NSAIDs to Prevent Breast Cancer Recurrence? An Unanswered Question J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-15 Ernest Hawk, Karen Colbert Maresso, Powel Brown
A large body of evidence spanning preclinical, observational, and clinical data supports the potential use of nonsteroidal anti-inflammatory agents (NSAIDs) for cancer prevention, and possibly as adjuncts to cancer treatment. NSAIDs hold great appeal in this regard because they are relatively safe and inexpensive, and aspirin offers the potential to prevent, treat, or palliate several common, chronic, age-related diseases (eg, prevention of cardiovascular events, cancer risk reduction, treatment of inflammatory conditions, pain management). To date, data supporting NSAID use for cancer risk reduction have been most compelling and consistent for colorectal cancer (CRC), where celecoxib and aspirin have shown efficacy in reducing the incidence of precancerous polyps and in reducing polyp/CRC incidence...
Effects of Celecoxib and Low-dose Aspirin on Outcomes in Adjuvant Aromatase Inhibitor–Treated Patients: CCTG MA.27 J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-15 Kathrin Strasser-Weippl, Michaela J Higgins, Judith-Anne W Chapman, James N Ingle, George W Sledge, George T Budd, Matthew J Ellis, Kathleen I Pritchard, Mark J Clemons, Tanja Badovinac-Crnjevic, Lei Han, Karen A Gelmon, Manuela Rabaglio, Catherine Elliott, Lois E Shepherd, Paul E Goss
Celecoxib and low-dose aspirin might decrease risk of breast cancer recurrence.
RE: Elevated Bladder Cancer in Northern New England: The Role of Drinking Water and Arsenic J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-14 Stella Koutros, Petra Lenz, Stephen M Hewitt, Masatoshi Kida, Michael Jones, Alan R Schned, Dalsu Baris, Ruth Pfeiffer, Molly Schwenn, Alison Johnson, Margaret R Karagas, Montserrat Garcia-Closas, Nathaniel Rothman, Lee E Moore, Debra T Silverman
In a large, population-based case–control study in New England, we recently reported a positive exposure-response relationship between cumulative arsenic intake from drinking water and bladder cancer risk (odds ratio [OR] for quartile 4 vs quartile 1 = 1.32, 95% confidence interval [CI] = 1.02 to 1.72; OR = 1.37, 95% CI = 1.03 to 1.82, for exposure lagged 40 years) (Supplementary Table 1, available online) (1). The mechanism by which arsenic induces bladder cancer is not well understood, although several studies have suggested arsenic may target important tumor-suppresser genes (p16, Rb) and disrupt cell cycle control (2). Here, we show heterogeneity in the arsenic–bladder cancer risk relationship by tumor expression of these cell cycle proteins.
Reduced Risk of Prostate Cancer With 5α-Reductase Inhibitors J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-14 Ian Thompson, Phyllis Goodman, Catherine Tangen
Prostate cancer (PCA) and lower urinary tract symptoms (LUTS) associated with aging and benign prostatic hyperplasia are ubiquitous in aging men. PCA has a high prevalence, causes considerable morbidity when metastatic, and is the third most common cause of cancer death in men (1). LUTS adversely affects quality of life and may result in recurrent infections and urinary retention, leading to morbidity and mortality among older men.
Risk of Prostate Cancer in Men Treated With 5α-Reductase Inhibitors—A Large Population-Based Prospective Study J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-14 Anna Wallerstedt, Peter Strom, Henrik Gronberg, Tobias Nordstrom, Martin Eklund
Studies have shown that 5α-reductase inhibitors (5-ARIs) decrease the risk for low-grade prostate cancer (PC), but results are conflicting concerning high-grade PCs. The objective of the present study is to evaluate the association between 5-ARI treatment for lower urinary tract symptoms and the risk for PC.
RE: Magnitude of Clinical Benefit of Cancer Drugs Approved by the US Food and Drug Administration J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-12 Nathan I Cherny, Urani Dafni, Jan Bogaerts, Nicola J Latino, George Pentheroudakis, Jean-Yves Douillard, Josep Tabernero, Christoph Zielinski, Martine J Piccart, Elisabeth G E de Vries
We appreciate the important contribution of Tibau et al. (1) in evaluation of the magnitude of clinical benefit of US Food and Drug Administration (FDA)–approved anticancer agents. The authors report the proportion of FDA-approved indications meeting the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) v1.0 threshold of scores for substantial clinical benefit (A and B for curative treatments or 4 or 5 for noncurative treatments, which the authors have used as a threshold for “meaningful clinical benefit”).
RE: The Rise of Radiomics and Implications for Oncologic Management J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-12 Jean-Philippe Foy, Catherine Durdux, Philippe Giraud, Jean-Emmanuel Bibault
Radiomics is the high-throughput extraction of large amounts of image features from radiographic images, as previously defined in 2012 by Lambin and colleagues in the first publication in the field (1). In the July 2017 issue of Journal (2), Verma and colleagues highlighted the rise of radiomics, which may provide new insights into precision medicine in the next decades. Although the general process of radiomics has been well described (3), a major pitfall should be addressed before these methods can be used to personalize treatments: the lack of standardized procedures for radiomics features extraction (2,3). Lambin et al. recently proposed the radiomics...
Risk Stratification for Melanoma: Models Derived and Validated in a Purpose-Designed Prospective Cohort J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-11 Catherine M Olsen, Nirmala Pandeya, Bridie S Thompson, Jean Claude Dusingize, Penelope M Webb, Adele C Green, Rachel E Neale, David C Whiteman
Risk stratification can improve the efficacy and cost-efficiency of screening programs for early detection of cancer. We sought to derive a risk stratification tool for melanoma that was suitable for the general population using only self-reported information.
