionated radiotherapy did not increase the rate of local control. The results of this short-course therapy were comparable to previous therapies of 1 to 2 years' duration. Induction and consolidation chemotherapy, as well as radiation dose, could be further intensified, since no death due to toxicity occurred among these patients.

Outcome of patients with a history of bilateral retinoblastoma treated for a second malignancy: the Memorial Sloan-Kettering experience.

BACKGROUND: Patients with bilateral retinoblastoma are well recognized to have a high risk of developing a second malignancy, but there are little published data regarding the outcome of these patients following treatment. PATIENTS AND METHODS: We identified 15 patients with a history of bilateral retinoblastoma who received treatment at Memorial Sloan-Kettering Cancer Center for a newly diagnosed second malignancy. The median age of second tumor occurrence was 18 years (range 10-32 years). Three patients later had a third tumor (18 tumors total). Tumor sites included facial structures in 14 cases and extremities in 4. Histologies included osteosarcoma (5), leiomyosarcoma (5), high-grade spindle cell sarcoma (3), malignant fibrous histiocytoma (3), malignant mesenchymoma (1), and angiosarcoma (1). RESULTS: Nine patients are alive: 7 disease free at a median of 29 months (range 6-214 months) and 2 with residual disease 59 and 148 months post-diagnosis of the second malignancy. Six patients have died at a median of 31 months (range 16-98 months) after diagnosis of the second malignancy. CONCLUSIONS: Patients with a history of bilateral retinoblastoma who develop a second malignancy may enjoy extended periods of survival. Aggressive therapy appropriate to the tumor histology and site is indicated.

Pediatric rhabdomyosarcoma of the head and neck.

PURPOSE: Survival for pediatric rhabdomyosarcoma has improved with the use of multidrug chemotherapy and external beam radiotherapy. This study was performed to determine survival in a cohort of patients treated on one of three multidrug treatment protocols for head and neck rhabdomyosarcoma and to identify factors that place patients at risk for treatment failure. METHODS: Pertinent prognostic variables including age, sex, subsite of origin, resectability, and TNM stage were analyzed by the Kaplan-Meier methods with comparisons between variables performed using the Prentice-Wilcoxon test statistic. RESULTS: Overall 5-year survival was 74% (95% confidence interval 64% to 84%). Local failure accounted for the cause of death in 10 patients, and 8 died of disseminated disease. On univariate analysis, each variable contributing to the TNM staging system was significant in determining survival; invasiveness (P = 0.01), size (P = 0.02), nodal metastases (P <0.01), and distant disease (P <0.01). CONCLUSION: Survival has improved for head and neck rhabdomyosarcoma treated with multimodality therapy. Patients with advanced-stage disease are at greatest risk for treatment failure and require the most aggressive therapy.

Chest wall rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma is the most common soft tissue sarcoma in the pediatric age group. The primary tumor site is an important prognostic determinant. Axial lesions are associated with decreased survival and provide a clinical challenge. METHODS: A retrospective analysis of the authors' institutional experience between 1972 and 1996 was performed. Patients were from a data base of 302 consecutive cases. RESULTS: Fifteen consecutive patients with chest wall rhabdomyosarcoma were identified. The median age was 16 years (range, 6 months-25 years). Median follow-up was 6.6 years (range, 10 months-18.5 years). Nine patients presented with a mass, six with pain, two with respiratory distress, and one with ulnar neuropathy. The median lesion size was 7 cm (range, 3-16 cm). A surgical procedure was the initial therapy for 13 of 15 patients. Fourteen patients received radiation therapy with a median dose of 4400 cGy. All but one were included in institutional-based trials using multiagent chemotherapy. At last follow-up, 10 patients were alive and disease free, with a median survival of 123 months (range, 51-221 months). Seven of ten survivors underwent a complete resection as their initial therapy. There was no surgical mortality, and only two patients had treatment-related complications. Of the five patients who died, two underwent complete resection as their initial therapy. All five patients had invasive tumors. Four were > 10 cm, 3 were of alveolar subtype, and 2 were embryonal. CONCLUSIONS: Complete resection of chest wall rhabdomyosarcoma is recommended. However, survival is possible for patients with microscopically positive surgical margins with the addition of chemotherapy and radiation.

