Children's Oncology Group's 2013 blueprint for research: Nursing discipline

Integration of the nursing discipline within cooperative groups conducting pediatric oncology clinical trials provides unique opportunities to maximize nursing's contribution to clinical care, and to pursue research questions that extend beyond cure of disease to address important gaps in knowledge surrounding the illness experience. Key areas of importance to the advancement of the nursing discipline's scientific knowledge are understanding the effective delivery of patient/family education, and reducing illness‐related distress, both of which are integral to facilitating parental/child coping with the diagnosis and treatment of childhood cancer, and to promoting resilience and well‐being of pediatric oncology patients and their families. Pediatr Blood Cancer 2013; 60: 1031–1036. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Hodgkin lymphoma

In childhood Hodgkin lymphoma, estimated 5 years survival rates exceed 90%. Long‐term survival continues to decline from delayed toxicities. Key findings from recent Children's Oncology Group trials include: (1) Radiotherapy selection may be based on early chemotherapy response assessed by both FDG‐PET and CT imaging, (2) A new prognostic factor score stratifies patients into risk categories; and (3) novel retrieval regimens were identified. A phase I/II trial is investigating Brentuximab vedotin (Bv) with gemcitabine in relapsed patients. A phase 3 trial will modify conventional chemotherapy and radiotherapy approaches through the addition of Bv, while incorporating translational biology to identify molecular targets. Pediatr Blood Cancer 2013; 60: 972–978. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Neuroblastoma

Estimated 5‐year survival rates for patients with non‐high‐risk and high‐risk neuroblastoma are 90% and 50%, respectively. Recent clinical trials have shown excellent outcomes with reduced therapy for non‐high‐risk disease. For patients with high‐risk neuroblastoma treated with chemoradiotherapy, surgery, and stem cell transplantation, the addition of anti‐disialoganglioside (GD2) immunotherapy plus cytokines improves survival. Upcoming trials will study the incorporation of targeted radionuclide therapy prior to myeloablative chemotherapy into high‐risk treatment. Phase 2 trials will investigate druggable target(s) including mTOR inhibition and GD2‐directed therapy in combination with chemotherapy for patients with recurrent neuroblastoma, and ALK inhibition for those with ALK‐aberrant tumors. Pediatr Blood Cancer 2013; 60: 985–993. © 2013 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Soft tissue sarcomas

In the US, approximately 850–900 children are diagnosed each year with soft tissue sarcomas (STS). Key findings from recent Children's Oncology Group (COG) clinical trials include safe reduction in therapy for low risk rhabdomyosarcoma (RMS), validation of FOXO1 fusion as a prognostic factor, a modest improvement in outcome for high‐risk RMS, and a biologically designed non‐cytotoxic therapy for pediatric desmoid tumor. Planned Phase 2 trials include targeted agents for VEGF/PDGF, mTOR, and IGF‐1R for children with RMS and VEGF for children with non‐RMS STS (NRSTS). For RMS, COG Phase 3 trials potentially will explore VEGF/mTOR inhibition or chemotherapy interval compression. For NRSTS, a COG Phase 3 trial will explore VEGF inhibition. Pediatr Blood Cancer 2013; 60: 1001–1008. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Radiation oncology

Radiation therapy (RT) is used to treat children with CNS tumors, solid tumors or Hodgkin lymphoma. Pediatric radiation oncologists have provided critical input into the development and implementation of concepts for clinical trials to further define the modality's role and test newer methods to reduce side effects or intensify therapy. The quality of pediatric oncology clinical trials that include radiation therapy is linked to the quality of guidelines. Radiation oncology is an adult medical specialty; thus, pediatric radiation oncologists are uniquely positioned to work with adult cancer investigators in the reorganized US National Cancer Institute Clinic Trials Network. Pediatr Blood Cancer 2013; 60: 1037–1043. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: acute lymphoblastic leukemia

Approximately 90% of the 2,000 children, adolescents, and young adults enrolled each year in Children's Oncology Group acute lymphoblastic leukemia (ALL) trials will be cured. However, high‐risk subsets with significantly inferior survival remain, including infants, newly diagnosed patients with age ≥10 years, white blood count ≥50,000/µl, poor early response or T‐cell ALL, and relapsed ALL patients. Effective strategies to improve survival include better risk stratification, optimizing standard chemotherapy and combining targeted therapies with cytotoxic chemotherapy, the latter of which is dependent upon identification of key driver mutations present in ALL. Pediatr Blood Cancer 2013; 60: 957–963. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Epidemiology

