Stephen A. Sands

Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the "Head Start" I and II protocols.

To determine the survival of infants and young children with non‐metastatic medulloblastoma using intensive myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue (AuHCR).

Regression of Recurrent Malignant Gliomas with Convection-Enhanced Delivery of Topotecan.

BACKGROUND Convection-enhanced delivery of chemotherapeutics for the treatment of malignant glioma is a technique that delivers drugs directly into a tumor and the surrounding interstitium through continuous, low-grade positive-pressure infusion. This allows high local concentrations of drug while overcoming the limitations imposed by toxicity and the blood-brain barrier in systemic therapies that prevent the use of many potentially effective drugs. OBJECTIVE To examine the safety profile of a conventional chemotherapeutic agent, topotecan, via convection-enhanced delivery in the treatment of recurrent malignant gliomas and secondarily to assess radiographic response and survival. METHODS We performed a prospective, dose-escalation phase Ib study of the topoisomerase-I inhibitor topotecan given by convection-enhanced delivery in patients with recurrent malignant gliomas. RESULTS Significant antitumor activity as described by radiographic changes and prolonged overall survival with minimal drug-associated toxicity was demonstrated. A maximum tolerated dose was established for future phase II studies. CONCLUSION Topotecan by convection-enhanced delivery has significant antitumor activity at concentrations that are nontoxic to normal brain. The potential for use of this therapy as a generally effective treatment option for malignant gliomas will be tested in subsequent phase II and III trials.

Long-term quality of life and neuropsychologic functioning for patients with CNS germ-cell tumors: From the First International CNS Germ-Cell Tumor Study

This study evaluated the quality of life and neuropsychologic functioning among patients enrolled between 1989 and 1993 in the First International CNS Germ-Cell Tumor Study. Quality-of-life questionnaires (Short Form-36 or Child Health Questionnaire) were completed on 43 patients at median follow-up of 6.1 years after diagnosis (range, 4.5-8.8 years), and intellectual and academic testing was performed on 22 patients. Psychosocial and physical functioning of patients aged 19 years and older at follow-up was within the average range, whereas the same functioning for patients aged 18 years and younger, as reported by their parents at follow-up, was low average and borderline, respectively. Overall psychosocial and physical health summary scores were positively correlated with age at diagnosis for both groups combined. Those who received CNS radiation therapy (n = 29) reported significantly worse physical health, but similar psychosocial health, compared with those treated without radiation. Neuropsychologic testing indicated full-scale and verbal IQ, reading, spelling, and math skills in the average range, and performance IQ in the low average range. Intelligence and math skills were positively correlated with age at diagnosis. Those with germinomas significantly outperformed those with nongerminomatous/ mixed tumors on all neuropsychological measures administered. Younger patients diagnosed with CNS germ-cell tumors are at increased risk for psychosocial and physical problems as well as neuropsychologic deficits. Exposure to irradiation adversely affects overall physical functioning, whereas tumor pathology appears to be a salient neurocognitive risk factor. Collaborative and randomized studies are required to further elucidate the late effects arising from factors such as age at diagnosis, tumor histology, level of irradiation therapy, and chemotherapy toxicity among these young and potentially curable patients.

Inhalation aromatherapy in children and adolescents undergoing stem cell infusion: results of a placebo-controlled double-blind trial

Objective: Though often lifesaving, stem cell transplantation (SCT) is a period of great distress for both child and parent.

Neuropsychological functioning of children treated with intensive chemotherapy followed by myeloablative consolidation chemotherapy and autologous hematopoietic cell rescue for newly diagnosed CNS tumors: An analysis of the Head Start II survivors

To evaluate the neuropsychological late effects amongst survivors treated on the Head Start II protocol between 1997 and 2003.

Craniopharyngioma Clinical Status Scale: a standardized metric of preoperative function and posttreatment outcome

OBJECT Controversy persists concerning the optimal treatment of craniopharyngiomas in children, and no standard outcome metric exists for comparison across treatment modalities, nor is there one that adequately reflects the multisystem dysfunction that may arise. METHODS The authors retrospectively analyzed the records of 86 consecutive children who underwent a uniform treatment paradigm of attempted radical resection performed by a single surgeon. Excluding 3 perioperative deaths and 3 patients with inadequate follow-up, 80 children (34 girls and 46 boys; mean age 9.56 years; mean follow-up 9.6 years) composed the study group (53 primary and 27 previously treated/recurrent tumors). Building on existing classification schemes proposed by De Vile for hypothalamic dysfunction and Wen for overall functional outcome, the authors devised a more nuanced classification system (Craniopharyngioma Clinical Status Scale [CCSS]) that assesses outcome across 5 axes, including neurological examination, visual status, pituitary function, hypothalamic dysfunction, and educational/occupational status at last follow-up (there is a 4-tiered grading scale in each domain, with increasing values reflecting greater dysfunction). RESULTS There was a significant increase in pituitary dysfunction following treatment-consistent with the high rates of diabetes insipidus and hypopituitarism common to the surgical management of craniopharyngiomas-and less dramatic deterioration in hypothalamic function or cognitive domains. Significant improvement in vision was also demonstrated, with no significant overall change in neurological status. Preoperative CCSS scores predicted postoperative outcome better than clinical characteristics like patient age, sex, tumor size, and the location or presence of hydrocephalus. CONCLUSIONS Preoperative CCSS scores predicted outcome with higher accuracy than clinical or imaging characteristics. In lieu of randomized trials, the CCSS may provide a useful outcome assessment tool for comparison across treatment paradigms and surgical approaches. Long-term follow-up is critical to the analysis of outcomes of craniopharyngioma treatment, given the often-delayed sequelae of all therapies and the high recurrence rates of these tumors.

