Genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors.

BACKGROUND: Neurocognitive deficits are common in pediatric brain tumor survivors. The use of single nucleotide polymorphism (SNP) analysis in DNA repair genes may identify children treated with radiation therapy for brain tumors at increased risk for treatment toxicity and adverse neurocognitive outcomes. MATERIALS: The Human 660W-Quad v1.0 DNA BeadChip analysis (Illumina) was used to evaluate 1048 SNPs from 59 DNA repair genes in 46 subjects. IQ testing was measured by the Wechsler Intelligence Scale for Children. Linear regression was used to identify the 10 SNPs with the strongest association with IQ scores while adjusting for radiation type. RESULTS: The low vs high IQ patient cohorts were well matched for time from first treatment to most recent IQ, first treatment age, sex, and treatments received. 5 SNPs on 3 different genes (CYP29, XRCC1, and BRCA1) and on 3 different chromosomes (10, 19, and 17) had the strongest association with most recent IQ score that was not modified by radiation type. Furthermore, 5 SNPs on 4 different genes (WRN, NR3C1, ERCC4, RAD51L1) on 4 different chromosomes (8, 5, 16, 14) had the strongest association with change in IQ independent of radiation type, first IQ, and years between IQ measures. CONCLUSIONS: SNPs offer the potential to predict adverse neurocognitive outcomes in pediatric brain tumor survivors. Our results require validation in a larger patient cohort. Improving the ability to identify children at risk of treatment related neurocognitive deficits could allow for better treatment stratification and early cognitive interventions.

Detectability of Small Low-Attenuation Lesions With Deep Learning CT Image Reconstruction: A 24-Reader Phantom Study.

BACKGROUND. Iterative reconstruction (IR) techniques are susceptible to contrast-dependent spatial resolution, limiting overall radiation dose reduction potential. Deep learning image reconstruction (DLIR) may mitigate this limitation. OBJECTIVE. The purpose of our study was to evaluate low-contrast detectability performance and radiation-saving potential of a DLIR algorithm in comparison with filtered back projection (FBP) and IR using a human multireader noninferiority study design and task-based observer modeling. METHODS. A dual-phantom construct, consisting of a low-contrast detectability module (21 low-contrast hypoattenuating objects in seven sizes [2.4-10.0 mm] and three contrast levels [-15, -10, -5 HU] embedded within liver-equivalent background) and a phantom, was imaged at five radiation exposures (CTDIvol range, 1.4-14.0 mGy; size-specific dose estimate, 2.5-25.0 mGy; 90%-, 70%-, 50%-, and 30%-reduced radiation levels and full radiation level) using an MDCT scanner. Images were reconstructed using FBP, hybrid IR (ASiR-V), and DLIR (TrueFidelity). Twenty-four readers of varying experience levels evaluated images using a two-alternative forced choice. A task-based observer model (detectability index [d']) was calculated. Reader performance was estimated by calculating the AUC using a noninferiority method. RESULTS. Compared with FBP and IR methods at routine radiation levels, DLIR medium and DLIR high settings showed noninferior performance through a 90% radiation reduction (except DLIR medium setting at 70% reduced level). The IR method was non-inferior to routine radiation FBP only for 30% and 50% radiation reductions. No significant difference in d' was observed between routine radiation FBP and DLIR high setting through a 70% radiation reduction. Reader experience was not correlated with diagnostic accuracy (R2 = 0.005). CONCLUSION. Compared with FBP or IR methods at routine radiation levels, certain DLIR algorithm weightings yielded noninferior low-contrast detectability with radiation reductions of up to 90% as measured by 24 human readers and up to 70% as assessed by a task-based observer model. CLINICAL IMPACT. DLIR has substantial potential to preserve contrast-dependent spatial resolution for the detection of hypoattenuating lesions at decreased radiation levels in a phantom model, addressing a major shortcoming of current IR techniques.

Tumor hypermetabolism confers resistance to immunotherapy.

