Carcinoembryonic antigen in children with neuroblastoma.

Plasma carcinoembryonic antigen (CEA) was assayed with a radioimmune procedure in 27 healthy control children. The upper limit of plasma CEA (mean +2 SD) was derived from healthy controls and was 3.35 ng/ml. This value was compared with those obtained from 15 children with active neuroblastoma, 7 with active embryonal rhabdomyosarcoma, 16 with treated neuroblastoma and without evidence of disease, 14 disease-free patients with embryonal rhabdomyosarcoma, and 17 patients still on therapy. The neuroblastoma and embryonal rhabdomyosarcoma patients with active disease had higher CEA values than did the successfully treated neuroblastoma and embryonal rhabdomyosarcoma patients. CEA plasma values greater than 3.35 ng/ml were found in 35% and 24% of patiens with neuroblastoma and embryonal rhabdomyosarcoma, respectively.

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.

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.

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.

The influence of extensive bone erosion on local control in non-orbital rhabdomyosarcoma of the head and neck.

To investigate a recent report suggesting extensive bone erosion (EBE) as an important prognostic factor in head and neck rhabdomyosarcoma, a retrospective review was performed of 32 patients with gross residual and/or metastatic non-orbital head and neck rhabdomyosarcoma treated between the years 1971-1987. Treatment consisted of surgery, radiation therapy (median primary dose, 5000 cGy) and combination chemotherapy according to the Memorial Sloan-Kettering Cancer Center (MSKCC) T2 and T6 protocols. The MSKCC staging system was used: Stage II, 23 patients; Stage III, 6 patients; and Stage IV, 3 patients. With a median follow-up of 48 months (range 17 months to 13 years), the overall survival and local control rates were 72% (23/32) and 75% (24/32), respectively. Local control was achieved in 11/11 patients without extensive bone erosion (Stages II, 9/9; III, 1/1; IV, 1/1) as compared to 13/21 patients (Stages II, 10/14; III, 2/5; IV, 1/2) with extensive bone erosion (p = 0.02). Our data appear to support the recently reported finding that extensive bone erosion is an important predictor of local failure.

Preliminary results of alternating combination chemotherapy (CT) and hyperfractionated radiotherapy (HART) in advanced rhabdomyosarcoma (RMS).

In an attempt to reduce treatment (Rx) related acute toxicity and improve protocol compliance without compromising local control nor overall survival, a Phase II single arm pilot employing alternating intensive multiagent CT and radiotherapy (RT) in children with gross residual or metastatic RMS was begun at Memorial Sloan-Kettering Cancer Center (MSKCC) in 1984. Hyperfractionated radiotherapy (HART) was adopted to allow for timely delivery of both the RT and CT. From July, 1984 through July, 1986 12 patients (pts), aged 2 to 23 yr (median 10 yr) were enrolled on study. CT treatment was delivered over approximately 14 months and included 2 induction and 5 maintenance cycles. The induction CT consisted of two repetitive cycles of Vincristine, Dactinomycin, Cyclophosphamide, Adriamycin, Bleomycin, and Methotrexate; the maintenance CT included the same agents as reduced drug doses. The HART was delivered to the primary site during cycle I of induction at fractions of 150 cGy BID to a total dose of 5400 cGy in 2 courses of 3000 cGy and 2400 cGy, respectively. One hundred percent of patients completed the recommended dose of HART; 0% required unplanned interruptions of HART due to treatment toxicity. With a median follow-up (f/u) from diagnosis of surviving patients of 25 months (range 20-30), the local control rate is 83% (10/12 pts) and the overall survival, 58% (7/12 pts). The median time (MT) to any failure, local or metastatic, is 9 months (mo); and to death, 14 mo. Comparison of results with 12 historical controls with concomitant split-course standard fractionation RT (180-200 cGy/per fraction) and T6 CT during a MSKCC trial from 1975-1984, matched by site and stage of primary, revealed that 9 pts (75%) completed the recommended dose of RT, and 7 pts (58%) required interruptions of RT. With a median f/u of 78 mo (range 34-109), the local control rate was 75% (9/12 pts) and the overall survival, 42% (5/12 pts). The MT to any failure was 14 mo; and to death, 18 mo. These results indicate that the mode of alternating CT and HART (HART T6) as employed in this pilot study is well tolerated. It appears to offer a significant improvement in protocol compliance over previous protocols using concomitant CT and RT without any apparent compromise in local primary control or survival rates with a median f/u suggestive of adequate elapsed time for the appearance of most relapses and deaths in advanced RMS.

Parameningeal rhabdomyosarcoma (including the orbit): results of orbital irradiation.

Twenty-three patients with parameningeal (including orbital rhabdomyosarcoma (RMS)) were treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between July 1971 and January 1983. Twenty were children with a mean age of 6 and 3 were adults. In 6 patients, the primary tumor was from the orbit, whereas the remaining 17 had other parameningeal primary sites. The tumors were in a very progressive local stage, with extensive destruction of the facial bones in 19 patients. Eight patients were treated with T2 chemotherapy protocol and 15 received T6. Seven patients received 5,000 to 7,200 rad delivered to the primary tumor in 11-16 weeks, 15 patients received between 4,500 to 5,000 rad in 4-7 weeks, and 1 patient received 3,000 rad in 3 weeks for residual microscopic disease following surgery. Two patients were treated with radiation to the whole brain; no patients received radiation of the whole central nervous axis (CNA). Fifteen of the 23 patients (65%) are alive and well with a medical follow-up time of 5 years. Two patients died of therapeutic complications and six died of tumor spread. In five patients, involvement of the central nervous system (CNS) was the cause of death. The prognosis of orbital RMS with parameningeal involvement is no better than in other tumors of parameningeal sites. In those patients who had impaired vision because of optic nerve damage prior to treatment, the vision did not improve following treatment. There was no impaired vision seen due to radiation damage of eye structures except in the lens.

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.

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.

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.

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)

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.