Efficacy of High-Dose Chemotherapy and Three-Dimensional Conformal Radiation for Atypical Teratoid/Rhabdoid Tumor: A Report From the Children's Oncology Group Trial ACNS0333.

PURPOSE: Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive, early-childhood brain tumor without standard effective treatment. To our knowledge, we conducted the first AT/RT-specific cooperative group trial, ACNS0333, to examine the efficacy and safety of intensive postoperative chemotherapy and focal radiation to treat AT/RT. PATIENTS AND METHODS: Patients from birth to 22 years of age with AT/RT were eligible. After surgery, they received 2 courses of multiagent chemotherapy, followed by 3 courses of high-dose chemotherapy with peripheral blood stem cell rescue and involved-field radiation therapy. Timing of radiation was based on patient age and disease location and extent. Central testing of tumor and blood for SMARCB1 status was mandated. Tumor molecular subclassification was performed retrospectively. The primary analysis was event-free survival (EFS) for patients < 36 months of age compared with a cooperative groups' historical cohort. Although accrual was based on the therapeutic question, potential prognostic factors, including age, tumor location, M stage, surgical resection, order of therapy, germline status, and molecular subtype, were explored. RESULTS: Of 65 evaluable patients, 54 were < 36 months of age. ACNS0333 therapy significantly reduced the risk of EFS events in patients < 36 months of age compared with the historical cohort (P < .0005; hazard rate, 0.43; 95% CI, 0.28 to 0.66). Four-year EFS and overall survival for the entire cohort were 37% (95% CI, 25% to 49%) and 43% (95% CI, 31% to 55%), respectively. Timing of radiation did not affect survival, and 91% of relapses occurred by 2 years from enrollment. Treatment-related deaths occurred in 4 patients. CONCLUSION: The ACNS0333 regimen dramatically improved survival compared with historical therapies for patients with AT/RT. Clinical characteristics and molecular subgrouping suggest prognostic differences. ACNS0333 results lay a foundation on which to build future studies and incorporate testing of new therapeutic agents.

Toxicity of Cancer Therapy in Adolescents and Young Adults (AYAs).

OBJECTIVES: To identify treatment-related toxicities that are either more frequent or more severe in the adolescent and young adult (AYA) oncology population. To explore differences in drug pharmacology and patient physiology that contribute to toxicities in the AYA population and to describe the impact of treatment-related toxicities on outcomes for AYA patients. DATA SOURCES: A PubMed search was undertaken using the key words Adolescent Young Adult Oncology, AYA, toxicity, bone marrow transplant, late effects, and chemotherapy. Additional toxicity information was also obtained from recent publications from cancer cooperative groups treating AYA patients. CONCLUSION: AYA patients often experience more severe toxicities than children when treated with identical chemotherapy regimens, which can interfere with successful administration of planned treatment, as well as have profound effects on quality of life. AYA patients with cancer face the dual challenge of disease biology associated with inferior response to treatment, thus necessitating treatment intensification, while at the same time suffering higher rates of specific toxicities such as vincristine-induced neuropathy, osteonecrosis, and treatment-related mortality caused by infection. IMPLICATIONS FOR NURSING PRACTICE: AYA patients are at a higher risk for toxicities from regimens that may be tolerated by younger patients. Staff should be aware of toxicities facing this population so that appropriate supportive care measures can be utilized. Future research on the pharmacology of drugs in adolescence, hormonal effects on drug-metabolizing enzymes, cumulative exposure to different drugs in combination, and risk and severity of specific toxicities will be critical to improving the treatment of AYA patients.

Chemotherapy medication errors in a pediatric cancer treatment center: prospective characterization of error types and frequency and development of a quality improvement initiative to lower the error rate.

BACKGROUND: Chemotherapy medication errors occur in all cancer treatment programs. Such errors have potential severe consequences: either enhanced toxicity or impaired disease control. Understanding and limiting chemotherapy errors are imperative. PROCEDURE: A multi-disciplinary team developed and implemented a prospective pharmacy surveillance system of chemotherapy prescribing and administration errors from 2008 to 2011 at a Children's Oncology Group-affiliated, pediatric cancer treatment program. Every chemotherapy order was prospectively reviewed for errors at the time of order submission. All chemotherapy errors were graded using standard error severity codes. Error rates were calculated by number of patient encounters and chemotherapy doses dispensed. Process improvement was utilized to develop techniques to minimize errors with a goal of zero errors reaching the patient. RESULTS: Over the duration of the study, more than 20,000 chemotherapy orders were reviewed. Error rates were low (6/1,000 patient encounters and 3.9/1,000 medications dispensed) at the start of the project and reduced by 50% to 3/1,000 patient encounters and 1.8/1,000 medications dispensed during the initiative. Error types included chemotherapy dosing or prescribing errors (42% of errors), treatment roadmap errors (26%), supportive care errors (15%), timing errors (12%), and pharmacy dispensing errors (4%). Ninety-two percent of errors were intercepted before reaching the patient. No error caused identified patient harm. Efforts to lower rates were successful but have not succeeded in preventing all errors. CONCLUSIONS: Chemotherapy medication errors are possibly unavoidable, but can be minimized by thoughtful, multispecialty review of current policies and procedures. Pediatr Blood Cancer 2013;601320-1324. © 2013 Wiley Periodicals, Inc.

