The 50 most-cited articles in Cancer, 2018

BACKGROUND: The American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate to provide annual updates on cancer occurrence and trends in the United States. METHODS: Data on new cancer diagnoses during 2001 through 2016 were obtained from the Centers for Disease Control and Prevention-funded and National Cancer Institute-funded population-based cancer registry programs and compiled by the North American Association of Central Cancer Registries. Data on cancer deaths during 2001 through 2017 were obtained from the National Center for Health Statistics' National Vital Statistics System. Trends in incidence and death rates for all cancers combined and for the leading cancer types by sex, racial/ethnic group, and age were estimated by joinpoint analysis and characterized by the average annual percent change during the most recent 5 years (2012-2016 for incidence and 2013-2017 for mortality). RESULTS: Overall, cancer incidence rates decreased 0.6% on average per year…

Autophagy is a conserved, self-degradation system that is critical for maintaining cellular homeostasis during stress conditions. Dysregulated autophagy has implications in health and disease. Specifically, in cancer, autophagy plays a dichotomous role by inhibiting tumor initiation but supporting tumor progression. Early results from clinical trials that repurposed hydroxychloroquine for cancer have suggested that autophagy inhibition may be a promising approach for advanced cancers. In this review of the literature, the authors present fundamental advances in the biology of autophagy, approaches to targeting autophagy, the preclinical rationale and clinical experience with hydroxychloroquine in cancer clinical trials, the potential role of autophagy in tumor immunity, and recent developments in next-generation autophagy inhibitors that have clinical potential. Autophagy is a promising target for drug development in cancer. Cancer 2018. © 2018 American Cancer Society.

BACKGROUND: It remains unclear whether high doses of glucocorticoids have a negative impact on the efficacy of checkpoint inhibitors. To control for the potential association between immune-related adverse events (irAEs) and improved survival, this study examined a unique cohort of patients who had the same irAE treated with varying glucocorticoid doses. METHODS: In total, 98 patients with melanoma who had ipilimumab-induced hypophysitis were identified retrospectively in the Partners Healthcare system using an automated electronic medical record query tool. Patients with melanoma who received ipilimumab at Massachusetts General Hospital without developing hypophysitis were listed in an actively maintained institutional patient database. Glucocorticoid doses for patients with hypophysitis were categorized as low dose (LD) or high dose (HD). Survival analyses were performed for patients who received ipilimumab monotherapy. RESULTS: Both overall survival (OS) and the time to treatment failure were significantly longer in the LD group compared with the HD group (hazard ratio, 0.24; P =…

BACKGROUND: Molecular tests have clinical utility for thyroid nodules with indeterminate fine-needle aspiration (FNA) cytology, although their performance requires further improvement. This study evaluated the analytical performance of the newly created ThyroSeq v3 test. METHODS: ThyroSeq v3 is a DNA- and RNA-based next-generation sequencing assay that analyzes 112 genes for a variety of genetic alterations, including point mutations, insertions/deletions, gene fusions, copy number alterations, and abnormal gene expression, and it uses a genomic classifier (GC) to separate malignant lesions from benign lesions. It was validated in 238 tissue samples and 175 FNA samples with known surgical follow-up. Analytical performance studies were conducted. RESULTS: In the training tissue set of samples, ThyroSeq GC detected more than 100 genetic alterations, including BRAF, RAS, TERT, and DICER1 mutations, NTRK1/3, BRAF, and RET fusions, 22q loss, and gene expression alterations. GC cutoffs were established to distinguish cancer from benign nodules with 93.9% sensitivity, 89.4% specificity,…

BACKGROUND: Patients with advanced cancer have high rates of psychological distress, including depression, anxiety, and spiritual despair. This study examined the effectiveness of individual meaning-centered psychotherapy (IMCP) in comparison with supportive psychotherapy (SP) and enhanced usual care (EUC) in improving spiritual well-being and quality of life and reducing psychological distress in patients with advanced cancer. METHODS: Patients (n = 321) were randomly assigned to IMCP (n = 109), SP (n = 108), or EUC (n = 104). Assessments were conducted at 4 time points: before intervention, midtreatment (4 weeks), 8 weeks after treatment, and 16 weeks after treatment. RESULTS: Significant treatment effects (small to medium in magnitude) were observed for IMCP, in comparison with EUC, for 5 of 7 outcome variables (quality of life, sense of meaning, spiritual well-being, anxiety, and desire for hastened death), with Cohen's d ranging from 0.1 to 0.34; no significant improvement was observed for patients receiving SP (d < 0.15 and P > .05 for all variables). The effect of IMCP was…

BACKGROUND: Phenotypic characterization of immune cells in the bone marrow (BM) of patients with acute myeloid leukemia (AML) is lacking. METHODS: T-cell infiltration was quantified on BM biopsies from 13 patients with AML, and flow cytometry was performed on BM aspirates (BMAs) from 107 patients with AML who received treatment at The University of Texas MD Anderson Cancer Center. The authors evaluated the expression of inhibitory receptors (programmed cell death protein 1 [PD1], cytotoxic T-lymphocyte antigen 4 [CTLA4], lymphocyte-activation gene 3 [LAG3], T-cell immunoglobulin and mucin-domain containing-3 [TIM3]) and stimulatory receptors (glucocorticoid-induced tumor necrosis factor receptor-related protein [GITR], OX40, 41BB [a type 2 transmembrane glycoprotein receptor], inducible T-cell costimulatory [ICOS]) on T-cell subsets and the expression of their ligands (41BBL, B7-1, B7-2, ICOSL, PD-L1, PD-L2, and OX40L) on AML blasts. Expression of these markers was correlated with patient age, karyotype, baseline next-generation sequencing for 28 myeloid-associated genes (including…