Advances in our understanding of tumor immune biology and development of cancer immunotherapies have led to improved outcomes for patients that suffer from aggressive cancers such as metastatic melanoma. Despite these advances, a significant proportion of patients still fail to benefit, and as a result, attention has shifted to understanding how cancer cells escape immune destruction. Of particular interest is the metabolic landscape of the tumor microenvironment, as recent studies have demonstrated how both competition for essential nutrients and depletion of specific amino acids can promote T cell dysfunction. Here, we will discuss the major energetic pathways engaged by both T cells and cancer cells, metabolic substrates present in the tumor microenvironment, and emerging therapeutic strategies that seek to improve T cell metabolic fitness and bolster the antitumor immune response.

Glycemic variability is associated with poor outcomes in pediatric hematopoietic stem cell transplant patients.

BACKGROUND: Among pediatric hematopoietic stem cell transplant (HSCT) recipients, abnormal glycemic control is shown to be associated with increased risk of transplant-related mortality, death from any cause, risk of infection, increased hospitalized, and intensive care days. Independent effects of higher glycemic variability, a component of glycemic control, have not been described. This study aimed to characterize risk factors for, and consequences of, higher glycemic variability in HSCT patients. PROCEDURE: Medical records for a cohort of 344 patients, age 0-30 years, who underwent first HSCT from 2007 to 2016 at Children's Hospital Colorado were retrospectively reviewed. Glucose coefficients of variation (CV) were analyzed for HSCT days -14 to 0 and 0-30, and patients were assessed for potential risk factors and outcomes. RESULTS: Roughly one-third of patients had pre-HSCT and day 0-30 glucose CV above the reported healthy adult range. Independent of HSCT type, doubling of pre-HSCT glucose CV was associated with a 4.91-fold (95% confidence interval [CI], 1.40-17.24) increased hazard of infection, as well as increased risk for intensive care hospitalization for allogenic HSCT patients. Multivariable analysis demonstrated that allogeneic HSCT patients had a 1.40- and 1.38-fold (95% CI, 0.98-1.99 and 1.00-1.91) increased hazard of death for every doubling of pre-HSCT and day 0-30 glucose CV, respectively. CONCLUSIONS: Just as with higher mean glucose, higher glycemic variability in the pediatric HSCT population is independently associated with significantly increased morbidity. Additional research is required to evaluate the utility of glucose control to mitigate these relationships and improve HSCT outcomes.

A study of knowledge, attitudes, and practices of primary care physicians toward anticoagulant therapy in patients with non-valvular atrial fibrillation in Shanghai, China.

BACKGROUND: As a large number of Community Health Service (CHS) centers in China face the majority of patients with non-valvular atrial fibrillation (NVAF), primary care physicians (PCPs) play a primary role in the prevention of embolization. Therefore, an awareness of anticoagulant management in patients with NVAF must be brought into focus among PCPs in China. This study investigated PCPs' knowledge, attitudes, and practices toward anticoagulant therapy in patients with NVAF, to help them understand their shortcomings regarding oral anticoagulant (OAC) therapy in preventing embolization. METHOD: This was a cross-sectional observational study of 462 PCPs in CHS centers across Shanghai. We used a self-administered questionnaire to collect data from September to December 2017. A stratified random cluster sampling was adopted in the 90 CHS centers with the family medicine residency program. RESULT: Among 462 participants, 69.3% (320/462) of females received a medical bachelor's degree and over 50% of participants had more than 10 years of work experience. Each section for knowledge, attitude, and practice were categorized as poor (≤39.0%), fair (40.0-69.0%), and good (≥70.0%). The level of knowledge of OAC therapy for patients with NVAF among PCPs was insufficient in over half (75.8%) of the participants. The majority (89.8%) of PCPs had a positive attitude and 68.0% had modest performance in the anticoagulant management of patients with NVAF. CONCLUSIONS: The knowledge and behaviors of PCPs were insufficient for OAC therapy to prevent embolization in patients with NVAF. The study also revealed that there is good potential for PCPs' educational interventions to positively impact the care of patients with NVAF.

