Childhood lymphoblastic cancer: subgroups defined by nonhuman primate antisera to human lymphatic leukemia cell antigens.

Lymphoblasts from 23 children with acute lymphocytic leukemia (ALL) and 10 with lymphoblastic lymphoma (LBL) were studied by complement-dependent microcytoxicity tests with two nonhuman primate antisera defining leukemia-associated and lymphoma-associated antigens. Cells form 15 patients with ALL and 1 with LBL reacted only with antiserum to chronic lymphatic leukemia (CLL). These group-I patients were predominantly female. Most were pancytopenic and lacked mediastinal widening and T-cell markers; lymphoblasts from 15 were periodic acid-Schiff-positive. Cells from 8 male patients reacted only with antiserum to converted lymphosarcoma (LS). All these group-II patients expressed T-cell markers; 5 had mediastinal enlargement and 2, an abdominal mass. Six of the 8 were PAS-negative. Cells from 9 patients reacted with both antisera. The group-III patients demonstrated some characteristics of each of the above groups. Patients whose lymphoblasts reacted with CLL antiserum presented with clinical and laboratory features indicative of a good prognosis, i.e., ALL with PAS positivity and no T-cell markers or localized mass. Patients whose cells reacted with LS antiserum often had bad prognostic features: mediastinal or abdominal mass, expression of T-cell markers, and PAS negativity. These antisera appear able to differentiate childhood ALL from LBL. The distinction is important prognostically and perhaps therapeutically.

Late effects of therapy in patients with paratesticular rhabdomyosarcoma. Intergroup Rhabdomyosarcoma Study Committee.

PURPOSE: We report on long-term health-related problems determined from extended follow-up of 86 children and adolescents who were treated for paratesticular rhabdomyosarcoma on the Intergroup Rhabdomyosarcoma Studies I and II (IRS I-II). PATIENTS AND METHODS: Patients were treated between 1972 and 1984, and ages at diagnosis ranged from 10 months to 19 years. The majority of these patients had initial retroperitoneal lymph node dissection (RLND) or sampling performed. RESULTS: Problems related to surgical procedures included bowel obstruction in nine patients, loss of normal ejaculatory function in eight, development of a hydrocele in five, and lymphedema of the leg in five. Sequelae related to radiotherapy were difficult to assess with the exception of three patients whose remaining testes were in the field of radiotherapy. In general, kidney and bladder function were normal in patients who received radiotherapy to the paraaortic lymph nodes and/or bladder. Four patients who had abdominal radiotherapy had chronic diarrhea. Two patients had urethral strictures and urethritis. Four patients had bone or soft tissue hypoplasia in the field of radiotherapy. Chemotherapy-related late effects were primarily hemorrhagic cystitis or gonadal dysfunction after cyclophosphamide. A third of the patients who received cyclophosphamide developed hemorrhagic cystitis, and half of these had extended periods of gross hematuria after therapy was discontinued. The testicular size was small in children whose testes were irradiated and in some who received cyclophosphamide. Tanner staging was normal in 45 patients for whom it was recorded. Elevated follicle-stimulating hormone (FSH) values or known azoospermia occurred in more than half the patients for whom data were available. CONCLUSIONS: A variety of sequelae related to therapy were determined in this patient population. These findings suggest that some aspects of therapy warrant reevaluation and that improved plans for follow-up care need to be provided.

Treatment of orbital rhabdomyosarcoma: survival and late effects of treatment--results of an international workshop.