BACKGROUND: Cancer survivors face psychosocial issues that increase their risk of suicide. This study examined the risk of suicide across cancer sites, with a focus on survivors of head and neck cancer (HNC). METHODS: The Surveillance, Epidemiology, and End Results 18-registry database (from 2000 to 2014) was queried for the top 20 cancer sites in the database, including HNC. The outcome of interest was suicide as a cause of death. The mortality rate from suicide was estimated for HNC sites and was compared with rates for 19 other cancer sites that were included in the study. Poisson regression was used to estimate adjusted rate ratios (aRRs) and 95% confidence intervals (CIs) for 1) HNC versus non-HNC sites (the other 19 cancer sites combined), and 2) HNC versus each individual cancer site. Models were stratified by sex, controlling for race, marital status, age, year, and stage at diagnosis. RESULTS: There were 404 suicides among 151,167 HNC survivors from 2000 to 2014, yielding a suicide rate of 63.4 suicides per 100,000 person-years. In this timeframe, there were 4493 suicides…

BACKGROUND: Women and their health care providers need a reliable answer to this important question: If a woman chooses to participate in regular mammography screening, then how much will this choice improve her chances of avoiding a death from breast cancer compared with women who choose not to participate? METHODS: To answer this question, we used comprehensive registries for population, screening history, breast cancer incidence, and disease-specific death data in a defined population in Dalarna County, Sweden. The annual incidence of breast cancer was calculated along with the annual incidence of breast cancers that were fatal within 10 and within 11 to 20 years of diagnosis among women aged 40 to 69 years who either did or did not participate in mammography screening during a 39-year period (1977-2015). For an additional comparison, corresponding data are presented from 19 years of the prescreening period (1958-1976). All patients received stage-specific therapy according to the latest national guidelines, irrespective of the mode of detection. RESULTS: The benefit for women…

BACKGROUND: Temporal trends in prostate cancer incidence and death rates have been attributed to changing patterns of screening and improved treatment (mortality only), among other factors. This study evaluated contemporary national-level trends and their relations with prostate-specific antigen (PSA) testing prevalence and explored trends in incidence according to disease characteristics with stage-specific, delay-adjusted rates. METHODS: Joinpoint regression was used to examine changes in delay-adjusted prostate cancer incidence rates from population-based US cancer registries from 2000 to 2014 by age categories, race, and disease characteristics, including stage, PSA, Gleason score, and clinical extension. In addition, the analysis included trends for prostate cancer mortality between 1975 and 2015 by race and the estimation of PSA testing prevalence between 1987 and 2005. The annual percent change was calculated for periods defined by significant trend change points. RESULTS: For all age groups, overall prostate cancer incidence rates declined approximately 6.5% per year from…

Although cancer often is referred to as "a disease of the genes," it is indisputable that the (epi)genetic properties of individual cancer cells are highly variable, even within the same tumor. Hence, preexisting resistant clones will emerge and proliferate after therapeutic selection that targets sensitive clones. Herein, the authors propose that quantitative image analytics, known as "radiomics," can be used to quantify and characterize this heterogeneity. Virtually every patient with cancer is imaged radiologically. Radiomics is predicated on the beliefs that these images reflect underlying pathophysiologies, and that they can be converted into mineable data for improved diagnosis, prognosis, prediction, and therapy monitoring. In the last decade, the radiomics of cancer has grown from a few laboratories to a worldwide enterprise. During this growth, radiomics has established a convention, wherein a large set of annotated image features (1-2000 features) are extracted from segmented regions of interest and used to build classifier models to separate individual patients into their…

Advances in cancer immunotherapy and a growing body of research have focused on the role of the antitumor response in breast cancer. Triple-negative breast cancer (TNBC) is the most immunogenic breast cancer subtype, and there is strong evidence that tumor-infiltrating lymphocytes in TNBC have prognostic value and are associated with clinical outcome and improved survival. Evading antitumor immunity is a hallmark for the development and progression of cancer. Immunotherapy studies have focused on the role of the programmed cell death-1 (PD-1) receptor/programmed death-ligand 1 (PD-L1) pathway in maintaining immunosuppression in the tumor microenvironment. Blockade of the PD-1/PD-L1 axis has emerged as a promising therapeutic option to enhance antitumor immunity and is actively being investigated in TNBC, with encouraging results. In this article, the authors review the current literature on checkpoint inhibitors in TNBC with a focus on PD-1/PD-L1 antibodies and discuss combination strategies and novel approaches for improving antitumor immunity and clinical outcome. Cancer…

BACKGROUND: The prognosis of patients who have Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) in which the tumor tissues harbor EBV have a better prognosis than those without EBV-related NPC. Therefore, the eighth edition of the TNM staging system could be modified for EBV-related NPC by incorporating the measurement of plasma EBV DNA. METHODS: In total, 979 patients with NPC who received intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Recursive partitioning analysis was conducted based on tumor (T) classification, lymph node (N) classification, and EBV DNA measurement to derive objectively the proposed stage groupings. The validity of the proposed stage groupings was confirmed in a prospective cohort of 550 consecutive patients who also received with IMRT. RESULTS: The pretreatment plasma EBV DNA level was identified as a significant, negative prognostic factor for progression-free survival and overall survival in univariate analysis (all P < .001) and multivariate analysis (all P < .05). Recursive partitioning analysis of the primary cohort…

BACKGROUND: Adolescents and young adults (AYAs) with cancer are at risk for poor psychosocial outcomes. This study aimed to determine whether a novel intervention targeting resilience resources would improve patient-reported resilience, quality of life, and psychological distress. METHODS: In this parallel, phase 2 randomized controlled trial, English-speaking AYAs (12-25 years old) with cancer were randomized to the Promoting Resilience in Stress Management (PRISM) intervention or usual care (UC). PRISM is a brief, skills-based intervention targeting stress management, goal setting, cognitive reframing, and meaning making. Participants completed surveys at enrollment and 6 months. Mixed effects regression models evaluated associations between PRISM and the primary outcome (10-item Connor-Davidson Resilience Scale scores) and secondary outcomes (generic and cancer-related quality of life [Pediatric Quality of Life modules], psychological distress [Kessler-6], and anxiety/depression [Hospital Anxiety and Depression]) at 6 months. RESULTS: Ninety-two AYAs were enrolled, were…

