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Dana-Farber Research Publication 05.01.2023

Welcome to Dana-Farber's Research News

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May 01, 2023

This twice-monthly newsletter highlights the research endeavors at Dana-Farber Cancer Institute, noting recently published papers available from PubMed where Dana-Farber faculty are listed as first or senior authors. If you are a Dana-Farber faculty member and you think your paper is missing from Research News, please let us know at: Michael_buller@dfci.harvard.edu.

Blood

High-Dose Melphalan Treatment Significantly Increases Mutational Burden at Relapse in Multiple Myeloma

Samur MK, Aktas Samur A, Fulciniti M, Shammas MA, Sperling AS, Richardson PG, Parmigiani G, Anderson KC, Munshi NC

High-dose melphalan (HDM) improves progression-free survival in multiple myeloma (MM), yet melphalan is a DNA-damaging alkylating agent; therefore, we assessed its mutational effect on surviving myeloma cells by analyzing paired MM samples collected at diagnosis and relapse in the IFM 2009 study. We performed deep whole-genome sequencing on samples from 68 patients, 43 of whom were treated with RVD (lenalidomide, bortezomib, and dexamethasone) and 25 with RVD + HDM. Although the number of mutations was similar at diagnosis in both groups (7137 vs 7230; P = .67), the HDM group had significantly more mutations at relapse (9242 vs 13?383, P = .005). No change in the frequency of copy number alterations or structural variants was observed. The newly acquired mutations were typically associated with DNA damage and double-stranded breaks and were predominantly on the transcribed strand. A machine learning model, using this unique pattern, predicted patients who would receive HDM with high sensitivity, specificity, and positive prediction value. Clonal evolution analysis showed that all patients treated with HDM had clonal selection, whereas a static progression was observed with RVD. A significantly higher percentage of mutations were subclonal in the HDM cohort. Intriguingly, patients treated with HDM who achieved complete remission (CR) had significantly more mutations at relapse yet had similar survival rates as those treated with RVD who achieved CR. This similarity could have been due to HDM relapse samples having significantly more neoantigens. Overall, our study identifies increased genomic changes associated with HDM and provides rationale to further understand clonal complexity.


Blood

Ipilimumab Plus Decitabine for Patients with MDS or AML in Posttransplant or Transplant-Naïve Settings

Garcia JS, Flamand Y, Penter L, Mendez LM, Cullen N, Arihara Y, Pfaff K, Wolff JO, Brunner AM, Galinsky I, Antin JH, Cutler C, Ho V, Luskin MR, Wadleigh M, Winer ES, Savell A, Leonard R, Robertson T, Davids MS, Rodig SJ, Ritz J, Wu CJ, DeAngelo DJ, Neuberg D, Stone RM, Soiffer RJ

Two articles in this week’s issue focus on the use of ipilimumab and decitabine for patients with myelodysplasia (MDS) and acute myeloid leukemia (AML) before and after hematopoietic stem cell transplantation (HSCT) for high-risk disease. In the first article, Garcia et al report on the results of a phase 1 trial of the combination in 54 patients, demonstrating overall response rate of 52% in patients who are HSCT-naïve and 20% in patients post-HSCT; responses are usually short-lived. In the second article, Penter and colleagues characterize gene expression responses to therapy and conclude that decitabine acts directly to clear leukemic cells while ipilimumab acts on infiltrating lymphocytes in marrow and extramedullary sites. Responses are determined by leukemic cell burden and by the frequency and phenotype of infiltrating lymphocytes. Increasing bone marrow regulatory T cells is identified as a potential contributor to checkpoint inhibitor escape.


