The 50 most-cited articles in Cancer, 2016

BACKGROUND: Annual updates on cancer occurrence and trends in the United States are provided through an ongoing collaboration among the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This annual report highlights the increasing burden of liver and intrahepatic bile duct (liver) cancers. METHODS: Cancer incidence data were obtained from the CDC, NCI, and NAACCR; data about cancer deaths were obtained from the CDC's National Center for Health Statistics (NCHS). Annual percent changes in incidence and death rates (age-adjusted to the 2000 US Standard Population) for all cancers combined and for the leading cancers among men and women were estimated by joinpoint analysis of long-term trends (incidence for 1992-2012 and mortality for 1975-2012) and short-term trends (2008-2012). In-depth analysis of liver cancer incidence included an age-period-cohort analysis and an incidence-based estimation of person-years of life lost because of the…

BACKGROUND: Cancer and its treatment lead to increased financial distress for patients. To the authors' knowledge, to date, no standardized patient-reported outcome measure has been validated to assess this distress. METHODS: Patients with AJCC Stage IV solid tumors receiving chemotherapy for at least 2 months were recruited. Financial toxicity was measured by the COmprehensive Score for financial Toxicity (COST) measure. The authors collected data regarding patient characteristics, clinical trial participation, health care use, willingness to discuss costs, psychological distress (Brief Profile of Mood States [POMS]), and health-related quality of life (HRQOL) as measured by the Functional Assessment of Cancer Therapy: General (FACT-G) and the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires. Test-retest reliability, internal consistency, and validity of the COST measure were assessed using standard-scale construction techniques. Associations between the resulting factors and other variables were assessed using multivariable analyses. RESULTS: A…

BACKGROUND: Predicting survival is uniquely difficult in patients with pancreatic cancer who receive chemotherapy. The authors developed a systemic inflammation response index (SIRI) based on peripheral neutrophil, monocyte, and lymphocyte counts and evaluated the ability of the SIRI to predict the survival of patients with pancreatic cancer who received chemotherapy. METHODS: The SIRI was developed in a training set of 177 patients who had advanced pancreatic cancer and received palliative chemotherapy. The ability of the SIRI to predict a patient's survival after chemotherapy was validated in 2 independent cohorts (n = 397). RESULTS: Compared with patients who had an SIRI <1.8, patients in the training cohort who had an SIRI ≥1.8 had a shorter time to progression (TTP) (hazard ratio [HR], 2.348; 95% confidence interval, 1.559-3.535; P = .003) and shorter overall survival (OS) (HR, 2.789; 95% confidence interval, 1.897-4.121; P < .001). Comparable TTP and OS findings were observed in 2 independent validation cohorts. Multivariate analysis confirmed that the SIRI was an independent…

Thyroid nodules are very common, and thyroid cancer is currently the fifth leading cancer diagnosis in women. The American Thyroid Association has led the development and revision of guidelines for the management of patients with thyroid nodules and differentiated thyroid cancer (DTC). The most current revision was published in the January 2016 issue of the journal Thyroid. The current guidelines have 101 recommendations, with 8 figures and 17 tables that are hopefully helpful to those treating patients with thyroid nodules and cancer. The primary goals of the American Thyroid Association Guidelines Task Force were to use the current evidence to guide recommendations and yet be as helpful and practical as possible within the scope and strength of the evidence. The current review focuses on new and significantly revised recommendations that may very well change clinical practice. The author notes 3 new basic principles that have emerged in this guidelines revision: 1) the management of thyroid nodules, including the decision to perform a fine-needle aspiration biopsy as well as…

Informal/family caregivers are a fundamental source of care for cancer patients in the United States, yet the population of caregivers and their tasks, psychosocial needs, and health outcomes are not well understood. Changes in the nature of cancer care and its delivery, along with the growing population of survivors and their caregivers, warrant increased attention to the roles and demands of caregiving. This article reviews current evidence presented at a 2-day meeting examining the state of the science of informal cancer caregiving that was convened by the National Cancer Institute and the National Institute of Nursing Research. The meeting sought to define who is an informal cancer caregiver, summarize the state of the science in informal cancer caregiving, and describe both the kinds of interventions developed to address caregiving challenges and the various outcomes used to evaluate their impact. This article offers recommendations for moving science forward in 4 areas: 1) improving the estimation of the prevalence and burden of informal cancer caregiving; 2) advancing the…

BACKGROUND: Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome characterized by a very high lifetime cancer risk and an early age at diagnosis of a wide cancer spectrum. Precise estimates for the risk of first and subsequent cancers are lacking. METHODS: The National Cancer Institute's Li-Fraumeni Syndrome Study includes families meeting the diagnostic criteria for LFS or Li-Fraumeni-like syndrome, and individuals with a germline TP53 mutation, choroid plexus carcinoma, adrenocortical carcinoma, or ≥3 cancers. Herein, we estimated the cumulative risk and annual hazards for first and second cancers among TP53 mutation carriers (TP53 positive [TP53+]) using MATLAB statistical software. RESULTS: This study evaluated 286 TP53+ individuals from 107 families. The cumulative cancer incidence was 50% by age 31 years among TP53+ females and 46 years among males, and nearly 100% by age 70 years for both sexes. Cancer risk was highest after age 20 years for females, mostly due to breast cancer, whereas among males the risk was higher in childhood and later…

Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the United States, and their age-adjusted risk is 5 per 1 million population. These less frequent melanomas are dissimilar to their more common cutaneous melanoma relative, with differing risk factors, primary treatment, anatomic spread, molecular changes, and responses to systemic therapy. Once uveal melanoma becomes metastatic, therapy options are limited and are often extrapolated from cutaneous melanoma therapies despite the routine exclusion of patients with uveal melanoma from clinical trials. Clinical trials directed at uveal melanoma have been completed or are in progress, and data from these well designed investigations will help guide future directions in this orphan disease. Cancer 2016;122:2299-2312. © 2016 American Cancer Society.