Emerging biologic subsets and new prognostic markers are significantly and adversely affecting curability after standard chemoimmunotherapy for aggressive B-cell lymphomas. The identification of concurrent MYC and B-cell CLL/lymphoma 2 (BCL2) deregulation, whether at a genomic or protein level, has opened a new era of investigation within the most common subtype of aggressive B-cell lymphomas. Double-hit lymphoma (DHL), defined as a dual rearrangement of MYC and BCL2 and/or B-cell CLL/lymphoma 6 (BCL6) genes, is an uncommon subset accounting for 5% to 7% of all diffuse large B-cell lymphomas (DLBCLs), and long-term survivors are rare. Double-expressor lymphoma (DEL), defined as overexpression of MYC and BCL2 proteins not related to underlying chromosomal rearrangements, is not a distinct entity in the current World Health Organization classification but accounts for 20% to 30% of DLBCL cases and also has poor outcomes. There are many practical considerations related to identifying, determining the prognosis of, and managing DHL and DEL.

BACKGROUND: In 2016, the Microsimulation Screening Analysis-Colon (MISCAN-Colon) model was used to inform the US Preventive Services Task Force colorectal cancer (CRC) screening guidelines. In this study, 1 of 2 microsimulation analyses to inform the update of the American Cancer Society CRC screening guideline, the authors re-evaluated the optimal screening strategies in light of the increase in CRC diagnosed in young adults. METHODS: The authors adjusted the MISCAN-Colon model to reflect the higher CRC incidence in young adults, who were assumed to carry forward escalated disease risk as they age. Life-years gained (LYG; benefit), the number of colonoscopies (COL; burden) and the ratios of incremental burden to benefit (efficiency ratio [ER] = ΔCOL/ΔLYG) were projected for different screening strategies. Strategies differed with respect to test modality, ages to start (40 years, 45 years, and 50 years) and ages to stop (75 years, 80 years, and 85 years) screening, and screening intervals (depending on screening modality). The authors then determined the model-recommended…

BACKGROUND: In contrast to lung cancer, few precision treatments are available for colorectal cancer (CRC). One rapidly emerging treatment target in CRC is ERBB2 (human epidermal growth factor receptor 2 [HER2]). Oncogenic alterations in HER2, or its dimerization partner HER3, can underlie sensitivity to HER2-targeted therapies. METHODS: In this study, 8887 CRC cases were evaluated by comprehensive genomic profiling for genomic alterations in 315 cancer-related genes, tumor mutational burden, and microsatellite instability. This cohort included both colonic (7599 cases; 85.5%) and rectal (1288 cases; 14.5%) adenocarcinomas. RESULTS: A total of 569 mCRCs were positive for ERBB2 (429 cases; 4.8%) and/or ERBB3 (148 cases; 1.7%) and featured ERBB amplification, short variant alterations, or a combination of the 2. High tumor mutational burden (≥20 mutations/Mb) was significantly more common in ERBB-mutated samples, and ERBB3-mutated CRCs were significantly more likely to have high microsatellite instability (P<.002). Alterations affecting KRAS (27.3%) were significantly underrepresented…

Background The objective of this study was to evaluate the effect of a probiotic combination on the severity of oral mucositis (OM), which is a common, unpreventable complication induced by radiochemotherapy in patients with nasopharyngeal carcinoma who undergo concurrent radiochemotherapy (CCRT). Methods Eligible patients (n = 99) with locally advanced nasopharyngeal carcinoma who were undergoing CCRT were randomly assigned (2:1) to receive a probiotic combination or placebo during radiochemotherapy, and the incidence of severe OM (grade 3 or higher) was the primary endpoint. Results Patients taking the probiotic combination showed a significant reduction in the severity of OM. The incidences of grade 0, 1, 2, and 3 OM in the placebo group and the probiotic combination group were 0% and 12.07%, 0% and 55.17%, 54.29% and 17.24%, and 45.71% and 15.52%, respectively. Furthermore, CCRT greatly lowered the number of immune cells, whereas the probiotic combination markedly lowered the reduction rates of CD4 + T cells (76.59% vs 52.85%; P < .05), CD8 + T cells (62.94% vs 29.76%; P < .05),…

Melanoma is one of the most highly mutated malignancies, largely as a function of its generation through ultraviolet light and other mutational processes. The wide array of mutations in both "driver" and "passenger" genes can present a confusing array of data for practitioners, particularly within the context of the recent revolutions in targeted and immune therapy. Although mutations in BRAF V600 clearly confer sensitivity to BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors, the clinical implications of most other mutations are less often discussed and understood. In this review, we provide an overview of the high-frequency genomic alterations and their prognostic and therapeutic relevance in melanoma.

