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Purpose: While limited resources can make high-quality, comprehensive, coordinated cancer care provision challenging in rural settings, rural cancer patients often rely on local hospitals for care. To develop resources and strategies to support high-quality local cancer care, it is critical to understand the current experiences of rural cancer care physicians, including perceived strengths and challenges of providing cancer care in rural areas.  METHODS: Semi-structured interviews were conducted with 13 cancer providers associated with all 12 non-metropolitan/rural Iowa hospitals that diagnose or treat >100 cancer patients annually. Iterative thematic analysis was conducted to develop domains., Findings: Participants identified geographic proximity and sense of community as strengths of local care. They described decision-making processes and challenges related to referring patients to larger centers for complex procedures, including a lack of dedicated navigators to facilitate and track transfers between institutions and occasional lack of respect from academic physicians. Participants reported a desire for strengthening collaborations with larger urban/academic cancer centers, including access to educational opportunities, shared resources and strategies to collect and monitor data on quality, and clinical trials., Conclusions: Rural cancer care providers are dedicated to providing high-quality care close to home for their patients and would welcome opportunities to increase collaboration with larger centers to improve coordination and comprehensiveness of care, collect and monitor data on quality of care, and access continuing education opportunities. Further research is needed to develop implementation approaches that will extend resources, services, and expertise to rural providers to facilitate high-quality cancer care for all cancer patients., (© 2024 The Authors. The Journal of Rural Health published by Wiley Periodicals LLC on behalf of National Rural Health Association.)

Triple-negative breast cancer (TNBC) is a very heterogeneous and aggressive breast cancer subtype with a high risk of mortality, even if diagnosed early. The mainstay of early-stage breast cancer includes systemic chemotherapy and surgery, with or without radiation therapy. More recently, immunotherapy is approved to treat TNBC, but managing immune-rated adverse events while balancing efficacy is a challenge. The purpose of this review is to highlight the current treatment recommendations for early-stage TNBC and the management of immunotherapy toxicities.

Purpose: The College of American Pathologists (CAP) has developed a guideline on testing for mismatch repair (MMR) and microsatellite instability (MSI) for patients considered for immune checkpoint inhibitor therapy. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations., Methods: The CAP guideline was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel subsequently reviewed the content and the recommendations., Results: The ASCO Endorsement Panel determined that the recommendations from the CAP guideline, published on August 3, 2022, are clear, thorough, and based on the most relevant scientific evidence. ASCO endorses Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: Guideline From the College of American Pathologists in Collaboration With the Association for Molecular Pathology and Fight Colorectal Cancer ., Recommendations: Within the guideline, MMR immunohistochemistry (IHC), MSI polymerase chain reaction, and MSI next-generation sequencing are all recommended testing options for colorectal cancer, MMR-IHC and MSI-polymerase chain reaction for gastroesophageal and small bowel cancer, and only MMR-IHC for endometrial cancer. No recommendation in favor of any testing method over another could be made for any other cancer. Tumor mutational burden was not recommended as a surrogate for DNA MMR deficiency. If MMR deficiency consistent with Lynch syndrome is detected, it should be communicated to the treating physician.Additional information is available at www.asco.org/molecular-testing-and-biomarkers-guidelines.

Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines., Methods: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV)., Findings: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44)., Interpretation: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer., Funding: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH)., Competing Interests: TKC reports grants, personal fees and non-financial support from Merck, BMS, Exelixis, Astra Zeneca, Eli Lilly, Eisai, Novartis, GSK, Pfizer, EMD Serono; stocks in Pionyr, Tempest, outside the submitted work; In addition, TKC reports patent: pending International Patent Application No. PCT/US2018/12209, entitled “PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response,” filed January 3, 2018, claiming priority to U.S. Provisional Patent Application No. 62/445,094, filed January 11, 2017; pending International Patent Application No. PCT/US2018/058430, entitled “Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy,” filed October 31, 2018, claiming priority to U.S. Provisional Patent Application No. 62/581,175, filed November 3, 2017; TKC sits on National Comprehensive Cancer Network kidney panel. CL reports grants from Genentech/ImCore. ZB reports non-financial support from Bristol Myers Squibb, grants from Genentech/ImCore, personal fees from UpToDate, outside the submitted work. ALS reports non-financial support from Astellas and Pfizer outside the submitted work. GdLL reports personal fees from Boehringer Ingelheim, Pfizer, AstraZeneca; grants from AstraZeneca, Merck Sharp & Dohme, EMD Serono, AstraZeneca, Blueprint Medicines, Tesaro, Bavarian Nordic, Novartis, G1 Therapeutics, Adaptimmune, BMS, GSK, Abbvie, Rgenix, Pfizer, Roche, Genentech, Eli Lilly, Janssen; personal fees from Boehringer Ingelheim, Pfizer, E.R. Squibb Sons, LLC, Janssen; all outside the submitted work. CH reports grants from Merck, Bayer, Genentech, AstraZeneca, Bausch Health; Consulting fees from Tempus, Genzyme, EMD Sorono, payment or honoraria from OncLive/MJH Life Sciences, support for attending meetings and/or travel from Merck, participation on a data safety monitoring or advisory board of Henry Ford Cancer Institute, Hoosier Cancer Research Network; Leadership or fiduciary role in Wayne County Medical Society of Southeast Michigan; Stock or stock options in Johnson and Johnson, all outside the submitted work. EAG reports Consulting fees from Alexion Inc, Picnic Health, AbbVie, CTI Biopharma, Genentech Inc., Novartis, Celgene/Bristol Myers-Squibb, Takeda oncology, Taiho Oncology and Research Funding from Genentech Inc, Astex Pharmaceuticals, and BluePrint Medicines, outside the submitted work. SH reports grants/research supports from ASCO TAPUR, Astellas; honoraria or consultation fees from Sanofi, Aveo Oncology, outside the submitted work. SB reports Consulting fees from BMS, Exelexis, Eisai, Pfizer, Myovant, SeaGen; Payment or honoraria from Exelexis, Eisai, BMS; Participation on a Data Safety Monitoring Board or Advisory Board from SeaGen, Pfizer, Myovant; Stock or stock options in Natera; outside the submitted work. MJ reports grants from AstraZeneca, Pfizer; Eisai, personal fees from Seagen, Sanofi, outside the submitted work. NTNG reports personal fees from Novocure, outside the submitted work. RRM reports Advisory board/consultant—Aveo, AstraZeneca, Bayer, Bristol Myers Squib, Calithera, Caris, Dendreon, Exelixis, Janssen, Merck, Myovant, Novartis, Pfizer, Sanofi, Sorrento therapeutics, Pfizer, Tempus, Vividion, unrelated to this work. SMR reports advisory for Roche, Janssen, Sanofi, and EUSA Pharma, unrelated to this work. PV reports institutional research funding from Sanofi; stocks or stock options in Novavax, Biontech. HAZ acknowledges support from Georgia NCORP. CRF reports grants from Merck Foundation, grants from NCCN/Pfizer, grants from National Cancer Institute, other from National Cancer Institute, other from Patient-Centered Outcomes Research Institute, outside the submitted work. SM reports support from National Cancer Institute, and Intl Assoc. for the Study of Lung Cancer during the conduct of the study; and personal fees from National Geographic outside the submitted work. DF reports Grants or contracts from Merck, Viracor, Astellas; Support for attending meetings and/or travel from Viracor; outside the submitted work. JLW reports grants from NIH during the conduct of the study; personal fees from Roche, Westat, Flatiron Health, Melax Tech, IBM Watson Health, ownership of HemOnc.org LLC, grants from AACR; outside the submitted work. TMW-D reports grants from BMS, Merck & Co, GSK/Tesaro, Janssen; personal fees from Exicure, Shattuck Labs, SITC, Merck & Co, Caris Life Sciences, outside the submitted work. C-YH, SRKS, CJ, LBW, UW, TEO'C, OAP, EJK, HS, RN, TKN, RQ, MP, BHM, SADP, KR, BF, DYR, MKA, HS, DRR, YS, and SB have nothing to disclose. The content is solely the responsibility of the authors and does not necessarily represent the US Food and Drug Administration official views or policies., (© 2023 The Author(s).)