BACKGROUND: Biliary tract cancers (BTCs) typically present at an advanced stage, and systemic chemotherapy is often of limited benefit. METHODS: Hybrid capture-based comprehensive genomic profiling (CGP) was performed for 412 intrahepatic cholangiocarcinomas (IHCCAs), 57 extrahepatic cholangiocarcinomas (EHCCAs), and 85 gallbladder carcinomas (GBCAs). The mutational profile was correlated with the clinical outcome of standard and experimental therapies for 321 patients. Clinical variables, detected mutations, and administered therapies were correlated with overall survival (OS) in a Cox regression model. RESULTS: The most frequent genetic aberrations (GAs) observed were tumor protein 53 (TP53; 27%), cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B; 27%), KRAS (22%), AT-rich interactive domain-containing protein 1A (ARID1A; 18%), and isocitrate dehydrogenase 1 (IDH1; 16%) in IHCCA; KRAS (42%), TP53 (40%), CDKN2A/B (17%), and SMAD4 (21%) in EHCCA; and TP53 (59%), CDKN2A/B (19%), ARID1A (13%), and ERBB2 (16%) in GBCA. Fibroblast growth factor receptor (FGFR; 11%) and IDH mutations…

BACKGROUND: The current study was conducted to evaluate the performance of magnetic resonance (MR)-ultrasound-guided fusion biopsy in diagnosing clinically significant prostate cancer (csCaP). METHODS: A total of 1042 men underwent multiparametric MR imaging (mpMRI) and fusion biopsy consecutively in a prospective trial (2009-2014). An expert reader graded mpMRI regions of interest (ROIs) as 1 to 5 using published protocols. The fusion biopsy device was used to obtain targeted cores from ROIs (when present) followed by a fusion image-guided, 12-core systematic biopsy in all men, even if no suspicious ROI was noted. The primary endpoint of the study was the detection of csCaP (ie, Gleason score ≥ 7). RESULTS: Among 825 men with ≥ 1 suspicious ROI of ≥ grade 3, 289 (35%) were found to have csCaP. Powerful predictors of csCaP were ROI grade (grade 5 vs grade 3: odds ratio, 6.5 [P<.01]) and prostate-specific antigen density (each increase of 0.05 ng/mL/cc: odds ratio, 1.4 [P<.01]). Combining systematic and targeted biopsies resulted in the detection of more patients with csCaP (289…

BACKGROUND: Antibodies inhibiting the programmed death receptor 1 (PD-1) have demonstrated significant activity in the treatment of advanced cutaneous melanoma. The efficacy and safety of PD-1 blockade in patients with uveal melanoma has not been well characterized. METHODS: Fifty-eight patients with stage IV uveal melanoma received PD-1 or PD-1 ligand (PD-L1) antibodies between 2009 and 2015 at 9 academic centers. Patients who were evaluable for response were eligible for the analysis. Imaging was performed every 12 weeks and at the investigators' discretion. Safety and clinical efficacy outcomes, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively determined. RESULTS: Of 56 eligible patients, 48 (86%) had received prior therapy, and 35 (63%) had received treatment with ipilimumab. Three patients had an objective response to ipilimumab, and 8 had stable disease as their best response. Thirty-eight patients (68%) received pembrolizumab, 16 (29%) received nivolumab, and 2 (4%) received atezolizumab. Objective tumor…

BACKGROUND: A cancer diagnosis during adolescence or young adulthood may negatively influence social well-being. The existing literature concerning the social well-being of adolescents and young adults (AYAs) with cancer was reviewed to identify gaps in current research and highlight priority areas for future research. METHODS: A systematic review of the scientific literature published in English from 2000 through 2014 was performed. Eligible studies included patients and survivors diagnosed between the ages of 15 to 39 years that reported on social well-being domains in the City of Hope Cancer Survivor Quality of Life Model. Each article was reviewed for relevance using a standardized template. A total of 253 potential articles were identified. After exclusions, a final sample of 26 articles identified domains of social well-being that are believed to be understudied among AYAs with cancer: 1) educational attainment, employment, and financial burden; 2) social relationships; and 3) supportive care. Articles were read in their entirety, single coded, and summarized according to…

BACKGROUND: Cancer-related financial burden has been linked to cancer survivors (CS) forgoing/delaying medical care, skipping follow-up visits, and discontinuing medications. To the authors' knowledge, little is known regarding the effect of financial burden on the health-related quality of life of CS. METHODS: The authors analyzed 2011 Medical Expenditure Panel Survey data. Financial burden was present if one of the following problems was reported: borrowed money/declared bankruptcy, worried about paying large medical bills, unable to cover the cost of medical care visits, or other financial sacrifices. The following outcomes were evaluated: Physical Component Score (PCS) and Mental Component Score (MCS) of the 12-Item Short-Form Health Survey (SF-12), depressed mood, psychological distress, and worry related to cancer recurrence. The authors also assessed the effect of the number of financial problems on these outcomes. RESULTS: Of the 19.6 million CS analyzed, 28.7% reported financial burden. Among them, the average PCS (42.3 vs 44.9) and MCS (48.1 vs 52.1) were lower for those…