BACKGROUND: The aims of this study were to prospectively assess symptoms of anxiety and depression among survivors of colorectal cancer (CRC), to compare these survivors with a normative population, and to identify subgroups at risk for experiencing symptoms of anxiety and/or depression across a 4-year time period. Also, the impact on health-related quality of life (HRQOL) was studied. METHODS: The population-based Eindhoven Cancer Registry was used to select patients diagnosed with CRC between 2000 and 2009. The Hospital Anxiety and Depression Scale and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (HRQOL) were completed by patients in 2010 (n = 2625 [73% response rate]), 2011, 2012, and 2013 and by an age- and sex-matched normative sample (n = 315) in 2011. RESULTS: Patients reported a significantly higher prevalence of depression (19.0% vs 12.8%) and anxiety (20.9% vs 11.8%) in comparison with the norm. Anxiety was stable, whereas depression scores changed over time, although this was not clinically relevant. A longer time…

BACKGROUND: Assessing trends in breast cancer survival among young women who are largely unaffected by breast cancer screening will provide important information regarding improvements in the effectiveness of cancer care for breast cancer in the last few decades. METHODS: The cohort for this study consisted of women who were diagnosed with breast cancer between ages 20 and 39 years from the Surveillance, Epidemiology, and End Results program's 9-registry areas from 1975 to 2015. Trends in the breast cancer incidence rate and survival were assessed among young women. RESULTS: Among women aged 20 to 39 years, breast cancer incidence increased from 24.6 per 100,000 in 1975 to 31.7 per 100,000 in 2015 (annual percent change, 0.5; 95% confidence interval [CI], 0.4-0.6). Among women with breast cancer, 5-year breast-cancer-specific survival increased significantly from 74.0% during 1975 to 1979 to 88.5% during 2010 to 2015 (hazard ratio for dying from breast cancer for 2010-2015 vs 1975-1979, 0.37; 95% CI, 0.32-0.41). The increase in cancer-specific survival reached a plateau in 2005;…

BACKGROUND: Incidence of graft-versus-host disease (GVHD) in haploidentical bone marrow (BM) transplants using posttransplantion cyclophosphamide (PT-Cy) is low, whereas GVHD using mobilized peripheral blood stem cells (PBSC) ranges between 30% and 40%. METHODS: To evaluate the effect of stem cell source in haploidentical transplantation with PT-Cy, we analyzed 451 patients transplanted for acute myeloid leukemia or acute lymphoblastic leukemia reported to the European Society for Blood and Marrow Transplantation. RESULTS: BM was used in 260 patients, and PBSC were used in 191 patients. The median follow-up was 21 months. Engraftment was lower in BM (92% vs 95%, P < 0.001). BM was associated with a lower incidence of stage II-IV and stage III-IV acute GVHD (21% vs 38%, P ≤ .01; and 4% vs 14%, P < .01, respectively). No difference in chronic GVHD, relapse, or nonrelapse mortality were found for PBSC or BM. The 2-year overall survival (OS) was 55% versus 56% (P = .57) and leukemia-free survival (LFS) was 49% versus 54% (P = .74) for BM and PBSC, respectively. On multivariate analysis,…

BACKGROUND: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is selective for both EGFR-TKI-sensitizing and T790M (threonine-to-methionine substitution at codon 790)-resistance mutations. The authors present long-term follow-up data from a preplanned, pooled analysis of phase 2 studies, the AZD9291 First Time in Patients Ascending Dose Study (AURA) extension trial (clincialtrials.gov identifier NCT01802632) and the AURA2 trial (NCT02094261). METHODS: Patients with centrally confirmed, T790M mutation-positive, advanced non-small cell lung cancer received osimertinib 80 mg once daily until disease progression or study discontinuation. Response was assessed by a blinded, independent, central review using Response Evaluation Criteria in Solid Tumors, version 1.1. The primary endpoint was the objective response rate. RESULTS: In total, 411 patients received osimertinib (second line, 129 patients; third line or later, 282 patients). At the data cutoff date of November 1, 2016, the median treatment exposure was 16.4 months…

BACKGROUND: Optimal prognostic and predictive biomarkers for patients with advanced-stage cancer patients who received immunotherapy (IO) are lacking. Inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), and the platelet-to-lymphocyte ratio (PLR), are readily available. The authors investigated the association between these markers and clinical outcomes of patients with advanced-stage cancer who received IO. METHODS: A retrospective review was conducted of 90 patients with advanced cancer who received treatment on phase 1 clinical trials of IO-based treatment regimens. NLR, MLR, and PLR values were log-transformed and treated as continuous variables for each patient. Overall survival (OS), progression-free survival (PFS), and clinical benefit were used to measure clinical outcomes. For univariate associations and multivariable analyses, Cox proportional-hazards models or logistic regression models were used. RESULTS: The median patient age was 63 years, and most were men (59%). The most common histologies were melanoma (33%)…

BACKGROUND The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing among older adults. It is unknown whether these trends can be explained by human papillomavirus (HPV) and whether HPV‐related tumors remain associated with an improved prognosis among older patients. METHODS In a retrospective study of OPSCCs diagnosed from 1995 to 2013 at 2 National Comprehensive Cancer Network–designated cancer centers, p16 immunohistochemistry and in situ hybridization (ISH) for HPV‐16, high‐risk DNA, and/or E6/E7 RNA were performed. The median age at diagnosis was compared by p16 and ISH tumor status. Trends in age were analyzed with nonparametric trends. Survival was analyzed with the Kaplan‐Meier method and Cox proportional hazards models. RESULTS Among 239 patients, 144 (60%) were p16‐positive. During 1998‐2013, the median age increased among p16‐positive patients (Ptrend = .01) but not among p16‐negative patients (Ptrend = .71). The median age of p16‐positive patients increased from 53 years (interquartile range [IQR] in 1995‐2000, 45‐65 years) to 58 years (IQR for…

Individuals with breast and ovarian cancer susceptibility gene 1 (BRCA1) or BRCA2 germline mutations have a significantly increased lifetime risk for breast and ovarian cancers. BRCA-mutant cancer cells have abnormal homologous recombination (HR) repair of DNA. In these tumors, the base excision repair (BER) pathway is important for cell survival. The poly(adenosine diphosphate-ribose) polymerase (PARP) enzymes play a key role in BER, and PARP inhibitors are effective in causing cell death in BRCA-mutant cells while sparing normal cells-a concept called synthetic lethality. PARP inhibitors are the first cancer therapeutics designed to exploit synthetic lethality. Recent clinical trials in BRCA-mutant, metastatic breast cancer demonstrated improved outcomes with single-agent PARP inhibitors (olaparib and talazoparib) over chemotherapy. However, resistance to PARP inhibitors remains a challenge. Primarily due to myelosuppression, the combination of PARP inhibitors with chemotherapy has been difficult. Novel combinations with chemotherapy, immunotherapy, and other targeted therapies…

