Leslie S. Kersun

Phase II Study on the Effect of Disease Sites, Age, and Prior Therapy on Response to Iodine-131-Metaiodobenzylguanidine Therapy in Refractory Neuroblastoma

PURPOSE To evaluate the effect of disease sites and prior therapy on response and toxicity after iodine-131-metaiodobenzylguanidine (131I-MIBG) treatment of patients with resistant neuroblastoma. PATIENTS AND METHODS One hundred sixty-four patients with progressive, refractory or relapsed high-risk neuroblastoma, age 2 to 30 years, were treated in a limited institution phase II study. Patients with cryopreserved hematopoietic stem cells (n = 148) were treated with 18 mCi/kg of 131I-MIBG. Those without hematopoietic stem cells (n = 16) received 12 mCi/kg. Patients were stratified according to prior myeloablative therapy and whether they had measurable soft tissue involvement or only bone and/or bone marrow disease. RESULTS Hematologic toxicity was common, with 33% of patients receiving autologous hematopoietic stem cell support. Nonhematologic grade 3 or 4 toxicity was rare, with 5% of patients experiencing hepatic, 3.6% pulmonary, 10.9% infectious toxicity, and 9.7% with febrile neutropenia. The overall complete plus partial response rate was 36%. The response rate was significantly higher for patients with disease limited either to bone and bone marrow, or to soft tissue (compared with patients with both) for patients with fewer than three prior treatment regimens and for patients older than 12 years. The event-free survival (EFS) and overall survival (OS) times were significantly longer for patients achieving response, for those older than 12 years and with fewer than three prior treatment regimens. The OS was 49% at 1 year and 29% at 2 years; EFS was 18% at 1 year. CONCLUSION The high response rate and low nonhematologic toxicity with 131I-MIBG suggest incorporation of this agent into initial multimodal therapy of neuroblastoma.

Tumor response and toxicity with multiple infusions of high dose 131I‐MIBG for refractory neuroblastoma

131I Metaiodobenzylguanidine (131I‐MIBG) is an effective targeted radiotherapeutic for neuroblastoma with response rates greater than 30% in refractory disease. Toxicity is mainly limited to myelosuppression. The aim of this study was to determine the response rate and hematologic toxicity of multiple infusions of 131I‐MIBG.

A revision of the intensity of treatment rating scale: Classifying the intensity of pediatric cancer treatment

We previously developed a reliable and valid method for classifying the intensity of pediatric cancer treatment. The Intensity of Treatment Rating Scale (ITR‐2.0) 1 classifies treatments into four operationally defined levels of intensity and is completed by pediatric oncology specialists based on diagnosis, stage, and treatment data from the medical record. Experience with the ITR‐2.0 and recent changes in treatment protocols indicated the need for a minor revision and revalidation.

Primary non-hodgkin's lymphoma of bone in children

BACKGROUND Primary non-Hodgkins lymphoma of bone, often more simply referred to as primary lymphoma of bone, is a rare subset of non-Hodgkins lymphoma in children. There are only a few small series of primary lymphoma of bone in children with long-term follow-up, and none have appeared in the orthopaedic literature. METHODS A review of our institutions Pediatric Tumor Registry identified fifteen cases of primary lymphoma of bone among 306 cases of diagnosed non-Hodgkins lymphoma between 1970 and 2003. Retrospective evaluation included collection of demographic, clinical, radiographic, treatment, and follow-up data. A univariate analysis was used to assess the prognostic significance of risk factors with respect to survival of patients from this series and in a summary analysis of data collected from similar series in the literature. RESULTS The patients included ten male and five female patients with a mean age of 11.6 years. Most patients had a presenting complaint of pain and had swelling and/or tenderness on physical examination. Eight children had a solitary bone lesion, and seven had multiple bone lesions. Overall, the mean number of bones involved was 3.1 per patient. The femur and the pelvis were the most frequently involved bones. The ten surviving patients were followed for a mean of 13.6 years. Five patients died: three of disease progression, one of treatment-related complications, and one of an unrelated cause. The mean time from diagnosis to death was 2.1 years. Nine patients received chemotherapy only, whereas six patients received a combination of chemotherapy and radiation therapy. In the present study, an age of nine years or less was predictive of poor survival (p < 0.05). In the summary analysis of cases collected from the literature, advanced stage, young age, non-large-cell histology, and multiple-bone involvement were predictive of poor survival (p < 0.05). CONCLUSIONS On the basis of the present series and a comprehensive review of similar series in the literature involving patients with primary lymphoma of bone, it appears that younger age, advanced-stage disease, multiple-bone involvement, and non-large-cell histology are associated with decreased survival as compared with older age, localized disease, single-bone involvement, and large-cell histology, respectively.

Training in difficult conversations: a national survey of pediatric hematology-oncology and pediatric critical care physicians.

BACKGROUND In pediatric oncology and critical care, physicians give difficult news, including discussions regarding palliative care and comfort measures, but there are minimal data regarding fellowship program preparation for this task. PURPOSE We surveyed graduates of pediatric hematology/oncology and critical care fellowships regarding communication training to describe teaching methods, assess which were helpful, and determine whether comfort level is related to training experiences. METHODS A 12-question Web survey was sent to physicians completing fellowship in the previous 5 years. RESULTS Of 345 fellows identified, 171 (50%) responded. Prior training included observing senior physicians (100%), being observed (78%), reading (56%), lectures (46%), role-play (20%), workshops (16%), simulation (13%), and videos (13%). Observing senior physicians was thought most helpful. More years since training (p < 0.0005) and frequent difficult conversations (p = 0.009) were predictors of current comfort. Only workshops were associated with feeling better prepared at the end of training (p = 0.019). CONCLUSIONS Training may help physicians feel prepared for difficult conversations, but ongoing experience was strongly associated with comfort level.