Guidelines Insights: Acute Lymphoblastic Leukemia, Version 1.2019.

Survival outcomes for older adults with acute lymphoblastic leukemia (ALL) are poor and optimal management is challenging due to higher-risk leukemia genetics, comorbidities, and lower tolerance to intensive therapy. A critical understanding of these factors guides the selection of frontline therapies and subsequent treatment strategies. In addition, there have been recent developments in minimal/measurable residual disease (MRD) testing and blinatumomab use in the context of MRD-positive disease after therapy. These NCCN Guidelines Insights discuss recent updates to the NCCN Guidelines for ALL regarding upfront therapy in older adults and MRD monitoring/testing in response to ALL treatment.

Early mortality of stage IV non-small cell lung cancer in the United States.

Background: Early mortality is a major deterrent to oncologic management, often preventing delivery of therapy or leading to administration of treatment that offers limited benefit from aggressive interventions. Due to more recent progress in therapeutic options for stage IV non-small cell lung cancer (NSCLC) patients, identifying those at high risk of early mortality (within 30 days) could have implications for treatment selection. Because early mortality following diagnosis of metastatic non-small cell lung cancer (NSCLC) is not well-characterized, this investigation evaluated national trends and predictors thereof. Material and methods: The National Cancer Database was queried for cases of pathologically confirmed metastatic NSCLC with complete vital status and clinical information, diagnosed between 2006 and 2014. Multivariable logistic regression ascertained factors associated with 30-day mortality. Results: Of 346,681 patients, 45,861 (13%) experienced early mortality over the past decade, which remained relatively constant over time. Predictors of early mortality included advancing age (>65 years), male gender, Caucasian race, non-private insurance, lower income, greater comorbidities, residence in metropolitan and/or lesser-educated areas, treatment at community centers, patients with no prior history of cancer and regional differences (p < .01 for all). Early mortality was highest in patients older than 80 years with multiple comorbidities (29%). The majority of patients (71%) who died within 30 days did not receive any therapy. Conclusions: A fair proportion of NSCLC patients experience early mortality, which has not decreased over time. The majority of patients with early mortality do not receive treatment. Prognostic factors for early mortality should be considered during initial evaluation and subsequent follow-up of these patients. Doing so may impact systemic treatment selection by medical oncologists, management of (oligo)metastatic disease by radiation and surgical oncologists and cost-effective administration of these therapies in the stage IV NSCLC population.

Bevacizumab in the treatment of radiation injury for children with central nervous system tumors.

PURPOSE: Radiation-induced injury is a well-described toxicity in children receiving radiation therapy for tumors of the central nervous system. Standard therapy has historically consisted primarily of high-dose corticosteroids, which carry significant side effects. Preclinical models suggest that radiation necrosis may be mediated in part through vascular endothelial growth factor (VEGF) overexpression, providing the rationale for use of VEGF inhibitors in the treatment of CNS radiation necrosis. We present the first prospective experience examining the safety, feasibility, neurologic outcomes, and imaging characteristics of bevacizumab therapy for CNS radiation necrosis in children. METHODS: Seven patients between 1 and 25 years of age with neurologic deterioration and MRI findings consistent with radiation injury or necrosis were enrolled on an IRB-approved pilot feasibility study. Patients received bevacizumab at a dose of 10 mg/kg intravenously every 2 weeks for up to 6 total doses. RESULTS: Five patients (83%) were able to wean off corticosteroid therapy during the study period and 4 patients (57%) demonstrated improvement in serial neurologic exams. All patients demonstrated a decrease in T1-weighted post-gadolinium enhancement on MRI, while 5 (71%) showed a decrease in FLAIR signal. Four patients developed a progressive disease of their underlying tumor during bevacizumab therapy. CONCLUSIONS: Our experience lends support to the safety and feasibility of bevacizumab administration for the treatment of radiation necrosis for appropriately selected patients within the pediatric population.

Pulmonary toxicity in paediatric patients with relapsed or refractory Hodgkin lymphoma receiving brentuximab vedotin.

