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Abstract Pediatric low-grade gliomas (pLGGs) exhibit heterogeneous prognoses and variable responses to treatment, leading to tumor progression and adverse outcomes in cases where complete resection is unachievable. Early prediction of treatment responsiveness and suitability for immunotherapy has the potential to improve clinical management and outcomes. Here, we present a radiogenomic analysis of pLGGs, integrating MRI and RNA sequencing data. We identify three immunologically distinct clusters, with one group characterized by increased immune activity and poorer prognosis, indicating potential benefit from immunotherapies. We develop a radiomic signature that predicts these immune profiles with over 80% accuracy. Furthermore, our clinicoradiomic model predicts progression-free survival and correlates with treatment response. We also identify genetic variants and transcriptomic pathways associated with progression risk, highlighting links to tumor growth and immune response. This radiogenomic study in pLGGs provides a framework for the identification of high-risk patients who may benefit from targeted therapies.

PurposeMedulloblastoma is one of the most common malignant brain tumors in children. To date, the treatment of average-risk (non-metastatic, completely resected) medulloblastoma includes craniospinal radiation therapy and adjuvant chemotherapy. Modern treatment modalities and now risk stratification of subgroups have extended the survival of these patients, exposing the long-term morbidities associated with radiation therapy. Prior to advances in molecular subgrouping, we sought to reduce the late effects of radiation in patients with average-risk medulloblastoma.MethodsWe performed a single-arm, multi-institution study, reducing the dose of craniospinal irradiation by 25% to 18 Gray (Gy) with the goal of maintaining the therapeutic efficacy as described in CCG 9892 with maintenance chemotherapy.ResultsTwenty-eight (28) patients aged 3-30 years were enrolled across three institutions between April 2001 and December 2010. Median age at enrollment was 9 years with a median follow-up time of 11.7 years. The 3-year relapse-free (RFS) and overall survival (OS) were 79% (95% confidence interval [CI] 58% to 90%) and 93% (95% CI 74% to 98%), respectively. The 5-year RFS and OS were 71% (95% CI 50% to 85%) and 86% (95% CI 66% to 94%), respectively. Toxicities were similar to those seen in other studies; there were no grade 5 toxicities.ConclusionsGiven the known neurocognitive adverse effects associated with cranial radiation therapy, studies to evaluate the feasibility of dose reduction are needed. In this study, we demonstrate that select patients with average-risk medulloblastoma may benefit from a reduced craniospinal radiation dose of 18 Gy without impacting relapse-free or overall survival.Clinical Trial RegistrationClinicalTrials.gov identifier: NCT00031590

Abstract Objective Rapid developments in understanding the molecular mechanisms underlying cognitive deficits in neurodevelopmental disorders have increased expectations for targeted, mechanism‐based treatments. However, translation from preclinical models to human clinical trials has proven challenging. Poor reproducibility of cognitive endpoints may provide one explanation for this finding. We examined the suitability of cognitive outcomes for clinical trials in children with neurofibromatosis type 1 (NF1) by examining test‐retest reliability of the measures and the application of data reduction techniques to improve reproducibility. Methods Data were analyzed from the STARS clinical trial (n = 146), a multi‐center double‐blind placebo‐controlled phase II trial of lovastatin, conducted by the NF Clinical Trials Consortium. Intra‐class correlation coefficients were generated between pre‐ and post‐performances (16‐week interval) on neuropsychological endpoints in the placebo group to determine test‐retest reliabilities. Confirmatory factor analysis was used to reduce data into cognitive domains and account for measurement error. Results Test‐retest reliabilities were highly variable, with most endpoints demonstrating unacceptably low reproducibility. Data reduction confirmed four distinct neuropsychological domains: executive functioning/attention, visuospatial ability, memory, and behavior. Test‐retest reliabilities of latent factors improved to acceptable levels for clinical trials. Applicability and utility of our model was demonstrated by homogeneous effect sizes in the reanalyzed efficacy data. Interpretation These data demonstrate that single observed endpoints are not appropriate to determine efficacy, partly accounting for the poor test‐retest reliability of cognitive outcomes in clinical trials in neurodevelopmental disorders. Recommendations to improve reproducibility are outlined to guide future trial design.

The RNA polymerase II C-terminal domain acts as a hub to coordinate transcription and nascent mRNA processing. Here the authors identify a phosphorylation-dependent switch in thetrans-to-cisisomerization of proline in the CTD heptad repeats that make those repeats susceptible to further modifications by regulatory enzymes.