As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Expert knowledge is often shared among multidisciplinary academic teams at tumor boards (TBs) across the country, but these conversations exist in silos and do not reach the wider oncology community., Objective: Using an oncologist-only question and answer (Q&A) website, we sought to document expert insights from TBs at National Cancer Institute-designated Comprehensive Cancer Centers (NCI-CCCs) to provide educational benefits to the oncology community., Methods: We designed a process with the NCI-CCCs to document and share discussions from the TBs focused on areas of practice variation on theMednet, an interactive Q&A website of over 13,000 US oncologists. The faculty translated the TB discussions into concise, non-case-based Q&As on theMednet. Answers were peer reviewed and disseminated in email newsletters to registered oncologists. Reach and engagement were measured. Following each Q&A, a survey question asked how the TB Q&As impacted the readers' practice., Results: A total of 23 breast, thoracic, gastrointestinal, and genitourinary programs from 16 NCI-CCC sites participated. Between December 2016 and July 2021, the faculty highlighted 368 questions from their TBs. Q&As were viewed 147,661 times by 7381 oncologists at 3515 institutions from all 50 states. A total of 277 (75%) Q&As were viewed every month. Of the 1063 responses to a survey question on how the Q&A affected clinicians' practices, 646 (61%) reported that it confirmed their current practice, 163 (20%) indicated that a Q&A would change their future practice, and 214 (15%) reported learning something new., Conclusions: Through an online Q&A platform, academics at the NCI-CCCs share knowledge outside the walls of academia with oncologists across the United States. Access to up-to-date expert knowledge can reassure clinicians' practices, significantly impact patient care in community practices, and be a source of new knowledge and education., (©Maitri Kalra, Elizabeth Henry, Kelly McCann, Meghan S Karuturi, Jean G Bustamante Alvarez, Amanda Parkes, Robert Wesolowski, Mei Wei, Sarah S Mougalian, Gregory Durm, Angel Qin, Caitlin Schonewolf, Meghna Trivedi, Avan J Armaghani, Frederick H Wilson, Wade T Iams, Anita A Turk, Praveen Vikas, Michael Cecchini, Sam Lubner, Priyadarshini Pathak, Kristen Spencer, Vadim S Koshkin, Matthew K Labriola, Catherine H Marshall, Katy E Beckermann, theMednet.org NCI-CCC Tumor Board Program Collaborative Group, Marina N Sharifi, Anthony C Bejjani, Varsha Hotchandani, Samir Housri, Nadine Housri. Originally published in JMIR Cancer (https://cancer.jmir.org), 19.05.2022.)

The oncogenic role of estrogen receptor (ER) signaling in breast cancer has long been established. Interaction of estrogen with estrogen receptor (ER) in the nucleus activates genomic pathways of estrogen signaling. In contrast, estrogen interaction with the cell membrane-bound G-protein-coupled estrogen receptor (GPER) activates the rapid receptor-mediated signaling transduction cascades. Aberrant estrogen signaling enhances mammary epithelial cell proliferation, survival, and angiogenesis, hence is an important step towards breast cancer initiation and progression. Meanwhile, a growing number of studies also provide evidence for estrogen's pro- or anti-inflammatory roles. As other articles in this issue cover classic ER and GPER signaling mediated by estrogen, this review will discuss the crucial mechanisms by which estrogen signaling influences chronic inflammation and how that is involved in breast cancer. Xenoestrogens acquired from plant diet or exposure to industrial products constantly interact with and alter innate estrogen signaling at various levels. As such, they can modulate chronic inflammation and breast cancer development. Natural xenoestrogens generally have anti-inflammatory properties, which is consistent with their chemoprotective role in breast cancer. In contrast, synthetic xenoestrogens are proinflammatory and carcinogenic compounds that can increase the risk of breast cancer. This article also highlights important xenoestrogens with a particular focus on their role in inflammation and breast cancer. Improved understanding of the complex relationship between estrogens, inflammation, and breast cancer will guide clinical research on agents that could advance breast cancer prevention and therapy.

