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PURPOSE: Systemic therapy with atezolizumab and bevacizumab can extend life for patients with advanced hepatocellular carcinoma (HCC). However, there is substantial variability in response to therapy and overall survival. Although current prognostic models have been validated in HCC, they primarily consider covariates that may be reflective of the severity of the underlying liver disease of patients with HCC. We developed and internally validated a classification and regression tree (CART) to identify patient characteristics associated with risks of early mortality, at or before 6 months from treatment initiation. METHODS: This retrospective cohort study used the nationwide Flatiron Health electronic health record-derived deidentified database and included patients with a diagnosis of HCC after January 1, 2020, who received initial systemic therapy with atezolizumab and bevacizumab. CART was developed from available baseline clinical and demographic information to predict mortality within 6 months from treatment initiation. Model characteristics were compared to the albumin-bilirubin (ALBI) model and was further validated against a contemporary validation cohort of patients after a data update. RESULTS: A total of 293 patients were analyzed. The CART identified seven cohorts of patients from baseline demographic and laboratory characteristics. The model had an area under the receiver operating curve (AUROC) of 0.739 (95% CI, 0.683 to 0.794) for predicting 6-month mortality. This model was internally valid and performed more favorably than the ALBI model, which had an AUROC of 0.608 (95% CI, 0.557 to 0.660). The model applied to the contemporary validation cohort (n = 111) had an AUROC of 0.666 (95% CI, 0.506 to 0.826). CONCLUSION: Using CART, we identified unique cohorts of patients with HCC treated with atezolizumab and bevacizumab with distinct risks of early mortality. This approach outperformed the ALBI model and used clinical and laboratory characteristics that are readily available to oncologists caring for these patients.
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Anticorpos Monoclonais Humanizados , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Masculino , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
INTRODUCTION: Despite several therapeutic advancements, the proportion of patients with advanced biliary tract cancers (BTC) surviving 5 years from diagnosis remains dismal. The increasing recognition of targetable genetic alterations in BTCs has ushered in a new era in the treatment of these patients. Newer therapeutic agents targeting mutations such as isocitrate dehydrogenase (IDH), fibroblastic growth factor receptor (FGFR), human epidermal growth factor receptor (HER), and so on have established a new standard of care for treatment upon progression on frontline therapy in patients with disease harboring these mutations. AREAS COVERED: The current review aims to concisely summarize progress with various targeted therapy options for BTC. We also briefly discuss future directions in clinical and translational research for the adoption of a personalized approach for the treatment of unresectable or advanced BTC. EXPERT OPINION: Several new agents continue to emerge as feasible treatment options for patients with advanced BTC harboring targetable mutations. There is a growing need to identify mechanisms to conquer primary and acquired resistance to these agents. The identification of potential biomarkers that predict response to targeted therapy may be helpful in adopting a more tailored approach. All patients receiving treatment for advanced BTC should undergo tissue genomic profiling at diagnosis.
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Antineoplásicos , Neoplasias do Sistema Biliar , Terapia de Alvo Molecular , Mutação , Medicina de Precisão , Humanos , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/genética , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Taxa de Sobrevida , Progressão da Doença , AnimaisRESUMO
Modulation of autophagy, specifically its inhibition, stands to transform the capacity to effectively treat a broad range of cancers. However, the clinical efficacy of autophagy inhibitors has been inconsistent. To delineate clinical and epidemiological features associated with autophagy inhibition and a positive oncological clinical response, a retrospective analysis of patients is conducted treated with hydroxychloroquine, a known autophagy inhibitor. A direct correlation between smoking status and inhibition of autophagy with hydroxychloroquine is identified. Recognizing that smoking is associated with elevated circulating levels of carbon monoxide (CO), it is hypothesized that supplemental CO can amplify autophagy inhibition. A novel, gas-entrapping material containing CO in a pre-clinical model is applied and demonstrated that CO can dramatically increase the cytotoxicity of autophagy inhibitors and significantly inhibit the growth of tumors when used in combination. These data support the notion that safe, therapeutic levels of CO can markedly enhance the efficacy of autophagy inhibitors, opening a promising new frontier in the quest to improve cancer therapies.