Children's Oncology Group's 2013 blueprint for research: Behavioral science

Behavioral science has long played a central role in pediatric oncology clinical service and research. Early work focused on symptom relief related to side effects of chemotherapy and pain management related to invasive medical procedures. As survival rates improved, the focused has shifted to examination of the psychosocial impact, during and after treatment, of pediatric cancer and its treatment on children and their families. The success of the clinical trials networks related to survivorship highlights an even more critical role in numerous domains of psychosocial research and care. Within the cooperative group setting, the field of behavioral science includes psychologists, social workers, physicians, nurses, and parent advisors. The research agenda of this group of experts needs to focus on utilization of psychometrically robust measures to evaluate the impact of treatment on children with cancer and their families during and after treatment ends. Over the next 5 years, the field of behavioral science will need to develop and implement initiatives to expand use of standardized neurocognitive and behavior batteries; increase assessment of neurocognition using technology; early identification of at‐risk children/families; establish standards for evidence‐based psychosocial care; and leverage linkages with the broader behavioral health pediatric oncology community to translate empirically supported research clinical trials care to practice. Pediatr Blood Cancer 2013; 60: 1048–1054.

Implementation of multi-site neurocognitive assessments within a pediatric cooperative group: Can it be done?†

Neurocognitive functioning is an important construct in childhood cancer survivorship, given the potential neurotoxicity of central nervous system (CNS) diseases and treatments and the relevance for important functional outcomes in adulthood. However, within pediatric oncology cooperative groups there have been significant barriers to neurocognitive data collection that have historically resulted in incomplete data (<30% compliance), thereby limiting progress in understanding the neurocognitive functioning of survivors. This paper describes the development, feasibility, and potential efficacy of a brief neurocognitive battery to maximize collection of psychometrically robust neurocognitive data within a pediatric cooperative group. We hypothesized that a novel set of procedures could result in collection of data from over 80% of eligible children.

Health-related quality of life after allogeneic hematopoietic stem cell transplantation for sickle cell disease.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy that affects over 100,000 people in the United States. Patients with SCD are known to experience suboptimal health-related quality of life (HRQoL). In addition to the physical manifestations of SCD, psychological and social stress, along with academic difficulties, secondary to the chronicity of the disease and its complications often affect patients with SCD. Although medical therapy of SCD has improved, allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative therapy. The objective of this study was to measure HRQoL before and after allo-HCT by assessing physical, psychological, and social functioning in patients with SCD who have undergone reduced-toxicity conditioning (busulfan/fludarabine/alemtuzumab) followed by allo-HCT. Patients < 21 years of age undergoing allo-HCT (matched siblings and unrelated donors) for SCD and their primary caregiver were enrolled using either the English or Spanish version of the PedsQoL 4.0. Data were collected at 3 time points: before allo-HCT and on days 180 and 365 after allo-HCT. The change in HRQoL from baseline was assessed with unadjusted and adjusted mixed-effects models in which subjects were treated as random effects, and variance component structure was used. Seventeen patients and 23 primary caregivers were enrolled and reported a mean overall HRQoL of 66.05 (SD, 15.62) and 72.20 (SD, 15.50) at baseline, respectively. In the patient-reported analysis with adjusted mixed-effects models, the estimated improvements in overall HRQoL were 4.45 (SE, 4.98; P = .380) and 16.58 (SE, 5.06; P = .003) at 180 and 365 days, respectively, after allo-HCT. For parent-reported overall HRQoL, the estimated improvements were 1.57 (SE, 4.82; P = .747) and 9.28 (SE, 4.62; P = .053) at 180 and 365 days, respectively, after allo-HCT. Similar results were found across the physical, social, and emotional HRQoL domains with mixed-effects models after adjustment of demographic and medical variables. In addition to the alleviation of clinical manifestations of SCD, these patients demonstrated significant improvement in most aspects of HRQoL by 1 year after allo-HCT. These data represent the trajectory of HRQoL during the initial year of follow-up within this population and should be integrated into the decision-making process when considering allo-HCT in patients with SCD.

Long-Term Follow-Up of Children Treated for High-Grade Gliomas: Children's Oncology Group L991 Final Study Report

PURPOSE High-grade gliomas of the CNS are characterized by poor treatment response and prognosis for long-term survival. The Childrens Oncology Group (COG) L991 study investigated the neuropsychological, behavioral, and quality of life (QoL) outcomes after treatment on the Childrens Cancer Group (CCG) trial for high-grade gliomas (CCG-945). PATIENTS AND METHODS Fifty-four patients (29 males, 25 females) with a median age of 8.8 years at diagnosis (range, 0.2 to 19.5 years) were enrolled at 25 institutions in North America, representing 81% of available survivors; median length of follow-up was 15.1 years (range, 9.5 to 19.2 years), and median age at study evaluation was 23.6 years (range, 11.3 to 36 years). Standardized tests of neuropsychological functioning and QoL were performed. Descriptive statistics summarized principal findings, and one-way analysis of variance identified potential predictors of outcomes. RESULTS With an average follow-up time of 15 years, survivors demonstrated intellectual functioning within the low-average range. Executive functioning and verbal memory were between the low-average and borderline ranges. In contrast, visual memory and psychomotor processing speed were between the borderline and impaired ranges, respectively. Approximately 75% of patient reported overall QoL within or above normal limits for both physical and psychosocial domains. Nonhemispheric tumor location (midline or cerebellum), female sex, and younger age at treatment emerged as independent risk factors. CONCLUSION These results serve as a benchmark for comparison with future pediatric high-grade glioma studies, in addition to identifying at-risk cohorts that warrant further research and proactive interventions to minimize late effects while striving to ensure survival.