Investigators worldwide have for over 40 years conducted case–control studies aimed at determining the causes of childhood cancer. The central challenge to conducting such research is the rarity of childhood cancer, thus many studies aggregate cases through clinical trials organizations such as COG. Rarity also precludes the use of prospective study designs, which are less prone to recall and selection biases. Despite these challenges a substantial literature on childhood cancer etiology has emerged but few strong environmental risk factors have been identified. Genetic studies are thus now coming to the fore with some success. The ultimate aim of epidemiologic studies is to reduce the population burden of childhood cancer by suggesting preventive measures or possibly by enabling early detection. Pediatr Blood Cancer 2013; 60: 1059–1062. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Non‐Hodgkin lymphoma

Non‐Hodgkin lymphomas account for approximately 7% of cancers diagnosed in patients less than 20 years of age, with approximately 800 cases diagnosed annually at COG institutions. With current therapies, cure rates range from 70% to over 90%, even for children with disseminated disease. However, two major challenges need to be overcome: (i) to optimize upfront treatment to prevent relapse since prognosis for patients with relapsed disease remains poor and (ii) minimize long‐term side effects in survivors. Hence, the future initiatives for the treatment of pediatric NHL are to utilize novel targeted therapies to not only improve outcomes but to decrease bystander organ toxicities and late effects. Pediatr Blood Cancer 2013; 60: 979–984. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Bone tumors

In the US, approximately 650 children are diagnosed with osteosarcoma and Ewing sarcoma (ES) each year. Five‐year survival ranges from 65% to 75% for localized disease and <30% for patients with metastases. Recent findings include interval‐compressed five drug chemotherapy improves survival with localized ES. In osteosarcoma a large international trial investigating the addition of ifosfamide/etoposide or interferon to standard therapy has completed accrual. For ES an ongoing trial explores the addition of cyclophosphamide/topotecan to interval‐compressed chemotherapy. Trials planned by the Children's Oncology Group will investigate new target(s) including IGF‐1R and mTOR in ES, and RANKL and GD2 in osteosarcoma. Pediatr Blood Cancer 2013; 60: 1009–1015. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Renal tumors

Renal malignancies are among the most prevalent pediatric cancers. The most common is favorable histology Wilms tumor (FHWT), which has 5‐year overall survival exceeding 90%. Other pediatric renal malignancies, including anaplastic Wilms tumor, clear cell sarcoma, malignant rhabdoid tumor, and renal cell carcinoma, have less favorable outcomes. Recent clinical trials have identified gain of chromosome 1q as a prognostic marker for FHWT. Upcoming studies will evaluate therapy adjustments based on this and other novel biomarkers. For high‐risk renal tumors, new treatment regimens will incorporate biological therapies. A research blueprint, viewed from the perspective of the Children's Oncology Group, is presented. Pediatr Blood Cancer 2013; 60: 994–1000. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Rare tumors

In the US, approximately 2,000 children are diagnosed with rare cancers each year, with 5‐year survival ranging from <20% for children with advanced carcinomas to >95% for children with intraocular retinoblastoma or localized germ cell tumors. During the last years, 12 clinical studies have been successfully completed in children with retinoblastoma, liver tumors, germ cell tumors, and infrequent malignancies, including therapeutic, epidemiologic, and biologic studies. Current efforts are centered in the development of large international collaborations to consolidate evidence‐based definitions and risk stratifications that will support international Phase 3 clinical trials in germ cell tumors, hepatoblastoma, and other rare cancers. Pediatr Blood Cancer 2013; 60: 1016–1021. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Cancer control and supportive care

In cancer control research, the objective is to reduce overall morbidity and mortality by decreasing acute and delayed treatment‐related toxicities in all children with cancer. To date, the Children's Oncology Group (COG) has focused on infection, neurocognition, quality of life (QoL), and nutrition/antiemetics. COG is conducting randomized controlled trials (RCTs) to determine prophylaxis strategies that will reduce infections in high‐risk populations. Two RCTs are determining if modafinil or computerized cognitive training improve cognitive functioning in pediatric brain tumor patients. QoL is being assessed in acute leukemia patients. Improved supportive care outcomes will only occur when the most effective interventions are established. Pediatr Blood Cancer 2013; 60: 1027–1030. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Adolescent and young adult oncology