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Hidroxicloroquina , Neoplasias Pulmonares , Masculino , Humanos , Hidroxicloroquina/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Monóxido de Carbono/farmacologia , Próstata , Estudos Retrospectivos , AutofagiaRESUMO
PURPOSE: PARP inhibitors (PARPi) provide an effective maintenance option for patients with BRCA- or PALB2-mutated pancreatic cancer. However, mechanisms of PARPi resistance and optimal post-PARPi therapeutic strategies are poorly characterized. EXPERIMENTAL DESIGN: We collected paired cell-free DNA samples and post-PARPi clinical data on 42 patients with advanced, platinum-sensitive pancreatic cancer who were treated with maintenance rucaparib on NCT03140670, of whom 32 developed progressive disease. RESULTS: Peripherally detected, acquired BRCA or PALB2 reversion variants were uncommon (5/30; 16.6%) in patients who progressed on rucaparib. Reversions were significantly associated with rapid resistance to PARPi treatment (median PFS, 3.7 vs. 12.5 months; P = 0.001) and poor overall survival (median OS, 6.2 vs. 23.0 months; P < 0.0001). All patients with reversions received rechallenge with platinum-based chemotherapy following PARPi progression and experienced faster progression on this therapy than those without reversion variants (real-world time-to-treatment discontinuation, 2.4 vs. 5.8 months; P = 0.004). Of the patients who progressed on PARPi and received further chemotherapy, the OS from initiation of second-line therapy was significantly lower in those with reversion variants than in those without (5.5 vs. 12.0 months, P = 0.002). Finally, high levels of tumor shedding were independently associated with poor outcomes in patients who received rucaparib. CONCLUSIONS: Acquired reversion variants were uncommon but detrimental in a population of patients with advanced BRCA- or PALB2-related pancreatic ductal adenocarcinoma who received maintenance rucaparib. Reversion variants led to rapid progression on PARPi, rapid failure of subsequent platinum-based treatment, and poor OS of patients. The identification of such variants in the blood may have both predictive and prognostic value. See related commentary by Tsang and Gallinger, p. 5005.
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Neoplasias Ovarianas , Neoplasias Pancreáticas , Feminino , Humanos , Neoplasias Ovarianas/patologia , Proteína BRCA2/genética , Prognóstico , Indóis , Inibidores de Poli(ADP-Ribose) Polimerases , Platina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Proteína BRCA1/genética , Proteína do Grupo de Complementação N da Anemia de Fanconi/genéticaRESUMO
Outcomes for patients with advanced pancreatic cancer have improved in the past 12 years, mainly because of progress made in systemic therapies. New treatment strategies for advanced pancreatic cancer include switch maintenance with cytotoxic therapies, induction maintenance, and the utilization of targeted agents for patients with actionable variants, as well as ongoing development of cytotoxic regimens, such as NALIRIFOX. The activity of immunotherapy has been disappointing to date, but novel combinations and identifying appropriate patient populations may further unlock its potential.
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Antineoplásicos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/etiologia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Imunoterapia , Neoplasias PancreáticasRESUMO
PURPOSE: Hepatocellular carcinoma (HCC) is a common and deadly form of liver cancer. Combination atezolizumab and bevacizumab has improved the outcomes for patients with advanced disease. We sought to determine the impact of etiology on outcomes of patients treated with atezolizumab and bevacizumab. METHODS: This study used a real-world database. The primary outcome was overall survival (OS) by etiology of HCC; the secondary outcome was real-world time to treatment discontinuation (rwTTD). Time-to-event analyses was performed by the Kaplan-Meier method; the log-rank test to assess for differences by etiology from date of first receipt of atezolizumab and bevacizumab. The Cox proportional hazards model was used to calculate hazard ratios. RESULTS: In total, 429 patients were included (n = 216 Viral-HCC; n = 68 Alcohol-HCC; n = 145, NASH-HCC). The median overall survival for the entire cohort was 9.4 months (95% CI 7.1-10.9). Compared with Viral-HCC, the hazard ratio (HR) of death was 1.11 (95% CI 0.74-1.68, p = 0.62) for Alcohol-HCC and was 1.34 (95% CI 0.96-1.86, p = 0.08) for NASH-HCC. The median rwTTD for the entire cohort was 5.7 months (95% CI 5.0-7.0 months). The HR of rwTTD was 1.24 (95% CI 0.86-1.77, p = 0.25) for Alcohol-HCC and was 1.31 (95% CI 0.98-1.75, p = 0.06) in reference to TTD with Viral-HCC. CONCLUSIONS: In this real-world cohort of patients with HCC receiving first-line atezolizumab and bevacizumab, we did not identify an association between etiology and OS or rwTTD. This suggests that the efficacy of atezolizumab and bevacizumab may be similar across HCC etiologies. Further prospective studies are needed to confirm these findings.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Bevacizumab , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , EtanolRESUMO