PURPOSE: Orbital rhabdomyosarcoma (RMS) historically has been associated with an excellent survival rate. The majority of patients are cured with the use of both chemotherapy and radiation therapy, but a significant number experience important late sequelae of treatment. In an attempt to determine optimal therapy in relation both to cure and to sequelae, the experience of the four international collaborative groups (Intergroup Rhabdomyosarcoma Study Group [IRSG], International Society of Paediatric Oncology [SIOP] Sarcoma Committee, German Collaborative Soft Tissue Sarcoma Group [CWS], and Italian Cooperative Soft Tissue Sarcoma Group [ICG] studies) was shared at an international workshop. PATIENTS AND METHODS: A total of 306 eligible patients were identified from group records (186 from IRS, 43 from SIOP MMT, 40 from CWS, and 37 from ICG). Median age was 6.8 years, and median follow-up was 6.5 years. Eighty percent of patients received radiation therapy (RT) as part of primary therapy, but there were significant differences in the use of RT between the individual groups (93% in IRSG, 76% in ICG, and 70% in CWS, but only 37% in the SIOP MMT group). RESULTS: At 10 years, event-free and overall survival for the whole cohort were 77% (range, 71% to 81%) and 87% (range, 82% to 92%), respectively. There was no difference in overall survival between the collaborative groups regardless of differences in the use of initial RT. In total, 34 (12%) of 273 survivors had not received RT, although this varied between the different groups (41% in the SIOP MMT group, 20% in CWS, 7% in ICG, and 6% in IRSG). There was no difference in overall survival for the whole cohort regardless of whether radiotherapy was used as part of initial therapy (86% at 10 years for both). CONCLUSION: These data suggest that a subset of patients with orbital RMS can be cured without systematic local therapy, although the total burden of treatment (primary therapy and treatment for relapse) must be taken into account when assessing the implications for late sequelae.

Preservation of the bladder in patients with rhabdomyosarcoma.

PURPOSE: To review the pathologic findings from children with gross residual rhabdomyosarcoma (RMS) of the bladder and compare the treatment outcome of those who underwent cystectomy with those who did not. PATIENTS AND METHODS: Primary and follow-up records and pathology specimens for 28 patients with gross residual disease entered onto the intergroup Rhabdomyosarcoma Study (IRS) III were reviewed. These patients were assigned to receive 20 weeks of multiagent induction chemotherapy and 4 weeks of radiotherapy. Future therapy decisions were based on clinical and histologic evaluation at 20 weeks. RESULTS: All patients had a clinical and histologic response. Thirteen patients underwent cystectomy at intervals that ranged from 1.5 to 38 months after the start of therapy. All but one patient are alive and well without recurrence. Reasons for cystectomy included presumed evidence of tumor growth from imaging studies, findings at cystoscopy, or histologic interpretation of biopsies. In 12 of 14 specimens from 15 patients who retained their bladder, no tumor cells were seen at first or second evaluation. In cystectomy specimens, tumor cellularity was markedly reduced and all tumor cells were in varying degrees of cellular maturation. Review of primary tumor specimens showed a greater degree of cellular maturation in patients with retained bladders than in those who underwent cystectomy. CONCLUSION: Bladder RMS is responsive to chemotherapy and radiotherapy. Twelve of 26 patients showed complete loss of tumor cells after induction therapy. Cystectomy specimens showed diminished tumor cells with varying degrees of cellular maturation. It is hypothesized that these tumors may have shown further maturation and ultimate loss of matured cells with continuing therapy.

Second malignant neoplasms in children treated for rhabdomyosarcoma. Intergroup Rhabdomyosarcoma Study Committee.

PURPOSE: This study was performed to determine the incidence and risk factors involved in the development of a second malignant neoplasm (SMN) after treatment of primary rhabdomyosarcoma (RMS) in patients enrolled onto Intergroup Rhabdomyosarcoma Studies I and II (IRS I and II). PATIENTS AND METHODS: There were 1,770 patients with primary RMS entered onto IRS I and II between 1972 and 1984. They were treated with chemotherapy and, in most instances, radiotherapy according to randomized or assigned regimens based on clinical grouping. Median follow-up time for these patients was 8.4 years. Incidence density (ID) was calculated for each study and for treatment and age groups. The 10-year cumulative incidence was estimated for each study. RESULTS: Twenty-two SMNs have been reported through 1991. The most common tumor type was a bone sarcoma followed by acute nonlymphoblastic leukemia (ANLL). The median time to the development of an SMN was 7 years (range, 1 11/12 to 15 9/12 years). The 10-year cumulative incidence rate was 1.7% for both studies. ID and cumulative incidence estimates were highest for patients who received both an alkylating agent and radiotherapy. The majority of patients for whom family histories were available had either neurofibromatosis themselves or a family history that suggested the Li-Fraumeni syndrome (LFS). CONCLUSION: The results of this study suggest that genetic abnormalities play a prominent role in the development of an SMN after therapy for a primary RMS. Chemotherapy with an alkylating agent and radiotherapy play significant roles in the development of an SMN compared with patients who received only one of these therapeutic modalities.