Blood

Mechanisms of Response and Resistance to Combined Decitabine and Ipilimumab for Advanced Myeloid Disease

Penter L, Liu Y, Wolff JO, Yang L, Taing L, Jhaveri A, Southard J, Cullen NM, Pfaff KL, Cieri N, Oliveira G, Ranasinghe S, Leonard R, Robertson T, Morgan EA, Li S, Rodig SJ, Cibulskis C,
Gabriel S, Ritz J, Neuberg DS, Hodi FS, Davids MS, Livak KJ, Altreuter J, Michor F, Soiffer RJ,
Garcia JS, Wu CJ

The challenge of eradicating leukemia in patients with acute myelogenous leukemia (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either after allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naïve setting. Integrative transcriptome-based analysis of 304 961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells. Clinical responses were predominantly driven by decitabine-induced cytoreduction. Evidence of immune activation was only apparent after ipilimumab exposure, which altered CD4+ T-cell gene expression, in line with ongoing T-cell differentiation and increased frequency of marrow-infiltrating regulatory T cells. For post-HSCT samples, relapse could be attributed to insufficient clearing of malignant clones in progenitor cell populations. In contrast to AML/MDS bone marrow, the transcriptomes of leukemia cutis samples from patients with durable remission after ipilimumab monotherapy showed evidence of increased infiltration with antigen-experienced resident memory T cells and higher expression of CTLA-4 and FOXP3. Altogether, activity of combined decitabine and ipilimumab is impacted by cellular expression states within the microenvironmental niche of leukemic cells. The inadequate elimination of leukemic progenitors mandates urgent development of novel approaches for targeting these cell populations to generate long-lasting responses. This trial was registered at www.clinicaltrials.gov as #NCT02890329.


 

Cell Stem Cell

Graded BMP Signaling within Intestinal Crypt Architecture Directs Self-Organization of the Wnt-Secreting Stem Cell Niche

Kraiczy J, McCarthy N, Tie G, Madha S, Shivdasani RA

Signals from the surrounding niche drive proliferation and suppress differentiation of intestinal stem cells (ISCs) at the bottom of intestinal crypts. Among sub-epithelial support cells, deep sub-cryptal CD81+ PDGFRAlo trophocytes capably sustain ISC functions ex vivo. Here, we show that mRNA and chromatin profiles of abundant CD81- PDGFRAlo mouse stromal cells resemble those of trophocytes and that both populations provide crucial canonical Wnt ligands. Mesenchymal expression of key ISC-supportive factors extends along a spatial and molecular continuum from trophocytes into peri-cryptal CD81- CD55hi cells, which mimic trophocyte activity in organoid co-cultures. Graded expression of essential niche factors is not cell-autonomous but dictated by the distance from bone morphogenetic protein (BMP)-secreting PDGFRAhi myofibroblast aggregates. BMP signaling inhibits ISC-trophic genes in PDGFRAlo cells near high crypt tiers; that suppression is relieved in stromal cells near and below the crypt base, including trophocytes. Cell distances thus underlie a self-organized and polar ISC niche.


 

Journal of Clinical Oncology

Evaluation of Standard Response Assessment in Neuro-Oncology, Modified Response Assessment in Neuro-Oncology, and Immunotherapy Response Assessment in Neuro-Oncology in Newly Diagnosed and Recurrent Glioblastoma

Youssef G, Rahman R, Bay C, Wang W, Arnaout O, Bi WL, Chang YS, DeSalvo M, Flood TF,
Gerstner ER, Gonzalez Castro LN, Guenette JP, Kim AE, Lee EQ, McFaline-Figueroa JR, Potter CA, Reardon DA, Huang RY, Wen PY

PURPOSE: The Response Assessment in Neuro-Oncology (RANO) criteria are widely used in high-grade glioma clinical trials. We compared the RANO criteria with updated modifications (modified RANO [mRANO] and immunotherapy RANO [iRANO] criteria) in patients with newly diagnosed glioblastoma (nGBM) and recurrent GBM (rGBM) to evaluate the performance of each set of criteria and inform the development of the planned RANO 2.0 update.

MATERIALS AND METHODS: Evaluation of tumor measurements and fluid-attenuated inversion recovery (FLAIR) sequences were performed by blinded readers to determine disease progression using RANO, mRANO, iRANO, and other response assessment criteria. Spearman's correlations between progression-free survival (PFS) and overall survival (OS) were calculated.