Advances in genomic diagnostics hold promise for improved care of rare hematologic diseases. Here, we describe a novel targeted therapeutic approach for Ghosal hematodiaphyseal dysplasia, an autosomal recessive disease characterized by severe normocytic anemia and bone abnormalities due to loss-of-function mutations in thromboxane A synthase 1 (TBXAS1). TBXAS1 metabolizes prostaglandin H2 (PGH2), a cyclooxygenase (COX) product of arachidonic acid, into thromboxane A2. Loss-of-function mutations in TBXAS result in an increase in PGH2 availability for other PG synthases. The current treatment for Ghosal hematodiaphyseal dysplasia syndrome consists of corticosteroids. We hypothesize that nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit COX-1 and COX-2, could ameliorate the effects of TBXAS1 loss and improve hematologic function by reducing prostaglandin formation. We treated 2 patients with Ghosal hematodiaphyseal dysplasia syndrome, an adult and a child, with standard doses of NSAIDs (aspirin or ibuprofen). Both patients had rapid improvements concerning hematologic parameters and inflammatory markers without adverse events. Mass spectrometry analysis demonstrated that urinary PG metabolites were increased along with proinflammatory lipoxygenase (LOX) products 5-hydroxyeicosatetraenoic acid and leukotriene E4. Our data show that NSAIDs at standard doses surprisingly reduced both COX and LOX products, leading to the resolution of cytopenia, and should be considered for first-line treatment for Ghosal hematodiaphyseal dysplasia syndrome.
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Anemia Refratária , Anemia , Pancitopenia , Adulto , Criança , Humanos , Anemia Refratária/tratamento farmacológico , Anemia Refratária/genética , Anti-Inflamatórios não Esteroides/uso terapêutico , Anemia/tratamento farmacológico , Prostaglandina H2 , Síndrome , Transtornos da Insuficiência da Medula ÓsseaRESUMO
Background: Sorafenib has consistently served as the control arm in multiple randomized clinical trials (RCTs) evaluating novel therapies for advanced hepatocellular carcinoma (HCC) for more than a decade. Analyzing trends in clinical outcomes of patients treated with sorafenib for the same indication over time offers the opportunity for unique insight into the evolution of clinical trial conduct and potential non-drug factors impacting outcomes. Methods: We identified RCTs in patients with treatment-naïve advanced HCC where sorafenib was compared to another systemic therapy or placebo. We extracted trial-level demographic, clinicopathologic, and outcome data (overall survival [OS], progression-free survival [PFS], objective response rate [ORR], and duration of therapy). Sample-weighted linear regression was used to identify temporal trends with significance set at p ≤ 0.05. Results: Sixteen RCTs (9 phase III and 7 phase II) enrolling 4,086 patients treated with sorafenib were included in the analysis. Included trials enrolled patients from 2005 to 2019. OS has significantly improved by 4.5 months from 2005 to 2019 (p = 0.048) over time. Thirteen studies provided data on PFS using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, with no significant change over time (p = 0.69). ORR assessed by RECIST 1.1 has significantly improved by 6.0% over time (p = 0.003). Median duration of therapy with sorafenib has decreased by 53% since the enrollment of the first clinical trial in 2005, from 23.1 weeks to 12.2 weeks (p = 0.0037). There was no significant change in patient demographics were identified over time to explain the OS findings. Conclusion: The median OS of patients with advanced HCC treated with sorafenib has improved significantly over 15 years. At the same time, the median duration of therapy with sorafenib has decreased. The reason for these findings was not explained by changing demographics of patients enrolled in these trials and has implications for ongoing clinical trials.
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BACKGROUND: The antiangiogenic tyrosine kinase inhibitor regorafenib provides a survival benefit in patients with previously treated metastatic colorectal cancer (CRC). Antiangiogenic therapy causes hypoxic stress within tumor cells, which activates autophagy as a survival mechanism. The histone deacetylase inhibitor (HDAC) entinostat increases dependence on autophagy through epigenetic mechanisms. Hydroxychloroquine (HCQ) blocks autophagy by blunting lysosomal acidification. We hypothesized that HCQ and entinostat would be tolerable with regorafenib and potentiate the antitumor response. METHODS: This was a 3+3 phase I trial of HCQ and entinostat with regorafenib in patients with metastatic CRC. The primary objective was safety, and the secondary objective was clinical efficacy. RESULTS: Twenty patients received study therapy. Six evaluable patients were enrolled at each of the three planned dose levels, one patient at an intermediate dose level, and one additional patient withdrew consent after 4 days to receive treatment closer to home. One dose-limiting toxicity was noted in the study at dose level 2 (grade 3 fatigue). Seven patients discontinued therapy due to related toxicities; rapid weight loss was near universal, with a median weight loss of 4.4 kg (range 1.5-12.2 kg) in the first 2 weeks of treatment. No objective responses were observed. CONCLUSION: The combination of regorafenib, HCQ, and entinostat was poorly tolerated without evident activity in metastatic CRC. CLINICALTRIALS.GOV IDENTIFIER: NCT03215264.