Using Medicare Claims to Examine Long-term Prostate Cancer Risk of Finasteride in the Prostate Cancer Prevention Trial J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-09 Joseph M Unger, Dawn L Hershman, Cathee Till, Catherine M Tangen, William E Barlow, Scott D Ramsey, Phyllis J Goodman, Ian M Thompson
Investigators have used administrative claims to better understand cancer outcomes when a research question cannot feasibly be examined within a study. The Prostate Cancer Prevention Trial (PCPT) showed that seven years of finasteride reduced prostate cancer (PC) risk by 25% in men age 55 years or older. However, it was unclear whether the observed reduction in PC for finasteride participants would be maintained after finasteride discontinuation.
Lung Cancer, Smoking, and Obesity: It’s Complicated J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-06 Jonathan M Samet
Obesity is an established cause of cancer and causally linked specifically to cancers of selected sites, including, for example, endometrial cancer, kidney cancer, and esophageal cancer (adenocarcinoma) (1). Three main mechanisms have been postulated as underlying the increased cancer risk associated with obesity: 1) the actions of sex hormones affected by obesity; 2) insulin resistance and insulin-like growth factor 1; and 3) adipokine pathophysiology and systemic inflammation (2). The hormonal hypothesis has site specificity while the latter two mechanisms are general to carcinogenesis. For lung cancer, the worldwide leading cause of cancer death, the evidence from single studies and from systematic reviews and meta-analyses have been mixed, but consistent, in indicating an inverse relationship between body mass index (BMI) and lung cancer risk. However, the evidence has been limited...
Overall and Central Obesity and Risk of Lung Cancer: A Pooled Analysis J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-06 Danxia Yu, Wei Zheng, Mattias Johansson, Qing Lan, Yikyung Park, Emily White, Charles E Matthews, Norie Sawada, Yu-Tang Gao, Kim Robien, Rashmi Sinha, Arnulf Langhammer, Rudolf Kaaks, Edward L Giovannucci, Linda M Liao, Yong-Bing Xiang, DeAnn Lazovich, Ulrike Peters, Xuehong Zhang, Bas Bueno-de-Mesquita, Walter C Willett, Shoichiro Tsugane, Yumie Takata, Stephanie A Smith-Warner, William Blot, Xiao-Ou Shu
The obesity–lung cancer association remains controversial. Concerns over confounding by smoking and reverse causation persist. The influence of obesity type and effect modifications by race/ethnicity and tumor histology are largely unexplored.
Brain Connectivity and Cognitive Flexibility in Nonirradiated Adult Survivors of Childhood Leukemia J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-05 Thibo Billiet, Iris Elens, Charlotte Sleurs, Anne Uyttebroeck, Rudi D’Hooge, Jurgen Lemiere, Sabine Deprez
This study aimed to assess functional and structural brain connectivity in adult childhood leukemia survivors and the link with cognitive functioning and previously identified risk factors such as intrathecal methotrexate dose and age at start of therapy.
Genomic Amplifications and Distal 6q Loss: Novel Markers for Poor Survival in High-risk Neuroblastoma Patients J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-05 Pauline Depuydt, Valentina Boeva, Toby D Hocking, Robrecht Cannoodt, Inge M Ambros, Peter F Ambros, Shahab Asgharzadeh, Edward F Attiyeh, Valérie Combaret, Raffaella Defferrari, Matthias Fischer, Barbara Hero, Michael D Hogarty, Meredith S Irwin, Jan Koster, Susan Kreissman, Ruth Ladenstein, Eve Lapouble, Geneviève Laureys, Wendy B London, Katia Mazzocco, Akira Nakagawara, Rosa Noguera, Miki Ohira, Julie R Park, Ulrike Pötschger, Jessica Theissen, Gian Paolo Tonini, Dominique Valteau-Couanet, Luigi Varesio, Rogier Versteeg, Frank Speleman, John M Maris, Gudrun Schleiermacher, Katleen De Preter
Neuroblastoma is characterized by substantial clinical heterogeneity. Despite intensive treatment, the survival rates of high-risk neuroblastoma patients are still disappointingly low. Somatic chromosomal copy number aberrations have been shown to be associated with patient outcome, particularly in low- and intermediate-risk neuroblastoma patients. To improve outcome prediction in high-risk neuroblastoma, we aimed to design a prognostic classification method based on copy number aberrations.
Development and Validation of a Novel RNA Sequencing–Based Prognostic Score for Acute Myeloid Leukemia J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-03-01 Mei Wang, Johan Lindberg, Daniel Klevebring, Christer Nilsson, Sören Lehmann, Henrik Grönberg, Mattias Rantalainen
Recent progress in sequencing technologies allows us to explore comprehensive genomic and transcriptomic information to improve the current European LeukemiaNet (ELN) system of acute myeloid leukemia (AML).
The Landscape of Somatic Genetic Alterations in Breast Cancers From ATM Germline Mutation Carriers J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-28 Britta Weigelt, Rui Bi, Rahul Kumar, Pedro Blecua, Diana L Mandelker, Felipe C Geyer, Fresia Pareja, Paul A James, Fergus J Couch, Diana M Eccles, Fiona Blows, Paul Pharoah, Anqi Li, Pier Selenica, Raymond S Lim, Gowtham Jayakumaran, Nic Waddell, Ronglai Shen, Larry Norton, Hannah Y Wen, Simon N Powell, Nadeem Riaz, Mark E Robson, Jorge S Reis-Filho, Georgia Chenevix-Trench
Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair. No TP53 mutations were found in the ATM-associated BCs. Analysis of an independent data set confirmed that germline ATM variants and TP53 somatic mutations are mutually exclusive. Our findings indicate that ATM-associated BCs often harbor bi-allelic inactivation of ATM, are phenotypically distinct from BRCA1/2-associated BCs, lack HRD-related mutational signatures, and that TP53 and ATM genetic alterations are likely epistatic.