Results of treatment of malignant germ cell tumors in 93 children: a report from the Childrens Cancer Study Group.

We report treatment results in 93 children entered on study from 1978 to 1984 with malignant germ cell tumors (MGCTs), excluding dysgerminoma and tumors of the testis or brain. The estimated 4-year survival and event-free survival (EFS) for all 93 patients were 54% and 49%, respectively. For 30 children with ovarian tumors, the estimated 4-year survival was 67% and EFS was 63%. For 63 children with nongonadal tumors, survival and EFS were 48% and 42%, respectively. The comparison of EFS between ovarian and nongonadal tumors was significant at P = .03. The treatment plan included a second-look surgical procedure after 18 weeks of chemotherapy. Over half of 36 patients evaluated as having a residual mass present immediately before second-look surgery had no malignant tumor after review of surgical specimens. Age greater than 11 years at diagnosis, incomplete removal of tumor at first surgery, and more than one structure or organ involved at diagnosis increased the risk for adverse event. The histologic subtype of the primary tumor was not related to outcome. Diagnosis was verified by independent pathologic review, and treatment was uniform. Seventeen percent of all registered patients (21 of 127) were excluded because of ineligible pathologic diagnoses; sixty percent (13 of 21) were immature teratomas.

Ewing's sarcoma of soft tissues in childhood: a report from the Intergroup Rhabdomyosarcoma Study, 1972 to 1991.

PURPOSE: One hundred thirty of 2,792 patients (5%) registered on three Intergroup Rhabdomyosarcoma Study clinical trials (IRS-I, -II, and -III) from 1972 to 1991 had an extraosseous Ewing's sarcoma (EOE). We report here the results of multimodality therapy for this tumor. PATIENTS AND METHODS: The 130 patients were less than 21 years of age; 70 (54%) were males. Primary tumor sites were on the trunk in 41 patients, an extremity in 34, the head/neck in 23, the retroperitoneum/pelvis in 21, and other sites in 11. One hundred fourteen patients had no metastases at diagnosis. In 21 patients, the tumor was completely resected; in 30, the localized or regional tumor was grossly resected, and in 63 patients, grossly visible sarcoma was left behind. Sixteen patients (12%) had distant metastases at diagnosis. All patients were given multiagent chemotherapy and most received irradiation (XRT); none were treated with bone marrow transplantation. RESULTS: One hundred seven patients (82%) achieved a complete response. At 10 years, 62%, 61%, and 77% of the patients were alive after treatment on IRS-I, IRS-II, or IRS-III therapeutic protocols, respectively, similar to figures obtained in all IRS patients. At last follow-up evaluation, 42 patients had died of progressive tumor and one of infection. Survival at 10 years was most likely for patients with tumor that arose in the head and neck, extremities, and trunk, and for those who underwent grossly complete tumor removal before initiation of chemotherapy. For patients with localized, gross residual tumor, adding doxorubicin (DOX) to the combination of vincristine, dactinomycin, cyclophosphamide (VAC), and XRT did not significantly improve survival in 39 patients (62% alive at 10 years) compared with that of 24 patients treated with VAC and XRT without DOX (65% alive at 10 years, P = .93). CONCLUSION: This series indicated that EOE in children is similar to rhabdomyosarcoma (RMS) in its response to multimodal treatment. No benefit was apparent from the addition of DOX to VAC chemotherapy in patients with gross residual EOE.