Because few large studies of pediatric ependymoma treatment are available, the authors believed that a retrospective review of treatment outcomes from a single institution would yield potentially valuable information regarding potential prognostic factors. In this article, they report their 20‐year institutional experience with this disease.Medical records were reviews of patients with intracranial ependymoma who received their initial treatment at the Children''s Hospital of Philadelphia (CHOP)/Hospital of the University of Pennsylvania (HUP) between January 1980 and December 2000. Of the 61 patients who were identified, 49 patients underwent primary therapy at CHOP/HUP and formed the basis for the study. Actuarial overall survival (OS) and progression‐free survival (PFS) were determined by the Kaplan‐Meier method. Univariate and multivariate analyses were performed using the log‐rank test and Cox proportional‐hazards models.With median follow‐up of 110.2 months, the 5‐year OS and PFS rates were 66.2% and 40.7%, respectively. Older age and higher radiation dose significantly predicted for improved OS. Anaplastic histology predicted for decreased PFS. Cervical spinal cord extension resulted in decreased OS primarily caused by failures outside the primary site. Patients who had a favorable prognosis (aged ≥3 years, no dissemination or cord extension, complete resection, and radiation dose ≥54 grays [Gy]) had 5‐year OS and PFS rates of 83.1% and 60.6%, respectively.In this study of patients with pediatric intracranial ependymoma, OS and PFS rates were concordant with the rates published in other modern series. The finding of a dose response up to 54 Gy supported the current trend toward dose escalation. Tumor extension to the cervical spine was identified as a predictor for failure outside of the primary site. Although the survival rates were encouraging, there is still significant room for improvement in the management of this disease. Cancer 2007. © 2007 American Cancer Society. [ABSTRACT FROM AUTHOR]

Let $p$ be a fixed odd prime. In this paper we prove an exponent conjecture of Bousfield, namely that the $p$-exponent of the spectrum $\Phi SU(n)$ is $(n-1) + \nu_p((n-1)!)$ for $n \geq 2$. It follows from this result that the $p$-exponent of $\Omega^{q} SU(n) \langle i \rangle$ is at least $(n-1) + \nu_p((n-1)!)$ for $n \geq 2$ and $i,q \geq 0$, where $SU(n) \langle i \rangle$ denotes the $i$-connected cover of $SU(n)$. [ABSTRACT FROM AUTHOR]

Most patients with intracranial germinomas will be cured and become long-term survivors. Physicians caring for these patients should recognize that these patients may be at risk for disease-related and/or treatment-related late sequelae. We report the case of a 27-year-old man who developed testicular seminoma 16 years after treatment for intracranial germinoma. Like their testicular cancer counterparts, long-term survivors of intracranial germinomas may have a susceptibility to develop a subsequent germ cell tumor. These patients require lifelong medical follow-up and should be encouraged to perform testicular self-examination at the appropriate age. [ABSTRACT FROM AUTHOR]

Colorectal cancer, the third most common cancer in U.S. adults, can be detected early through colonoscopy. Thorough bowel preparation facilitates successful colonoscopy. Effectiveness, tolerability, and costs of 3 bowel preparations were compared in patients undergoing outpatient screening colonoscopy. In this prospective, randomized, single-blind study, comparing three preparation protocols, 209 of 276 consented subjects completed (Protocol [N = 67] = HalfLytely© 1 L × 2 doses and bisacodyl 5 mg delayed release tablets × 2 tablets; Protocol 2 [N = 74] = MiraLAX® 5 tablespoons × 2 doses and bisacodyl 5 mg tablets × 2 tablets; and Protocol 3 [N = 68] = MoviPrep 1 L × 2 doses). Patients completed symptom diaries and a gastroenterologist rated effectiveness. Most subjects were White females, aged 59 years (mean). Protocol 1 was the most effective regimen, but Protocol 2 was the most tolerable and cost-effective. While the three bowel protocol differences were not statistically significant for all outcomes measured, there were clinically meaningful differences. As Protocol 1 was most effective, HalfLytely© and bisacodyl is recommended for patients prior to colonoscopy. For patients who cannot tolerate HalfLytely© or MoviPrep, or with financial concerns, Protocol 2 (MiraLAX® & bisacodyl) is alternatively recommended.