BACKGROUND: The chronicity status of breast cancer survivors suggests a growing need for cancer rehabilitation. Currently, the use of technology is a promising strategy for providing support, as reflected in the emergence of research interest in Web-based interventions in cancer survivorship. METHODS: A randomized controlled trial was conducted that included a total of 81 participants who had completed adjuvant therapy (except hormone treatment) for stage I to IIIA breast cancer. Participants were randomly assigned to an 8-week Internet-based, tailored exercise program (n = 40) or to a control group (n = 41).The instruments used at baseline, 8 weeks, and 6-month follow-up were the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and its breast cancer module, the Brief Pain Inventory, the handgrip dynamometer, the isometric abdominal test, the back dynamometer, the multiple sit-to-stand test, and the Piper Fatigue Scale. RESULTS: After the intervention, the telerehabilitation group had significantly improved scores for global health…

BACKGROUND: In the current study, the authors attempted to describe the incidence, most common sites, and mortality of second primary malignancies among survivors of common cancers. METHODS: The authors identified patients aged ≥18 years who were diagnosed with a primary malignancy from the 10 most common cancer sites (prostate, breast, lung, colon, rectum, bladder, uterus, kidney, melanoma, and non-Hodgkin lymphoma) between 1992 and 2008 from Surveillance, Epidemiology, and End Results data. Factors associated with the incidence of second primary malignancies were explored using bivariable and multivariable models, and mortality attributable to first and second primary malignancies was examined. RESULTS: A cohort of 2,116,163 patients was identified, 170,865 of whom (8.1%) developed a second primary malignancy. Survivors of bladder cancer had the highest risk of developing a second cancer. In a multivariable model controlling for age, race, tumor grade, stage of disease, marital status, educational level, and income, a history of non-Hodgkin lymphoma (hazard ratios of 2.70 and…

BACKGROUND: With prior reports indicating a lack of progress in survival improvement in older adolescents and young adults (AYAs) aged 15 to 39 years with cancer compared with both younger and older patients with cancer, the current analysis provides an update of survival trends of cancers among AYAs, children, and older adults. METHODS: Data from the National Cancer Institute Surveillance, Epidemiology, and End Results database for 13 regions were used to ascertain survival trends of the 34 most frequent cancers diagnosed in AYAs compared with children and older adults. RESULTS: As of 2002 through 2006, the 5-year relative survival rate for all invasive cancers in AYAs was 82.5% (standard error, 0.2%). In AYAs, 14 cancers demonstrated evidence of a statistically significant improvement in their 5-year relative survival since 1992. Survival improved less in AYAs than in children for acute myeloid leukemia and medulloblastoma. Fourteen cancers had survival improvements that were found to be less in AYAs compared with older adults, including hepatic carcinoma, acute myeloid leukemia,…

BACKGROUND: Hepatocellular carcinoma (HCC) incidence has been increasing in the United States for several decades; and, as the incidence of hepatitis C virus (HCV) infection declines and the prevalence of metabolic disorders rises, the proportion of HCC attributable to various risk factors may be changing. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare linkage were used to calculate population attributable fractions (PAFs) for each risk factor over time. Patients with HCC (n = 10,708) who were diagnosed during the years 2000 through 2011 were compared with a 5% random sample of cancer-free controls (n = 332,107) residing in the Surveillance, Epidemiology, and End Results areas. Adjusted odds ratios (ORs) and PAFs were calculated for HCV, hepatitis B virus (HBV), metabolic disorders, alcohol-related disorders, smoking, and genetic disorders. RESULTS: Overall, the PAF was greatest for metabolic disorders (32%), followed by HCV (20.5%), alcohol (13.4%), smoking (9%), HBV (4.3%), and genetic disorders (1.5%). The PAF for all factors combined was 59.5%. PAFs…

BACKGROUND: Therapeutic antibodies against programmed cell death receptor 1 (PD-1) are considered front-line therapy in metastatic melanoma. The efficacy of PD-1 blockade for patients with biologically distinct melanomas arising from acral and mucosal surfaces has not been well described. METHODS: A multi-institutional, retrospective cohort analysis identified adults with advanced acral and mucosal melanoma who received treatment with nivolumab or pembrolizumab as standard clinical practice through expanded access programs or published prospective trials. Objective responses were determined using investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival and overall survival were assessed using the Kaplan-Meier method. RESULTS: Sixty individuals were identified, including 25 (42%) with acral melanoma and 35 (58%) with mucosal melanoma. Fifty-one patients (85%) had received previous therapy, including 77% who had previously received ipilimumab. Forty patients (67%) received pembrolizumab at a dose of 2 mg/kg or 10 mg/kg, and 20…

Cholangiocarcinomas are rare biliary tract tumors that are often challenging to diagnose and treat. Cholangiocarcinomas are generally categorized as intrahepatic or extrahepatic depending on their anatomic location. The majority of patients with cholangiocarcinoma do not have any of the known or suspected risk factors and present with advanced disease. The optimal evaluation and management of patients with cholangiocarcinoma requires thoughtful integration of clinical information, imaging studies, cytology and/or histology, as well as prompt multidisciplinary evaluation. The current review focuses on recent advances in the diagnosis and treatment of patients with cholangiocarcinoma and, in particular, on the role of endoscopy, surgery, transplantation, radiotherapy, systemic therapy, and liver-directed therapies in the curative or palliative treatment of these individuals. Cancer 2016;122:1349-1369. © 2016 American Cancer Society.