Purpose: To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitor (ICPi) therapy., Methods: A multidisciplinary panel of medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to update the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 through 2021., Results: A total of 175 studies met the eligibility criteria of the systematic review and were pertinent to the development of the recommendations. Because of the paucity of high-quality evidence, recommendations are based on expert consensus., Recommendations: Recommendations for specific organ system-based toxicity diagnosis and management are presented. While management varies according to the organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, except for some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert ≤ grade 1. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids. Corticosteroids should be tapered over the course of at least 4-6 weeks. Some refractory cases may require other immunosuppressive therapy. In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, except for endocrinopathies that have been controlled by hormone replacement. Additional information is available at www.asco.org/supportive-care-guidelines., Competing Interests: Reprint Requests: Bryan J. SchneiderResearch Funding: Merck Jarushka NaidooHonoraria: Bristol Myers Squibb, AstraZeneca/MedImmune, Merck, Daiichi Sankyo/Lilly, TakedaConsulting or Advisory Role: Bristol Myers Squibb, AstraZeneca/MedImmune, Roche/Genentech, Daiichi Sankyo/Lilly, Takeda, Pfizer, Kaleido BiosciencesResearch Funding: Merck, AstraZeneca, Roche/GenentechTravel, Accommodations, Expenses: Bristol Myers Squibb, AstraZeneca/MedImmune Bianca D. SantomassoConsulting or Advisory Role: Celgene, Janssen, Legend Biotech, Incyte, In8BioResearch Funding: ADC Therapeutics Sherry AdkinsConsulting or Advisory Role: CelgeneTravel, Accommodations, Expenses: Celgene Milan AnadkatStock and Other Ownership Interests: Anthem, Humana, Perrigo, Walgreens Boots Alliance, Abbott Laboratories, Merck, AbbVie, Amgen, Bristol Myers Squibb, Celgene, CVS Health, Gilead Sciences, Incyte, Johnson & Johnson, Lilly, Medtronic, Mylan, Pfizer, Procter & Gamble, United Health Group, Regeneron, Roche, Moderna Therapeutics (I), Dexcom, Quest DiagnosticsHonoraria: Adgero Biopharmaceuticals, Boehringer Ingelheim, Novocure, AbbVie, UCB, InnovadermConsulting or Advisory Role: Adgero Biopharmaceuticals, Boehringer Ingelheim, Novocure, Kintara TherapeuticsResearch Funding: AnaptysBio, Boehringer Ingelheim, Biogen, InflamRx, Lutris, Novartis, OnQuality Pharmaceuticals, Veloce Pharmaceuticals, XBiotech, UCB, AbbVie, Lilly Michael B. AtkinsStock and Other Ownership Interests: Werewolf Pharma, PyxisConsulting or Advisory Role: Genentech, Novartis, Bristol Myers Squibb, Merck, Exelixis, Eisai, Agenus, Arrowhead Pharmaceuticals, Werewolf Pharma, Surface Oncology, Iovance Biotherapeutics, Pyxis, Pneuma Respiratory, Leads Biolabs, Fathom Biotechnology, AVEO, Cota Healthcare, Neoleukin Therapeutics, Adagene, Idera, Ellipses Pharma, AstraZeneca, PACT Pharma, Seattle Genetics, Pfizer, ScholarRock, Asher Bio, Calithera Biosciences, Takeda, SanofiResearch Funding: Bristol Myers Squibb Kelly J. BrassilEmployment: Pack HealthHonoraria: Oncology Nursing Society, WebMD, M Consulting, i3 HealthResearch Funding: AbbVie, Daiichi Sankyo, Astellas Pharma, Genentech, Sanofi, GlaxoSmithKlineTravel, Accommodations, Expenses: Pack Health Jeffrey M. CaterinoStock and Other Ownership Interests: Motive Medical IntelligenceConsulting or Advisory Role: Wellstat TherapeuticsResearch Funding: Stago, Entegrion, JDP Therapeutics, AstraZeneca Ian ChauHonoraria: Lilly, Eisai, ServierConsulting or Advisory Role: Lilly, Bristol Myers Squibb, MSD Oncology, Merck Serono, Roche/Genentech, AstraZeneca, Pierre Fabre, Boehringer Ingelheim, Incyte, OncXerna Therapeutics, Astellas Pharma, GlaxoSmithKline, Eisai, SotioResearch Funding: Janssen-Cilag, LillyTravel, Accommodations, Expenses: MSD, Merck Serono, Lilly, Bristol Myers Squibb, Eisai Marianne J. DaviesSpeakers' Bureau: AstraZeneca, Genentech/Roche, Merck, Bristol Myers Squibb Marc S. ErnstoffStock and Other Ownership Interests: GE Healthcare, Bristol Myers SquibbResearch Funding: Alkermes, EMD SeronoTravel, Accommodations, Expenses: ImmuNext, AlkermesOther Relationship: Bristol Myers Squibb Leslie FecherConsulting or Advisory Role: Via Oncology, Hoosier Cancer Research Network, ElsevierResearch Funding: Merck, Incyte, Bristol Myers Squibb, Pfizer/EMD Serono, Array BioPharma, Kartos TherapeuticsOther Relationship: Array BioPharmaUncompensated Relationships: NCCN, American Association of Clinical Endocrinology, ASCO Monalisa GhoshResearch Funding: Novartis, Celgene Jennifer S. MammenStock and Other Ownership Interests: Johnson & Johnson, Bristol-Myers SquibbConsulting or Advisory Role: Five Prime Therapeutics Aung NaingConsulting or Advisory Role: Novartis, CytomX Therapeutics, OncoSec, STCube Pharmaceuticals Inc, Kymab, Takeda (I), CSL Behring (I), Horizon Pharma (I), Genome & CompanyResearch Funding: NCI, EMD Serono, MedImmune, Atterocor, Amplimmune, ARMO BioSciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance BioSciences Inc, Healios, Lilly, Kymap, PsiOxus Therapeutics, Immune Deficiency Foundation (I), Arcus Biosciences, NeoImmuneTech, ImmuneOncia, Surface Oncology, Baxalta (I), Jeffrey Modell Foundation (I), Chao Physician-Scientist Awards (I)Travel, Accommodations, Expenses: ARMO BioSciences Loretta J. NastoupilHonoraria: Celgene, Gilead Sciences, Novartis, Bayer, Janssen Oncology, Pfizer, Gamida Cell, TG Therapeutics, Bristol Myers Squibb, ADC Therapeutics, Morphosys, Epizyme, GenmabResearch Funding: TG Therapeutics, Janssen Biotech, Celgene, Genentech/Roche, LAM Therapeutics, Epizyme, Novartis, IgM Biosciences, Caribou Biosciences, Gilead Sciences, Allogene Therapeutics, Takeda Tanyanika PhillipsTravel, Accommodations, Expenses: City of Hope Alexander SpiraLeadership: NEXT Oncology VirginiaStock and Other Ownership Interests: LillyHonoraria: CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen Oncology, Novartis, Bristol Myers Squibb, BayerConsulting or Advisory Role: Array BioPharma, Incyte, Amgen, Novartis, AstraZeneca/MedImmune, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Merck, Bristol Myers Squibb, Takeda, Janssen Research & DevelopmentResearch Funding: Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, LAM Therapeutics, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone Oncology, Plexxikon, Amgen, Loxo, Daiichi Sankyo, ADC Therapeutics, Janssen Oncology, Mirati Therapeutics, Rubius Therapeutics Maria Suarez-AlmazorConsulting or Advisory Role: Agile Therapeutics, AMAG Pharmaceuticals, AbbVie/Genentech, Avenue Therapeutics, Gilead Sciences, ChemoCentryx, Celgene/Bristol Myers Squibb Umang SwamiConsulting or Advisory Role: Seattle Genetics John A. ThompsonConsulting or Advisory Role: Calithera Biosciences, Clinical Care Options/NCCN, BJ Bioscience, Alpine Immune Sciences, Neoleukin Therapeutics, Academy for Continued Healthcare Learning, Meeting Sites Pro, Regeneron, AVEO, Bristol Myers SquibbResearch Funding: Roche, Pfizer, Agensys, Five Prime Therapeutics, Trillium Therapeutics, Merck, Novartis, Xencor, Incyte Praveen VikasStock and Other Ownership Interests: Moderna Therapeutics, NovavaxResearch Funding: Sanofi Yinghong WangConsulting or Advisory Role: Tillotts Pharma, Azurrx Pharma Jeffrey S. WeberStock and Other Ownership Interests: CytomX Therapeutics, Biond, Protean Biodiagnostics, NeximmuneHonoraria: Bristol Myers Squibb, Merck, Genentech, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Amgen, Roche, Celldex, CytomX Therapeutics, Novartis, Sellas Life Sciences, WindMIL, Takeda, Moderna Therapeutics, Jounce Therapeutics, Kirin Pharmaceuticals, Regeneron, Idera, OncosecConsulting or Advisory Role: Celldex, Bristol Myers Squibb, Merck, Genentech, Roche, Amgen, AstraZeneca, GlaxoSmithKline, Daiichi Sankyo, CytomX Therapeutics, Novartis, Sellas Life Sciences, WindMIL, Jounce Therapeutics, Moderna Therapeutics, Kirin Pharmaceuticals, Protean Biodiagnostics, Idera, OncosecResearch Funding: Bristol Myers Squibb, Merck, GlaxoSmithKline, Genentech, Astellas Pharma, Incyte, Roche, Novartis, NextCure, Moderna TherapeuticsPatents, Royalties, Other Intellectual Property: Named on a patent submitted by Moffitt Cancer Center for an IPILIMUMAB biomarker, named on a patent for 41BB induced TIL by Moffitt Cancer CenterTravel, Accommodations, Expenses: Bristol Myers Squibb, GlaxoSmithKline, Roche, Celldex, Amgen, Merck, AstraZeneca, Genentech, Novartis Pauline FunchainConsulting or Advisory Role: EisaiResearch Funding: Pfizer, Bristol Myers Squibb, Taiho OncologyNo other potential conflicts of interest were reported.