RESULTS: Five hundred twenty-six nGBM and 580 rGBM cases were included. Spearman's correlations were similar between RANO and mRANO (0.69 [95% CI, 0.62 to 0.75] v 0.67 [95% CI, 0.60 to 0.73]) in nGBM and rGBM (0.48 [95% CI, 0.40 to 0.55] v 0.50 [95% CI, 0.42 to 0.57]). In nGBM, requirement of a confirmation scan within 12 weeks of completion of radiotherapy to determine progression was associated with improved correlations. Use of the postradiation magnetic resonance imaging (MRI) as baseline scan was associated with improved correlation compared with use of the pre-radiation MRI (0.67 [95% CI, 0.60 to 0.73] v 0.53 [95% CI, 0.42 to 0.62]). Evaluation of FLAIR sequences did not improve the correlation. Among patients who received immunotherapy, Spearman's correlations were similar among RANO, mRANO, and iRANO.

CONCLUSION: RANO and mRANO demonstrated similar correlations between PFS and OS. Confirmation scans were only beneficial in nGBM within 12 weeks of completion of radiotherapy, and there was a trend in favor of the use of postradiation MRI as the baseline scan in nGBM. Evaluation of FLAIR can be omitted. The iRANO criteria did not add significant benefit in patients who received immune checkpoint inhibitors.


 

Journal of the National Cancer Institute

Survival in Male Breast Cancer Over the Past 3 Decades

Leone JP, Freedman RA, Tolaney SM, Winer EP, Lin NU, Hassett MJ

BACKGROUND: Breast cancer mortality in women has declined statistically significantly over the past several years. In men, it is unclear whether survival has changed over time. We evaluated changes in breast cancer-specific survival (BCSS) and overall survival (OS) in male breast cancer over the past 3 decades.

METHODS: We evaluated men diagnosed with breast cancer between 1988 and 2017, reported in the Surveillance, Epidemiology, and End Results registry. Patients were categorized into 3 groups by year of diagnosis: 1988-1997, 1998-2007, and 2008-2017. BCSS and OS were estimated by Kaplan-Meier, and differences between groups were compared by log-rank test. Multivariable Cox regression evaluated the independent association of year of diagnosis with BCSS and OS. All tests were 2-sided.

RESULTS: We included 8481 men. Overall, BCSS at 5?years was 83.69%, 83.78%, and 84.41% in groups 1988-1997, 1998-2007, and 2008-2017, respectively (P?=?.86). There was no statistically significant difference in BCSS between the 3 groups within each stage of disease. Among all patients, OS at 5?years was 64.61%, 67.31%, and 69.05% in groups 1988-1997, 1998-2007, and 2008-2017, respectively (P?=?.01). In adjusted Cox models, each additional year of diagnosis had no statistically significant association with BCSS (hazard ratio = 1.00, 95% confidence interval = 0.99 to 1.01, P?=?.75), but there was statistically significant improvement in OS (hazard ratio = 0.99, 95% CI = 0.98 to 0.99, P?=?.009).

CONCLUSIONS: Over the past 3 decades, there has been no statistically significant improvement in BCSS in male breast cancer. Changes in OS over time are consistent with increasing life expectancy. Efforts to improve BCSS in male breast cancer are warranted.


 

JAMA Oncology

Efficacy and Safety of Nivolumab Plus Ipilimumab vs Nivolumab Alone for Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: The Phase 2 CheckMate 714 Randomized Clinical Trial

Haddad R

IMPORTANCE: There remains an unmet need to improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

OBJECTIVE: To evaluate clinical benefit of first-line nivolumab plus ipilimumab vs nivolumab alone in patients with R/M SCCHN.

DESIGN, SETTING, AND PARTICIPANTS: The CheckMate 714, double-blind, phase 2 randomized clinical trial was conducted at 83 sites in 21 countries between October 20, 2016, and January 23, 2019. Eligible participants were aged 18 years or older and had platinum-refractory or platinum-eligible R/M SCCHN and no prior systemic therapy for R/M disease. Data were analyzed from October 20, 2016 (first patient, first visit), to March 8, 2019 (primary database lock), and April 6, 2020 (overall survival database lock).

INTERVENTIONS: Patients were randomized 2:1 to receive nivolumab (3 mg/kg intravenously [IV] every 2 weeks) plus ipilimumab (1 mg/kg IV every 6 weeks) or nivolumab (3 mg/kg IV every 2 weeks) plus placebo for up to 2 years or until disease progression, unacceptable toxic effects, or consent withdrawal.