Survival after relapse in children and adolescents with rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Study Group.

BACKGROUND: Despite advances in therapy, nearly 30% of children with rhabdomyosarcoma experience progressive or relapsed disease, which is often fatal. PATIENTS AND METHODS: To facilitate the development of a retrieval therapy protocol, we studied potential risk factors that were predictive of survival after first relapse in 605 children who were enrolled onto three consecutive Intergroup Rhabdomyosarcoma Study Group protocols. RESULTS: The median survival time from first recurrence was 0.8 years; the estimated percentage of patients who survived 5 years from first recurrence was 17% +/- 2% (mean +/- SD). Univariate analysis showed that tumor histology was an important predictor of 5-year survival (P <.001): the 5-year survival rate was 64% for patients with botryoid tumors (n = 19), 26% for patients with embryonal tumors (n = 313), and 5% for patients with alveolar or undifferentiated sarcoma (n = 273). Further analysis identified prognostic factors within histologic subtypes (P <.001). For patients with embryonal tumors, the estimated 5-year survival rate was 52% for patients who initially presented with stage 1 or group I disease, 20% for those with stage 2/3 or group II/III disease, and 12% for those with group IV disease. For patients with stage 1/group I disease, estimated 5-year survival rates were higher for patients with local (72%) or regional (50%) recurrence than for those with distant (30%) recurrence. Among patients with alveolar or undifferentiated sarcoma, only the disease group predicted outcome: the 5-year survival estimate was 40% for group I versus 3% for groups II through IV. We identified a "favorable risk" group (approximately 20% of patients) whose 5-year estimated survival rate was near 50%; for all other patients, the estimated survival was near 10%. CONCLUSION: This analysis demonstrates that the probability of 5-year survival after relapse for rhabdomyosarcoma is dependent on several factors at the time of initial diagnosis, including histologic subtype, disease group, and stage. These findings will form the basis of a multi-institutional risk-adapted relapse protocol for childhood rhabdomyosarcoma.

Which patients with microscopic disease and rhabdomyosarcoma experience relapse after therapy? A report from the soft tissue sarcoma committee of the children's oncology group.

PURPOSE: To identify which patients with rhabdomyosarcoma and microscopic residual disease (group II) are likely to not respond to therapy. PATIENTS AND METHODS: Six hundred ninety-five patients with group II tumors received chemotherapy and 90% received radiation therapy on Intergroup Rhabdomyosarcoma Study (IRS)-I to IRS-IV (1972 to 1997). Tumors were subgrouped depending on the presence of microscopic residual disease only (subgroup IIa), resected positive regional lymph nodes, (subgroup IIb), or microscopic residual disease and resected positive regional lymph nodes (subgroup IIc). RESULTS: Overall, the 5-year failure-free survival rate (FFSR) was 73%, and patients with embryonal rhabdomyosarcoma treated on IRS-IV fared especially well (5-year FFSR, 93%; n = 90). Five-year FFSRs differed significantly by subgroup (IIa, 75% and n = 506; IIb, 74% and n = 101; IIc, 58% and n = 88; P = .0037) and treatment (IRS-I, 68%; IRS-II, 67%; IRS-III, 75%; IRS-IV, 87%; P < .001). Multivariate analysis revealed positive associations between primary site (favorable), histology (embryonal), subgroup IIa or IIb, treatment (IRS-III/IV), and better FFSRs. Patterns of treatment failure revealed local failure to be 8%, regional failure, 4%, and distant failure, 14%. The relapse pattern noted over the course of IRS-I to IRS-IV shows a decrease in the systemic relapse rates, particularly for patients with embryonal histology, suggesting that improvement in FFSRs is primarily a result of improved chemotherapy. CONCLUSION: Group II rhabdomyosarcoma has an excellent prognosis with contemporary therapy as used in IRS-III/IV, and those less likely to respond can be identified using prognostic factors: histology, subgroup, and primary site. Patients with embryonal rhabdomyosarcoma are generally cured, although patients with alveolar rhabdomyosarcoma or undifferentiated sarcoma, particularly subgroup IIc at unfavorable sites, continue to need better therapy.

Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease.

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%, respectively. Three-year FFS rates with VAC, VAI, and VIE were 75%, 77%, and 77%, respectively (P =.42). No significant difference in outcome was noted with HF-RT versus C-RT (P =.85 and P =.90, respectively). Overall, patients with embryonal tumors benefited from intensive three-drug chemotherapy in IRS-IV (3-year FFS, 83%). The improvement was seen for patients with stage I or stage II/III, group 1/2 disease, many of whom received VA chemotherapy on IRS-III. Patients with stage 2/3, group 3 disease had similar outcomes on IRS-III and IRS-IV. Three-year FFS for the nonrandomized patient subsets was 75% with renal abnormalities; 81% for paratesticular, group 1 cases; and 91% for group 1/2 orbit or eyelid tumors. Patients with paratesticular primaries had poorer outcomes if they were more than 10 years old (3-year FFS, 63% v 90%). Myelosuppression occurred in most patients, but toxic deaths occurred in less than 1%. CONCLUSION: VAC and VAI or VIE with surgery (with or without RT), are equally effective for patients with local or regional rhabdomyosarcoma and are more effective for embryonal tumors than therapies used previously. Younger patients with group 1 paratesticular embryonal tumors and all patients with group 1/2 orbit or eyelid tumors can usually be cured with VA chemotherapy along with postoperative RT for group 2 disease.

Interstitial radiation therapy in the treatment of childhood soft-tissue sarcomas.

Between 1971 and 1985, 12 children and adolescents aged 0.7 to 19 years (median 4.7 years) with localized residual soft-tissue sarcomas (STS) underwent interstitial radiation therapy (IRT) at our institution. Eight received IRT as a component of initial therapy, and four were treated for recurrent or persistent disease. Tumor sites were head and neck (6), pelvis (4), extremity (1), and retroperitoneum (1). The radionuclides employed were Iridium-192 (9), Iodine-125 (2), and Californium-252 (1). The median prescribed dose in the Iridium-192 group was 3960 cGy (1955-7300). Seven of eight children receiving IRT during initial therapy have maintained local control, and six remain without evidence of disease for a median follow-up time of 5.8 years (2.0-16.0). One of the four patients treated for recurrent disease is free of disease after salvage surgery, and the other three are dead of disease. Multidisciplinary evaluation of the nine patients with more than 2 years of follow-up revealed functional and cosmetic effects of IRT to be minimal. IRT can be an effective method of delivering high dose irradiation in childhood sarcomas while reducing the deleterious effects in adjacent normal tissues.

Radiation therapy for rhabdomyosarcoma: local failure risk for Clinical Group III patients on Intergroup Rhabdomyosarcoma Study II.

PURPOSE: A subset of 362 pediatric patients with rhabdomyosarcoma was selected from a total of 532 eligible IRS-II patients in Clinical Group III to assess the local and regional failure rates following radiotherapy and to determine patient, tumor, and treatment factors contributing to the risk for local and regional failure. METHODS AND MATERIALS: The study population was selected from all eligible IRS-II Clinical Group III patients. Excluded patients were those with "special pelvic" primary sites whose protocol management restricted radiotherapy (n = 123), and those who were removed from the study before radiotherapy was to begin, or because it was omitted (n = 47). A binary recursive partitioning model was used to identify subgroups of the remaining 362 patients at risk of local or regional failure. RESULTS: The local (only) failure rate was 17% (95% confidence interval, 13-21%), and the local (all) failure rate was 20% (95% confidence interval, 16-24%). The 5-year actuarial risk of local (all) failure was 22% (95% confidence interval, 18-27%). The risk of regional (nodal) failure was between 2% and 23%. Increasing tumor size predicted an increased local failure risk. Primary tumors located above the clavicle had a reduced risk of local failure. The binary recursive partitioning model identified a subset of patients at high risk of local failure. Those patients had primary tumors in the chest, pelvic region, extremity, or trunk, or tumors > 10 cm in diameter. Their local failure rate was 35% (compared to 15% for the remaining patients). The subset of patients at high risk for regional (nodal) failure had node involvement at diagnosis and a primary tumor originating at a site other than orbit, parameningeal, or trunk. Compliance with radiation treatment guidelines approached but did not achieve statistical significance as a predictive factor for local failure. By univariate analysis, factors not influencing local failure risk were age, race, gender, adenopathy, and histology. CONCLUSION: Radiation therapy and chemotherapy administered to Clinical Group III patients entered into the IRS-II protocol produced sustained local control in most cases. Knowledge of the factors which predict an increased risk of local or regional failure will facilitate the design of new treatment strategies.