RE: Effectiveness of Pharmaceutical Smoking Cessation Aids in a Nationally Representative Cohort of American Smokers J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-28 Saul Shiffman, Joe G Gitchell
We read with interest Leas et al.’s analysis of the Current Population Survey data (1) relating the use of pharmacotherapy to outcome in attempts to quit smoking, particularly as a decade ago we published a similar analysis on some of the same data (2), not cited by Leas et al. We strongly agree with the editorial by Tindle and Greevy that a major issue in the analysis is serious confounding when treatment is assigned clinically or self-selected (3). This is a classic case of the well-known “confounding by indication” (4,5) (or by “severity”) problem, in which treatment is primarily used by those who already have the most severe conditions and are the most prone to poor outcomes. Leas et al. undertook heroic efforts...
Response J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-28 John P Pierce, Eric C Leas, Tarik Benmarhnia, David R Strong
In the early 1990s, a series of randomized trials demonstrated the efficacy of both pharmaceutical aids with behavioral therapy for smoking cessation and treatments for metastatic breast cancer. These treatments were approved by the US Food and Drug Administration and quickly disseminated into clinical practice. A decade later, the population mean survival following a metastatic breast cancer diagnosis had improved 50%, demonstrating the effectiveness of the treatment (1); however, there was no improvement in the proportion of smokers who had successfully quit (2). A critical public health question is how to account for the apparent lack of translation of quitting success into the population.
Role of Acid Sphingomyelinase and Ceramide in Mechano-Acoustic Enhancement of Tumor Radiation Responses J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-28 Ahmed El Kaffas, Azza Al-Mahrouki, Amr Hashim, Niki Law, Anoja Giles, Gregory J Czarnota
High-dose radiotherapy (>8–10 Gy) causes rapid endothelial cell death via acid sphingomyelinase (ASMase)–induced ceramide production, resulting in biologically significant enhancement of tumor responses. To further augment or solicit similar effects at low radiation doses, we used genetic and chemical approaches to evaluate mechano-acoustic activation of the ASMase-ceramide pathway by ultrasound-stimulated microbubbles (USMB).
Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-28 Maeve A Lowery, Winston Wong, Emmet J Jordan, Jonathan W Lee, Yelena Kemel, Joseph Vijai, Diana Mandelker, Ahmet Zehir, Marinela Capanu, Erin Salo-Mullen, Angela G Arnold, Kenneth H Yu, Anna M Varghese, David P Kelsen, Robin Brenner, Erica Kaufmann, Vignesh Ravichandran, Semanti Mukherjee, Michael F Berger, David M Hyman, David S Klimstra, Ghassan K Abou-Alfa, Catherine Tjan, Christina Covington, Hannah Maynard, Peter J Allen, Gokce Askan, Steven D Leach, Christine A Iacobuzio-Donahue, Mark E Robson, Kenneth Offit, Zsofia K Stadler, Eileen M O’Reilly
Identification of pathogenic germline alterations (PGAs) has important clinical and therapeutic implications in pancreas cancer. We performed comprehensive germline testing (GT) in an unselected prospective cohort of patients with exocrine pancreatic neoplasms with genotype and phenotype association to facilitate identification of prognostic and/or predictive biomarkers and examine potential therapeutic implications.
Breast Cancer Risk Model Requirements for Counseling, Prevention, and Screening J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-27 Mitchell H Gail, Ruth M Pfeiffer
Incorporation of polygenic risk scores and mammographic density into models to predict breast cancer incidence can increase discriminatory accuracy (area under the receiver operating characteristic curve [AUC]) from 0.6 for models based only on epidemiologic factors to 0.7. It is timely to assess what impact these improvements will have on individual counseling and on public health prevention and screening strategies, and to determine what further improvements are needed.
Randomized Noninferiority Trial of Telephone vs In-Person Disclosure of Germline Cancer Genetic Test Results J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-27 Angela R Bradbury, Linda J Patrick-Miller, Brian L Egleston, Michael J Hall, Susan M Domchek, Mary B Daly, Pamela Ganschow, Generosa Grana, Olufunmilayo I Olopade, Dominique Fetzer, Amanda Brandt, Rachelle Chambers, Dana F Clark, Andrea Forman, Rikki Gaber, Cassandra Gulden, Janice Horte, Jessica M Long, Terra Lucas, Shreshtha Madaan, Kristin Mattie, Danielle McKenna, Susan Montgomery, Sarah Nielsen, Jacquelyn Powers, Kim Rainey, Christina Rybak, Michelle Savage, Christina Seelaus, Jessica Stoll, Jill E Stopfer, Xinxin (Shirley) Yao
Germline genetic testing is standard practice in oncology. Outcomes of telephone disclosure of a wide range of cancer genetic test results, including multigene panel testing (MGPT) are unknown.
Activity of HSP90 Inhibiton in a Metastatic Lung Cancer Patient With a Germline BRCA1 Mutation J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-26 Susana Cedrés, Enriqueta Felip, Cristina Cruz, Ana Martinez de Castro, Nuria Pardo, Alejandro Navarro, Alex Martinez-Marti, Jordin Remon, Jorge Zeron-Medina, Judith Balmaña, Alba Llop-Guevara, Josep M Miquel, Irene Sansano, Paolo Nuciforo, Francesco Mancuso, Violeta Serra, Ana Vivancos
Heat shock proteins (HSPs) are molecular chaperones that maintain proteins in their correct conformation to ensure stability and protect carcinoma cells from apoptosis. HSP90 inhibitors (HSP90i) block multiple targets simultaneously, and despite responses in a selected population, no HSP90i have yet been approved. We present a patient with a lung tumor with an exceptional response to cisplatin/gemcitabine in combination with HSP90i, which nowadays continues with HSP90i maintenance after three years. Whole-exome sequencing of the lung tumor unveiled a BRCA1/2 deficiency mutational signature, and mutation analysis confirmed a germline BRCA1 mutation. The striking efficacy of HSP90i plus chemotherapy vs chemotherapy alone was reproduced in a patient-derived xenograft (PDX) model from a breast cancer patient with a BRCA1 mutation (mean tumor volume [SD], No. of tumors: vehicle 8.38 [7.07] mm3, n = 3; HSP90i 4.18 [1.93] mm3, n = 5; cisplatin plus gemcitabine 3.31 [1.95] mm3, n = 5; cisplatin plus gemcitabine plus HSP90i 0.065 [0.076] mm3, n = 6). This case and the PDX demonstrate the efficacy for therapeutic inhibition of HSP90 in a BRCA-mutated patient, opening a new potential avenue for better identifying patients who might benefit most from HSP90i.