BACKGROUND: Patients with incurable cancer face many physical and emotional stressors, yet little is known about their coping strategies or the relationship between their coping strategies, quality of life (QOL), and mood. METHODS: As part of a randomized trial of palliative care, this study assessed baseline QOL (Functional Assessment of Cancer Therapy-General), mood (Hospital Anxiety and Depression Scale), and coping (Brief COPE) in patients within 8 weeks of a diagnosis of incurable lung or gastrointestinal cancer and before randomization. To examine associations between coping strategies, QOL, and mood, we used linear regression, adjusting for patients' age, sex, marital status, and cancer type. RESULTS: There were 350 participants (mean age, 64.9 years), and the majority were male (54.0%), were married (70.0%), and had lung cancer (54.6%). Most reported high utilization of emotional support coping (77.0%), whereas fewer reported high utilization of acceptance (44.8%), self-blame (37.9%), and denial (28.2%). Emotional support (QOL: β = 2.65, P < .01; depression: β = -0.56, P =…

BACKGROUND: The National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) is the universal framework for toxicity reporting in oncology trials. The objective of this study was to develop a CTCAE-compatible modified barium swallow (MBS) grade for the purpose of grading pharyngeal dysphagia as a toxicity endpoint in cooperative-group organ-preservation trials for head and neck cancer (HNC). It was hypothesized that a 5-point, CTCAE-compatible MBS grade (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST]) based on the interaction of pharyngeal residue and laryngeal penetration/aspiration ratings would be feasible and psychometrically sound. METHODS: A modified Delphi exercise was conducted for content validation, expert consensus, and operationalization of DIGEST criteria. Two blinded raters scored 100 MBSs conducted before or after surgical or nonsurgical organ preservation. Intrarater and interrater reliability was tested with weighted κ values. Criterion validity against oropharyngeal swallow efficiency (OPSE), the Modified Barium Swallow Impairment…

Hepatocellular carcinoma (HCC) is a heterogeneous disease that remains highly prevalent in many Asian countries and is the second most common cause of cancer-related mortality worldwide. Significant differences exist between Eastern and Western populations on many key aspects of HCC, contributing to the potential different treatment outcomes and challenges of clinical trial design and data interpretation. In this review, the authors compare HCC in Asia versus the West and highlight 1) differences in terms of epidemiology and trends and their correlation with etiology, 2) differences in genetics and how they relate to underlying etiology, 3) differences in treatment approaches based on existing guidelines and consensus statements, and 4) differences in clinical outcomes for Asian versus non-Asian patients with HCC in clinical trials and the implications for future clinical trial design. Cancer 2016;122:3430-3446. © 2016 American Cancer Society.

BACKGROUND: Mutations in the tumor protein 53 (TP53) gene predict a poor prognosis in patients with acute myeloid leukemia (AML). METHODS: Peripheral blood or bone marrow samples from 293 patients with newly diagnosed AML were analyzed with targeted, amplicon-based, next-generation sequencing-based mutation analysis. RESULTS: TP53 mutations were identified in 53 patients (18%; 45 were missense mutations). In 13 of the 53 patients, the most common pattern of amino acid substitution was a substitution of arginine to histidine on different codons. The clinical characteristics, pattern of mutations, response to different therapies, and outcomes of patients with AML-TP53-mutated (n = 53) versus wild-type TP53 (n = 240) were compared. TP53 mutations were significantly more likely in patients who had a complex karyotype; abnormalities of chromosome 5, 7, and 17; and therapy-related AML. Patients who had TP53-mutated AML had significantly lower incidence of mutations in Fms-like tyrosine kinase 3 (FLT3), rat sarcoma (RAS), and nucleophosmin (NPM1) and higher incidence of coexisting MPL…

BACKGROUND: Two large-scale prostate cancer screening trials using prostate-specific antigen (PSA) have given conflicting results in terms of the efficacy of such screening. One of those trials, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, previously reported outcomes with 13 years of follow-up. This study presents updated findings from the PLCO trial. METHODS: The PLCO trial randomized subjects from 1993 to 2001 to an intervention or control arm. Intervention-arm men received annual PSA tests for 6 years and digital rectal examinations for 4 years. This study used a linkage with the National Death Index to extend mortality follow-up to a maximum of 19 years after randomization. RESULTS: Men were randomized to the intervention arm (n = 38,340) or the control arm (n = 38,343). The median follow-up time was 14.8 years (25th/75th, 12.7/16.5 years) in the intervention arm and 14.7 years (25th/75th, 12.6/16.4 years) in the control arm. There were 255 deaths from prostate cancer in the intervention arm and 244 deaths from prostate cancer in the control arm;…

BACKGROUND: Although colorectal cancer (CRC) screening guidelines recommend initiating screening at age 50 years, the percentage of cancer cases in younger patients is increasing. To the authors' knowledge, the national treatment patterns and outcomes of these patients are largely unknown. METHODS: The current study was a population-based, retrospective cohort study of the nationally representative Surveillance, Epidemiology, and End Results registry for patients diagnosed with CRC from 1998 through 2011. Patients were categorized as being younger or older than the recommended screening age. Differences with regard to stage of disease at diagnosis, patterns of therapy, and disease-specific survival were compared between age groups using multinomial regression, multiple regression, Cox proportional hazards regression, and Weibull survival analysis. RESULTS: Of 258,024 patients with CRC, 37,847 (15%) were aged <50 years. Young patients were more likely to present with regional (relative risk ratio, 1.3; P<.001) or distant (relative risk ratio, 1.5; P<.001) disease. Patients with CRC…

Each year, 70,000 adolescents and young adults (AYAs) between ages 15 and 39 years in the United States are diagnosed with cancer. In 2006, a National Cancer Institute (NCI) Progress Review Group (PRG) examined the state of science associated with cancer among AYAs. To assess the impact of the PRG and examine the current state of AYA oncology research, the NCI, with support from the LIVESTRONG Foundation, sponsored a workshop entitled "Next Steps in Adolescent and Young Adult Oncology" on September 16 and 17, 2013, in Bethesda, Maryland. This report summarizes the findings from the workshop, opportunities to leverage existing data, and suggestions for future research priorities. Multidisciplinary teams that include basic scientists, epidemiologists, trialists, biostatisticians, clinicians, behavioral scientists, and health services researchers will be essential for future advances for AYAs with cancer.

