Rhabdomyosarcoma: review of the Children's Oncology Group (COG) Soft-Tissue Sarcoma Committee experience and rationale for current COG studies

The prognosis for children and adolescents with rhabdomyosarcoma (RMS) has improved with refinements in multi-modal therapy. Since 1972, the Intergroup Rhabdomyosarcoma Study Group (now the Children's Oncology Group Soft-Tissue Sarcoma Committee) has conducted serial studies for RMS. This review describes the IRSG and COG experience with RMS, presents the current risk stratification definitions, and provides rationale for the current generation of COG RMS studies.     

Loss of antibody titers and effectiveness of revaccination in post-chemotherapy pediatric sarcoma patients

BACKGROUND: Little is known about the effects of chemotherapy on patient antibody titers to vaccine-preventable infectious diseases; thus, there is no standard protocol for revaccinating post-chemotherapy patients. PROCEDURES: To assess losses of detectable antibody titers due to chemotherapy, we retrospectively examined antibody titers for tetanus, varicella, measles, mumps, rubella, hepatitis B, and polio in 109 pediatric sarcoma patients. We also evaluated revaccination data to determine current practices and efficacy of revaccination. We limited our sample to osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma patients to control for the chemotherapy regimen patients received. RESULTS: Patients had pre-treatment detectable antibody titer that fell within the range of healthy children's antibody titers. However, 71% of patients had post-chemotherapy negative titers for at least one infectious disease. Patients most commonly had negative titers for hepatitis B (64%). Few patients had negative titers for measles (14%), mumps (9%), rubella (4%), polio 1 (0%), polio 2 (2.9%), polio 3 (4.8%), tetanus (5%), or varicella (11%). Revaccinations most frequently administered were hepatitis B and polio. CONCLUSIONS: Our findings suggest that post-chemotherapy patients may need to be revaccinated against certain vaccine-preventable diseases including hepatitis B, tetanus, varicella, polio, measles, mumps, and rubella. Larger studies need to be performed to establish guidelines for revaccinating post-chemotherapy pediatric patients.     

Mapping the Epidemiology of Kaposi Sarcoma and Non‐Hodgkin Lymphoma Among Children in Sub‐Saharan Africa: A Review

Children with human immunodeficiency virus (HIV) have an increased risk of developing Kaposi Sarcoma (KS) and non‐Hodgkin lymphoma (NHL) compared to HIV‐negative children. We compiled currently published epidemiologic data on KS and NHL among children in sub‐Saharan Africa (SSA). Among countries with available data, the median incidence of KS was 2.05/100,000 in the general pediatric population and 67.35/100,000 among HIV‐infected children. The median incidence of NHL was 1.98/100,000 among the general pediatric population, while data on NHL incidence among HIV‐infected children were lacking. Larger regional studies are needed to better address the dearth of epidemiologic information on pediatric KS and NHL in SSA.     

Kaposi Sarcoma of Childhood: Inborn or Acquired Immunodeficiency to Oncogenic HHV‐8

Kaposi sarcoma (KS) is an endothelial malignancy caused by human herpes virus‐8 (HHV‐8) infection. The epidemic and iatrogenic forms of childhood KS result from a profound and acquired T cell deficiency. Recent studies have shown that classic KS of childhood can result from rare single‐gene inborn errors of immunity, with mutations in WAS, IFNGR1, STIM1, and TNFRSF4. The pathogenesis of the endemic form of childhood KS has remained elusive. We review childhood KS pathogenesis and its relationship to inherited and acquired immunodeficiency to oncogenic HHV‐8.     

Favorable response to soft tissue sarcoma therapy in an adolescent with embryonal renal sarcoma

Embryonal renal sarcomas were first identified in 1995 among banked tumor samples originally classified as adult Wilms tumor. Few long-term remissions were observed when these rare tumors were treated with chemotherapy usually used for childhood Wilms. Data were collected from the medical record of an adolescent female with embryonal renal sarcoma and treated with sarcoma-directed chemotherapy and radiation. At 66 months following diagnosis, the patient has no evidence of tumor but has experienced severe renal dysfunction and ovarian failure. We believe there is a subset of patients with disseminated embryonal renal sarcoma that respond to intense sarcoma-directed therapy.     

Genome‐wide analysis of acute leukemia and clonally related histiocytic sarcoma in a series of three pediatric patients

Pediatric histiocytic sarcoma (HS) clonally related to anteceding leukemia is a rare malignancy with poor outcome. We performed a molecular characterization of HS and the corresponding leukemia by methylation arrays and whole‐exome sequencing and found a variety of aberrations in both entities with deletions of CDKN2A/B as a recurrent finding. Furthermore, data from genome‐wide mutation analysis from one patient allowed the reconstruction of a sequence of tumorigenesis of leukemia and HS lesions including the acquisition of a putatively activating KRAS frameshift deletion (p.A66fs). Our results provide an insight into the genetic landscape of pediatric HS clonally related to anteceding leukemia.     