Screening for psychosocial risk at pediatric cancer diagnosis: the psychosocial assessment tool.

Background To investigate the feasibility of integrating an evidence-based screening tool of psychosocial risk in pediatric cancer care at diagnosis. Methods Parents of children newly diagnosed with cancer received either the Psychosocial Assessment Tool (PAT; n=52) or psychosocial care as usual (n=47; PAU), based on their date of diagnosis and an alternating monthly schedule. Time to completion of the PAT, time to communication of PAT results to clinical care teams, distribution of PAT risk scores, and identification of psychosocial risks in the medical record were examined. Results Of families receiving the PAT, 88% completed it within 48 hours. PAT was scored and results communicated within 48 hours in 98% of cases. Most families (72%) were classified as Universal risk based on the underlying Pediatric Psychosocial Preventative Health Model, 24% were classified as Targeted risk, and 4% scored in the Clinical range. Significantly more psychosocial risks were recorded in the medical record during PAT intervals than during PAU. Conclusions An evidence-based psychosocial screener is feasible in pediatric oncology care and is associated with documentation of psychosocial risks in the medical record. Although the majority of families report low levels of psychosocial risk, about one-quarter report problems.

Association of psychosocial risk screening in pediatric cancer with psychosocial services provided

Objective: How screening for psychosocial risk in pediatric oncology may relate to the number and type of psychosocial services provided is a critical step in linking screening with treatment. We predicted that screening at diagnosis would be associated with the delivery of more psychosocial services over 8 weeks and that these services would be consistent with Universal, Targeted, or Clinical psychosocial risk level based on the Pediatric Psychosocial Preventative Health Model (PPPHM).

Establishment of an 11-year cohort of 8733 pediatric patients hospitalized at United States free-standing children's hospitals with de novo acute lymphoblastic leukemia from health care administrative data.

Background:Acute lymphoblastic leukemia (ALL) accounts for almost one quarter of pediatric cancer in the United States. Despite cooperative group therapeutic trials, there remains a paucity of large cohort data on which to conduct epidemiology and comparative effectiveness research studies. Research Design:We designed a 3-step process utilizing International Classification of Diseases-9 Clinical Modification (ICD-9) discharge diagnoses codes and chemotherapy exposure data contained in the Pediatric Health Information System administrative database to establish a cohort of children with de novo ALL. This process was validated by chart review at 1 of the pediatric centers. Results:An ALL cohort of 8733 patients was identified with a sensitivity of 88% [95% confidence interval (CI), 83%–92%] and a positive predictive value of 93% (95% CI, 89%–96%). The 30-day all cause inpatient case fatality rate using this 3-step process was 0.80% (95% CI, 0.63%–1.01%), which was significantly different than the case fatality rate of 1.40% (95% CI, 1.23%–1.60%) when ICD-9 codes alone were used. Conclusions:This is the first report of assembly and validation of a cohort of de novo ALL patients from a database representative of free-standing children’s hospitals across the United States. Our data demonstrate that the use of ICD-9 codes alone to establish cohorts will lead to substantial patient misclassification and result in biased outcome estimates. Systematic methods beyond the use of just ICD-9 codes must be used before analysis to establish accurate cohorts of patients with malignancy. A similar approach should be followed when establishing future cohorts from administrative data.

Pediatric primary bone lymphoma-diffuse large B-cell lymphoma: morphologic and immunohistochemical characteristics of 10 cases.

Most primary bone lymphomas (PBLs) are diffuse large B-cell lymphomas (DLBCLs). Pediatric PBL-DLBCL has a favorable prognosis but remains poorly characterized. Herein, 10 such cases are detailed. They involved 11- to 20-year-old males with bone lesions that were often painful. They were diagnosed often after months to years of symptoms, suggesting an indolent disease. All were successfully treated with chemotherapy with or without radiotherapy (0.5- to 24-year followup). Biopsy revealed that the lymphomas were paratrabecular or diffuse and were medium- to large-sized with round to irregular nuclei, dispersed chromatin, indistinct to small nucleoli, and abundant cytoplasm. Other features included varying levels of necrosis, cytoplasmic retraction, and myeloid hyperplasia. All cases marked as mature B cells, and most were CD10+ (7/10). Typical centroblastic morphologic features with nucleoli were rare, multilobated nuclei were uncommon, and CD10 negativity did not predict poor prognosis, unlike in the adult PBL-DLBCL. These findings suggest that pediatric and adult PBL-DLBCLs are distinct entities.

Screening for depression and anxiety in adolescent cancer patients.

The goals of this study were to evaluate the feasibility of depression and anxiety screening in on-therapy adolescents with cancer, determine the prevalence of depression and anxiety in this sample, and assess the concordance between patient and oncologist report of patient symptoms. Forty-one adolescents (ages 12 to 18 y) undergoing cancer therapy in an outpatient oncology clinic completed the Beck Youth Inventory II (BYI II) Depression and Anxiety scales. Treating oncologists independently rated patient depression and anxiety. Ninety-eight percent of patients agreed to participate and average time to measure completion was <15 minutes. Mean T-scores for the BDI-Y (Depression module) and BAI-Y (Anxiety module) for most were not different than published norms. Three and 2 patients scored in the moderate-extremely elevated range of the BAI-Y and BDI-Y, respectively. There were no associations between scores and sex, age, diagnosis, time since diagnosis, or treatment intensity. A depression and anxiety-screening program is feasible in the outpatient pediatric oncology setting. Rates of adolescent self-reported anxiety and depression are low, although oncologists perceived more patient distress. This is an area for future investigation.