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Neoplasias Colorretais , Hidroxicloroquina , Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidas , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Humanos , Hidroxicloroquina/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Piridinas , Redução de PesoRESUMO
Malnutrition is exceedingly common in cancer patients, with some of the highest rates seen in gastrointestinal (GI) malignancies. Malnutrition and cachexia in cancer patients is associated with worse quality of life, poor treatment tolerance, and increased morbidity and mortality. The importance of early recognition of malnutrition in cancer patients is key, and numerous screening tools have been validated to aid practitioners in this diagnosis. In this paper, we summarize the importance of identifying and managing malnutrition in GI cancer patients as well as its impact on clinical outcomes. We then focus on presenting our own novel quality improvement project that aims to expand access to dietitian services in a GI cancer clinic at a large safety-net hospital system. Utilizing evidence-based quality improvement methodologies including the Model for Improvement and Plan-Do-Study-Act cycles, we increased the proportion of GI oncology patients seen by a dietitian from 5% to 20% from October 2018 to July 2019. In particular, we outline the challenges faced in the implementation process of a malnutrition screening tool built into the electronic medical record in an outpatient oncology clinic. We focus on the tool's ability to capture a greater number of patients with malnutrition and its clinical impact.
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Neoplasias Gastrointestinais , Desnutrição , Caquexia/diagnóstico , Caquexia/etiologia , Caquexia/terapia , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/terapia , Humanos , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Desnutrição/etiologia , Avaliação Nutricional , Melhoria de Qualidade , Qualidade de VidaRESUMO
ABSTRACT: Despite representing only 5% of all annual cancer diagnoses in the United States, pancreatic cancer is projected to become the second leading cause of cancer-related death within the next 10 years. Progress in the treatment of advanced pancreatic cancer has been slow. Systemic therapies rely on combination cytotoxic agents, with limited options at progression. Recently, poly(ADP-ribose) polymerase inhibitors have demonstrated clinical activity in patients with advanced pancreatic cancer and pathogenic variants in BRCA1, BRCA2, and PALB2. In this review, we discuss the development of poly(ADP-ribose) polymerase inhibitors in pancreatic cancer, relevant clinical trials, and future directions.
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Neoplasias Pancreáticas , Inibidores de Poli(ADP-Ribose) Polimerases , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêuticoRESUMO
PURPOSE: Opioid-induced constipation (OIC) is the most common side effect in patient-prescribed opioids for cancer pain treatment. Current guidelines recommend routine prescription of a laxative for preventing OIC in all patients prescribed an opioid unless a contraindication exists. We determined patterns of prescription of laxative agents in patients with lung cancer initiating opioids. METHODS: We performed a retrospective cohort study evaluating the prescription of laxatives for OIC to adult patients with incident lung cancer seen in the Veteran's Affairs (VA) system, between January 1, 2003, and December 31, 2016. Exposure to laxative agents was categorized as follows: none, docusate monotherapy, docusate plus another laxative, and other laxatives only. Prevalence of OIC prophylaxis was analyzed using descriptive statistics. Linear regression was performed to identify time trends in the prescription of OIC prophylaxis. RESULTS: Overall, 130,990 individuals were included in the analysis. Of these, 87% of patients received inadequate prophylaxis (75% no prophylaxis and 12% docusate alone), while 5% received OIC prophylaxis with the unnecessary addition of docusate to another laxative. Through the study period, laxative prescription significantly decreased, while all other categories of OIC prophylaxis were unchanged. We noted an inverse relationship with OIC prophylaxis and likelihood of a diagnosis of constipation at 3 and 6 months. CONCLUSIONS: In this study of veterans with lung cancer, almost 90% received inadequate or inappropriate OIC prophylaxis. Efforts to educate physicians and patients to promote appropriate OIC prophylaxis in combination with systems-level changes are warranted.