Testing Positive on a Multigene Panel Does Not Suffice to Determine Disease Risks J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-26 Hormuzd A Katki, Mark H Greene, Maria Isabel Achatz
Historically, cancer genetic testing has been limited to single-gene testing in families who fulfill susceptibility syndrome criteria. Today, next-generation sequencing-based multigene panel tests are commonly used when the syndrome is unclear, multiple genes might explain the phenotype, or when single-gene testing fails to detect a pathogenic germline mutation (1). Panel prices have plummeted, and families with minimal cancer family history in the syndromic spectrum of the mutated gene are currently being tested. However, the penetrance of strongly pathogenic germline mutations varies dramatically by testing indication, family history pattern, and other risk factors. This underappreciated fact will require a paradigm shift regarding how clinicians counsel patients about disease risks implied by mutations found on multigene panel testing.
Beyond Expert Opinion: Progress in the Development of Evidence-Based Screening Guidelines for Survivors of Childhood Cancer J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-26 David C Hodgson, Tara O Henderson
In this issue of the Journal, Teepen et al. provide important new findings from the Dutch DCOG‐LATER study that support early surveillance strategies to reduce the burden of colorectal cancer (CRC) in childhood cancer survivors (1). This is of particular importance because second cancers are the greatest cause of premature mortality in adult survivors of childhood cancer. The British Childhood Cancer Survivor Study, for example, found that gastrointestinal malignancies contributed the greatest absolute excess risk among childhood cancer survivors older than age 40 years, and the cumulative incidence of CRC for survivors treated with abdominopelvic radiotherapy (RT) was 1.4% by age 50 years (2). This and other large cohort studies have demonstrated that platinum-based chemotherapy and abdominal or pelvic RT increase CRC risk up to three to four times...
Response J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-26 Ariadna Tibau, Consolación Molto, Eitan Amir
We thank Cherny and colleagues for their comments about our article. Our use of the term “arbitrary” to describe the cutoffs utilized in the European Society of Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) was not meant to reflect a criticism of the development of this tool. It was simply an observation that the assessments of value in health care (which in the case of ESMO-MCBS is based on both efficacy and safety) are continuous measures that exist over a spectrum. Typically, attempts to dichotomize a continuous variable are subject to some arbitrary decisions. This is supported by data that show that there is only fair correlation between the assessment of value by ESMO-MCBS and other value frameworks despite the use of the same constructs of clinical benefit (1–3). Additionally,...
Differences in TP53 Mutation Carrier Phenotypes Emerge From Panel-Based Testing J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-26 Huma Q Rana, Rebecca Gelman, Holly LaDuca, Rachel McFarland, Emily Dalton, Jennifer Thompson, Virginia Speare, Jill S Dolinsky, Elizabeth C Chao, Judy E Garber
Li-Fraumeni syndrome (LFS) has traditionally been identified by single-gene testing (SGT) of TP53 triggered by clinical criteria, but the widespread use of multigene panel tests (MGPTs) has upended this paradigm. We sought to compare the personal and family cancer histories of TP53-positive result (TP53+) carriers who were identified by either MGPT or SGT.
Risk of Breast, Prostate, and Colorectal Cancer Diagnoses Among HIV-Infected Individuals in the United States J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-26 Anna E Coghill, Eric A Engels, Maria J Schymura, Parag Mahale, Meredith S Shiels
Although people living with HIV or AIDS (PLWHA) are at higher risk for many cancers, breast, prostate, and colorectal cancer rates are lower in this patient population. Because these tumors are often screen-detected, these inverse associations could be driven by HIV-related differences in utilization of cancer screening.
Opportunities to Understand Unique Cancer Risks in Global HIV-Infected Populations J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-26 Marie-Josèphe Horner, Satish Gopal
In this issue, Coghill and colleagues (1) describe reduced incidence of three common screen-detectable cancers among people living with HIV relative to the general population of the United States. Findings from the population-based HIV/AIDS Cancer Match Study show a 37% reduced incidence of breast cancer, 52% reduced incidence of prostate cancer, and 31% to 49% reduced incidence of rectal cancer, proximal colon, and distal colon cancer, respectively, among people living with HIV.
Colorectal Adenomas and Cancers After Childhood Cancer Treatment: A DCOG-LATER Record Linkage Study J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-26 Jop C Teepen, Judith L Kok, Flora E van Leeuwen, Wim J E Tissing, Wil V Dolsma, Helena J van der Pal, Jacqueline J Loonen, Dorine Bresters, Birgitta Versluys, Marry M van den Heuvel-Eibrink, Eline van Dulmen-den Broeder, Marleen H van den Berg, Margriet van der Heiden-van der Loo, Michael Hauptmann, Marjolijn C Jongmans, Lucy I Overbeek, Marc J van de Vijver, Leontien C M Kremer, Cécile M Ronckers, B M P Aleman, M H van den Berg, D Bresters, H N Caron, L A Daniels, W Dolsma, E van Dulmen-den Broeder, M A Grootenhuis, C J Haasbeek, J G den Hartogh, M Hauptmann, M van der Heiden-van der Loo, M M van den Heuvel-Eibrink, N Hollema, G O Janssens, M C Jongmans, M W M Jaspers, J L Kok, L C M Kremer, F E van Leeuwen, J Loonen, J H Maduro, S J C M M Neggers, F Oldenburger, L I Overbeek, H J van der Pal, A Postma, J G de Ridder-Sluiter, C M van Rij, C M Ronckers, J C Teepen, R J Tersteeg, W J E Tissing, A B Versluys, M J van de Vijver, J Zsíros
Although colorectal adenomas serve as prime target for colorectal cancer (CRC) surveillance in other high-risk groups, data on adenoma risk after childhood cancer are lacking. We evaluated the risk of histologically confirmed colorectal adenomas among childhood cancer survivors. A secondary aim was to assess CRC risk.