BACKGROUND: For many childhood cancers, survival is lower among non-Hispanic blacks and Hispanics in comparison with non-Hispanic whites, and this may be attributed to underlying socioeconomic factors. However, prior childhood cancer survival studies have not formally tested for mediation by socioeconomic status (SES). This study applied mediation methods to quantify the role of SES in racial/ethnic differences in childhood cancer survival. METHODS: This study used population-based cancer survival data from the Surveillance, Epidemiology, and End Results 18 database for black, white, and Hispanic children who had been diagnosed at the ages of 0 to 19 years in 2000-2011 (n = 31,866). Black-white and Hispanic-white mortality hazard ratios and 95% confidence intervals, adjusted for age, sex, and stage at diagnosis, were estimated. The inverse odds weighting method was used to test for mediation by SES, which was measured with a validated census-tract composite index. RESULTS: Whites had a significant survival advantage over blacks and Hispanics for several childhood cancers. SES…

BACKGROUND: Little is known regarding whether growing awareness of the financial toxicity of a cancer diagnosis and its treatment has increased clinician engagement or changed the needs of current patients. METHODS: The authors surveyed patients with early-stage breast cancer who were identified through population-based sampling from 2 Surveillance, Epidemiology, and End Results (SEER) regions and their physicians. The authors described responses from approximately 73% of surgeons (370 surgeons), 61% of medical oncologists (306 medical oncologists), 67% of radiation oncologists (169 radiation oncologists), and 68% of patients (2502 patients). RESULTS: Approximately one-half (50.9%) of responding medical oncologists reported that someone in their practice often or always discusses financial burden with patients, as did 15.6% of surgeons and 43.2% of radiation oncologists. Patients indicated that financial toxicity remains common: 21.5% of white patients and 22.5% of Asian patients had to cut down spending on food, as did 45.2% of black and 35.8% of Latina patients. Many patients…

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse side effect of many chemotherapeutic agents, affecting >60% of patients with cancer. Moreover, CIPN persists long into survivorship in approximately 20% to 30% of these patients. To the authors' knowledge, no drugs have been approved to date by the US Food and Drug Administration to effectively manage chemotherapy-induced neuropathic pain. The majority of the drugs tested for the management of CIPN aim at symptom relief, including pain and paresthesia, yet are not very efficacious. The authors propose that there is a need to acquire a more thorough understanding of the etiology of CIPN so that effective, mechanism-based, disease-modifying interventions can be developed. It is important to note that such interventions should not interfere with the antitumor effects of chemotherapy. Mitochondria are rod-shaped cellular organelles that represent the powerhouses of the cell, in that they convert oxygen and nutrients into the cellular energy "currency" adenosine triphosphate. In addition, mitochondria regulate cell…

BACKGROUND: Increasing demands on health care systems require patients to take on more active roles in their health. Effective self-management has been linked to improved health outcomes, and evidence shows that effective self-management is linked to health literacy (HL). HL is an important predictor of successful self-management in other chronic diseases but has had minimal testing in cancer. METHODS: A scoping review was conducted to examine and summarize what is known about the association between HL and self-management behaviors and health service utilization in the cancer setting. The methodological framework articulated by Arksey and O'Malley was used and was further refined with the Joanna Briggs Institute methodology. Inclusion criteria included the following: peer review; publication in English; and adult patients and caregivers of all races, ethnicities, and cultural groups. Use of a validated instrument to measure HL was required. RESULTS: The search yielded 2414 articles. After the removal of duplicates and the performance of title scans and abstract reviews, the number…

BACKGROUND: Retroperitoneal sarcomas (RPS) are rare tumors for which complete surgical resection remains the mainstay of treatment. The objective of the current study was to determine the impact of hospital case volume on outcomes in patients with RPS. METHODS: A total of 6950 patients with primary RPS who underwent surgical resection were identified from the National Cancer Data Base (1998-2011). Treating hospitals were classified by annual case volume; low-volume hospitals (LVHs) and high-volume hospitals (HVHs) were defined as those with ≤10 cases per year and >10 cases per year, respectively. Overall survival (OS) was compared using Kaplan-Meier curves. Cox proportional hazard models were created to compare risks. RESULTS: Of the 1131 reporting hospitals, the majority (1127 hospitals; 99.6%) were LVHs treating the majority of patients (6270 patients; 90.2%). Patients treated at LVHs were more likely to have lower grade and smaller tumors, receive radiotherapy, and undergo incomplete macroscopic (R2) resection. Patients treated at HVHs had lower 30-day readmission rates (1.8% vs…

BACKGROUND: The purpose of the current study was to determine quality of life and tumor control from a prospective phase 2 clinical trial evaluating deintensified chemoradiotherapy for favorable risk, human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma. METHODS: ). The primary study endpoint was the pathologic complete response rate based on biopsy of the primary site and dissection of pretreatment positive lymph node regions. The pathologic complete response rate as previously reported was 86%. Herein, the authors report secondary endpoint measures of local control, regional control, cause-specific survival, distant metastasis-free survival, and overall survival, and patient-reported outcomes (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [EORTC QLQ-C30] and the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events [PRO-CTCAE]). RESULTS: A total of 44 patients enrolled with a median follow-up of 36 months (88% with ≥2 years). The 3-year local control, regional control,…