Hypothalamic-pituitary-adrenal function following cranial irradiation.

We assessed the effect of cranial irradiation on hypothalamic-pituitary (HP)-adrenal function in 17 patients (12 females, 5 males) treated with cranial/ craniospinal irradiation for acute leukemia (2 patients) or tumors distant from the hypothalamus and pituitary (8 medulloblastoma, 3 astrocytoma, 3 rhabdomyosarcoma, 1 ependymoma). Estimated doses of radiation (RT) to the HP region ranged from 18 to 72 Gy. Thirteen of seventeen patients were also treated with chemotherapy. Patients were a median of 3.75 years of age (1.5-19 years) at diagnosis and were studied at a median of 5 years (0.1-20 years) after RT. Patients received corticotropin-releasing factor (oCRF, 1 microgram/kg i.v.), and sampling for cortisol and ACTH levels was performed at -15, 0, 15, 30, 60, 90 and 120 min. The-5- and 0-min levels were combined for a standardized baseline value (Base). Cortisol levels at 0, Base, 30 and 120 min, as well as the peak cortisol response, were significantly lower in the patients. Twelve of seventeen patients' peak cortisol levels fell below the normal range. The patients' mean integrated values for cortisol (area under the curve) were not, however, different from controls. The ACTH responses to oCRF did not differ between patients and controls. No relationship was observed between ACTH or cortisol responses and the time elapsed from treatment or dose of HP RT. Further, in 10 of 12 patients, 0-min dehydroepiandrosterone sulfate levels were lower than the expected normal mean levels for age, sex and pubertal status, and in 4 of these 10 patients the values were below the normal range. These data suggest that some patients treated with HP RT may be at risk for adrenal insufficiency.

Kinetics of primary tumor regression with chemotherapy: implications for the timing of surgery.

PURPOSE: The kinetics of tumor regression during administration of chemotherapy has relevance to the timing of surgery. The aim of this study was characterization of the time course of primary tumor regression in initially unresectable rhabdomyosarcoma, hepatoblastoma, and neuroblastoma patients. We also estimated the total cell number in the primary tumor at diagnosis. METHODS: Tumor volumes of 24 pediatric patients with either unresectable rhabdomyosarcoma, hepatoblastoma, or neuroblastoma were determined by using computerized three-dimensional reconstruction from serial computed tomography (CT) scans during chemotherapy. Cell densities were calculated by counting cell numbers in high-power fields and dividing by area and section thickness. Cell number at diagnosis was then calculated. RESULTS: Median tumor volumes at diagnosis were 175 cc, 748 cc, and 738 cc for rhabdomyosarcoma, neuroblastoma, and hepatoblastoma, respectively. The median tumor cell counts were 31, 68, and 59 x 10(10) cells/tumor for rhabdomyosarcoma, neuroblastoma, and hepatoblastoma, respectively. The tumor regression was most rapid during the first two cycles, and little change in volume was observed after three cycles. CONCLUSION: Rapid initial reduction in primary tumor volume with chemotherapy was observed in rhabdomyosarcoma, neuroblastoma, and hepatoblastoma. These data suggest that second-look resection may be feasible after two to three cycles of chemotherapy. This hypothesis may be tested by randomizing the timing of second-look surgical intervention.

Pulmonary function in children treated for rhabdomyosarcoma.