Purpose: To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with chimeric antigen receptor (CAR) T-cell therapy., Methods: A multidisciplinary panel of medical oncology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to develop the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 to 2021., Results: The systematic review identified 35 eligible publications. Because of the paucity of high-quality evidence, recommendations are based on expert consensus., Recommendations: The multidisciplinary team issued recommendations to aid in the recognition, workup, evaluation, and management of the most common CAR T-cell-related toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, B-cell aplasia, cytopenias, and infections. Management of short-term toxicities associated with CAR T cells begins with supportive care for most patients, but may require pharmacologic interventions for those without adequate response. Management of patients with prolonged or severe CAR T-cell-associated cytokine release syndrome includes treatment with tocilizumab with or without a corticosteroid. On the basis of the potential for rapid decline, patients with moderate to severe immune effector cell-associated neurotoxicity syndrome should be managed with corticosteroids and supportive care.Additional information is available at www.asco.org/supportive-care-guidelines., Competing Interests: Reprint Requests: Bianca D. SantomassoConsulting or Advisory Role: Celgene, Janssen, Legend Biotech, Incyte, In8BioResearch Funding: ADC Therapeutics (Inst) Loretta J. NastoupilHonoraria: Celgene, Gilead Sciences, Novartis, Bayer, Janssen Oncology, Pfizer, Gamida Cell, TG Therapeutics, Bristol Myers Squibb, ADC Therapeutics, Morphosys, Epizyme, GenmabResearch Funding: TG Therapeutics, Janssen Biotech, Celgene, Genentech/Roche, LAM Therapeutics, Epizyme, Novartis, IgM Biosciences, Caribou Biosciences, Gilead Sciences, Allogene Therapeutics, Takeda Sherry AdkinsConsulting or Advisory Role: CelgeneTravel, Accommodations, Expenses: Celgene Bryan J. SchneiderResearch Funding: Merck Milan AnadkatStock and Other Ownership Interests: Anthem, Humana, Perrigo, Walgreens Boots Alliance, Abbott Laboratories, Merck, AbbVie, Amgen, Bristol Myers Squibb, Celgene, CVS Health, Gilead Sciences, Incyte, Johnson & Johnson, Lilly, Medtronic, Mylan, Pfizer, Procter & Gamble, United Health Group, Regeneron, Roche, Moderna Therapeutics, Dexcom, Quest DiagnosticsHonoraria: Adgero Biopharmaceuticals, Boehringer Ingelheim, Novocure, AbbVie, UCB, InnovadermConsulting or Advisory Role: Adgero Biopharmaceuticals, Boehringer Ingelheim, Novocure, Kintara TherapeuticsResearch Funding: AnaptysBio, Boehringer Ingelheim, Biogen, InflaRx, Lutris, Novartis, OnQuality Pharmaceuticals, Veloce Pharmaceuticals, XBiotech, UCB, AbbVie, Lilly Michael B. AtkinsStock and Other Ownership Interests: Werewolf Pharma, PyxisConsulting or Advisory Role: Genentech, Novartis, Bristol Myers Squibb, Merck, Exelixis, Eisai, Agenus, Arrowhead Pharmaceuticals, Werewolf Pharma, Surface Oncology, Iovance Biotherapeutics, Pyxis, Pneuma Respiratory, Leads Biolabs, Fathom Biotechnology, Aveo, Cota Healthcare, Neoleukin Therapeutics, Adagene, Idera, Ellipses Pharma, AstraZeneca, PACT Pharma, Seattle Genetics, Pfizer, Scholar Rock, Asher Bio, Calithera Biosciences, Takeda, SanofiResearch Funding: Bristol Myers Squibb Kelly J. BrassilEmployment: Pack HealthHonoraria: Oncology Nursing Society, WebMD, M Consulting, i3 HealthResearch Funding: AbbVie, Daiichi Sankyo, Astellas Pharma, Genentech, Sanofi, GlaxoSmithKlineTravel, Accommodations, Expenses: Pack Health Jeffrey M. CaterinoStock and Other Ownership Interests: Motive Medical IntelligenceConsulting or Advisory Role: Wellstat TherapeuticsResearch Funding: Stago, Entegrion, JDP Therapeutics, AstraZeneca Ian ChauHonoraria: Lilly, Eisai, ServierConsulting or Advisory Role: Lilly, Bristol Myers Squibb, MSD Oncology, Merck Serono, Roche/Genentech, AstraZeneca, Pierre Fabre, Boehringer Ingelheim, Incyte, OncXerna Therapeutics, Astellas Pharma, GlaxoSmithKline, Eisai, SotioResearch Funding: Janssen-Cilag, LillyTravel, Accommodations, Expenses: MSD, Merck Serono, Lilly, Bristol Myers Squibb, Eisai Marianne J. DaviesSpeakers' Bureau: AstraZeneca, Genentech/Roche, Merck, Bristol Myers Squibb Marc S. ErnstoffStock and Other Ownership Interests: GE Healthcare, Bristol Myers SquibbResearch Funding: Alkermes, EMD SeronoTravel, Accommodations, Expenses: ImmuNext, AlkermesOther Relationship: Bristol Myers Squibb Leslie FecherConsulting or Advisory Role: Via Oncology, Hoosier Cancer Research Network, ElsevierResearch Funding: Merck, Incyte, Bristol Myers Squibb, Pfizer/EMD Serono, Array