Brentuximab vedotin (Bv) is becoming increasingly important in the treatment of Hodgkin lymphoma (HL), with improved outcomes and an overall favourable toxicity profile. However, Bv is associated with severe pulmonary toxicity when combined with bleomycin, suggesting that additive toxicity may be an important consideration. Furthermore, little has been published on tolerability in paediatric patients. We retrospectively evaluated the occurrence of pulmonary toxicity of Bv in 19 paediatric and young adult patients with relapsed or refractory HL. Patient characteristics, baseline health status, treatment regimens including cumulative doses of Bv, bleomycin, gemcitabine, radiation and carmustine, and the occurrence of pulmonary toxicity were collected. Seven (36·8%) of the 19 patients were treated with Bv. The odds of pulmonary toxicity were 4·0-fold higher (95% confidence interval 0·55-29·18) in patients exposed to Bv compared to unexposed patients in univariate analysis (P = 0·17). Similar results were found in multivariable analysis. Pulmonary toxicity occurred frequently in our cohort and was more common in patients who received Bv than in patients who did not receive Bv, although this was not statistically significant. Because patients with HL are exposed to a myriad of therapies with potential for pulmonary toxicity, continuing to evaluate the risk associated with Bv is critical.

Pediatric versus adult meningioma: comparison of epidemiology, treatments, and outcomes using the Surveillance, Epidemiology, and End Results database.

Pediatric meningiomas, which account for < 1% of all meningiomas, are thought to have unique features, including being more aggressive than their adult counterparts. The goal of this investigation was to compare pediatric and adult meningiomas in a large head-to-head comparison. We used the Surveillance, Epidemiology, and End Result (SEER) datasets to compare meningioma demographics, first treatments, and outcomes among children/adolescents (0-21 years), young adults (22-45 years), and older adults (> 45 years). During 2004-2012, SEER contained 59148 patients age 0-107 years diagnosed with meningioma, with children/adolescents accounting for 381 (0.64%) patients. Unlike older and young adults, children/adolescents with meningioma did not demonstrate female predominance, and had an equal 1:1 male-to-female ratio. Children/adolescents also had almost three-times as many spinal tumors (13.1%) than young adults (4.2%) and older adults (4.4%). Both children/adolescents and young adults had undergone more gross total resections (both 43%) versus older adults (25%), and were treated more with radiation (14.6%, and 12.0% respectively) than their older counterparts (8.5%). In addition, both children/adolescents and young adults had significantly lower all-cause mortality (4.5% in both) than older adults (24.6%), during median 35-month follow-up. Inherent limitations of the SEER datasets restrict our ability to answer important questions regarding comparisons of tumor grading, histological diagnosis, cause-specific mortality, and neurofibromatosis status. Pediatric meningiomas appear distinct from their adult counterparts as they do not display the typical female predominance and include more clinically relevant spinal tumors. More extensive surgeries, greater use of radiation therapy, and lower all-cause mortality were seen in both children/adolescents and young adults, which raises questions regarding the perceived uniquely aggressive nature of pediatric meningiomas. However, due to the significant limitations of the SEER datasets, our results must be interpreted cautiously and stand only to foster novel questions, which would be better answered in well-designed, prospective studies.

Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases.