Chemotherapy, radiation therapy, and surgical intervention have markedly improved the survival of patients treated for rhabdomyosarcoma. Unfortunately, the therapy may have deleterious effects on the lung. Pulmonary functions tests were obtained from 17 patients treated for rhabdomyosarcoma because of our concern regarding potential pulmonary dysfunction in this group of patients who had received bleomycin, which is known to be associated with lung injury. Mean age at the time of the diagnosis of rhabdomyosarcoma was 10.1 (+/- 7.2) years (range 0.01-23.5 years). The mean age at the time of pulmonary function testing was 17.0 (+/- 7.5) years (range 5.8-34.0 years). Study patients reportedly had no pulmonary symptoms. Approximately 87% of study patients had a restrictive ventilatory impairment on pulmonary function testing as measured by total lung capacity (TLC) values less than the lower limit of normal. Approximately 70% of study patients had carbon monoxide diffusing capacity (DLCO) values less than the lower limit of normal. There were no significant differences in pulmonary function parameters when male study patients were compared to female study patients. There was a statistically significant lower forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio (P=0.03) and percent predicted forced expiratory flow at 25-75% of the FVC (FEF25-75; P=0.03) in the group of patients diagnosed with rhabdomyosarcoma over 8 years of age as compared to those individuals diagnosed under 8 years of age. In addition, there were no statistically significant differences in pulmonary function when the variables of sex and age at diagnosis (as outlined above) were studied in combination. In summary, we identified a high incidence of restrictive ventilatory abnormalities in a group of individuals (predominantly children) treated for rhabdomyosarcoma as well as a significantly lower FEV1/FVC ratio and percent predicted FEF25-75 in the group of patients diagnosed with the neoplasm over 8 years of age. Individuals caring for such patients are encouraged to obtain pre- and sequential posttreatment pulmonary function tests.

Preliminary results of phase I/II study of high-dose-rate intraoperative radiation therapy for pediatric tumors.

Ten children with locally advanced or recurrent tumors were treated on a Phase I/II study to assess the feasibility and toxicity of intraoperative radiotherapy (IORT) for primary and recurrent pediatric solid malignancies at high risk for local recurrence. Eligible patients include all primary and recurrent pediatric solid tumors that are amenable to resection and have residual microscopic or gross disease after surgery. In all cases, after a gross tumor resection was performed, a flexible, transparent, multichannel applicator was placed and secured within the tumor bed. Once the position of the applicator was optimized, the applicator catheters were attached to the cables of a high-dose-rate remote afterloader, and 1,200 cGy prescribed to 0.5-1.0 cm from the applicator was delivered to the tumor bed via the remote afterloader. One patient with a malignant teratoma developed a peri-rectal abscess 1 month after treatment; no other complications were noted. The 2-year actuarial local recurrence-free and distant metastases-free survival were 80% and 59%, respectively, with a median follow-up of 12 months (range: 3-18 months). The preliminary results suggest that high-dose-rate IORT is a safe and feasible modality for pediatric tumors at high risk for local recurrence. Longer follow-up will be needed to assess fully the toxicity and efficacy of this approach.

Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy.

PURPOSE: To test intensive alkylator-based therapy in desmoplastic small round-cell tumor (DSRCT). PATIENTS AND METHODS: Patients received the P6 protocol, which has seven courses of chemotherapy. Courses 1, 2, 3, and 6 included cyclophosphamide 4,200 mg/m2, doxorubicin 75 mg/m2, and vincristine (HD-CAV). Courses 4, 5, and 7 consisted of ifosfamide 9 g/m2 and etoposide 500 mg/m2 for previously untreated patients, or ifosfamide 12 g/m2 and etoposide 1,000 mg/m2 for previously treated patients. Courses started after neutrophil counts reached 500/microL and platelet counts reached 100,000/microL. Tumor resection was attempted. Post-P6 treatment options included radiotherapy and a myeloablative regimen of thiotepa (900 mg/m2) plus carboplatin (1,500 mg/m2), with stem-cell rescue. RESULTS: Ten previously untreated and two previously treated patients have completed therapy. The male-to-female ratio was 11:1. Ages were 7 to 22 years (median, 14). The largest masses were infradiaphragmatic (n = 11) or intrathoracic (n = 1). Other findings included serosal implants (n = 11), regional lymph node invasion (n = 8), ascites or pleural effusion (n = 7), and metastases to liver (n = 5), lungs (n = 4), distant lymph nodes (n = 3), spleen (n = 2), and skeleton (n = 2). Tumors uniformly responded to HD-CAV, but there were no complete pathologic responses. One patient died at 1 month from tumor-related Budd-Chiari syndrome. Of seven patients who achieved a complete remission (CR), five remain in CR 9, 12, 13, 33, and 38 months from the start of P6, one patient died of infection at 12 months (autopsy-confirmed CR), and one patient relapsed 4 months off therapy. Of four patients who achieved a partial remission (PR), one remains progression-free at 34 months and three developed progressive disease. Five patients received local radiotherapy: three were not assessable for response, but in two patients, antitumor effect was evident. Four patients received thiotepa/carboplatin: two were in CR and remain so, and two patients had measurable disease that did not respond. CONCLUSION: For control of DSRCT, our experience supports intensive use of HD-CAV, aggressive surgery to resect visible disease, radiotherapy to high-risk sites, and myeloablative chemotherapy with stem-cell rescue in selected cases.