BioPharma, Kartos TherapeuticsOther Relationship: Array BioPharmaUncompensated Relationships: NCCN, American Association of Clinical Endocrinology, ASCO Pauline FunchainConsulting or Advisory Role: EisaiResearch Funding: Pfizer, Bristol Myers Squibb, Taiho Oncology Jennifer S. MammenStock and Other Ownership Interests: Johnson & Johnson, Bristol Myers SquibbConsulting or Advisory Role: Five Prime Therapeutics Jarushka NaidooHonoraria: Bristol Myers Squibb, AstraZeneca/MedImmune, Merck, Daiichi Sankyo/Lilly, TakedaConsulting or Advisory Role: Bristol Myers Squibb, AstraZeneca/MedImmune, Roche/Genentech, Daiichi Sankyo/Lilly, Takeda, Pfizer, Kaleido BiosciencesResearch Funding: Merck, AstraZeneca, Roche/GenentechTravel, Accommodations, Expenses: Bristol Myers Squibb, AstraZeneca/MedImmune Aung NaingConsulting or Advisory Role: Novartis, CytomX Therapeutics, OncoSec, STCube Pharmaceuticals Inc, Kymab, Takeda (I), CSL Behring (I), Horizon Pharma (I), Genome & CompanyResearch Funding: NCI, EMD Serono, MedImmune, Atterocor, Amplimmune, ARMO BioSciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance BioSciences Inc, Healios, Lilly, Kymab, PsiOxus Therapeutics, Immune Deficiency Foundation (I), Arcus Biosciences, NeoImmuneTech, ImmuneOncia, Surface Oncology, Baxalta (I), Jeffrey Modell Foundation (I), Chao Physician-Scientist AwardsTravel, Accommodations, Expenses: ARMO BioSciences Tanyanika PhillipsTravel, Accommodations, Expenses: City of Hope Alexander SpiraLeadership: NEXT Oncology VirginiaStock and Other Ownership Interests: Eli LillyHonoraria: CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen Oncology, Novartis, Bristol Myers Squibb, BayerConsulting or Advisory Role: Array BioPharma (Inst), Incyte, Amgen, Novartis, AstraZeneca/MedImmune (Inst), Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Merck (Inst), Bristol Myers Squibb (Inst), Takeda, Janssen Research & DevelopmentResearch Funding: Roche (Inst), AstraZeneca (Inst), Boehringer Ingelheim (Inst), Astellas Pharma (Inst), MedImmune (Inst), Novartis (Inst), Newlink Genetics (Inst), Incyte (Inst), AbbVie (Inst), Ignyta (Inst), LAM Therapeutics (Inst), Trovagene (Inst), Takeda (Inst), Macrogenics (Inst), CytomX Therapeutics (Inst), LAM Therapeutics (Inst), Astex Pharmaceuticals (Inst), Bristol Myers Squibb (Inst), Loxo (Inst), Arch Therapeutics (Inst), Gritstone (Inst), Plexxikon (Inst), Amgen (Inst), Loxo (Inst), Daiichi Sankyo (Inst), ADCT (Inst), Janssen Oncology (Inst), Mirati Therapeutics (Inst), Rubius (Inst) Maria Suarez-AlmazorConsulting or Advisory Role: Agile Therapeutics, AMAG Pharmaceuticals¸ Abbvie/Genentech, Avenue Therapeutics, Gilead Sciences, ChemoCentryx, Celgene/Bristol Myers Squibb Umang SwamiConsulting or Advisory Role: Seattle Genetics John A. ThompsonConsulting or Advisory Role: Calithera Biosciences, Clinical Care Options/NCCN, BJ Bioscience, Alpine Immune Sciences, Neoleukin Therapeutics, Academy for Continued Healthcare Learning, Meeting Sites Pro, Regeneron, AVEO, Bristol Myers SquibbResearch Funding: Roche, Pfizer, Agensys, Five Prime Therapeutics, Trillium Therapeutics, Merck, Novartis, Xencor, Five Prime Therapeutics, Incyte Praveen VikasStock and Other Ownership Interests: NovavaxResearch Funding: Sanofi Yinghong WangConsulting or Advisory Role: Tillotts Pharma, Azurrx Pharma Jeffrey S. WeberStock and Other Ownership Interests: CytomX Therapeutics, Biond, Protean Biodiagnostics, NeximmuneHonoraria: Bristol Myers Squibb, Merck, Genentech, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Amgen, Roche, Celldex, CytomX Therapeutics, Novartis, Sellas Life Sciences, WindMIL, Takeda, Moderna Therapeutics, Jounce Therapeutics, Kirin Pharmaceuticals, Regeneron, Idera, OncosecConsulting or Advisory Role: Celldex, Bristol Myers Squibb, Merck¸ Genentech, Roche, Amgen, AstraZeneca, GlaxoSmithKline, Daiichi Sankyo, CytomX Therapeutics, Novartis, Sellas Life Sciences, WindMIL, Jounce Therapeutics, Moderna Therapeutics, Kirin Pharmaceuticals, Protean Biodiagnostics, Idera, OncosecResearch Funding: Bristol Myers Squibb, Merck, GlaxoSmithKline, Genentech, Astellas Pharma, Incyte, Roche, Novartis, NextCure (Inst), Moderna Therapeutics (Inst)Patents, Royalties, Other Intellectual Property: Named on a patent submitted by Moffitt Cancer Center for an IPILIMUMAB biomarker, named on a patent from Biodesix for a PD-1 antibody biomarker, and named on a patent for 41BB-induced TIL by Moffitt Cancer CenterTravel, Accommodations, Expenses: Bristol Myers Squibb, GlaxoSmithKline, Roche, Celldex, Amgen, Merck, AstraZeneca, Genentech, Novartis Monalisa GhoshResearch Funding: Celgene (Inst)No other potential conflicts of interest were reported.

