Rene Y. McNall-Knapp

Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma

Preclinical models show sequence‐dependent synergy with the combination of temozolomide and irinotecan, and a Phase I trial has demonstrated the combination to be tolerable and active in children with relapsed solid tumors. Because responses were seen in patients with Ewing sarcoma (ES) on that trial, additional patients were treated with this combination following study completion.

The relationship of parental overprotection, perceived vulnerability, and parenting stress to behavioral, emotional, and social adjustment in children with cancer

To examine the relationship of self‐reported parental overprotection, perceived child vulnerability, and parenting stress to parent‐reported behavioral, emotional, and social adjustment of children currently on treatment for cancer.

Cognitive outcome in pediatric brain tumor survivors: Delayed attention deficit at long-term follow-up

Treatment of childhood brain tumors has often been associated with long‐term cognitive morbidity in children. Our previous research identified age at diagnosis, polytherapy and brain radiation dose as treatment factors affecting neuropsychological outcome most strongly in children with cancer 1 . Our current goal was to measure the change across different cognitive functions.

Impact of a Parent-Based Interdisciplinary Intervention for Mothers on Adjustment in Children Newly Diagnosed With Cancer

OBJECTIVE To determine if maternal distress predicts child adjustment outcomes or if child adjustment outcomes predict maternal distress among children newly diagnosed with cancer, and if a parent-focused intervention has downstream effects on child adjustment. METHODS Mothers (n = 52) were randomly assigned to a clinic-based, interdisciplinary intervention for parents of children newly diagnosed with cancer. Measures of maternal distress and child adjustment were collected at baseline, posttreatment, and follow-up. RESULTS A lagged relationship was identified between maternal distress and child internalizing symptoms, but not externalizing symptoms. The parent intervention reduced child internalizing and externalizing symptoms at follow-up. Only the child internalizing symptoms effect was mediated by reduced maternal distress. The child externalizing symptoms effect was mediated by unobserved parent factors. CONCLUSIONS This study provides support for illness adjustment and coping models that emphasize the role of parent factors in driving child adjustment outcomes and is encouraging for future parent-focused intervention research.

Reversible posterior leukoencephalopathy syndrome in children undergoing induction therapy for acute lymphoblastic leukemia

We present three cases of children with acute neurologic changes while undergoing induction chemotherapy for acute lymphoblastic leukemia (ALL). These cases fall into the spectrum of reversible posterior leukoencephalopathy syndrome (RPLS), including abrupt alterations in mental status, headache, seizures, visual changes, hypertension, and characteristic findings on magnetic resonance imaging. Although the underlying mechanism of RPLS is still under investigation, the appropriate treatment and management of the acute event is becoming clearer. Early treatment of hypertension, control of seizure activity, and withdrawal of inciting agents can lead to rapid reversal of symptoms and return to baseline functioning. Pediatr Blood Cancer 2007;49:198–203.

Persistent psychosocial problems in children who develop posterior fossa syndrome after medulloblastoma resection.

Posterior fossa syndrome (PFS) occurs in approximately 20% of patients after resection of a tumor from the posterior fossa. Few descriptions of persistent psychosocial consequences exist. We assessed whether the development of PFS is associated with increased risk for emotional, behavioral, and social problems after the cessation of cancer treatment.

Reducing irinotecan‐associated diarrhea in children

Irinotecan is increasingly being used in pediatric oncology. Amelioration of diarrhea associated with protracted irinotecan administration may reduce morbidity and improve dose intensity. In this review, we discuss what is known about the pathogenesis of this toxicity as well as potential predisposing genetic factors. We comprehensively summarize the literature regarding available prevention and treatment strategies, and report data on the use of cephalosporin prophylaxis in 51 patients treated on various pediatric trials. This approach is feasible in children and allows for tolerance of higher doses of protracted irinotecan. Pediatr Blood Cancer 2008; 50:201–207.

Motexafin-Gadolinium and Involved Field Radiation Therapy for Intrinsic Pontine Glioma of Childhood: A Children's Oncology Group Phase 2 Study

PURPOSE To evaluate the effects on 1-year event-free survival (EFS) and overall survival (OS) of combining motexafin and gadolinium (MGd), a potent radiosensitizer, with daily fractionated radiation therapy in children with newly diagnosed intrinsic pontine gliomas. METHODS AND MATERIALS Patients with newly diagnosed intrinsic pontine glioma were treated with MGd daily for 5 consecutive days each week, for a total of 30 doses. Patients received a 5- to 10-min intravenous bolus of MGd, 4.4 mg/kg/day, given 2 to 5 h prior to standard dose irradiation. Radiation therapy was administered at a daily dose of 1.8 Gy for 30 treatments over 6 weeks. The total dose was 54 Gy. RESULTS Sixty eligible children received MGd daily, concurrent with 6 weeks of radiation therapy. The estimated 1-year EFS was 18%±5%, and the estimated 1-year OS was 53%±6.5%. The most common grade 3 to 4 toxicities were lymphopenia, transient elevation of liver transaminases, and hypertension. CONCLUSIONS Compared to historical controls, the addition of MGd to a standard 6-week course of radiation did not improve the survival of pediatric patients with newly diagnosed intrinsic pontine gliomas.

Extended phase I evaluation of vincristine, Irinotecan, temozolomide, and antibiotic in children with refractory solid tumors

The combination of irinotecan, temozolomide, and vincristine is appealing because of potentially synergistic mechanisms of action and non‐overlapping toxicities. This phase I study was designed to determine the toxicity and maximum tolerated dose (MTD) of escalating daily protracted doses of irinotecan given in this combination. With extended accrual, we more fully explored the toxicity of multiple courses at the MTD.

Illness Uncertainty, Global Psychological Distress, and Posttraumatic Stress in Pediatric Cancer: A Preliminary Examination Using a Path Analysis Approach

OBJECTIVE To investigate the relationship of illness uncertainty (IU) to global psychological distress (GPD) and posttraumatic stress symptomatology (PTSS) using a path analysis approach. METHODS Participants were 105 caregivers (MAge = 36.9 years, standard deviation [SD] = 8.7) of children (MAge = 8.6 years, SD = 5.0) with newly diagnosed cancer. A path analysis model examined the indirect and direct effects of each IU subscale on PTSS through GPD.  RESULTS  The final model accounted for 47.30% of the variance in PTSS, and the ambiguity facet of IU had a significant indirect effect on PTSS through GPD. Lack of clarity and unpredictability were not significant predictors.  CONCLUSIONS Ambiguity experienced by parents may be salient in the development of PTSS. Future research should examine these relationships longitudinally in larger samples to better understand adjustment in parents of children with cancer.