The discipline of Adolescent and Young Adult (AYA) Oncology addresses compelling medical and psychosocial needs of AYA patients across the spectrum of cancer survivorship. To be successful, extraordinary collaboration involving multiple scientific disciplines and specialties is required. While AYA Oncology is international in scope, recent AYA‐focused studies conducted in the Children's Oncology Group (COG) have documented survival disparities, toxicity differences, and biological insights that provide the basis for new COG trials and initiatives for this population. This experience will be useful in leveraging the new United States National Cancer Institute Clinical Trials Network to transform AYA Oncology research. Pediatr Blood Cancer 2013; 60: 1055–1058. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Acute myeloid leukemia

For the 365 children diagnosed with acute myeloid leukemia in the US annually, 5‐year survival for patients on COG trials with low, intermediate, and high risk disease is 83%, 62%, and 23%, respectively. Recent advances include improved therapeutic stratification, improved survival with dose intensification, and further elucidation of the heterogeneity specific to childhood AML. These discoveries now guide current strategy incorporating targeted agents to pathways specific to childhood AML as well as evaluating methods to increase the sensitivity of the leukemic stem cell, first in Phase II feasibility trials followed by Phase III efficacy trials of the most promising agents. Acute myeloid leukemia in children, though with similar subgroups to adults, remains uniquely different based upon quite different prevalence of subtypes as well as overall response to therapy. The Children's Oncology Group's research agenda builds upon earlier efforts to better elucidate the leukemogenic steps distinct to childhood AML in order to more scientifically develop and test novel therapeutic approaches to the treatment and ultimate cure for children with this disorder. Pediatr Blood Cancer 2013; 60: 964–971. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Survivorship and outcomes

Improvements in the treatment of childhood cancer have resulted in over 360,000 survivors of childhood cancer in the U.S. There is now a heightened recognition of the need to reduce treatment‐related sequelae and optimize the quality of life of children treated for cancer. Survivorship studies conducted in the cooperative group setting have provided us with important information on long‐term intellectual function, organ toxicity, reproductive outcomes, second cancers, late mortality, and disparities in outcomes. Ongoing health education initiatives have helped standardize the follow‐up care for childhood cancer survivors and facilitate the early transfer of health‐related information to patients, families, and healthcare providers. Pediatr Blood Cancer 2013; 60: 1063–1068. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Stem cell transplantation

The role of SCT in pediatric oncology has continued to evolve with the introduction of new therapeutic agents and immunological insights into cancer. COG has focused its efforts on the study of hematopoietic stem cell transplantation in the treatment of pediatric malignancies in several major multi‐institutional Phase II and Phase III studies. These studies include addressing the impact of allogenicity in ALL (ASCT0431), and establishing autologous stem cell transplant as the standard of care in neuroblastoma. Reducing transplant‐associated toxicity was addressed in the ASCT0521 study, where the TNFα inhibitor etanercept was tested for the treatment of idiopathic pneumonia syndrome. Impact of cell dose was explored in the single versus tandem umbilical cord blood study CTN‐0501, in close collaboration with the BMT‐CTN. Pediatr Blood Cancer 2013; 60: 1044–1047. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2013 blueprint for research: Central nervous system tumors

In the US, approximately 2,500 children are diagnosed annually with brain tumors. Their survival ranges from >90% to <10%. For children with medulloblastoma, the most common malignant brain tumor, 5‐year survival ranges from >80% (standard‐risk) to 60% (high‐risk). For those with high‐grade gliomas (HGGs) including diffuse intrinsic pontine gliomas, 5‐year survival remains <10%. Sixty‐five percent patients with ependymoma are cured after surgery and radiation therapy depending on the degree of resection and histopathology of the tumor. Phase II trials for brain tumors will investigate agents that act on cMET, PDGFRA, or EZH2 in HGG, DIPG, or medulloblastoma, respectively. Phase III trials will explore risk‐based therapy stratification guided by molecular and clinical traits of children with medulloblastoma or ependymoma. Pediatr Blood Cancer 2013; 60: 1022–1026. © 2012 Wiley Periodicals, Inc.     

Children's Oncology Group's 2023 blueprint for research: Surgery

Surgery plays a crucial role in the treatment of children with solid malignancies. A well-conducted operation is often essential for cure. Collaboration with the primary care team is important for determining if and when surgery should be performed, and if performed, an operation must be done in accordance with well-established standards. The long-term consequences of surgery also need to be considered. Indications and objectives for a procedure vary. Providing education and developing and analyzing new research protocols that include aims relevant to surgery are key objectives of the Surgery Discipline of the Children's Oncology Group. The critical evaluation of emerging technologies to ensure safe, effective procedures is another key objective. Through research, education, and advancing technologies, the role of the pediatric surgeon in the multidisciplinary care of children with solid malignancies will continue to evolve.