BACKGROUND: The randomized phase 3 ELOQUENT-2 study (NCT01239797) evaluated the efficacy and safety of elotuzumab plus lenalidomide and dexamethasone (ELd) versus lenalidomide and dexamethasone (Ld) in relapsed/refractory multiple myeloma (RRMM), and to date, has the longest follow-up of any monoclonal antibody in patients with RRMM. METHODS: In this extended 4-year follow-up of the ELOQUENT-2 trial, the coprimary endpoints of progression-free survival (PFS) and overall response rate as well as the secondary endpoint of overall survival were assessed. In the absence of head-to-head trials comparing Ld-based triplet regimens to guide treatment selection, 4 randomized controlled trials-ELOQUENT-2, ASPIRE, TOURMALINE-MM1, and POLLUX-were indirectly compared to provide insight into the relative efficacy of these regimens in RRMM. RESULTS: Data at 4 years were consistent with 2- and 3-year follow-up data: ELd reduced the risk of disease progression/death by 29% versus Ld (hazard ratio, 0.71) while maintaining safety. The greatest PFS benefit among the assessed subgroups was observed in…

The appropriate negative margin width for women undergoing breast-conserving surgery for both ductal carcinoma in situ (DCIS) and invasive carcinoma is controversial. This review examines the available data on the margin status for invasive breast cancer and DCIS, and highlights the similarities and differences in tumor biology and standard treatments that affect the local recurrence (LR) risk and, therefore, the optimal surgical margin. Consensus guidelines support a negative margin, defined as no ink on tumor, for invasive carcinoma treated with breast-conserving therapy. Because of differences in the growth pattern and utilization of systemic therapy, a margin of 2 mm has been found to minimize the LR risk for women with DCIS undergoing lumpectomy and radiation therapy (RT). Wider negative margins do not improve local control for DCIS or invasive carcinoma when they are treated with lumpectomy and RT. Re-excision for negative margins should be individualized, and the routine practice of performing additional surgery to obtain a wider negative margin is not supported by the…

BACKGROUND: The purpose of this study was to evaluate the influence of sex and race/ethnicity upon prevalence trends of human papillomavirus (HPV) in oropharyngeal cancer (OPC) and survival after OPC. METHOD: This was a cohort study of patients included in the United States National Cancer Database who had been diagnosed with OPC between 2010 and 2015. Outcomes were HPV status of tumor specimens and overall survival. Sex- and race-stratified trends in HPV prevalence were estimated using generalized linear modeling. The influence of sex, race, and HPV tumor status on overall survival was compared by Kaplan-Meier method and Cox Proportional Hazards models. RESULTS: This analysis included 20,886 HPV-positive and 10,364 HPV-negative OPC patients. The prevalence of HPV-positive tumors was higher among men (70.6%) than women (56.3%) and increased significantly over time at a rate of 3.5% and 3.2% per year among men and women, respectively. The prevalence of HPV-positive tumors was highest among whites (70.2%), followed by Hispanics (61.3%), Asians (55.8%), and blacks (46.3%). Blacks and…

BACKGROUND: The highly selective oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib has demonstrated significant activity in adult and pediatric TRK fusion cancers. In the current study, the authors describe the clinical course of children with locally advanced TRK fusion sarcoma who were treated preoperatively with larotrectinib and underwent subsequent surgical resection. METHODS: A total of 24 children were treated on a pediatric phase 1 trial of larotrectinib (ClinicalTrials.gov identifier NCT02637687). Five children who had a documented TRK fusion sarcoma and underwent surgical resection were included in the current analysis. Tumor response (Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1) and surgical outcomes were collected prospectively. RESULTS: A total of 5 patients (median age, 2 years; range, 0.4-12 years) had locally advanced infantile fibrosarcoma (3 patients) or soft-tissue sarcoma (2 patients). Four patients had disease that was refractory to standard therapy. All 5 patients achieved a partial response to larotrectinib by version 1.1 of…

BACKGROUND: Low skeletal muscle radiodensity (SMD) is related to higher mortality in several cancers, but the association with colorectal cancer (CRC) prognosis is unclear. METHODS: This observational study included 3262 men and women from the Kaiser Permanente Northern California population diagnosed between 2006 and 2011 with AJCC stages I to III CRC. The authors evaluated hazard ratios (HRs) of low SMD for all-cause and CRC-specific mortality, assessed by computed tomography using optimal stratification, compared with patients with normal SMD. They also evaluated the cross-classification of categories of low versus normal SMD and muscle mass (MM) with outcomes. RESULTS: The median follow-up was 6.9 years. Optimal stratification cutpoints for SMD were 32.5 in women and 35.5 in men. In multivariate-adjusted analyses, among patients with CRC, those with low SMD demonstrated higher overall (HR, 1.61; 95% confidence interval [95% CI], 1.36-1.90) and CRC-specific (HR, 1.74; 95% CI, 1.38-2.21) mortality when compared with those with normal SMD levels. Patients with low SMD and low MM…

BACKGROUND Central nervous system Langerhans cell histiocytosis (CNS‐LCH) brain involvement may include mass lesions and/or a neurodegenerative disease (LCH‐ND) of unknown etiology. The goal of this study was to define the mechanisms of pathogenesis that drive CNS‐LCH. METHODS Cerebrospinal fluid (CSF) biomarkers including CSF proteins and extracellular BRAF V600E DNA were analyzed in CSF from patients with CNS‐LCH lesions compared with patients with brain tumors and other neurodegenerative conditions. Additionally, the presence of BRAF V600E was tested in peripheral mononuclear blood cells (PBMCs) as well as brain biopsies from LCH‐ND patients, and the response to BRAF‐V600E inhibitor was evaluated in 4 patients with progressive disease. RESULTS Osteopontin was the only consistently elevated CSF protein in patients with CNS‐LCH compared with patients with other brain pathologies. BRAF V600E DNA was detected in CSF of only 2/20 (10%) cases, both with LCH‐ND and active lesions outside the CNS. However, BRAF V600E + PBMCs were detected with significantly higher frequency at all stages…