Second malignant neoplasms in long-term survivors of childhood rhabdomyosarcoma.

BACKGROUND: The occurrence of second malignant neoplasms (SMNs) in successfully treated pediatric patients with cancer has been an area of increasing concern because survival of these patients has improved with intensification of therapy. Therefore, the incidence of SMNs in long term survivors of childhood rhabdomyosarcoma (RMS) was studied. METHODS: From 1970 to 1989, 210 newly diagnosed patients (median age, 9.7 years; range, 1 month to 27 years) with RMS were treated at Memorial Sloan-Kettering Cancer Center (New York, NY). Multimodality treatment included chemotherapy, surgery, and radiotherapy, when indicated. There were 130 long term survivors (> 2 years off therapy) with a median follow-up of 9 years (range, 2-20 years). The cumulative dose of each chemotherapeutic agent and the radiation doses each patient received were reviewed. Statistical analysis was performed by comparison with the Connecticut Tumor Registry data. RESULTS: Seven patients developed a SMN, including three with acute nonlymphoblastic leukemia (ANLL) and four with solid tumors. Acute nonlymphoblastic leukemia developed a median of 4.5 years after diagnosis. Of the solid tumors, 3 developed within the radiation field at a median of 10 years after diagnosis, whereas the fourth occurred 9.3 years after initial diagnosis in a patient who did not receive radiotherapy. All seven patients with SMNs received total dactinomycin doses higher than the median (9.6 mg/M2) for the group. All three patients with ANLL received total cyclophosphamide doses higher than the median (16.8 g/M2). Moreover, six of the seven patients received a dose of radiotherapy greater than 4000 cGy. The standardized incidence ratio was: 17.07 (95% confidence interval, 6.68-35.18; P < 0.0001). CONCLUSIONS: Multimodality therapy has improved long term survival for patients with childhood RMS. The combination of high dose radiotherapy and chemotherapy appears to increase the risk for developing a second malignancy.

Correction of neutropenia with rHuG-CSF after loss of response to rHuGM-CSF following autologous bone marrow transplant.

We describe a patient who presented with graft failure following autologous BMT, with an initial response of the neutrophil count to rHuGM-CSF but eventual loss of this response. Subsequently, this patient responded to rHuG-CSF. This could be explained by the fact that rHuG-CSF stimulates both early and late myeloid progenitor cells whereas rHuGM-CSF stimulates mainly the intermediate myeloid progenitor cells. This finding suggests that rHuG-CSF should be investigated for the treatment of patients with graft failure following ABMT.

The effect of age at diagnosis on outcome in rhabdomyosarcoma.

BACKGROUND: Survival for rhabdomyosarcoma appears to be more favorable in children and adolescents compared with adults. To determine the significance of age at diagnosis as a prognostic indicator in rhabdomyosarcoma, we performed a retrospective analysis of a combined pediatric and adult rhabdomyosarcoma data base. METHODS: Pertinent prognostic variables, including age, TNM stage, histopathologic subtype, anatomic site, resectability, radiation to the primary site, and dose intensity of chemotherapy, were compared in a Cox proportional hazards model with mortality as the outcome variable. RESULTS: Age at diagnosis (P = 0.0001) and local tumor invasiveness (P < 0.0001), distant parenchymal metastases (P < 0.0001), regional lymph node involvement (P = 0.0027), and histopathologic subtype (P = 0.0446) contributed information to the proportional hazards model. CONCLUSIONS: Age at diagnosis is an independent predictor of outcome in patients with rhabdomyosarcoma along with tumor invasiveness, metastases, regional lymph node involvement, and histopathologic subtype.