MAIN OUTCOMES AND MEASURES: The primary end points were objective response rate (ORR) and duration of response between treatment arms by blinded independent central review in the population with platinum-refractory R/M SCCHN. Exploratory end points included safety.

RESULTS: Of 425 included patients, 241 (56.7%; median age, 59 [range, 24-82] years; 194 males [80.5%]) had platinum-refractory disease (nivolumab plus ipilimumab, n?=?159; nivolumab, n?=?82) and 184 (43.3%; median age, 62 [range, 33-88] years; 152 males [82.6%]) had platinum-eligible disease (nivolumab plus ipilimumab, n?=?123; nivolumab, n?=?61). At primary database lock, the ORR in the population with platinum-refractory disease was 13.2% (95% CI, 8.4%-19.5%) with nivolumab plus ipilimumab vs 18.3% (95% CI, 10.6%-28.4%) with nivolumab (odds ratio [OR], 0.68; 95.5% CI, 0.33-1.43; P?=?.29). Median duration of response for nivolumab plus ipilimumab was not reached (NR) (95% CI, 11.0 months to NR) vs 11.1 months (95% CI, 4.1 months to NR) for nivolumab. In the population with platinum-eligible disease, the ORR was 20.3% (95% CI, 13.6%-28.5%) with nivolumab plus ipilimumab vs 29.5% (95% CI, 18.5%-42.6%) with nivolumab. The rates of grade 3 or 4 treatment-related adverse events with nivolumab plus ipilimumab vs nivolumab were 15.8% (25 of 158) vs 14.6% (12 of 82) in the population with platinum-refractory disease and 24.6% (30 of 122) vs 13.1% (8 of 61) in the population with platinum-eligible disease.

CONCLUSIONS AND RELEVANCE: The CheckMate 714 randomized clinical trial did not meet its primary end point of ORR benefit with first-line nivolumab plus ipilimumab vs nivolumab alone in platinum-refractory R/M SCCHN. Nivolumab plus ipilimumab was associated with an acceptable safety profile. Research to identify patient subpopulations in R/M SCCHN that would benefit from nivolumab plus ipilimumab over nivolumab monotherapy is warranted.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02823574.


 

Lancet Oncology

Current Drug Development and Trial Designs in Neuro-Oncology: Report from the First American Society of Clinical Oncology and Society for Neuro-Oncology Clinical Trials Conference

Rahman R, Brastianos PK, Wen PY, Piantadosi S

Successful drug development for people with cancers of the CNS has been challenging. There are multiple barriers to successful drug development including biological factors, rarity of the disease, and ineffective use of clinical trials. Based upon a series of presentations at the First Central Nervous System Clinical Trials Conference hosted by the American Society of Clinical Oncology and the Society for Neuro-Oncology, we provide an overview on drug development and novel trial designs in neuro-oncology. This Review discusses the challenges of therapeutic development in neuro-oncology and proposes strategies to improve the drug discovery process by enriching the pipeline of promising therapies, optimising trial design, incorporating biomarkers, using external data, and maximising efficacy and reproducibility of clinical trials.


 

Molecular Cell

Structural and Functional Properties of mSWI/SNF Chromatin Remodeling Complexes Revealed Through Single-Cell Perturbation Screens

Otto JE, Ursu O, Wu AP, Winter EB, Cuoco MS, Ma S, Qian K, Michel BC, Buenrostro JD, Berger B, Regev A, Kadoch C

The mammalian SWI/SNF (mSWI/SNF or BAF) family of chromatin remodeling complexes play critical roles in regulating DNA accessibility and gene expression. The three final-form subcomplexes-cBAF, PBAF, and ncBAF-are distinct in biochemical componentry, chromatin targeting, and roles in disease; however, the contributions of their constituent subunits to gene expression remain incompletely defined. Here, we performed Perturb-seq-based CRISPR-Cas9 knockout screens targeting mSWI/SNF subunits individually and in select combinations, followed by single-cell RNA-seq and SHARE-seq. We uncovered complex-, module-, and subunit-specific contributions to distinct regulatory networks and defined paralog subunit relationships and shifted subcomplex functions upon perturbations. Synergistic, intra-complex genetic interactions between subunits reveal functional redundancy and modularity. Importantly, single-cell subunit perturbation signatures mapped across bulk primary human tumor expression profiles both mirror and predict cBAF loss-of-function status in cancer. Our findings highlight the utility of Perturb-seq to dissect disease-relevant gene regulatory impacts of heterogeneous, multi-component master regulatory complexes.