INTRODUCTION: Brain metastases are common in metastatic melanoma and radiosurgery is often utilized for local control. Immune checkpoint inhibitors (CPIs) play a central role in contemporary melanoma management; however, there is limited data exploring outcomes and potential toxicities for patients treated with CPIs and radiosurgery. METHODS: We retrospectively identified all consecutive cases of newly diagnosed melanoma brain metastases (MBM) treated with Gamma Knife radiosurgery at a single institution between 2012 and 2017, and included only patients that initiated CPIs within 8 weeks before or after radiosurgery. RESULTS: Thirty-eight patients were included with a median follow-up of 31.6 months. Two-year local control was 92%. Median time to out-of-field CNS and extra-CNS progression were 8.4 and 7.9 months, respectively. Median progression-free survival (PFS) was 3.4 months and median overall survival (OS) was not reached (NR). Twenty-five patients (66%) received anti-CTLA4 and 13 patients (34%) received anti-PD-1+/-anti-CTLA4. Compared with anti-CTLA4, patients that received anti-PD-1+/-anti-CTLA4 had significant improvements in time to out-of-field CNS progression (p = 0.049), extra-CNS progression (p = 0.015), and PFS (p = 0.043), with median time to out-of-field CNS progression of NR vs. 3.1 months, median time to extra-CNS progression of NR vs. 4.4 months, and median PFS of 20.3 vs. 2.4 months. Six patients (16%) developed grade ≥ 2 CNS toxicities (grade 2: 3, grade 3: 3, grade 4/5: 0). CONCLUSIONS: Excellent outcomes were observed in patients that initiated CPIs within 8 weeks of undergoing radiosurgery for newly diagnosed MBM. There appears to be an advantage to anti-PD-1 or combination therapy compared to anti-CTLA4.

Radiation-induced Cataracts in Children With Brain Tumors Receiving Craniospinal Irradiation.

Radiation is a well-known cause of the development of cataracts. For children with brain tumors, craniospinal irradiation (CSI) would be expected to result in a significant risk of cataract development. We reviewed the incidence of cataracts in children with brain tumors who received CSI at our institution. Of 45 children who received CSI and had ophthalmologic examinations, 13 developed cataracts. The median time to develop cataracts was 27.6 months. Seven children underwent surgery for cataract. Given this high incidence of cataracts, we suggest routine eye examinations for all children receiving CSI.

Implementation and operation of incident learning across a newly-created health system.

PURPOSE: The purpose of this work is to describe our experience launching an expanded incident learning system for patient safety and quality that takes into account aspects beyond therapeutic dose delivery, specifically imaging/simulation incidents, medical care incidents, and operational issues. METHODS: Our ILS was designed for a newly created health system comprised of a midsized academic hospital and two smaller community hospitals. The main design goal was to create a highly sensitive system to capture as much information throughout the department as possible. Reports were classified according to incidents and near misses involving therapeutic radiation, imaging/simulation, and patient care (not involving radiation), unsafe conditions, operational issues, and accolades/suggestions. Reports were analyzed according to impact on various steps in the process of care. Actions made in response to reports were assessed and characterized by intervention reliability. RESULTS: A total of 1125 reports were submitted in the first 23 months. For all three departments, therapeutic radiation incidents and near misses consisted of less than one-third of all reports submitted. For the midsized academic department, operational issues and unsafe conditions comprised the largest percentage of reports (70%). Although the majority of reports impacted steps related to the technical aspects of treatment (simulation, planning, and treatment delivery), 20% impacted other steps such as scheduling or clinic visits. More than 160 actions were performed in response to reports. Of these actions, 63 were quality improvement interventions to improve practices, while 97 were learning actions for raising awareness. CONCLUSIONS: We have developed an ILS that identifies issues related to the entire process of care delivery in radiation oncology, as evidenced by frequent and varied reported events. By identifying a broad spectrum of issues in a department, opportunities for improvement can be identified.

Using 4DCT-ventilation to characterize lung function changes for pediatric patients getting thoracic radiotherapy.