Purpose: To update recommendations of the ASCO systemic therapy for hormone receptor (HR)-positive metastatic breast cancer (MBC) guideline., Methods: An Expert Panel conducted a systematic review to identify new, potentially practice-changing data., Results: Fifty-one articles met eligibility criteria and form the evidentiary basis for the recommendations., Recommendations: Alpelisib in combination with endocrine therapy (ET) should be offered to postmenopausal patients, and to male patients, with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA -mutated, ABC, or MBC following prior endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. Clinicians should use next-generation sequencing in tumor tissue or cell-free DNA in plasma to detect PIK3CA mutations. If no mutation is found in cell-free DNA, testing in tumor tissue, if available, should be used as this will detect a small number of additional patients with PIK3CA mutations. There are insufficient data at present to recommend routine testing for ESR1 mutations to guide therapy for HR-positive, HER2-negative MBC. For BRCA1 or BRCA2 mutation carriers with metastatic HER2-negative breast cancer, olaparib or talazoparib should be offered in the 1st-line through 3rd-line setting. A nonsteroidal aromatase inhibitor (AI) and a CDK4/6 inhibitor should be offered to postmenopausal women with treatment-naïve HR-positive MBC. Fulvestrant and a CDK4/6 inhibitor should be offered to patients with progressive disease during treatment with AIs (or who develop a recurrence within 1 year of adjuvant AI therapy) with or without one line of prior chemotherapy for metastatic disease, or as first-line therapy. Treatment should be limited to those without prior exposure to CDK4/6 inhibitors in the metastatic setting.Additional information can be found at www.asco.org/breast-cancer-guidelines., Competing Interests: Reprint Requests: 2318 Mill Road, Suite 800, Alexandria, VA 22314; guidelines@asco.org Debra L. BartonResearch Funding: Merck Lesley J. FallowfieldHonoraria: Voluntis, Genomic Health, NanoString Technologies, Novartis, Pfizer, MSD, Novartis, AbbVie, Clovis OncologyConsulting or Advisory Role: Puma Biotechnology, Voluntis, AstraZeneca, Takeda, Genomic Health/Exact Sciences, Lilly, Seagen, RocheResearch Funding: Bristol Myers Squibb, Novartis, LillyTravel, Accommodations, Expenses: Genomic Health Stephen R. D. JohnstonHonoraria: Pfizer, Novartis, Eisai, AstraZeneca, Roche, LillyConsulting or Advisory Role: Lilly, Puma Biotechnology, Novartis, PfizerResearch Funding: Pfizer, Puma BiotechnologyExpert Testimony: Novartis Jennifer K. LittonHonoraria: UpToDateConsulting or Advisory Role: Pfizer, AstraZeneca, Medivation/Pfizer, Ayala PharmaceuticalsSpeakers' Bureau: Physicans' Education Resource, UpToDate, Med Learning Group, Medscape, Prime Oncology, Clinical Care Options, MedpageResearch Funding: Genentech, Pfizer, EMD Serono, AstraZeneca, Zenith Epigenetics, MerckPatents, Royalties, Other Intellectual Property: UptoDateTravel, Accommodations, Expenses: Physicans' Education Resource, Med Learning Group, Medscape, Clinical Care OptionsOther Relationship: Medivation/Pfizer Praveen VikasStock and Other Ownership Interests: Moderna Therapeutics, NovavaxResearch Funding: Sanofi Rachel L. YungResearch Funding: Novartis, Odonate Therapeutics, American Cancer Society/Pfizer Hope S. RugoHonoraria: Puma Biotechnology, MylanConsulting or Advisory Role: SamsungResearch Funding: Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Lilly, Genentech, Merck, Immunomedics, Odonate Therapeutics, Daiichi Sankyo, Seattle Genetics, Sermonix Pharmaceuticals, AstraZenecaTravel, Accommodations, Expenses: Pfizer, Novartis, Macrogenics, Mylan, Daiichi Sankyo, AstraZeneca Spain, MerckOpen Payments Link: https://openpaymentsdata.cms.gov/summaryNo other potential conflicts of interest were reported.