Healing rates of treated and untreated bone lesions in histiocytosis X.

Evaluation of the response of histiocytosis X to various forms of treatment is difficult, because presentation patterns are protean and the disease can be self-limited. A retrospective evaluation was made of the healing of 42 histiocytosis X bone lesions, in 21 patients treated in variety of ways, using serial radiographs and a semiquantitative scoring system. Treatments included various combinations of surgery (simple biopsy or curettage), radiotherapy (200 to 1,200 centi-Gray [cGy]), chemotherapy (according to various protocols), and local steroid injection. Median times to a given degree of healing were similar across treatment groups and in untreated lesions. It was concluded that mode of treatment does not exert a strong influence on the rate of healing of histiocytosis X bone lesions. Some healing should be apparent 4 months after diagnosis, but complete healing may take many months. Treatment of histiocytosis X bone lesions is indicated only if intense pain or risk of fracture or deformity are present.

Rhabdoid tumors of soft tissues: a clinicopathologic study of 26 cases enrolled on the Intergroup Rhabdomyosarcoma Study.

Twenty-six cases of malignant soft tissue tumors with features similar to renal rhabdoid tumors were identified among approximately 3,000 childhood sarcomas entered on Intergroup Rhabdomyosarcoma Studies I-III. The tumors consisted of polygonal cells with vesicular nuclei and prominent nucleoli and cytoplasmic intermediate filament inclusions as identified by electron microscopy and immunohistochemistry. The growth pattern was predominantly solid or solid-trabecular. Immunohistochemistry showed vimentin, wide spectrum keratin, and epithelial membrane antigen to be the most consistent antigenic phenotypes. Eleven patients were infants less than 1 year of age. The tumors affected predominantly soft tissues of proximal extremities, trunk, and retroperitoneum/pelvis/abdomen. Nineteen patients died within 1 to 82 months (median, 6 months) from the start of treatment. Five patients have survived the disease for 2 to 13 years. When compared with the survival analysis of 991 Intergroup Rhabdomyosarcoma Study II patients, it was obvious that this group of tumors fares very poorly (P less than .001). The tumor belongs to the group of soft tissue neoplasms showing mesenchymal and subtle epithelial differentiation, similar to epithelioid sarcoma. Because of its identifiable histology, site and age distribution, and poor outcome, it warrants a status as an independent entity.

Management of neoplasms of the head and neck in children. II. Malignant tumors.

The otolaryngologist who treats children must have knowledge of the neoplasms that can occur in childhood. Such tumors are usually mesenchymal in origin and may be benign or malignant. Diagnosis and management of the more common benign tumors are undertaken by the otolaryngologist because local excision is generally curative. The proper treatment of malignant lesions requires a more extensive, multidisciplinary team, which includes a pediatric oncologist, diagnostic and therapeutic radiologist, and pathologist, in addition to the otolaryngologist. This article outlines the types of malignant neoplasms that occur in childhood and discusses current approaches to therapy.