PURPOSE: A form of lung functional imaging has been developed that uses 4DCT data to calculate ventilation (4DCT-ventilation). Because 4DCTs are acquired as standard-of-care to manage breathing motion during radiotherapy, 4DCT-ventilation provides functional information at no extra dosimetric or monetary cost. 4DCT-ventilation has yet to be described in children. 4DCT-ventilation can be used as a tool to help assess post-treatment lung function and predict for future clinical thoracic toxicities for pediatric patients receiving radiotherapy to the chest. The purpose of this work was to perform a preliminary evaluation of 4DCT-ventilation-based lung function changes for pediatric patients receiving radiotherapy to the lungs. METHODS: The study used four patients with pre and postradiotherapy 4DCTs. The 4DCTs, deformable image registration, and a density-change-based algorithm were used to compute pre and post-treatment 4DCT-ventilation images. The post-treatment 4DCT-ventilation images were compared to the pretreatment 4DCT-ventilation images for a global lung response and for an intrapatient dose-response (providing an assessment for dose-dependent regional dose-response). RESULTS: For three of the four patients, a global ventilation decline of 7-37% was observed, while one patient did not demonstrate a global functional decline. Dose-response analysis did not reveal an intrapatient dose-response from 0 to 20 Gy for three patients while one patient demonstrated increased 4DCT-ventilation decline as a function of increasing lung doses up to 50 Gy. CONCLUSIONS: Compared to adults, pediatric patients have unique lung function, dosimetric, and toxicity profiles. The presented work is the first to evaluate spatial lung function changes in pediatric patients using 4DCT-ventilation and showed lung function changes for three of the four patients. The early changes demonstrated with lung function imaging warrant further longitudinal work to determine whether the imaging-based early changes can be predicted for long-term clinical toxicity.

NCCN Guidelines Insights: Acute Lymphoblastic Leukemia, Version 1.2017.

The prognosis for patients with newly diagnosed acute lymphoblastic leukemia (ALL) has improved with the use of more intensive chemotherapy regimens, tyrosine kinase inhibitors, targeted agents, and allogeneic hematopoietic cell transplantation. However, the management of relapsed or refractory (R/R) ALL remains challenging and prognosis is poor. The NCCN Guidelines for ALL provide recommendations on standard treatment approaches based on current evidence. These NCCN Guidelines Insights summarize treatment recommendations for R/R ALL and highlight important updates, and provide a summary of the panel's discussion and underlying data supporting the most recent recommendations for R/R ALL management.

Hypofractionated re-irradiation to the brainstem in children with recurrent brain tumors.

To characterize radiation necrosis following hypofractionated brainstem re-irradiation in pediatric patients, we reviewed 23 cases with 28 tumors invading or abutting brainstem and treated with hypofractionated re-irradiation from 2004 to 2014. Re-irradiation delivered total doses of 16-30 Gy in two to five fractions. The most commons regimens used were 24 Gy in three fractions and 25 Gy in five fractions. At median follow-up of 12.8 months, median overall survival was 14.7 months and eight in-field recurrences were detected (median time 10.5 months). Five patients experienced symptomatic brainstem necrosis, and all having received 24 Gy in three fractions. Hypofractionated brainstem re-irradiation may be safer in five fractions.

Survival benefit of postoperative radiation in papillary meningioma: Analysis of the National Cancer Data Base.

AIM/BACKGROUND: Papillary meningioma represents a rare subset of World Health Organization (WHO) Grade III meningioma that portends an overall poor prognosis. There is relatively limited data regarding the benefit of postoperative radiation therapy (PORT). We used the National Cancer Data Base (NCDB) to compare overall survival (OS) outcomes of surgically resected papillary meningioma cases undergoing PORT compared to post-operative observation. MATERIALS AND METHODS: The NCDB was queried for patients with papillary meningioma, diagnosed between 2004 and 2013, who underwent upfront surgery with or without PORT. Overall survival (OS) was determined using the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) analyses were performed. RESULTS: In total, 190 patients were identified; 89 patients underwent PORT, 101 patients were observed. Eleven patients received chemotherapy (6 with PORT, 5 without). 2-Year OS was significantly improved with PORT vs. no PORT (93.0% vs. 74.4%), as was 5-year OS (78.5% vs. 62.5%) (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.27-0.85; p = 0.01). On MVA, patients receiving PORT had improved OS compared to observation (HR, 0.41; 95% CI, 0.22-0.76; p = 0.005). On subset analysis by age group, the benefit of PORT vs. no PORT was significant in patients ≤18 years (n = 13), with 2-year OS of 85.7% vs. 50.0% (HR, 0.08; 95% CI, 0.01-0.80; p = 0.032) and for patients >18 years (n = 184), with 2-year OS of 94.7% vs. 76.1% (HR, 0.55; 95% CI, 0.31-1.00; p = 0.049), respectively. CONCLUSIONS: In this large contemporary analysis, PORT was associated with improved survival for both adult and pediatric patients with papillary meningioma. PORT should be considered in those who present with this rare, aggressive tumor.