The novel coronavirus disease 2019 (COVID-19) pandemic has caused catastrophic damage to human life across the globe along with social and financial hardships. According to the Johns Hopkins University Coronavirus Resource Center, more than 41.3 million people worldwide have been infected, and more than 1,133,000 people have died as of October 22, 2020. At present, there is no available vaccine and a scarcity of efficacious therapies. However, there is tremendous ongoing effort towards identifying effective drugs and developing novel vaccines. Early data from Adaptive COVID-19 Treatment Trials (ACTT) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) and compassionate use study have shown promise for remdesivir, leading to emergency authorization by the Food and Drug Administration (FDA) for treatment of hospitalized COVID-19 patients. However, several randomized studies have now shown no benefit or increased adverse events associated with remdesivir treatment. Drug development is a time-intensive process and requires extensive safety and efficacy evaluations. In contrast, drug repurposing is a time-saving and cost-effective drug discovery strategy geared towards using existing drugs instead of de novo drug discovery. Treatments for cancer and COVID-19 often have similar goals of controlling inflammation, inhibiting cell division, and modulating the host microenvironment to control the disease. In this review, we focus on anti-cancer drugs that can potentially be repurposed for COVID-19 and are currently being tested in clinical trials., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Borcherding et al.)

Background: National guidelines recommend chemotherapy as the mainstay of treatment for stage IV colon cancer, with primary tumor resection (PTR) reserved for patients with symptomatic primary or curable disease. The aims of this study were to characterize the treatment modalities received by patients with stage IV colon cancer and to determine the patient-, tumor-, and hospital-level factors associated with those treatments., Methods: Patients diagnosed with stage IV colon cancer in 2014 were extracted from the SEER Patterns of Care initiative. Treatments were categorized into chemotherapy only, PTR only, PTR + chemotherapy, and none/unknown., Results: The total weighted number of cases was 3,336; 17% of patients received PTR only, 23% received chemotherapy only, 41% received PTR + chemotherapy, and 17% received no treatment. In multivariable analyses, compared with chemotherapy only, PTR + chemotherapy was associated with being married (odds ratio [OR], 1.9), having bowel obstruction (OR, 2.55), and having perforation (OR, 2.29), whereas older age (OR, 5.95), Medicaid coverage (OR, 2.46), higher T stage (OR, 3.51), and higher N stage (OR, 6.77) were associated with PTR only. Patients who received no treatment did not have more comorbidities or more severe disease burden but were more likely to be older (OR, 3.91) and non-Hispanic African American (OR, 2.92; all P<.05). Treatment at smaller, nonacademic hospitals was associated with PTR (± chemotherapy)., Conclusions: PTR was included in the treatment regimen for most patients with stage IV colon cancer and was associated with smaller, nonacademic hospitals. Efforts to improve guideline implementation may be beneficial in these hospitals and also in non-Hispanic African American and older populations.

Immunotherapy has revolutionized the treatment of both hematological malignancies and solid tumors. The use of immunotherapy has improved outcome for patients with cancer across multiple tumor types, including lung, melanoma, ovarian, genitourinary, and more recently breast cancer with durable responses seen even in patients with widespread metastatic disease. Despite the promising results, immunotherapy still helps only a subset of patients due to overall low response rates. Moreover, the response to immunotherapy is highly cancer specific and results have not been as promising in cancers that are considered less immunogenic. The strategies to improve immunotherapy responses have focused on biomarker selection, like PD-L1 status, and usage of combinatorial agents, such as chemotherapy, targeted therapy, and radiotherapy. Of particular interest, DNA-damaging agents have the potential to enhance the response to immunotherapy by promoting neoantigen release, increasing tumor mutational burden, and enhancing PD-L1 expression. Poly-ADP-ribose polymerase (PARP) inhibitors are one such class of drugs that has shown synergy with immunotherapy in preclinical and early clinical studies. PARP-based therapies work through the inhibition of single-strand DNA repair leading to DNA damage, increased tumor mutational burden, making the tumor a more attractive target for immunotherapy. Of the solid tumors reviewed, breast, ovarian, and prostate cancers have demonstrated efficacy in the combination of PARP inhibition and immunotherapy, predominately in BRCA -mutated tumors. However, initial investigations into wildtype BRCA and gastrointestinal tumors have shown moderate overall response or disease control rates, dependent on the tumor type. In contrast, although a number of clinical trials underway, there is a paucity of published results for the use of the combination in lung or urothelial cancers. Overall this article focuses on the promise of combinatorial PARP inhibition and immunotherapy to improve patient outcomes in solid tumors, summarizing both early results and looking toward ongoing trials., (Copyright © 2020 Vikas, Borcherding, Chennamadhavuni and Garje.)

Purpose: To update the American Society of Clinical Oncology endorsement of the Cancer Care Ontario recommendations on the Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage, Operable Breast Cancer., Methods: Two phase III trials-the Trial Assigning Individualized Options for Treatment (TAILORx) in women with hormone receptor-positive, node-negative tumors and the Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy (MINDACT) trial-provided the evidence for this update., Updated Recommendations: Shared decision making between clinicians and patients is appropriate for adjuvant systemic therapy for breast cancer. For patients older than age 50 years and whose tumors have Onco type DX recurrence scores less than 26, and for patients age 50 years or younger whose tumors have Onco type DX recurrence scores less than 16, there is little to no benefit from chemotherapy. Clinicians may offer endocrine therapy alone for these patients. For patients age 50 years or younger with recurrence scores of 16 to 25, clinicians may offer chemoendocrine therapy. Patients with recurrence scores greater than 30 should be considered candidates for chemoendocrine therapy. Based on informal consensus, the Panel recommends that oncologists may offer chemoendocrine therapy to patients with Onco type DX scores of 26 to 30.The MammaPrint assay could be used to guide decisions on withholding adjuvant systemic chemotherapy in patients with hormone receptor-positive lymph node-negative breast cancer and in select patients with lymph node-positive cancers. In both patients with node-positive and node-negative disease, evidence of clinical utility of the MammaPrint assay was only apparent in those determined to be at high clinical risk; the Panel thus did not recommend use of MammaPrint assay in patients determined to be at low clinical risk. Remaining recommendations from the 2016 ASCO guideline endorsement are unchanged.Additional information is available at www.asco.org/breast-cancer-guidelines.

