Optimizing Postoperative Surveillance of Pediatric Low-Grade Glioma Using Tumor Behavior Patterns.

BACKGROUND: Pediatric low-grade gliomas are among the most common childhood neoplasms, yet their post-treatment surveillance remains nonstandardized, relying on arbitrarily chosen imaging intervals. OBJECTIVE: To optimize postoperative magnetic resonance imaging (MRI) surveillance protocols for pediatric low-grade gliomas. METHODS: Patients aged 0 to 21 yr with pediatric low-grade gliomas, treated between 1990 and 2016 were retrospectively analyzed. The timing of surveillance imaging and radiologic tumor outcomes were extracted, and the effect of patient age, tumor location, histology, and extent of resection as prognostic factors was studied. An algorithm was developed to analyze the detection efficacy and cost of all possible surveillance protocols. RESULTS: A total of 517 patients were included with a median follow-up of 7.7 yr (range: 2-25.1 yr) who underwent 8061 MRI scans (mean 15.6 scans per patient). Tumor recurrence was detected radiologically in 292 patients (56.5%), of whom, 143 underwent reoperation. The hazards ratio (HR) of recurrence was higher in patients who underwent biopsy (HR = 3.60; 95% confidence interval (CI): 2.45-5.30; P < .001), subtotal resection (HR = 2.97; 95% CI: 2.18-4.03; P < .001), and near-total resection (HR = 2.03; 95% CI: 1.16-3.54; P = .01), compared to patients with gross total resection (GTR). For all patients, an 8-image surveillance protocol at 0, 3, 6, 12, 24, 36, 60, and 72 mo (total cost: $13 672 per patient) yielded comparative detection rates to the current 15-image protocol ($25 635). For patients who underwent GTR, a 6-image protocol at 0, 3, 9, 24, 36, and 60 mo ($10 254) is sufficient. CONCLUSION: Our data suggest that postoperative surveillance of pediatric low-grade gliomas can be effectively performed using less frequent imaging compared to current practice, thereby improving adherence to follow-up, and quality-of-life, while reducing costs.

A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer.

BACKGROUND: Preclinical models show that an antiangiogenic regimen at low-dose daily (metronomic) dosing may be effective against chemotherapy-resistant tumors. We undertook a prospective, open-label, single-arm, multi-institutional phase II study to evaluate the efficacy of a "5-drug" oral regimen in children with recurrent or progressive cancer. PROCEDURE: Patients ≤21 years old with recurrent or progressive tumors were eligible. Treatment consisted of continuous oral celecoxib, thalidomide, and fenofibrate, with alternating 21-day cycles of low-dose cyclophosphamide and etoposide. Primary endpoint was to assess, within eight disease strata, activity of the 5-drug regimen over 27 weeks. Blood and urine angiogenesis markers were assessed. RESULTS: One hundred one patients were enrolled; 97 began treatment. Median age was 10 years (range: 191 days-21 years); 47 (49%) were female. Disease strata included high-grade glioma (HGG, 21 patients), ependymoma (19), low-grade glioma (LGG, 12), bone tumors (12), medulloblastoma/primitive neuroectodermal tumor (PNET, 8), leukemia (4), neuroblastoma (3), and miscellaneous tumors (18). Treatment was generally well tolerated; most common toxicities were hematologic. Twenty-four (25%) patients completed 27 weeks therapy without progression, including HGG: 1 (5%), ependymoma: 7 (37%), LGG: 7 (58%), medulloblastoma/PNET: 1, neuroblastoma: 1, and miscellaneous tumors: 7 (39%). Best response was complete response (one patient with medulloblastoma), partial response (12), stable disease (36), progressive disease (47), and inevaluable (1). Baseline serum thrombospondin levels were significantly higher in patients successfully completing therapy than in those who progressed (P = 0.009). CONCLUSION: The 5-drug regimen was well tolerated. Clinical activity was demonstrated in some but not all tumor strata.

Suicide ideation in pediatric and adult survivors of childhood brain tumors.

Survivors of pediatric brain tumors are at risk for long-term psychological morbidities. The current study investigated the prevalence and predictors of suicide ideation (SI) in a clinical sample of youth and adult survivors. Retrospective chart reviews were completed for 319 survivors of pediatric brain tumors who were assessed via clinical interview during routine neuro-oncology clinic visits between 2003 and 2007. Survivors were, on average, 18.0 years of age (SD = 4.9) and 10 years from diagnosis (SD = 5.0) at their most recent follow-up. The most common diagnosis was low-grade glioma (n = 162) followed by embryonal tumors (PNET/medulloblastoma; n = 64). Multivariable logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CI) for SI. Nearly 12 % of survivors (11.7 %, n = 37) reported SI. Five survivors (1.5 %) had documented suicide attempts, though none were fatal. In a multivariable model, adjusting for sex and age, history of depression (OR = 20.6, 95 % CI = 4.2-101.1), psychoactive medication treatment (OR = 4.5, 95 % CI = 1.8-11.2), observation or surgery only treatment (OR = 3.7, 95 % CI = 1.5-9.1), and seizures (OR = 3.6, 95 % CI = 1.1-11.1) were significantly associated with SI in survivors. Survivors of pediatric brain tumors appear to be at risk for experiencing SI. Our results underscore the importance of a multidisciplinary approach to providing follow-up care for childhood brain tumor survivors, including routine psychological screenings.

Medical, psychological, cognitive and educational late-effects in pediatric low-grade glioma survivors treated with surgery only.

BACKGROUND: Surgical resection is often the only treatment necessary for pediatric low-grade gliomas (LGGs) and is thought to define a population with an excellent long-term prognosis. The goal of this study was to describe the multidimensional late-effects of pediatric LGG survivors treated exclusively with surgery. METHODS: A retrospective chart review of "surgery-only" LGG survivors followed at Dana-Farber/Children's Hospital Cancer Care was undertaken. Patients had to be diagnosed with an LGG before the age of 22 years, treated with "surgery-only" and be at least 2 years from diagnosis. RESULTS: Sixty survivors were eligible with a median age at the time of review of 16.3 years and the median time since diagnosis of 8.4 years. Tumor locations were predominantly posterior fossa (47%) or cortical (33%). Eighty-five percent of patients had at least one ongoing late-effect, and 28% had three or more. The most common late-effects consisted of motor dysfunction (43%), visual problems (32%), anxiety (19%), social difficulties (19%), seizure disorders (17%), depression (15%), poor coordination/ataxia (14%), behavioral problems (13%), and endocrinopathies (10%). Nine patients had a history of suicidal ideation; two with suicide attempts. The mean full-scale IQ was normal, however, the number of survivors scoring one standard deviation below the mean was twice the expected number. Special education services were utilized by more than half of the survivors. CONCLUSIONS: "Surgery-only" LGG survivors may be more affected by their tumor and its resection than previously appreciated. A prospective study is needed to address this survivor population.