BACKGROUND Indisulam possesses anticancer properties through down‐regulation of various cell‐cycle checkpoint molecules, thereby blocking the phosphorylation of retinoblastoma protein and inducing p53 and p21. Indisulam exhibits synergy with nucleoside analogs and topoisomerase inhibitors. METHODS The authors designed a phase 2 study of indisulam in combination with idarubicin and cytarabine in patients who had relapsed/refractory acute myeloid leukemia AML and high‐risk myelodysplastic syndrome. In stage 1, patients received intravenous indisulam at 400 mg/m 2 on days 1 and 8 of a 28‐day cycle. If they had no response, then patients received same dose schedule of indisulam followed by intravenous idarubicin 8 mg/m 2 daily for 3 days and cytarabine 1.0 g/m 2 over 24 hours daily on days 9 through 12 (for those aged < 60 years) or days 9 through 11 (for those aged > 60 years) of a 28‐day cycle. Primary endpoints included the overall response rate, and secondary objectives included overall survival. RESULTS Forty patients were enrolled. Of the 37 evaluable patients, 31 received…

BACKGROUND: Biliary tract cancers are rare, aggressive neoplasms. Most patients present with advanced/unresectable or metastatic disease at diagnosis, and no second-line regimen has demonstrated clinical benefit. This was a phase 2 study evaluating the efficacy and safety of regorafenib in patients who had advanced/unresectable or metastatic disease after receiving standard therapy. METHODS: In this single arm-study, patients with advanced/unresectable or metastatic biliary tract cancer who failed at least 1 line of systemic chemotherapy received regorafenib once daily on a schedule of 21-days on/7-days off in a 28-day cycle. Patients initially received a standard 160 mg dose. After toxicity assessments in the first 3 patients, the dose was reduced to 120 mg for subsequent patients, as preplanned. The primary endpoint was progression-free survival (PFS). Secondary objectives included overall survival (OS), the objective response rate, and the disease control rate. RESULTS: Forty-three patients received at least 1 dose of regorafenib, and 34 patients who received at least 1 cycle of…

Although many of the 16,000 children in the United States diagnosed who are with cancer each year could benefit from pediatric palliative care, these services remain underused. Evidence regarding the barriers impeding access to comprehensive palliative care is dispersed in the literature, and evidence specific to pediatric oncology remains particularly sparse. The purpose of the current review was to synthesize the existing literature regarding these barriers and the strategies offered to address them. The authors completed a literature search using the PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science databases. In total, 71 articles were reviewed. Barriers to accessing pediatric palliative care were categorized according to the 4 levels of a modified socioecological model (ie, barriers related to policy/payment, health systems, organizations, and individuals). Major themes identified at each level included: 1) the lack of consistent and adequate funding mechanisms at the policy/payment level, 2) the lack of pediatric palliative care…

BACKGROUND The investigation of exercise training in metastatic breast cancer has received minimal attention. This study determined the feasibility and safety of aerobic training in metastatic breast cancer. METHODS Sixty‐five women (age, 21‐80 years) with metastatic (stage IV) breast cancer (57% were receiving chemotherapy, and >40% had ≥ 2 lines of prior therapy) were allocated to an aerobic training group (n = 33) or a stretching group (n = 32). Aerobic training consisted of 36 supervised treadmill walking sessions delivered thrice weekly between 55% and 80% of peak oxygen consumption (VO2peak) for 12 consecutive weeks. Stretching was matched to aerobic training with respect to location, frequency, duration, and intervention length. The primary endpoint was aerobic training feasibility, which was a priori defined as the lost to follow‐up (LTF) rate (<20%) and attendance (≥70%). Secondary endpoints were safety, objective outcomes (VO2peak and functional capacity), and patient‐reported outcomes (PROs; quality of life). RESULTS One of the 33 patients (3%) receiving aerobic training…

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, because ICIs block coinhibitory molecules on T cells and other immune cells, unleashing them to mediate tumor cell killing, they also can disrupt the maintenance of immunological tolerance to self-antigens. Compared with chemotherapy, ICIs have a different toxicity profile, especially the occurrence of autoimmune-like manifestations against multiple organ systems, including endocrine glands, commonly referred to as immune-related adverse events. The aim of this review was to provide practical recommendations regarding the proper assessment and clinical management related to the new onset of endocrinopathies after the use of ICIs in patients with cancer. Cancer 2018;124:1111-21. © 2018 American Cancer Society.

Background The outcomes of patients with relapsed or refractory (R‐R) acute lymphoblastic leukemia (ALL) are poor. Inotuzumab ozogamicin and blinatumomab have single‐agent activity in R‐R ALL. Their addition to low‐intensity chemotherapy may further improve the outcomes of patients with ALL in their first relapse. Methods The chemotherapy was lower in intensity than conventional hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone and was called mini‐hyperfractionated cyclophosphamide, vincristine, and dexamethasone (or mini‐HCVD). Inotuzumab was given on day 3 of each of the first 4 cycles at 1.8 to 1.3 mg/m 2 for cycle 1, and this was followed by 1.3 to 1.0 mg/m 2 for subsequent cycles. From patient 39 onward, the inotuzumab dose was reduced and fractionated into weekly doses (0.6 and 0.3 mg/m 2 during cycle 1 and 0.3 and 0.3 mg/m 2 during subsequent cycles), and blinatumomab was administered for up to 4 cycles after inotuzumab therapy. Results Forty‐eight patients with Philadelphia chromosome–negative ALL with a median age of 39 years were treated during…

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is a very common malignancy in which most patients present with localized disease. Recurrent and metastatic disease is rare, and there is no standard therapy. These tumors frequently overexpress the epidermal growth factor receptor (EGFR). We conducted a phase 2 trial to determine the response rate to therapy with erlotinib, an EGFR tyrosine kinase inhibitor, in patients with locoregionally recurrent or metastatic CSCC that was not amenable to curative treatment (NCT01198028). METHODS: Eligible patients had CSCC not amenable to curative intent therapy. Patients who had previously received anti-EGFR targeted therapy were excluded. All patients received oral therapy with erlotinib 150 mg daily. Response was assessed every 8 weeks, and treatment continued until progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was overall response rate according to RECIST 1.1 criteria. RESULTS: A total of 39 patients received treatment during the trial; 29 of these patients were evaluable for response. The overall…