 

Nature

Clonal Haematopoiesis and Risk of Chronic Liver Disease

Wong WJ, Emdin C, Bick AG, Zekavat SM, Niroula A, Pirruccello JP, Dichtel L, Griffin G, Uddin MM, Gibson CJ, Kovalcik V, Lin AE, McConkey ME, Vromman A, Sellar RS, Kim PG, Agrawal M, Loh PR, McCarroll S, Chung RT, Corey K, Ebert BL, Natarajan P

Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio?=?2.01, 95% confidence interval (95%?CI)?[1.46,?2.79]; P?


 

Nature Cancer

Landscape of Prostate-Specific Membrane Antigen Heterogeneity and Regulation in AR-Positive and AR-Negative Metastatic Prostate Cancer

Bakht MK, Yamada Y, Ku SY, Venkadakrishnan VB, Mizuno K, Ahn SH, Seo JH, Garcia MM, Long HW, Freedman M, Belanger AP, Nguyen QD, Beltran H

Tumor expression of prostate-specific membrane antigen (PSMA) is lost in 15-20% of men with castration-resistant prostate cancer (CRPC), yet the underlying mechanisms remain poorly defined. In androgen receptor (AR)-positive CRPC, we observed lower PSMA expression in liver lesions versus other sites, suggesting a role of the microenvironment in modulating PSMA. PSMA suppression was associated with promoter histone 3 lysine 27 methylation and higher levels of neutral amino acid transporters, correlating with 18F-fluciclovine uptake on positron emission tomography imaging. While PSMA is regulated by AR, we identified a subset of AR-negative CRPC with high PSMA. HOXB13 and AR co-occupancy at the PSMA enhancer and knockout models point to HOXB13 as an upstream regulator of PSMA in AR-positive and AR-negative prostate cancer. These data demonstrate how PSMA expression is differentially regulated across metastatic lesions and in the context of the AR, which may inform selection for PSMA-targeted therapies and development of complementary biomarkers.


 

Nature Genetics

Genomic and Transcriptomic Analysis of Checkpoint Blockade Response in Advanced Non-Small Cell Lung Cancer

Ravi A, Arniella MB, Holton M, Freeman SS, Naranbhai V, Stewart C, Leshchiner I, Akiyama Y,
Sakhi M, Kamesan V, Ricciuti B, Digumarthy SR, Mino-Kenudson M, Jänne PA, Awad MM, Shaw AT, Hacohen N, Getz G, Gainor JF

Anti-PD-1/PD-L1 agents have transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC). To expand our understanding of the molecular features underlying response to checkpoint inhibitors in NSCLC, we describe here the first joint analysis of the Stand Up To Cancer-Mark Foundation cohort, a resource of whole exome and/or RNA sequencing from 393 patients with NSCLC treated with anti-PD-(L)1 therapy, along with matched clinical response annotation. We identify a number of associations between molecular features and outcome, including (1) favorable (for example, ATM altered) and unfavorable (for example, TERT amplified) genomic subgroups, (2) a prominent association between expression of inducible components of the immunoproteasome and response and (3) a dedifferentiated tumor-intrinsic subtype with enhanced response to checkpoint blockade. Taken together, results from this cohort demonstrate the complexity of biological determinants underlying immunotherapy outcomes and reinforce the discovery potential of integrative analysis within large, well-curated, cancer-specific cohorts.