Hypofractionated Radiotherapy for Children With Diffuse Intrinsic Pontine Gliomas.

Children with diffuse intrinsic pontine gliomas have very poor outcomes, with nearly all children dying from disease. Standard therapy includes 6 weeks of radiation. There have been descriptions of using a shortened course of radiation. We describe our experience with a hypofractionated radiotherapy approach delivered over five treatments. In seven children, hypofractionated radiotherapy was well tolerated, but symptomatic radiation necrosis was seen in three of the children. Overall survival was slightly shorter than previously described in the literature. We are developing a prospective dose-finding protocol with the goal of tolerable short-course radiation treatment with outcomes comparable to conventional radiation.

Acute Lymphoblastic Leukemia, Version 2.2015.

Treatment of acute lymphoblastic leukemia (ALL) continues to advance, as evidenced by the improved risk stratification of patients and development of newer treatment options. Identification of ALL subtypes based on immunophenotyping and cytogenetic and molecular markers has resulted in the inclusion of Philadelphia-like ALL and early T-cell precursor ALL as subtypes that affect prognosis. Identification of Ikaros mutations has also emerged as a prognostic factor. In addition to improved prognostication, treatment options for patients with ALL have expanded, particularly with regard to relapsed/refractory ALL. Continued development of second-generation tyrosine kinase inhibitors and the emergence of immunotherapy, including blinatumomab and chimeric antigen receptor T-cell therapy, have improved survival. Furthermore, incorporation of minimal residual disease (MRD) monitoring has shown insight into patient outcomes and may lead to treatment modification or alternative treatment strategies in select populations. This excerpt focuses on the sections of the ALL guidelines specific to clinical presentation and diagnosis, treatment of relapsed/refractory ALL, and incorporation of MRD monitoring. To view the most recent complete version of these guidelines, visit NCCN.org.

Pediatric choroid plexus tumors: epidemiology, treatments, and outcome analysis on 202 children from the SEER database.

Choroid plexus papillomas (CPPs) and carcinomas (CPCs) are rare neoplasms that affect mostly children. Due to their rarity, their epidemiology and outcomes are incompletely understood. The National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program is a well-established population-based group of registries that collects and publishes cancer incidence and survival data representing approximately 28 % of the US population. SEER-STAT v8.1.2 was used to identify patients with ICD-O-3 codes for choroid plexus tumors in patients aged 0-19. Demographics, initial treatment, and follow-up data were collected. Statistical methods including Kaplan-Meier curves, log rank tests, and Cox proportional hazards regression were used to estimate associations between independent variables and survival. The SEER registries contained 107 CPPs (2004-2010) and 95 CPCs (1978-2010). Median follow-up was 38 and 40 months, respectively. More than 75 % of CPCs were diagnosed before the age of 5 years, versus 48 % for CPPs. Sixty-five percent of CPCs and 57 % of CPPs occurred in males. In both groups at least 90 % of children underwent surgical resection. Gross total resection (GTR) was achieved in 67.0 % of CPCs and 63.6 % of CPPs. Almost 17 % of CPCs were treated with radiation versus only 0.9 % of CPPs. More than 98 % of patients with CPP were alive at the last follow-up, versus 62 % of CPC patients. For CPC, surgery was significantly associated with increased overall survival, but contrary to previous reports, extent of surgical resection was not associated with survival. Age, sex, race, and radiation treatment also had no effect on survival. This report, using the SEER datasets, corroborates many findings of previous smaller studies on CPTs. CPC occurs in younger children, with a male predominance, and a much worse prognosis than CPP. As such, these tumors have been treated aggressively with high rates of GTR and radiation treatment. Despite these treatments, overall survival for CPC remains poor.