Novel Dual-Action Targeted Nanomedicine in Mice With Metastatic Thyroid Cancer and Pancreatic Neuroendocrine Tumors J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-22 Naris Nilubol, ZiQiang Yuan, Giulio F Paciotti, Lawrence Tamarkin, Carmen Sanchez, Kelli Gaskins, Esther M Freedman, Shugeng Cao, Jielu Zhao, David G I Kingston, Steven K Libutti, Electron Kebebew
The advantages of nanomedicines include preferential delivery of the payload directly to tumor tissues. CYT-21625 is the novel, first-in-class gold nanomedicine designed to target tumor vasculature and cancer cells by specifically delivering recombinant human tumor necrosis factor alpha (rhTNF) and a paclitaxel prodrug.
Innovation in the Treatment of Insomnia in Breast Cancer Survivors J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-20 Michael R Irwin
In this issue of the Journal, Zachariae et al. present a randomized controlled trial among breast cancer survivors with insomnia, comparing an Internet‐delivered cognitive behavioral therapy for insomnia (iCBT‐I) with a waitlist control (1). Outcomes were assessed via the Internet, including insomnia severity, sleep quality, and fatigue, as well as sleep diaries over two weeks. The active intervention, iCBT-I, showed robust improvements in insomnia severity and sleep quality, and also reduced daytime symptoms of fatigue, with effects maintained over a six-week follow-up.
Opening the Door for Immune Oncology Studies in Invasive Lobular Breast Cancer J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-20 Steffi Oesterreich, Peter C Lucas, Priscilla F McAuliffe, Tullia C Bruno, Dario A A Vignali
Invasive lobular breast cancer (ILC) is the second most common histological breast cancer subtype, after invasive ductal breast cancer (IDC). ILC accounts for approximately 10% to 15% of all breast cancers, with approximately 24 000–36 000 cases annually in the US only. The hallmark of ILC is loss of E-cadherin (CDH1), resulting in discohesive cancer cells that infiltrate the breast stroma in a single-file pattern (1). Unique clinical features that differentiate ILC from IDC include more frequent multifocal disease, growth patterns often resulting in higher stage at presentation, positive resection margins necessitating completion mastectomy (2–5), and metastatic sites (6,7). Despite better prognostic factors (eg, more estrogen receptor [ER]+, and lower levels of the proliferation marker Ki67), there is increasing evidence that patients with...
Immune Infiltration in Invasive Lobular Breast Cancer J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-20 Christine Desmedt, Roberto Salgado, Marco Fornili, Giancarlo Pruneri, Gert Van den Eynden, Gabriele Zoppoli, Françoise Rothé, Laurence Buisseret, Soizic Garaud, Karen Willard-Gallo, David Brown, Yacine Bareche, Ghizlane Rouas, Christine Galant, François Bertucci, Sherene Loi, Giuseppe Viale, Angelo Di Leo, Andrew R Green, Ian O Ellis, Emad A Rakha, Denis Larsimont, Elia Biganzoli, Christos Sotiriou
Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC.
Internet-Delivered Cognitive-Behavioral Therapy for Insomnia in Breast Cancer Survivors: A Randomized Controlled Trial J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-20 Robert Zachariae, Ali Amidi, Malene F Damholdt, Cecilie D R Clausen, Jesper Dahlgaard, Holly Lord, Frances P Thorndike, Lee M Ritterband
Insomnia is two to three times more prevalent in cancer survivors than in the general population, where it is estimated to be 10% to 20%. Cognitive-behavioral therapy for insomnia (CBT-I) is the recommended treatment for chronic insomnia, but meeting survivor needs remains a challenge. Internet-delivered CBT-I (iCBT-I) has been shown efficacious in otherwise healthy adults. We tested the efficacy of iCBT-I in breast cancer survivors with clinically significant sleep disturbance.
The Heterogeneity Between Lynch-Associated and Sporadic MMR Deficiency in Colorectal Cancers J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-20 Guo-Chen Liu, Ran-Yi Liu, Jun-Ping Yan, Xin An, Wu Jiang, Yi-Hong Ling, Jie-Wei Chen, Jin-Xin Bei, Xiao-Yu Zuo, Mu-Yan Cai, Ze-Xian Liu, Zhi-Xiang Zuo, Ji-Hong Liu, Zhi-Zhong Pan, Pei-Rong Ding
Previous studies demonstrated that prognosis of germline deficiency in mismatch repair protein (dMMR) was different from that of sporadic dMMR. The underlying mechanism has not been studied.
Alachlor Use and Cancer Incidence in the Agricultural Health Study: An Updated Analysis J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-17 Catherine C Lerro, Gabriella Andreotti, Stella Koutros, Won Jin Lee, Jonathan N Hofmann, Dale P Sandler, Christine G Parks, Aaron Blair, Jay H Lubin, Laura E Beane Freeman
The herbicide alachlor has been widely used in US agriculture since its introduction in 1969. Experimental animal studies show that alachlor causes tumors in vivo; however, few epidemiologic studies have examined associations with human cancer risk. We evaluated alachlor use and cancer incidence in the Agricultural Health Study, updating an earlier analysis that suggested associations with lymphohematopoietic cancers with an additional 540 142 person-years of follow-up and 5113 cancer cases.
Identifying Biomarkers for Risk of Premature Menopause Among Childhood Cancer Survivors May Lead to Targeted Interventions and Wellness Strategies J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-08 Shaneda Warren Andersen
Female survivors of childhood cancer are at risk of late effects of their cancer treatment including increased risk of premature menopause before age 40 years (1). Premature menopause causes infertility at an early age, and also is linked to other adverse health outcomes such as heart disease and osteoporosis (2). Identifying biomarkers that define risk strata for treatment-associated premature menopause may allow survivors to partake in targeted medical interventions aimed to reduce or prevent the consequences of premature menopause, such as fertility preservation procedures and prevention programs for cardiovascular diseases and osteoporosis.