BACKGROUND: In 2014, a national campaign was launched to increase colorectal cancer (CRC) screening rates in the United States to 80% by 2018; it is unknown whether there is sufficient colonoscopy capacity to reach this goal. This study estimated the number of colonoscopies needed to screen 80% of the eligible population with fecal immunochemical testing (FIT) or colonoscopy and determined whether there was sufficient colonoscopy capacity to meet the need. METHODS: The Microsimulation Screening Analysis-Colon model was used to simulate CRC screening test use in the United States (2014-2040); the implementation of a national screening program in 2014 with FIT or colonoscopy with 80% participation was assumed. The 2012 Survey of Endoscopic Capacity (SECAP) estimated the number of colonoscopies that were performed and the number that could be performed. RESULTS: If a national screening program started in 2014, by 2024, approximately 47 million FIT procedures and 5.1 million colonoscopies would be needed annually to screen the eligible population with a program using FIT as the primary…

BACKGROUND: Economic analyses of new technologies, such as proton-beam radiotherapy (PBT), are a public health priority. To date, no systematic review of the cost-effectiveness of PBT has been performed. METHODS: Systematic searches of PubMed, EMBASE, abstracts from American Society for Radiation Oncology and American Society of Clinical Oncology meetings, and the Cost-Effectiveness Analysis Registry were conducted (2000-2015) along with abstracts from the Particle Therapy Co-Operative Group of North America for both years of existence (2014-2015). Eighteen original investigations were analyzed. RESULTS: The cost-effectiveness for prostate cancer-the single most common diagnosis currently treated with PBT-was suboptimal. PBT was the most cost-effective option for several pediatric brain tumors. PBT costs for breast cancer were increased but were favorable for appropriately selected patients with left-sided cancers at high risk of cardiac toxicity and compared with brachytherapy for accelerated partial breast irradiation. For non-small cell lung cancer (NSCLC), the greatest…

BACKGROUND: An increase in thyroid cancers, predominantly papillary thyroid carcinoma (PTC), has been recently reported in children. METHODS: The histopathology of 28 consecutive PTCs from the northeast United States was reviewed. None of the patients (ages 6-18 years; 20 females, 8 males) had significant exposure to radiation. Nucleic acid from tumors was tested for genetic abnormalities (n = 27). Negative results were reevaluated by targeted next-generation sequencing. RESULTS: Seven of 27 PTCs (26%) had neurotrophic tyrosine kinase receptor (NTRK) fusion oncogenes (NTRK type 3/ets variant 6 [NTRK3/ETV6], n =5; NTRK3/unknown, n = 1; and NTRK type 1/translocated promoter region, nuclear basket protein [NTRK1/TPR], n = 1), including 5 tumors that measured >2 cm and 3 that diffusely involved the entire thyroid or lobe. All 7 tumors had lymphatic invasion, and 5 had vascular invasion. Six of 27 PTCs (22%) had ret proto-oncogene (RET) fusions (RET/PTC1, n = 5; RET/PTC3, n = 1); 2 tumors measured >2 cm and diffusely involved the thyroid, and 5 had lymphatic invasion, with vascular…

BACKGROUND: Growing evidence suggests that immunotherapy and radiation therapy can be synergistic in the treatment of cancer. This study was performed to determine the effect of the relative timing and type of immune checkpoint therapy on the response of melanoma brain metastases (BrMets) to treatment with stereotactic radiosurgery (SRS). METHODS: Seventy-five melanoma patients with 566 BrMets were treated with both SRS and immune checkpoint therapy between 2007 and 2015 at a single institution. Immunotherapy and radiosurgery treatment of any single lesion were considered concurrent if SRS was administered within 4 weeks of immunotherapy. The impact of the timing and type of immunotherapy on the lesional response was determined with the Wilcoxon rank-sum test, which was used to compare the median percent lesion volume change 1.5, 3, and 6 months after SRS treatment, with significance determined by P = .0167 according to the Bonferroni correction for multiple comparisons. RESULTS: Concurrent use of immunotherapy and SRS resulted in a significantly greater median percent reduction in…

BACKGROUND: NUT midline carcinoma is a rare and aggressive genetically characterized subtype of squamous cell carcinoma frequently arising from the head and neck. The characteristics and optimal management of head and neck NUT midline carcinoma (HNNMC) are unclear. METHODS: A retrospective review of all known cases of HNNMC in the International NUT Midline Carcinoma Registry as of December 31, 2014, was performed. Forty-eight consecutive patients were treated from 1993 to 2014, and clinicopathologic variables and outcomes for 40 patients were available for analyses; they composed the largest HNNMC cohort studied to date. Overall survival (OS) and progression-free survival (PFS) according to patient characteristics and treatment were analyzed. RESULTS: This study identified a 5-fold increase in the diagnosis of HNNMC from 2011 to 2014. The median age was 21.9 years (range, 0.1-81.7 years); the male and female proportions were 40% and 60%, respectively; and 86% had bromodomain containing 4-nuclear protein in testis (BRD4-NUT) fusion. The initial treatment was initial surgery with or…

BACKGROUND: The clinical efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) plus ponatinib has not been compared with that of HCVAD plus dasatinib in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in a randomized clinical trial. METHODS: The authors analyzed 110 patients with newly diagnosed Ph+ ALL who were enrolled in 2 consecutive, prospective, phase 2 clinical trials of frontline HCVAD with either dasatinib (63 patients) or ponatinib (47 patients). Propensity score analysis with 1:1 matching with the nearest neighbor matching method and inverse probability of treatment weighting (IPTW) analysis based on the propensity scores were performed to assess response rates, event-free survival (EFS), and overall survival (OS) between the cohorts. RESULTS: Propensity score matching identified 41 patients in each cohort. With propensity score matching, the 3-year EFS rates for patients treated with HCVAD plus ponatinib and HCVAD plus dasatinib were 69% and 46%, respectively (P =.04), and the 3-year OS…