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Quimioprevenção/estatística & dados numéricos , Laxantes/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Constipação Induzida por Opioides/prevenção & controle , Veteranos/estatística & dados numéricos , Adulto , Idoso , Analgésicos Opioides/efeitos adversos , Dor do Câncer/tratamento farmacológico , Dor do Câncer/epidemiologia , Quimioprevenção/métodos , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Constipação Induzida por Opioides/epidemiologia , Manejo da Dor/efeitos adversos , Cuidados Paliativos/métodos , Cuidados Paliativos/estatística & dados numéricos , Estudos RetrospectivosRESUMO
Mucositis is a common and feared complication of anticancer therapy that can affect up to 90% of certain populations of patients with cancer. Even seemingly uncomplicated mucositis, which is often self-limited, can result in intense patient discomfort and decline in quality of life. Severe mucositis can be complicated by uncontrolled pain, superinfection or systemic infection, bleeding, and dehydration, and severe mucositis can lead to interruptions or de-escalation in anticancer treatment, resulting in worse oncologic outcomes. This article provides an evidence-based summary to guide practicing oncologists in the assessment, prevention, and management of mucositis induced by chemotherapy, radiotherapy, and targeted therapy.
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Neoplasias/complicações , Qualidade de Vida/psicologia , Estomatite/induzido quimicamente , Estomatite/terapia , HumanosRESUMO
PURPOSE: The time it takes a performing site to activate a clinical trial can directly affect the ability to provide innovative and state-of-the-art care to patients. We sought to understand the process of activating an oncology clinical trial at a matrix National Cancer Institute-designated comprehensive cancer center. METHODS: A multidisciplinary team of stakeholders within the cancer center, university, and affiliate hospitals held a retreat to map out the process of activating a clinical trial. We applied classical quality improvement and Six Sigma methodology to determine bottlenecks and non-value-added time in activating a clinical trial. During this process, attention was paid to time to pass through each step, and perceived barriers and bottlenecks were identified through group discussions. RESULTS: The process map identified 66 steps with 12 decision points to activate a new clinical trial. The following two steps were instituted first: allow parallel scientific committee and institutional review board (IRB) review and allow the clinical research coordination committee, a group that determines university interest and feasibility, to review protocols independent of the IRB and scientific committee approval. The clinical research coordination committee continues to track the activation time, and this framework is used to identify additional improvement steps. CONCLUSION: By applying quality improvement methodologies and Six Sigma principles, we were able to identify redundancies in the process to activate a clinical trial. This allowed us to redesign the process of activating a clinical trial at a matrix comprehensive cancer center. More importantly, the process map provides a framework to maintain these gains and implement additional changes and serves as an example to deploy across the campus and at other similar institutions.
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Comitês de Ética em Pesquisa , Neoplasias , Ensaios Clínicos como Assunto , Humanos , Oncologia , National Cancer Institute (U.S.) , Neoplasias/terapia , Estados UnidosAssuntos
Ceramidas/uso terapêutico , Portadores de Fármacos/química , Leucemia Mieloide Aguda/tratamento farmacológico , Lipossomos/química , Esfingolipídeos/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Ceramidas/administração & dosagem , Sistemas de Liberação de Medicamentos , Humanos , Leucemia Mieloide Aguda/metabolismo , Nanoestruturas , Resultado do Tratamento , Vimblastina/farmacologia , Vimblastina/uso terapêuticoRESUMO
BACKGROUND: Optimum management of low-grade gliomas remains controversial, and widespread practice variation exists. This evidence-based meta-analysis evaluates the association of extent of resection, radiation, and chemotherapy with mortality and progression-free survival at 2, 5, and 10 years in patients with low-grade glioma. METHODS: A quantitative systematic review was performed. Inclusion criteria included controlled trials of newly diagnosed low-grade (World Health Organization Grades I and II) gliomas in adults. Eligible studies were identified, assigned a level of evidence for every endpoint considered, and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The relative risk of mortality and of progression at 2, 5, and 10 years was calculated for patients undergoing resection (gross total, subtotal, or biopsy), radiation, or chemotherapy. RESULTS: Gross total resection was significantly associated with decreased mortality and likelihood of progression at all time points compared to subtotal resection. Early radiation was not associated with decreased mortality; however, progression-free survival was better at 5 years compared to patients receiving delayed or no radiation. Chemotherapy was associated with decreased mortality at 5 and 10 years in the high-quality literature. Progression-free survival was better at 5 and 10 years compared to patients who did not receive chemotherapy. In patients with isocitrate dehydrogenase 1 gene (IDH1) R132H mutations receiving chemotherapy, progression-free survival was better at 2 and 5 years than in patients with IDH1 wild-type gliomas. CONCLUSIONS: Results from this review, the first to quantify differences in outcome associated with surgery, radiation, and chemotherapy in patients with low-grade gliomas, can be used to inform evidence-based management and future clinical trials.