A High-risk Haplotype for Premature Menopause in Childhood Cancer Survivors Exposed to Gonadotoxic Therapy J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-08 Russell J Brooke, Cindy Im, Carmen L Wilson, Matthew J Krasin, Qi Liu, Zhenghong Li, Yadav Sapkota, WonJong Moon, Lindsay M Morton, Gang Wu, Zhaoming Wang, Wenan Chen, Rebecca M Howell, Gregory T Armstrong, Smita Bhatia, Sogol Mostoufi-Moab, Kristy Seidel, Stephen J Chanock, Jinghui Zhang, Daniel M Green, Charles A. Sklar, Melissa M. Hudson, Leslie L. Robison, Wassim Chemaitilly, Yutaka Yasui
Childhood cancer survivors are at increased risk of therapy-related premature menopause (PM), with a cumulative incidence of 8.0%, but the contribution of genetic factors is unknown.
Associations Between Serum Bone Biomarkers in Early Breast Cancer and Development of Bone Metastasis: Results From the AZURE (BIG01/04) Trial J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2018-02-07 Janet Brown, Emma Rathbone, Samantha Hinsley, Walter Gregory, Fatma Gossiel, Helen Marshall, Roger Burkinshaw, Helen Shulver, Hasina Thandar, Gianfilippo Bertelli, Keane Maccon, Angela Bowman, Andrew Hanby, Richard Bell, David Cameron, Robert Coleman
Adjuvant therapies can prevent/delay bone metastasis development in breast cancer. We investigated whether serum bone turnover markers in early disease have clinical utility in identifying patients with a high risk of developing bone metastasis.
RE: Regional Nodal Irradiation After Breast-Conserving Surgery for Early HER2-Positive Breast Cancer: Results of a Subanalysis From the ALTTO Trial J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-21 Yazid Belkacemi, Abraham Kuten
We congratulate Gingras et al. for their report on regional node irradiation (RNI) in the human epidermal growth factor receptor 2 (HER2)–targeted therapy era (1). They suggest that RNI has no impact on disease-free survival (DFS) in node-positive (N+), HER2-positive breast cancer (BC) patients treated with conservative surgery, axillary node dissection (ALND), and whole breast irradiation. These results reported in the anti-HER2 era contradict RNI data from the MA20 and EORTC22922 trials (2,3).
Response J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-21 Isabelle Gingras, Hatem A Azim
We thank Belkacemi and colleagues for their interest in our recent work that evaluated the impact of regional nodal irradiation (RNI) in node-positive human epidermal growth factor receptor 2 (HER2)–positive breast cancer (BC). They made several arguments questioning the validity of our findings, and below we provide our response to their comments.
Prognostic Value of Clinical vs Pathologic Stage in Rectal Cancer Patients Receiving Neoadjuvant Therapy J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-20 Daniel Delitto, Thomas J George, Tyler J Loftus, Peihua Qiu, George J Chang, Carmen J Allegra, William A Hall, Steven J Hughes, Sanda A Tan, Christiana M Shaw, Atif Iqbal
Neoadjuvant chemoradiation is currently standard of care in stage II–III rectal cancer, resulting in tumor downstaging for patients with treatment-responsive disease. However, the prognosis of the downstaged patient remains controversial. This work critically analyzes the relative contribution of pre- and post-therapy staging to the anticipated survival of downstaged patients.
Risk of Soft-Tissue Sarcoma Among 69 460 Five-Year Survivors of Childhood Cancer in Europe J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-20 Chloe J Bright, Mike M Hawkins, David L Winter, Daniela Alessi, Rodrigue S Allodji, Francesca Bagnasco, Edit Bárdi, Andrea Bautz, Julianne Byrne, Elizabeth A M Feijen, Miranda M Fidler, Stanislaw Garwicz, Desiree Grabow, Thorgerdur Gudmundsdottir, Joyeeta Guha, Nadia Haddy, Momcilo Jankovic, Peter Kaatsch, Melanie Kaiser, Claudia E Kuehni, Helena Linge, Hilde Øfstaas, Cecile M. Ronckers, Roderick Skinner, Jop C. Teepen, Monica Terenziani, Giao Vu-Bezin, Finn Wesenberg, Thomas Wiebe, Carlotta Sacerdote, Zsuzsanna Jakab, Riccardo Haupt, Päivi Lähteenmäki, Lorna Zadravec Zaletel, Rahel Kuonen, Jeanette F. Winther, Florent de Vathaire, Leontien C. Kremer, Lars Hjorth, Raoul C Reulen
Childhood cancer survivors are at risk of subsequent primary soft-tissue sarcomas (STS), but the risks of specific STS histological subtypes are unknown. We quantified the risk of STS histological subtypes after specific types of childhood cancer.
Targeting BCR-ABL-Independent TKI Resistance in Chronic Myeloid Leukemia by mTOR and Autophagy Inhibition J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-20 Rebecca Mitchell, Lisa E M Hopcroft, Pablo Baquero, Elaine K Allan, Kay Hewit, Daniel James, Graham Hamilton, Arunima Mukhopadhyay, Jim O’Prey, Alan Hair, Junia V Melo, Edmond Chan, Kevin M Ryan, Véronique Maguer-Satta, Brian J Druker, Richard E Clark, Subir Mitra, Pawel Herzyk, Franck E Nicolini, Paolo Salomoni, Emma Shanks, Bruno Calabretta, Tessa L Holyoake, G Vignir Helgason
Imatinib and second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib have statistically significantly improved the life expectancy of chronic myeloid leukemia (CML) patients; however, resistance to TKIs remains a major clinical challenge. Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, a proportion of patients may have or develop BCR-ABL-independent resistance and fail ponatinib treatment. By modeling ponatinib resistance and testing samples from these CML patients, it is hoped that an alternative drug target can be identified and inhibited with a novel compound.