Management of neoplasms of the head and neck in children. 1. Benign tumors.

The otolaryngologist who treats children must have knowledge of the neoplasms that can occur in childhood. Such tumors are usually mesenchymal in origin and may be benign or malignant. Diagnosis and management of the more common benign tumors are undertaken by the otolaryngologist because local excision is generally curative. The proper treatment of malignant lesions requires a more extensive, multidisciplinary team, which includes a pediatric oncologist, diagnostic and therapeutic radiologist, and pathologist, in addition to the otolaryngologist. The purposes of this paper are to outline the types of benign and malignant neoplasms that occur in childhood and to discuss current approaches to therapy.

Synovial sarcoma in children: surgical lessons from a single institution and review of the literature.

BACKGROUND: Synovial sarcomas are malignant high-grade, soft-tissue neoplasms that account for 7% to 8% of all malignant soft-tissue tumors and are the most common nonrhabdomyosarcoma soft-tissue sarcomas in pediatric patients. STUDY DESIGN: A retrospective review of the records of children younger than 17 years with synovial sarcoma treated at the University of Texas MD Anderson Cancer Center from 1966 until 1999 was undertaken. Primary site, tumor size, tumor margins, surgical treatment, adjuvant therapy, local and distant recurrence, and survival were recorded for 42 patients. Overall survival (OS) and progression-free survival (PFS) rates were calculated by the Kaplan-Meier method. The PFS and OS comparisons were performed using the log-rank test. RESULTS: Forty-four patients were identified, but two patients were excluded because of incomplete records. The median followup duration for the 42 patients was 8.8 years (range 0.2 to 22.4 years). The 5-year progression-free survival and overall survival rates were 75.6% and 87.7%, respectively. Eleven patients were dead and four others had progressed but were alive without evidence of disease after further therapy. Intergroup Rhabdomyosarcoma Study (IRS) grouping and tumor invasiveness were found to be significant prognostic indicators (p < 0.01 and p = 0.02, respectively). Patients with initial gross total resection (IRS Groups I and II) and noninvasive tumors (T1) were most likely to have prolonged PFS and OS. Patients with small tumors (<5 cm) (p = 0.09) had better PFS and OS. Adjuvant radiation therapy appeared to be of benefit, and chemotherapy did not seem to impact PFS or OS. Tumors > or = 5 cm are associated with increased risk of local recurrence and distant metastases. CONCLUSIONS: Complete resection with clear, yet not necessarily large, margins remains the treatment of choice for synovial sarcoma in children. Adjuvant radiation therapy should possibly be considered in patients with clear margins (IRS Group I) and in patients with microscopic residual tumor (IRS Group II). Chemotherapy did not seem to impact PFS or OS. Lymph nodes should be evaluated for local regional disease.

Multidisciplinary management of pediatric soft-tissue sarcoma.

The management of pediatric soft-tissue sarcomas has improved drastically through the use of multimodal therapy. These tumors include rhabdomyosarcomas and nonrhabdomyosarcomas. Both are staged using physical, radiographic, and histologic evaluation, and both have intricate staging and grouping systems that correlate closely with prognosis. However, approaches to therapy for the two tumor types remain somewhat different. Rhabdomyosarcomas are treated primarily with chemotherapy. Surgical intervention is limited to initial biopsy, wide local excision when clear margins are feasible, and resection of residual disease. Radiation therapy is reserved for patients with persistent or recurrent disease and may be delivered by external beam or brachytherapy. Nonrhabdomyosarcomas are best treated primarily by surgical resection, although radiation and chemotherapy are now being used with some success. Another major difference concerns evaluation of lymphatics. Nonrhabdomyosarcomas in children frequently behave similarly to adult sarcomas, and less commonly involve regional lymph nodes, whereas pediatric patients with rhabdomyosarcomas often have nodal involvement necessitating surgical evaluation of regional lymph nodes as part of the staging protocol. Multimodal therapy has led to improved survival as well as better functional and cosmetic results. With further clinical trials and improved techniques such as brachytherapy and lymphatic mapping with sentinel node biopsy, we expect to continue to optimize therapy for pediatric patients with soft-tissue sarcomas.