Targeted immunotherapy for high-risk neuroblastoma--the role of monoclonal antibodies.

OBJECTIVE: To systematically review clinical trials evaluating anti-disialoganglioside (GD2) antibodies in treating high-risk neuroblastoma in children. DATA SOURCES: A literature search was conducted in PubMed/MEDLINE, International Pharmaceutical Abstracts, and Cumulative Index of Nursing and Allied Health Literature (all searches 1990-August 2012) using the terms neuroblastoma, immunotherapy, 3F8, ch14.18, and hu14.18. Meeting abstracts presented between 1990 and 2012 from the American Society of Clinical Oncology, European Society for Medical Oncology, the American Society of Pediatric Hematology Oncology, Society of Surgical Oncology, and the American Society of Hematology were also evaluated. STUDY SELECTION AND DATA EXTRACTION: All completed and ongoing clinical trials of anti-GD2 antibodies in neuroblastoma were included. References from selected articles were also reviewed to identify additional citations. DATA SYNTHESIS: In 1999, the results of a Children's Cancer Group trial established that consolidation therapy after induction, surgery, and radiation should include purged autologous stem cell rescue followed by maintenance with isotretinoin. Overall survival at 7 years with this regimen remains below 30%. Over the following decade, antibodies targeting GD2, a surface antigen found on the surface of neuroblastoma cells, have emerged as a major therapeutic development for high-risk neuroblastoma. Anti-GD2 antibodies incite immune-mediated cytotoxicity toward neuroblastoma cells when given as monotherapy or in combination with cytokines such as sargramostim (granulocyte-macrophage colony-stimulating factor) or aldesleukin (interleukin-2). Responses to anti-GD2 agents appear most notable in patients with minimal residual disease following standard therapy. A chimeric preparation, ch14.18, is the only anti-GD2 antibody to be evaluated in a large controlled clinical trial, in which it demonstrated overall survival of 86% at 2 years in patients with high-risk neuroblastoma. Older nonrandomized studies of ch14.18 monotherapy and 3F8, a murine antibody, suggest this survival rate remains between 50 and 85% at 5 years posttreatment. CONCLUSIONS: Multiple GD2-specific monoclonal antibodies have been researched over the last decade in patients diagnosed with high-risk neuroblastoma. One anti-GD2 antibody, ch14.18, was found to significantly improve event-free and overall survival of high-risk neuroblastoma. Therefore, the standard approach to treating high-risk neuroblastoma is likely to undergo a major shift once an anti-GD2 antibody becomes commercially available.

Treatment of osteoporosis/osteopenia in pediatric leukemia and lymphoma.

OBJECTIVE: To evaluate the efficacy and safety of various treatment options for osteopenia and osteoporosis secondary to cancer treatment in pediatric patients undergoing cancer therapy. DATA SOURCES: A systematic search of PubMed (1949-November 2008) and International Pharmaceutical Abstracts (to November 2008) was conducted using the following search terms: osteoporosis, osteopenia, pediatrics, cancer, neoplasms, chemotherapy, bisphosphonates, calcium, vitamin D, calcitonin, and physical therapy. STUDY SELECTION AND DATA EXTRACTION: All prospective studies that evaluated various osteoporosis treatment options in pediatric patients undergoing chemotherapy were included. Results from studies evaluating bisphosphonates and other treatments in children with osteoporosis due to other causes were also included if important safety and efficacy data were provided. Most commonly reported primary efficacy endpoints included comparisons of bone density parameters measured before and after treatment. DATA SYNTHESIS: Four clinical studies and 2 case reports describing treatment with bisphosphonates, specifically alendronate and pamidronate, for osteoporosis or osteopenia in pediatric cancer patients were identified. Results from the trials showed that these medications were efficacious in reducing bone mineral density loss during cancer therapy and were well tolerated in this special population. Primary efficacy endpoints included improvements in Z-scores measured by dual-energy X-ray absorptiometry scans. The most commonly reported adverse effects included hypocalcemia, mild stomach upset, and infusion-related hyperpyrexia. Four additional clinical trials involving the treatment of osteoporosis or osteopenia in children and adolescents who developed bone degeneration after chronic steroid therapy are also included. In these trials, treatment options such as calcitonin, and calcium and vitamin D supplementation were also shown to be beneficial. CONCLUSIONS: The clinical trials published to date are limited to only a few conducted in small populations of patients diagnosed with lymphoblastic leukemia or non-Hodgkin's lymphoma. However, alendronate and pamidronate both appeared to be effective options in improving bone mineral density scores with minimal adverse effects.