BRAF V600E Mutation-Assisted Risk Stratification of Solitary Intrathyroidal Papillary Thyroid Cancer for Precision Treatment J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-18 Yueye Huang, Shen Qu, Guangwu Zhu, Fei Wang, Rengyun Liu, Xiaopei Shen, David Viola, Rossella Elisei, Efisio Puxeddu, Laura Fugazzola, Carla Colombo, Barbara Jarzab, Agnieszka Czarniecka, Alfred K Lam, Caterina Mian, Federica Vianello, Linwah Yip, Garcilaso Riesco-Eizaguirre, Pilar Santisteban, Christine J O’Neill, Mark S Sywak, Roderick Clifton-Bligh, Bela Bendlova, Vlasta Sýkorová, Mingzhao Xing
Precise risk stratification-based treatment of solitary intrathyroidal papillary thyroid cancer (SI-PTC) that is larger than 1.0 cm and 4.0 cm or less is undefined.
Thyroid Cancer: Is It All in the Genes? J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-18 Electron Kebebew
Thyroid cancer represents one of the most biologically and clinically diverse solid malignancies. While most thyroid cancers originate from the follicular cells, the genetic alterations that drive these cancers are unique to each histologic subtype (1). Further, the behavior of thyroid cancer has a wide spectrum, from the commonly indolent and widespread papillary thyroid microcarcinoma (present in up to 35.6% of individuals at autopsy) to the uniformly rare and lethal undifferentiated thyroid cancer (2,3). Our understanding of the genetic events involved in thyroid cancer initiation and progression has grown, with some having translational implications for predicting thyroid cancer behavior and as therapeutic targets for advanced thyroid cancer (4).
Investigation of the Relationship Between Radiation Dose and Gene Mutations and Fusions in Post-Chernobyl Thyroid Cancer J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-18 Alexey A Efanov, Alina V Brenner, Tetiana I Bogdanova, Lindsey M Kelly, Pengyuan Liu, Mark P Little, Abigail I Wald, Maureen Hatch, Liudmyla Y Zurnadzy, Marina N Nikiforova, Vladimir Drozdovitch, Kiyohiko Mabuchi, Mykola D Tronko, Stephen J Chanock, Yuri E Nikiforov
Exposure to ionizing radiation during childhood is a well-established risk factor for thyroid cancer. However, the genetic mechanisms of radiation-associated carcinogenesis remain not fully understood.
PD-L1 Antibodies for EBV-Positive Gastric Cancer, Going Beyond PD-L1 Expression and Microsatellite Instability J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-15 Khaldoun Almhanna, Scott Antonia
Gastric adenocarcinoma is the second leading cause of cancer death worldwide, following lung cancer. The five-year survival rate of advanced metastatic disease is low. Combination chemotherapy results in improvement in overall survival in comparison with single-agent treatment or supportive care (1,2). Limited progress has been made by adding targeted therapy to the treatment of gastric cancer. The only two targeted agents approved by the US Food and Drug Administration (FDA) are ramucirumab (3,4), a VEGF antibody, and trastuzumab (5), which is indicated only in tumors with amplified human epidermal growth factor receptor 2 (Her-2). Both drugs have a modest impact on overall survival.
Glyphosate Use and Cancer Incidence in the Agricultural Health Study: An Epidemiologic Perspective J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-15 Elizabeth M Ward
In this issue of the Journal, Gabriela Adreiotti and colleagues report the results of an updated analysis of glyphosate exposure and cancer risk in the Agricultural Health Study (AHS) (1). The AHS, a prospective cohort study of 57 310 licensed pesticide applicators and 32 347 spouses in Iowa and North Carolina, was initiated in the early 1990s, in large part to address possible causes for the higher incidence of lymphohematopoietic and certain other cancers in farmers compared with the general population (2). From an epidemiologic perspective, designing a study to investigate cancer risk factors associated with farming is challenging because of the difficulty in establishing and recruiting a well-defined population, the large number of farming-related exposures that may be associated with cancer, and the need to create and validate...
Immune Activation and Benefit From Avelumab in EBV-Positive Gastric Cancer J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-15 Anshuman Panda, Janice M Mehnert, Kim M Hirshfield, Greg Riedlinger, Sherri Damare, Tracie Saunders, Michael Kane, Levi Sokol, Mark N Stein, Elizabeth Poplin, Lorna Rodriguez-Rodriguez, Ann W Silk, Joseph Aisner, Nancy Chan, Jyoti Malhotra, Melissa Frankel, Howard L Kaufman, Siraj Ali, Jeffrey S Ross, Eileen P White, Gyan Bhanot, Shridar Ganesan
Response to immune checkpoint therapy can be associated with a high mutation burden, but other mechanisms are also likely to be important. We identified a patient with metastatic gastric cancer with meaningful clinical benefit from treatment with the anti–programmed death–ligand 1 (PD-L1) antibody avelumab. This tumor showed no evidence of high mutation burden or mismatch repair defect but was strongly positive for presence of Epstein-Barr virus (EBV) encoded RNA. Analysis of The Cancer Genome Atlas gastric cancer data (25 EBV+, 80 microsatellite-instable [MSI], 310 microsatellite-stable [MSS]) showed that EBV-positive tumors were MSS. Two-sided Wilcoxon rank-sum tests showed that: 1) EBV-positive tumors had low mutation burden (median = 2.07 vs 3.13 in log10 scale, P < 10-12) but stronger evidence of immune infiltration (median ImmuneScore 2212 vs 1295, P < 10-4; log2 fold-change of CD8A = 1.85, P < 10-6) compared with MSI tumors, and 2) EBV-positive tumors had higher expression of immune checkpoint pathway (PD-1, CTLA-4 pathway) genes in RNA-seq data (log2 fold-changes: PD-1 = 1.85, PD-L1 = 1.93, PD-L2 = 1.50, CTLA-4 = 1.31, CD80 = 0.89, CD86 = 1.31, P < 10-4 each), and higher lymphocytic infiltration by histology (median tumor-infiltrating lymphocyte score = 3 vs 2, P < .001) compared with MSS tumors. These data suggest that EBV-positive low–mutation burden gastric cancers are a subset of MSS gastric cancers that may respond to immune checkpoint therapy.