Clear cell sarcoma of the stomach

Clear cell sarcoma (CCS) is a high grade soft tissue sarcoma with a distinct molecular profile. Gastrointestinal CCS is very rare and most reported cases are in adults. We describe a 10‐year‐old female with a 4‐month history of anemia who later developed fever, weight loss and abdominal pain. She was subsequently found to have a large infiltrative gastric mass. A diagnosis of CCS was confirmed by molecular and cytogenetic studies. This case illustrates the necessity of a multimodal approach, particularly the use of molecular studies, in the diagnostic evaluation of rare tumors presenting in unusual sites. Pediatr Blood Cancer 2009;53:214–216. © 2009 Wiley‐Liss, Inc.     

Juvenile Classic Kaposi'S Sarcoma: A Report Of Two Cases,One With Family History

Two cases of juvenile classic Kaposi's sarcoma (KS), one with family history, are described, and the natural history of KS is briefly reviewed. Case 1a war a child whose disease ran an aggressive course and did not respond to therapy. Case 1b was the mother of the child: She had a relapsed localized form that was treated by surgery and chemotherapy, and she has been disease free since 1990. The second juvenile case was a 4–year-old boy with a localized form that relapsed but was successfully treated by surgery, chemotherapy, and radiation therapy. He has been free of disease since 1986. Family history in juvenile KS has not previously been reported unrelated to acquired immunodeficiency syndrome in a Western country.     

Adjuvant chemotherapy for the treatment of advanced pediatric nonrhabdomyosarcoma soft tissue sarcoma: the National Cancer Institute experience

BACKGROUND: The survival of children and adolescents with advanced (unresectable or metastatic) nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) is poor. In order to clarify the role of combining chemotherapy with aggressive local control using surgery and/or radiation, we reviewed our institutional experience with the treatment of advanced pediatric NRSTS. PROCEDURE: We reviewed the charts of all patients less than 21 years treated for an advanced NRSTS at the National Cancer Institute (NCI) between 1983 and 2003. Tumor pathology was confirmed and demographic, disease, and treatment data were abstracted. Survival was calculated using standard methods. RESULTS: Of the 25 patients who were treated over the study period, 15 had metastatic disease and 10 had unresectable or incompletely resected disease at presentation. Twenty-one patients received chemotherapy consisting of the combination of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide, and the remaining 4 received regimens that included doxorubicin. Twenty patients (80%) had a complete (5/25) or partial (15/25) response after chemotherapy alone. After the combination of chemotherapy and local control, 14 patients (56%) had a complete response (CR). The estimated 5-year overall and event-free survival (EFS) for all patients was 0.50 (standard error = 0.11) and 0.34 (standard error = 0.10), respectively. CONCLUSIONS: The combination of chemotherapy with aggressive local control in this cohort of pediatric patients with advanced NRSTS yielded results comparable to those observed in patients with advanced sarcomas that are chemotherapy responsive. Prospective randomized trials are needed to quantify the contribution of chemotherapy and to determine the ideal regimen.     

Treatment results for patients with localized,completely resected (Group I) alveolar rhabdomyosarcoma on Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols III and IV, 1984–1997: A report from the Children's Oncology Group

Purpose

To assess local control, event‐free survival (EFS), and overall survival (OS) rates in 71 patients with localized, completely resected (Group I) alveolar rhabdomyosarcoma (ALV RMS) and their relation to radiation therapy (RT) on IRSG Protocols III and IV, 1984–1997.

Methods

Chart review and standard statistical procedures.

Patients and Tumors

Patients were 1–18 years at diagnosis (median, 6 years). Primary tumor sites were extremity/trunk (N = 54), head/neck (N = 9), genitourinary tract (N = 7), and perineum (N = 1). Thirty patients received VA ± C with RT; 41 received VA ± C alone. RT was assigned, not randomized.

Results

Fifty‐four patients had Stage 1 (favorable site, any size) or Stage 2 (unfavorable site, ≤5 cm) tumors. Eight‐year EFS was 90%, with 100% local control for 17 patients given RT. Eight‐year EFS was 88%, with 92% local control for 37 patients without RT; P = 0.52 for EFS comparisons, 0.3 for local control comparisons. In 17 Stage 3 patients (unfavorable site, tumors >5 cm, N0), 8‐year EFS was 84% with 100% local control in 13 patients given RT; 8‐year EFS was only 25% and local control 50% in 4 patients without RT. Local recurrence was the most common site of first failure in non‐irradiated patients.

Conclusion

Patients with Stage 1–2 ALV RMS had slightly but statistically insignificantly improved local control, EFS, and OS rates when local RT was given. The need for local RT in Stage 1–2 patients deserves evaluation in a randomized study. Local control, EFS, and OS rates were significantly improved in Stage 3 patients receiving local RT. Pediatr Blood Cancer. 2010;55:612–616. © 2010 Wiley‐Liss, Inc.