Ototoxicity is a well-established toxicity associated with a subgroup of antineoplastic therapies that includes platinum chemotherapy, radiation or surgery involving the ear and auditory nerve, and supportive care agents such as aminoglycoside antibiotics and loop diuretics. The reported prevalence of ototoxicity in patients who have received potentially ototoxic therapy ranges from 4% to 90% depending on factors such as age of the patient population, agent(s) used, cumulative dose, and administration techniques. The impact of ototoxicity on subsequent health-related and psychosocial outcomes in these patients can be substantial, and the burden of morbidity related to ototoxic agents is particularly high in very young children. Considerable interindividual variability in the prevalence and severity of ototoxicity has been observed among patients receiving similar treatment, suggesting genetic susceptibility as a risk factor. The development and testing of otoprotective agents is ongoing; however, to the author's knowledge, no US Food and Drug Administration-approved otoprotectants…

BACKGROUND: Curative treatment options for patients with early stage hepatocellular carcinoma (HCC) include resection, liver transplantation, and percutaneous ablation therapy. However, even patients with solitary HCC are not always amenable to these treatments. The authors prospectively investigated the clinical outcomes of patients who received stereotactic body radiotherapy (SBRT) for solitary HCC. METHODS: A phase 2 study involving SBRT and optional transarterial chemoembolization (TACE) was conducted in patients with Child-Pugh grade A or B and underlying, solitary HCC (greatest tumor dimension, ≤4 cm) who were unsuitable candidates for resection and radiofrequency ablation. The prescription dose was 35 to 40 grays in 5 fractions. The primary endpoint was 3-year local tumor control. RESULTS: From 2007 to 2012, 101 patients were enrolled, and 90 were evaluable with a median follow-up of 41.7 months (range, 6.8-96.2 months). Thirty-two patients were treatment-naïve, 20 were treated for newly diagnosed intrahepatic failure, and 38 were treated for residual or recurrent HCC as…

BACKGROUND: Frailty has been suggested as a construct for oncologists to consider in treating older cancer patients. Therefore, the authors assessed the potential of creating a deficit-accumulation frailty index (DAFI) from a largely self-administered comprehensive geriatric assessment (CGA). METHODS: Five hundred patients aged ≥65 years underwent a CGA before receiving chemotherapy. A DAFI was constructed, resulting in a 51-item scale, and cutoff values were examined for patients in the robust/nonfrail (cutoff value, 0.0 < 0.2), prefrail (cutoff value, 0.2 < 0.35), and frail (cutoff value, ≥ 0.35) groups. RESULTS: Two hundred and fifty patients (50%) were nonfrail, 197 (39%) were prefrail, and 52 (11%) were frail. Older patients (aged ≥ 80 years) and those who had lower education, were living alone, and had higher stage disease were associated with prefrail/frail status. Prefrail/frail patients were more likely to have grade ≥3 toxicity but not to have a dose delay or reduction, and they were more likely to discontinue drug and be hospitalized. The association with grade ≥3…

Soft tissue sarcoma is a term used to describe a heterogeneous group of many rare tumors. Since the initial description of activity of doxorubicin, several additional agents have been brought to bear in the treatment of these diseases. Despite 2 recent drug approvals, doxorubicin and ifosfamide remain the most effective chemotherapy drugs available for the treatment of majority of these tumors. Optimal dosing and administration influence outcomes because of the steep dose-response curves associated with these agents. The debate endures regarding whether patients who have advanced disease should routinely receive single agents sequentially or in combination. Adjuvant therapy remains similarly controversial, although meta-analyses do support its use. Contemporary treatment of soft tissue sarcoma routinely incorporates additional lines of treatment that have become available over the last 15 years. Fixed-dose-rate gemcitabine with or without docetaxel is a standard second-line treatment. In keeping with the paradigm shift favoring subset-specific therapy, several recent approvals are…

BACKGROUND: Recent reports suggest that mutations in the promoter of the gene encoding telomerase reverse transcriptase (TERT) affect thyroid cancer outcomes. METHODS: In all, 551 patients with differentiated thyroid cancer (DTC) enrolled in this study. The median follow-up duration was 4.8 years (interquartile range, 3.4-10.6 years). RESULTS: TERT promoter mutations were detected in 25 DTCs (4.5%): 2.8% in neither BRAF-mutated nor RAS-mutated tumors, 4.8% in BRAF-mutated tumors, and 11.3% in RAS-mutated tumors. Moreover, they were frequently observed in American Thyroid Association (ATA) high-risk and TNM stage III/IV groups (9.1% and 12.9%, respectively). The coexistence of BRAF or RAS with TERT promoter mutations increased aggressive clinicopathologic features, recurrence (hazard ratio [HR] for BRAF, 4.64; 95% confidence interval [CI], 1.42-15.18; HR for RAS, 5.36; 95% CI, 1.20-24.02), and mortality (HR for BRAF, 15.13; 95% CI, 1.55-148.23; HR for RAS, 14.75; 95% CI, 1.30-167.00), even after adjustments for the age at diagnosis and sex, although the significance was lost after…