MAX Mutations in Endometrial Cancer: Clinicopathologic Associations and Recurrent MAX p.His28Arg Functional Characterization J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-15 Christopher J Walker, Craig M Rush, Paola Dama, Matthew J O’Hern, Casey M Cosgrove, Jessica L Gillespie, Roman A Zingarelli, Blair Smith, Maggie E Stein, David G Mutch, Reena Shakya, Chia-Wen Chang, Karuppaiyah Selvendiran, Jonathan W Song, David E Cohn, Paul J Goodfellow
Genomic studies have revealed that multiple genes are mutated at varying frequency in endometrial cancer (EC); however, the relevance of many of these mutations is poorly understood. An EC-specific recurrent mutation in the MAX transcription factor p.His28Arg was recently discovered. We sought to assess the functional consequences of this hotspot mutation and determine its association with cancer-relevant phenotypes.
Relative Performance of HPV and Cytology Components of Cotesting in Cervical Screening J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-14 Mark Schiffman, Walter K Kinney, Li C Cheung, Julia C Gage, Barbara Fetterman, Nancy E Poitras, Thomas S Lorey, Nicolas Wentzensen, Brian Befano, John Schussler, Hormuzd A Katki, Philip E Castle
The main goal of cervical screening programs is to detect and treat precancer before cancer develops. Human papillomavirus (HPV) testing is more sensitive than cytology for detecting precancer. However, reports of rare HPV-negative, cytology-positive cancers are motivating continued use of both tests (cotesting) despite increased testing costs.
Glyphosate Use and Cancer Incidence in the Agricultural Health Study J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-09 Gabriella Andreotti, Stella Koutros, Jonathan N Hofmann, Dale P Sandler, Jay H Lubin, Charles F Lynch, Catherine C Lerro, Anneclaire J De Roos, Christine G Parks, Michael C Alavanja, Debra T Silverman, Laura E Beane Freeman
Glyphosate is the most commonly used herbicide worldwide, with both residential and agricultural uses. In 2015, the International Agency for Research on Cancer classified glyphosate as “probably carcinogenic to humans,” noting strong mechanistic evidence and positive associations for non-Hodgkin lymphoma (NHL) in some epidemiologic studies. A previous evaluation in the Agricultural Health Study (AHS) with follow-up through 2001 found no statistically significant associations with glyphosate use and cancer at any site.
RE: Hypofractionated Radiotherapy for Patients with Early-Stage Glottic Cancer: Patterns of Care and Survival J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-07 Jens Overgaard
An article in the Journal by Bledsoe et al. recently reported on patterns of care and survival in patients treated with radiotherapy for early-stage glottic carcinoma (1). A similar study by Stokes et al. was also published in the International Journal of Radiation Oncology * Biology * Physics (2). Both evaluated the role of hypofractionated radiotherapy using the National Cancer Database and identified almost the same patients. The results and conclusions, not surprisingly, were the same: that hypofractionated radiotherapy yielded a small overall survival benefit.
Response J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-07 Trevor J Bledsoe, Henry S Park, John M Stahl, Wendell G Yarbrough, Barbara A Burtness, Roy H Decker, Zain A Husain
Because of its increased convenience and decreased cost, once-daily hypofractionated radiotherapy (HFX; 2.25 Gy/fraction) has been adopted over other altered-fractionation schedules in the United States for the management of early-stage glottic cancer. In our patterns-of-care analysis, we found that over 80% of patients were treated with either hypofractionation (2.25 Gy/fraction) or conventional fractionation (CFX; 2.0 Gy/fraction); utilization rates of other altered-fractionation regimens were 2.6% or less. Given the low utilization rates of fractionation schedules not recommended by the National Comprehensive Cancer Network guidelines, we did not compare other altered-fractionation schedules to CFX. Therefore, we were not able to make conclusions regarding the optimal radiotherapy treatment schedule; we could only conclude that our findings suggest that HFX is superior to CFX.
Retuning the Radio in Radiobiology J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-03 Steven J Chmura, Philip P Connell, Ralph R Weichselbaum
The radiobiology research community has contributed immensely to cancer research, with far-reaching and consequential scientific insights, including demonstration that the chromosome is the target of radiation-induced mutations (Muller, Nobel prize, 1946), advances in DNA repair (Lindahl/Modrich/Sancar, Nobel prize, 2015), descriptions of hypoxia in cancer biology (first noted by Thomlinson/Gray in 1955  with eventual Lasker Prize to Ratcliffe/Semenza/Kaelin, 2016), identification of stem cells (Till/McCulloch, Lasker prize in 2005), and the work of Tolmach that presaged a fuller description of cell cycles (Hartwell/Hunt/Nurse, Nobel prize, 2001). Radiobiologic discoveries have transformed scientific disciplines well beyond the field of radiobiology. Furthermore, many radiobiology principles have slowly become embedded into larger scientific pursuits and clinical practice, such as multimodality chemoradiotherapy (2–4) and cancer immunotherapy (5–7).
Cost-effectiveness Analysis of Nivolumab for Treatment of Platinum-Resistant Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck J. Natl. Cancer Inst. (IF 12.589) Pub Date : 2017-11-03 Kathryn R Tringale, Kate T Carroll, Kaveh Zakeri, Assuntina G Sacco, Linda Barnachea, James D Murphy
The CheckMate 141 trial found that nivolumab improved survival for patients with recurrent or metastatic head and neck cancer (HNC). Despite the improved survival, nivolumab is much more expensive than standard therapies. This study assesses the cost-effectiveness of nivolumab for the treatment of HNC.
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