Background: Late-stage cancer diagnoses disproportionately occur in rural residents, frequently resulting in increased need for symptom management support with minimal access to these services. Oncology Associated Symptoms and Individualized Strategies (OASIS) is an eHealth symptom self-management intervention that was developed to provide cancer symptom self-management support and address this disparity., Purpose: To engage stakeholders about the symptom management needs and concerns of patients with advanced cancer living in rural areas., Methods: A 3-phased, mixed-methods design was used to (1) assess stakeholder needs and opinions; (2) develop a symptom self-management website; and (3) obtain usability feedback from potential users. Interviews with stakeholders (patients and clinic staff) from rural areas using a descriptive qualitative approach were analyzed; cross-cutting themes were identified; a symptom management web application was developed; and stakeholders completed a 12-item usability survey about the web application., Results: Patients (n = 16) and clinical staff (n = 10) participated in phase 1. Three major themes were identified: "symptom experience," "symptom management," and "technology." Through an iterative process using these results and evidence from the literature, the OASIS web application was developed. Usability testing with N = 126 stakeholders demonstrated that the web application is easy to use, contains relevant content, and has pleasing graphics. No differences were found among patients, family/friends, and staff. Both frequent and infrequent internet users positively evaluated the web application.  CONCLUSIONS: Rural stakeholders report significant symptom management needs, are interested in eHealth technologies, and perceived OASIS positively. Future research is needed to evaluate the feasibility, acceptability, and efficacy of OASIS., (© 2018 National Rural Health Association.)

Triple-negative breast cancer (TNBC) is a heterogeneous disease with poorer outcomes compared to other breast cancer subtypes. Contributing to the worse prognosis in TNBC is the higher rates of relapse and rapid progression after relapse. Advances in targeted therapeutics and conventional chemotherapy for TNBC have been stymied due to the lack of specific targets. Moreover, the responses to chemotherapy in TNBC lack durability, partially accounting for the higher rates of relapse. Immunotherapy, notably immune-checkpoint blockade, has shown to improve survival and maintain robust antitumor responses in both hematologic and solid malignancies. Unlike lung cancer, melanoma, and bladder cancer, most breast cancers are not inherently immunogenic and typically have low T cell infiltration. However, among breast cancer subtypes, TNBC is characterized by greater tumor immune infiltrate and higher degree of stromal and intratumoral tumor-infiltrating lymphocytes (TILs), a predictive marker for responses to immunotherapy. Moreover, in TNBC, the high number of stromal TILs is predictive of more favorable survival outcomes and response to chemotherapy. Immunotherapy is being extensively explored in TNBC and clinical trials are showing some promising results. This article focuses on the rationale for immunotherapy in TNBC, to explore and discuss preclinical data, results from early clinical trials, and to summarize some ongoing trials. We will also discuss the potential application of immunotherapy in TNBC from a clinician's perspective., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Immune checkpoints are a diverse set of inhibitory signals to the immune system that play a functional role in adaptive immune response and self-tolerance. Dysregulation of these pathways is a vital mechanism in the avoidance of immune destruction by tumor cells. Immune checkpoint blockade (ICB) refers to targeted strategies to disrupt the tumor co-opted immune suppression to enhance anti-tumor immunity. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) are two immune checkpoints that have the widest range of antibody-based therapies. These therapies have gone from promising approaches to Food and Drug Administration-approved first- and second-line agents for a number of immunogenic cancers. The burgeoning investigations of ICB efficacy in blood and solid cancers have underscored the importance of identifying the predictors of response and resistance to ICB. Identification of response correlates is made complicated by the observations of mixed reactions, or different responses in multiple lesions from the same patient, and delayed responses that can occur over a year after the induction therapy. Factors that can influence response and resistance in ICB can illuminate underlying molecular mechanisms of immune activation and suppression. These same response predictors can guide the identification of patients who would benefit from ICB, reduce off-target immune-relate adverse events, and facilitate the use of combinatorial therapies to increase efficacy. Here we review the underlying principles of immune checkpoint therapy and results of single-agent ICB clinical trials, and summarize the predictors of response and resistance., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Rural cancer patients face many challenges in receiving care, including limited availability of cancer treatments and cancer support providers (oncologists, social workers, mental healthcare providers, palliative care specialists, etc), transportation barriers, financial issues, and limited access to clinical trials. Oncologists and other cancer care providers experience parallel challenges in delivering care to their rural cancer patients. Although no one approach fully addresses the many challenges of rural cancer care, a number of promising strategies and interventions have been developed that transcend the issues associated with long travel distances. These include outreach clinics, virtual tumor boards, teleoncology and other telemedicine applications, workforce recruitment and retention initiatives, and provider and patient education programs. Given the projected increase in demand for cancer care due to the aging population and increasing number of Americans with health insurance through the Affordable Care Act, expansion of these efforts and development of new approaches are critical to ensure access to high-quality care.

Survival of patients with acute myelogenous leukemia (AML), particularly in younger patients, has improved in recent years due to improved understanding of disease biology, post remission therapies and supportive care. AML, however, remains difficult to treat as many patients will still ultimately relapse and die of their disease. This is particularly true in AML patients with identified FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) molecular mutations, which typically confers a poor prognosis. The FLT3-ITD mutation occurs in about one-quarter of patients diagnosed with AML. Oftentimes, these patients are referred for early allogeneic hematopoietic stem cell transplantation (HSCT) in hopes of overcoming this poor prognostic factor. Several studies have demonstrated some benefit with HSCT in patients with FLT3-ITD mutation. However, recent data suggested that FLT3-ITD mutation remains a poor prognostic factor even after early HSCT; these patients remain at risk for early relapse after transplantation, emphasizing ongoing efforts to explore maintenance therapy with FLT3-ITD inhibitors in the post-transplant setting.