Liposarcoma in patients younger than or equal to 22 years of age.

BACKGROUND: There have been few reported series of liposarcomas in patients younger than or equal to 22 years of age. METHODS: A retrospective analysis of all patients presenting with liposarcoma between 1949-1990 at Memorial Sloan-Kettering Cancer Center with age at diagnosis younger than or equal to 22 years was performed. Variables evaluated for their predictive effect on survival included anatomic location of the primary, size, and completeness of surgical resection. RESULTS: Eighteen patients were identified. Only 1 patient (6%) presented with a high-grade lesion, and in 13 patients (72%), the myxoid subtype was observed. All but one patient undergoing complete resection remain disease-free 1.3-29.1 years after treatment, while all patients with gross residual tumor have died from disease. Two of three patients with microscopic residual at resection are disease-free 2 and 11.8 years after diagnosis with the addition of external beam radiation therapy. CONCLUSIONS: The authors conclude that complete surgical resection is crucial for survival in young patients with liposarcoma and the external beam radiation therapy may be effective against microscopic residual.

The relationship between thallium uptake, blood flow, and blood pool activity in bone and soft tissue tumors.

Twenty patients with known primary untreated and recurrent bone and soft tissue tumors underwent thallium imaging and three-phase bone imaging in the same session. The ratio of thallium uptake in the tumor tissue to the contralateral normal tissue areas was compared with the same ratio for phase 1 (blood flow or arterial phase), phase 2 (blood pool), and phase 3 (delayed medroxy-diphosphonate, MDP, uptake). There was poor correlation between Tl uptake and phases 1 and 3 of the bone scan ratios; r = 0.37 and 0.46; P = 0.097 and 0.047, respectively. The thallium uptake ratios correlated well with blood pool ratios (phase 2) (r = 0.84 and P less than 0.01). In contrast to uptake into normal muscle, Tl-201 uptake into tumor is not highly dependent on blood flow alone and other factors predominate in determining its magnitude.

Germ cell tumors in children: gonadal and extragonadal.

Sixty-three pediatric patients with germ cell tumors are presented with details of symptoms, histological findings, staging, serological markers, treatment, and response to therapy. The primary sites were: ovarian 32, testicular 17, presacral 7, mediastinal 3, intraabdominal 2, vaginal 1, and right inguinal canal 1. These patients were treated with T2 (sequential use of dactinomycin, doxorubicin, vincristine, and cyclophosphamide, with or without radiation), T6 (combination chemotherapy with cyclophosphamide, bleomycin, dactinomycin, doxorubicin, methotrexate, vincristine), or VAB treatment protocols (velban, dactinomycin, bleomycin, cisplatin). The cure rate for stage I ovarian and testicular germ cell tumors was 100%; for stage III, all primary sites, 82% and for stage IV, all primary sites, 75%. Histology was prognostic in ovarian tumors of the immature malignant teratoma type; the neural type immature teratoma, grades II and III, had the worst prognosis. Initial debulking surgery in combination with chemotherapy and radiation plays an important role in germ cell tumors. Stages II, III, and IV germ cell tumors require aggressive treatment with surgery, radiation, and chemotherapy. For stage I patients, with primary ovarian malignant tumor, cure with surgery alone can be achieved in 50% of the cases and in testicular tumors in about 70% of the patients. For those with stage I and elevated serological markers, it is feasible to follow these markers and give no treatment until there is evidence of persistent elevation or a rise in titers after an initial fall. In those without elevated serological markers, one should take into consideration the size of the tumor and the histological type before taking the "wait and see" approach. These stage I tumors are highly curable when they first present but, if allowed to recur, chemotherapy may not offer the patient such a favorable response and cure rate.

Prognostic factors in bladder and bladder-prostate rhabdomyosarcoma.