Controversies in the management of paratesticular rhabdomyosarcoma: is staging retroperitoneal lymph node dissection necessary for adolescents with resected paratesticular rhabdomyosarcoma?

PURPOSE: Use of retroperitoneal lymph node dissection (RPLND) in paratesticular rhabdomyosarcoma (PTRMS) is controversial and has changed over the past 2 decades. The Intergroup Rhabdomyosarcoma Study Group (IRSG) required ipsilateral RPLND (IRPLND) for all patients with PTRMS treated on IRS-III (1984-91), but changed to clinical evaluation of RPLNs using computerized tomography (CT) in IRS-IV (1991 through 1997). In IRS-IV, only those patients with identified lymph node involvement on CT required surgical evaluation of the RPLNs. Nodal radiation therapy was administered only to patients with RPLNs recognized as positive; such patients received more intensive chemotherapy as well. Thus, they compared the incidence of recognized RPLN involvement using these 2 different approaches. They then analyzed patient outcome to determine whether this change in management affected outcome. METHODS: Eligible patients with group I or II PTRMS who were treated on IRS III (n = 100) or IRS IV (n = 134) were analyzed. Failure-free survival (FFS) and survival (S) rates were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: There was a significant change in the distribution of patients with group I versus II tumors from IRS-III to IRS-IV (group I, 68% in IRS-III versus 82% in IRS-IV). This was the result of decreased node recognition when CT was used to stage RPLNs in IRS-IV and was most notable for adolescents (>10 years of age). Overall, 3-year FFS was 92% for patients treated on IRS-III and 86% for those treated on IRS-IV (P =.10), whereas survival estimates were 96% and 92%, respectively (P =.30). Adolescents were at higher risk of RPLN relapse than were children (<10 years of age) and their FFS and survival were worse, regardless of IRS protocol. Furthermore, adolescents with recognized group II tumors experienced better 3-year FFS than those with group I tumors on IRS-IV (100% versus 68%, P =.06), most likely as a result of receiving radiotherapy and intensified chemotherapy. CONCLUSIONS: Use of only CT scan evaluation of RPLN in IRS-IV led to a decrease in identification of RPLN involvement in boys who present with localized PTRMS, and a higher rate of regional relapse as compared with IRS-III. Adolescents had much higher likelihood of RPLN disease, and they fared significantly worse than did younger children on both studies. Furthermore, adolescent boys with group I tumors experienced worse FFS than those with Group II tumors on IRS-IV, probably because some patients with group II tumors were not identified by CT imaging and thus received less effective therapy. These data suggest that adolescents should have ipsilateral RPLN dissection as part of their routine staging, and those with positive lymph nodes require intensified chemotherapy as well as nodal irradiation.

Pediatric orofacial and laryngopharyngeal rhabdomyosarcoma. An Intergroup Rhabdomyosarcoma Study report.

Eighty-nine children with localized rhabdomyosarcoma of orofacial and laryngopharyngeal sites were treated in accordance with the first and second Intergroup Rhabdomyosarcoma Study (IRS) protocols (IRS-I and IRS-II) between 1972 and 1984. Treatment included surgery (or biopsy) and chemotherapy for all patients and radiotherapy in the majority. The actuarial estimate of the three-year survival rate for all patients was 83% and did not differ significantly by primary site, histologic findings, or presence of adenopathy. A trend for a worse survival rate was seen in clinical group III patients and in those less than 5 years of age at diagnosis. Factors associated with an increased risk of local/regional relapse included omission of radiotherapy and a radiation dose of less than 40 Gy (4000 rad). We conclude that treatment of these patients as recommended in the IRS-I and IRS-II protocols results in very good local and regional tumor control and survival rates. Salvage therapy for local/regional recurrence may yield long-term remission and possibly cure.