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of >40%. Of the 2000 MCC cases per year in the United States, most are caused by the Merkel cell polyomavirus (MCPyV). Antibodies to MCPyV oncoprotein (T-antigens) have been correlated with MCC tumor burden. The present study assesses the clinical utility of MCPyV-oncoprotein antibody titers for MCC prognostication and surveillance. METHODS: MCPyV-oncoprotein antibody detection was optimized in a clinical laboratory. A cohort of 219 patients with newly diagnosed MCC were followed prospectively (median follow-up, 1.9 years). Among the seropositive patients, antibody titer and disease status were serially tracked. RESULTS: Antibodies to MCPyV oncoproteins were rare among healthy individuals (1%) but were present in most patients with MCC (114 of 219 patients [52%]; P < .01). Seropositivity at diagnosis independently predicted decreased recurrence risk (hazard ratio, 0.58; P = .04) in multivariate analyses adjusted for age, sex, stage, and immunosuppression. After initial treatment, seropositive…

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a standard of care for patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). The introduction of tyrosine kinase inhibitors (TKIs) to first-line therapy has improved overall outcomes; however, a significant proportion of patients still relapse after alloHSCT. Posttransplant TKI maintenance was demonstrated to reduce the risk of relapse in a large retrospective study and, therefore, should be considered a valuable option. This consensus paper, written on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, presents an overview of clinical studies on the use of TKIs after alloHSCT and proposes practical recommendations regarding the choice of TKI, treatment timing, and dosage. It is hoped that these recommendations will become the state of art in this field and, more importantly, lead to a reduction of Ph-positive ALL relapse after alloHSCT. Cancer 2016;122:2941-2951. © 2016 American Cancer Society.

BACKGROUND: Despite increasing data on the impact of the microbiome on cancer, the dynamics and role of the microbiome in infection during therapy for acute myelogenous leukemia (AML) are unknown. Therefore, the authors sought to determine correlations between microbiome composition and infectious outcomes in patients with AML who were receiving induction chemotherapy (IC). METHODS: Buccal and fecal specimens (478 samples) were collected twice weekly from 34 patients with AML who were undergoing IC. Oral and stool microbiomes were characterized by 16S ribosomal RNA V4 sequencing using an Illumina MiSeq system. Microbial diversity and genera composition were associated with clinical outcomes. RESULTS: Baseline stool α-diversity was significantly lower in patients who developed infections during IC compared with those who did not (P = .047). Significant decreases in both oral and stool microbial α-diversity were observed over the course of IC, with a linear correlation between α-diversity change at the 2 sites (P = .02). Loss of both oral and stool α-diversity was associated…

Persons with a family history (FH) of colorectal cancer (CRC) or adenomas that are not due to known hereditary syndromes have an increased risk for CRC. An understanding of these risks, screening recommendations, and screening behaviors can inform strategies for reducing the CRC burden in these families. A comprehensive review of the literature published within the past 10 years has been performed to assess what is known about cancer risk, screening guidelines, adherence and barriers to screening, and effective interventions in persons with an FH of CRC and to identify FH tools used to identify these individuals and inform care. Existing data show that having 1 affected first-degree relative (FDR) increases the CRC risk 2-fold, and the risk increases with multiple affected FDRs and a younger age at diagnosis. There is variability in screening recommendations across consensus guidelines. Screening adherence is <50% and is lower in persons under the age of 50 years. A provider's recommendation, multiple affected relatives, and family encouragement facilitate screening; insufficient…

Worldwide, the incidence of endometrial carcinoma (EC) is rapidly increasing, and the highest disease burden is reported in North America and Western Europe. Although the prognosis remains good for patients with are diagnosed with early stage EC, for those with recurrent or metastatic disease, the options are few, and the median overall survival is short. It is imperative to gain a greater understanding of all aspects of EC, limit its effect on scarce health care resources and, more importantly, prevent this cancer from significantly impacting future generations of women. An exciting new era of endometrial cancer research and clinical management has begun that incorporates biologically and clinically relevant genomic and clinicopathologic parameters. Continued collaborative research efforts and funding are essential if we are to advance our understanding of this disease and improve clinical outcomes. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2787-2798. © 2016 American Cancer Society.

BACKGROUND: The objective of this study was to develop a nomogram for refining prognostication for patients with nondisseminated nasopharyngeal cancer (NPC) staged with the proposed 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system. METHODS: Consecutive patients who had been investigated with magnetic resonance imaging, staged with the proposed 8th edition of the AJCC/UICC staging system, and irradiated with intensity-modulated radiotherapy from June 2005 to December 2010 were analyzed. A cohort of 1197 patients treated at Fujian Provincial Cancer Hospital was used as the training set, and the results were validated with 412 patients from Pamela Youde Nethersole Eastern Hospital. Cox regression analyses were performed to identify significant prognostic factors for developing a nomogram to predict overall survival (OS). The discriminative ability was assessed with the concordance index (c-index). A recursive partitioning algorithm was applied to the survival scores of the combined set to categorize the patients…

BACKGROUND: The determinants of outcomes for adult survivors of pediatric low-grade glioma (PLGG) are largely unknown. METHODS: This study collected population-based follow-up information for all PLGG patients diagnosed in Ontario, Canada from 1985 to 2012 (n = 1202) and determined factors affecting survival. The impact of upfront radiation treatment on overall survival (OS) was determined for a cohort of Ontario patients and an independent reference cohort from the Surveillance, Epidemiology, and End Results database. RESULTS: At a median follow-up of 12.73 years (range, 0.02-33 years), only 93 deaths (7.7%) were recorded, and the 20-year OS rate was 90.1% ± 1.1%. Children with neurofibromatosis type 1 had excellent survival and no tumor-related deaths during adulthood. Adverse risk factors included pleomorphic xanthoastrocytoma (P < .001) and a thalamic location (P < .001). For patients with unresectable tumors surviving more than 5 years after the diagnosis, upfront radiotherapy was associated with an approximately 3-fold increased risk of overall late deaths (hazard ratio [HR],…

Black women have a higher incidence of breast cancer before the age of 40 years, more severe disease at all ages, and an elevated mortality risk in comparison with white women. There is limited understanding of the contribution of social factors to these patterns. Elucidating the role of the social determinants of health in breast cancer disparities requires greater attention to how risk factors for breast cancer unfold over the lifecourse and to the complex ways in which socioeconomic status and racism shape exposure to psychosocial, physical, chemical, and other individual and community-level assaults that increase the risk of breast cancer. Research that takes seriously the social context in which black women live is also needed to maximize the opportunities to prevent breast cancer in this underserved group. Cancer 2016;122:2138-49. © 2016 American Cancer Society.