In order to examine surgical factors predictive of fatal outcome in patients presenting with histologically verified rhabdomyosarcoma of the urinary bladder, we performed a retrospective analysis of cases presenting between the years 1970 and 1985 and treated by protocol. Twenty-five patients were identified and data were complete for univariate and multivariate analysis on all. Staging was done according to the criteria of the International Union Against Cancer (TNM). Median age at presentation was 14.7 years and 10 patients were younger than 10 years. Median follow-up was 4.8 years overall and 8.4 years in survivors. Four patients presented with involvement of regional lymph nodes and three with distant metastases. Complete surgical resection, defined as negative microscopic margins, was accomplished by total cystectomy in 14 patients, and partial cystectomy in two. In this group cystectomy was performed prior to chemotherapy and radiation in five and after in 10 (persistent disease). Three salvage cystectomies were performed in patients who recurred after initial complete responses to chemotherapy and radiation therapy. Thirteen patients received a median of 3,000 cGy (range, 1,800 to 5,000 cGy) of external beam pelvic irradiation, and two received brachytherapy. All patients received multiple agent chemotherapy according to either the T2 or T6 protocol. There are 11 disease-free survivors (44%) and 10 of these have been followed for more than 6 years. One patient is alive with disease 6.5 years after diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiocurability of microscopic disease in childhood rhabdomyosarcoma with radiation doses less than 4,000 cGy.

In an attempt to evaluate the radiocurability of microscopic disease in childhood rhabdomyosarcoma (RMS) with total tumor doses of less than 4,000 cGy, we performed a retrospective analysis of all patients with microscopic residual RMS who were treated at the Memorial Sloan-Kettering Cancer Center (MSKCC) during the years 1970 to 1987. There were 32 patients ranging in age from 3 months to 22 years (median, 6 years) with microscopic residual of either (1) a localized primary tumor (MSKCC, stage IB; Intergroup Rhabdomyosarcoma Study [IRS] group IIA), 19 patients; or (2) an involved lymph node region with the primary tumor completely resected (MSKCC stage III; IRS group IIC), 13 patients. Twenty-nine of the 32 patients presented with embryonal histology. All patients were treated with combination chemotherapy (CT) and megavoltage external beam radiotherapy (RT). The RT was delivered in either conventional fractionation of 180 to 200 cGy daily (30 patients) or hyperfractionation of 150 cGy twice daily (two patients). Fifteen patients received RT doses of less than 4,000 cGy with a range of 3,000 to 3,600 cGy and a median value of 3,100 cGy; 17 patients received 4,000 cGy or more with a range of 4,000 to 6,000 cGy and a median value of 4,600 cGy. With a median follow-up of 11 years, the relapse-free survival was 25 of 32 patients (less than 4,000 cGy, 12 of 15; greater than or equal to 4,000 cGy, 13 of 17). The RT local control rate was 30 of 32 (less than 4,000 cGy, 14 of 15; greater than or equal to 4,000 cGy, 16 of 17 [P = .94]). Our results suggest that radiation doses of below 4,000 cGy, when combined with effective multiagent CT, may be sufficient for local control of microscopic disease in childhood embryonal RMS.

Factors predictive of mortality in pediatric extremity rhabdomyosarcoma.

In order to examine factors predictive of fatal outcome in children presenting with histologically confirmed extremity rhabdomyosarcoma, we performed a retrospective analysis of our institutional experience from 1970 to 1985. Thirty-five patients were identified and staged according to international criteria (TNM). Variables evaluated for their predictive effect on fatal outcome included (1) tumor invasiveness, (2) tumor size, (3) anatomic location of the primary, (4) regional lymph node involvement, (5) distant metastases at presentation, (6) complete surgical resection, (7) use of amputation, and (8) alveolar histologic subtype. Significant predictors of mortality included (1) tumor invasiveness (P less than or equal to .0001), (2) regional node involvement (P less than or equal to .0002), (3) distant metastases at the time of presentation (P less than or equal to .001), (4) alveolar histology (P less than or equal to .001), (5) size of primary (P less than or equal to .007), and (6) completeness of surgical resection (P less than or equal to .05). In multivariate analysis, local tumor invasiveness was the most important predictor of fatal outcome with an associated relative risk of 18. We conclude that local tumor invasiveness is the most important determinant of clinical stage.