BACKGROUND: The incidence of rectal cancer in patients younger than 50 years is increasing. To test the hypothesis that the biology in this younger cohort may differ, this study compared survival patterns, stratifying patients according to National Comprehensive Cancer Network (NCCN) guideline-driven care and age. METHODS: The National Cancer Data Base was queried for patients treated with curative-intent transabdominal resections with negative surgical margins for stage I to III rectal cancer between 2004 and 2014. Outcomes and overall survival for patients younger than 50 years and patients 50 years old or older were compared by subgroups based on NCCN guideline-driven care. RESULTS: A total of 43,106 patients were analyzed. Younger patients were more likely to be female and minorities, to be diagnosed at a higher stage, and to have travelled further to be treated at academic/integrated centers. Short- and long-term outcomes were significantly better for patients younger than 50 years, with age-specific survival rates calculated. Younger patients were more likely to receive…

BACKGROUND: Adequate social support for older adults is necessary to maintain quality of life and reduce mortality and morbidity. However, little is known regarding the social support needs of older adults with cancer. The objective of the current study was to examine social support needs, specifically the unmet needs, among older adults with cancer. METHODS: Medicare beneficiaries (those aged ≥65 years) with cancer were identified from the University of Alabama at Birmingham Health System Cancer Community Network. Social support needs were assessed using a modified version of the Medical Outcomes Study Social Support Survey. The authors defined an "unmet need" if participants reported having some/a little/never availability of support and requiring support for that need. RESULTS: Of the 1460 participants in the current study, the average age was 74 years (standard deviation, 5.8 years). Approximately two-thirds of participants (986 participants; 67.5%) reported having at least 1 social support need, with the highest needs noted in the emotional (49.5%) and physical (47.4%) support…

A significant proportion of prostate cancer diagnoses may be associated with a strong hereditary component. Men who have multiple single-gene polymorphisms and a family history of prostate cancer have a significantly greater risk of developing prostate cancer. Numerous single-gene alterations have been confirmed to increase the risk of prostate cancer. These include breast cancer genes 1 and 2 (BRCA1 and BRCA2, respectively), mutL homolog 1 (MLH1), mutS homologs 2 and 6 (MSH2 and MSH6, respectively), postmeiotic segregation increased 2 (PMS2), homeobox B13 (HOXB13), checkpoint kinase 2 (CHEK2), nibrin (NBN), BRCA1-interacting protein C-terminal helicase 1 (BRIP1), and ataxia telangiectasia mutated (ATM). Currently, there are no uniform guidelines on the definition of hereditary prostate cancer and genetic testing. With the advent of next-generation sequencing, which is capable of testing multiple genes simultaneously, and the approval of olaparib for BRCA1/BRCA2 or ATM-mutated, metastatic, castrate-resistant prostate cancer, it is being recognized that the results of genetic testing…

BACKGROUND: This study was designed to adapt the Elixhauser comorbidity index for 4 cancer-specific populations (breast, prostate, lung, and colorectal) and compare 3 versions of the Elixhauser comorbidity score (individual comorbidities, summary comorbidity score, and cancer-specific summary comorbidity score) with 3 versions of the Charlson comorbidity score for predicting 2-year survival with 4 types of cancer. METHODS: This cohort study used Texas Cancer Registry-linked Medicare data from 2005 to 2011 for older patients diagnosed with breast (n = 19,082), prostate (n = 23,044), lung (n = 26,047), or colorectal cancer (n = 16,693). For each cancer cohort, the data were split into training and validation cohorts. In the training cohort, competing risk regression was used to model the association of Elixhauser comorbidities with 2-year noncancer mortality, and cancer-specific weights were derived for each comorbidity. In the validation cohort, competing risk regression was used to compare 3 versions of the Elixhauser comorbidity score with 3 versions of the Charlson comorbidity…

Cancer pain remains a feared consequence of the disease and its treatment. Although prevalent, cancer pain can usually be managed through the skillful application of pharmacologic and nonpharmacologic interventions. Unfortunately, access to these therapies has been hampered by interventions designed to contain another serious public health problem: the opioid misuse epidemic. This epidemic and the unintended consequences of efforts to control this outbreak are leading to significant barriers to the provision of cancer pain relief. Oncologists and other professionals treating those with cancer pain will require new knowledge and tools to provide safe and effective pain control while preventing additional cases of substance use disorders (SUDs), helping patients in recovery to maintain sobriety, and guiding those not yet in recovery to seek treatment. How do these 2 serious epidemics intersect and affect oncology practice? First, oncology professionals will need to adopt practices to prevent SUDs by assessing risk and providing safe pain care. Second, oncology practices are likely to…

BACKGROUND: Soft-tissue sarcomas (STSs) are a heterogeneous group of malignant tumors that can be difficult to treat. This is particularly true after incomplete or unplanned excisions and especially for patients with American Joint Committee on Cancer stage III tumors, who are at high risk for relapse. Numerous studies have shown that an inadequate sarcoma excision is associated with a worse prognosis. However, other reports have suggested an improved prognosis for patients with an initial unplanned excision and subsequent re-excision in comparison with patients who undergo planned primary surgery. The purpose of this study was to determine the impact of an unplanned excision on treatment and subsequent oncologic and functional outcomes for patients with stage III extremity STS. METHODS: From the prospectively collected database at a tertiary-referral sarcoma center, all patients with stage III STS of the extremities treated between 1989 and 2010 were identified. Patient records were reviewed to identify patient demographics, tumor details, treatments, complications, and functional…