BACKGROUND: There has been increasing interest in the primary surgical treatment of patients with early T classification (T1-T2) oropharyngeal squamous cell carcinoma (OPSCC), with the stated goal of de-escalating or avoiding adjuvant treatment. Herein, the authors sought to determine the degree to which this interest has translated into changes in practice patterns, and the rates of adverse postoperative pathologic features. METHODS: Patients with T1 to T2 OPSCC in the National Cancer Data Base who were treated from 2004 through 2013 were categorized as receiving primary surgical or primary radiation-based treatment. Trends in treatment selection and factors related to the selection of primary surgery were examined. The rates of adverse pathologic features including positive surgical margins, extracapsular spread (ECS), and advanced T and N classifications after surgery were analyzed. RESULTS: Of 8768 patients with T1 to T2 OPSCC, 68% underwent primary surgical treatment, increasing from 56% in 2004 to 82% in 2013 (P<.0001). The highest versus lowest volume hospitals treated 78%…

BACKGROUND: Many young adult female cancer survivors (YAFCS) are at risk of experiencing premature menopause. The current study characterized the posttreatment fertility information needs, reproductive concerns, and decisional conflict regarding future options for posttreatment fertility preservation (FP) among YAFCS. METHODS: Participants completed a Web-based, anonymous survey between February and March 2015. The survey included investigator-designed questions of perceived information needs, the Reproductive Concerns After Cancer Scale, and the Decisional Conflict Scale. Analyses included Pearson correlation coefficients, independent-sample Student t tests, and multiple regression. RESULTS: There was a total of 346 participants with an average age of 29.9 years (SD = 4.1 years) who were 4.9 years from treatment (SD = 5.4 years [range, 0-27 years]). The main analyses focused on a subgroup of YAFCS with uncertain fertility status who had not previously undergone/attempted FP and either wanted future children or were unsure (179 women). Across fertility information topics, 43% to 62%…

Gastrointestinal stromal tumors (GISTs) are considered to be potentially malignant mesenchymal tumors of the gastrointestinal tract. Clinically relevant GISTs are rare; however, subclinical GISTs (mini-GISTs) (1-2 cm) and pathologic GISTs (micro-GISTs) (<1 cm) are frequently reported. Most mini-GISTs and almost all micro-GISTs of the stomach may exhibit benign clinical behavior, and only mini-GISTs with high-risk features may progress. For this review, a provisional algorithm was used to propose diagnostic and treatment strategies for patients with small GISTs. Because surgery is the only potentially curative treatment, in its application for small GISTs, the principles of sarcoma surgery should be maintained, and cost effectiveness should be considered. Indications for surgery include GISTs measuring ≥2 cm, symptomatic GISTs, and mini-GISTs with high-risk features (irregular borders, cystic spaces, ulceration, echogenic foci, internal heterogeneity, and tumor progression during follow-up); however, a preoperative pathologic diagnosis is infrequently obtained. For small intestinal…

BACKGROUND: Race-based survival in children and adolescents with hematologic malignancies has been a national challenge for decades. Large-scale investigations of age- and race-based survival trends over time in these patients have not previously been reported. The objective of this study was to investigate whether race- and age-related differences in pediatric and adolescent and young adult (AYA) leukemia and lymphoma survival persist and to what extent these differences have changed over time. METHODS: Using the Surveillance, Epidemiology, and End Results program, this study investigated the outcomes of black and white (1975-2012; n = 27,369) and white and Hispanic (1992-2012; n = 20,574) children (0-14 years old) and AYAs (15-39 years old) with acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and Hodgkin lymphoma (HL). Estimates of 5- and 10-year relative survival were compared over time. RESULTS: Trends showed a convergence of survival for white and black children with ALL but a divergence in survival for AYA patients. Hispanic children and AYAs both…

To evaluate histologic subtype and grade, which in turn guide the decision making for multimodality therapy, the workup of suspected sarcoma requires more material than can be obtained from a fine-needle aspiration. Either open or percutaneous core needle biopsy is indicated before a management decision is made. Percutaneous biopsy of a potentially malignant lesion is controversial, given the perceived potential for tumor seeding along the needle tract. However, the evidence that the latter is a significant risk is weak at best. To the authors' knowledge, among cases of patients with extremity sarcoma who have undergone core needle biopsy, only a few cases of needle tract seeding have been reported to date. Although en bloc excision of the needle tract with the primary tumor is often performed, this practice is not associated with improved oncologic outcomes; the evidence for excision of the needle tract is poor. For patients with gastrointestinal stromal tumors, there is a theoretical risk of peritoneal dissemination after percutaneous biopsy, but to the authors' knowledge this…

BACKGROUND: The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. To further investigate this relationship, the objective of the current study was to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological risk features. METHODS: Data from the National Cancer Data Base were analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer who were diagnosed from 1998 to 2006 with survival information through 2011. Pearson Chi-square tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was used to match cohorts.…