 

American Journal of Gastroenterology

Molecular Characteristics of Early-Onset Colorectal Cancer According to Detailed Anatomical Locations: Comparison with Later-Onset Cases

Ugai T, Haruki K, Chan AT, Akimoto N, Fujiyoshi K, Nishihara R, Giannakis M, Song M, Nowak JA, Ogino S


 

Blood Advances

Coping in Caregivers of Patients with Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplantation

Amonoo HL, Johnson PC, Nelson AM, Clay MA, Daskalakis E, Newcomb RA, Deary EC, Mattera EF, Yang D, Cronin K, Boateng K, El-Jawahri A


Blood Advances

Nelarabine Combination Therapy for Relapsed or Refractory T-Cell Acute Lymphoblastic Lymphoma/Leukemia

Shimony S, Liu Y, Valtis YK, Paolino JD, Place AE, Brunner AM, Weeks LD, Silverman LB,
Vrooman LM, Neuberg DS, Stone RM, DeAngelo DJ, Luskin MR


Blood Advances

Correcting the Record on Anemia of Aging — a Statistical Reanalysis

Fell GG, Nathan DG, Neuberg DS


 

Cancer

What's the Reality for CDK4/6 Inhibitors: Clinical Trials Real-World Evidence?

Trapani D, Mayer EL


 

Cancer

Effects of an Educational Physical Activity Intervention in Young Women with Newly Diagnosed Breast Cancer: Findings from the Young and Strong Study

Ligibel JA, Zheng Y, Barry WT, Emmons KM, Partridge AH


 

Cancer

One Fixed Dosing of a Poly (Adenosine Diphosphate Ribose) Polymerase Inhibitor Does Not Fit All

Liu JF


 

Cancer Chemotherapy and Pharmacology

A Phase I, First-In-Human Study of TAK-164, an Antibody-Drug Conjugate, In Patients with Advanced Gastrointestinal Cancers Expressing Guanylyl Cyclase C

Parikh A, Ryan DP, Cleary JM


 

Cancer Letters

MUC1-C is Necessary for SHP2 Activation and BRAF Inhibitor Resistance in BRAF(V600E) Mutant Colorectal Cancer

Morimoto Y, Yamashita N, Fushimi A, Haratake N, Daimon T, Bhattacharya A, Ahmad R, Kufe DW


 

Cancer Treatment Reviews

Epidemiology, Clinical Outcomes, and Unmet Needs of Patients with Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases: A Systematic Literature Review

Lin NU, Tolaney SM


 

Cannabis and Cannabinoid Research

Letter to the Editor: The Role of Cannabidiol in Cancer Care: Oncologist and Cancer Patient Perspectives

Nayak MM, Chai PR, Tung S, Sannes TS, Yusufov M, Braun IM


 

Cell Death and Disease

Quantifying Requirements for Mitochondrial Apoptosis in CAR T Killing of Cancer Cells

Pourzia AL, Olson ML, Bailey SR, Boroughs AC, Aryal A, Ryan J, Maus MV, Letai A


 

Cells

Copy Number Variation in Inflammatory Breast Cancer

Hazra A, Polyak K, Nakhlis F, Harrison BT, Giordano A, Overmoyer B, Lynce F


 

Clinical Breast Cancer

Fertility Preferences and Practices Among Young Women with Breast Cancer: Germline Genetic Carriers Versus Noncarriers

Lewinsohn R, Zheng Y, Peppercorn J, Come S, Snow C, Ginsburg ES, Partridge AH


 

Current Treatment Options in Oncology

New Developments in Systemic Management for High-Risk Early-Stage Hormone-Receptor-Positive, HER2-Negative Breast Cancer

Brett JO, Mayer EL


 

Developmental Cell

Smooth Muscle Contributes to the Development and Function of a Layered Intestinal Stem Cell Niche

McCarthy N, Tie G, Madha S, He R, Kraiczy J, Maglieri A, Shivdasani RA


 

Expert Review of Anticancer Therapy

Emerging Predictive Biomarkers in the Management of Bone and Soft Tissue Sarcomas

Haddox CL


 

Haematologica

Getting (T Cells) ENGaged

Baumeister SHC


 

Hematology/Oncology Clinics of North America

Fetal Hemoglobin Regulation in Beta-Thalassemia

Lu HY, Orkin SH, Sankaran VG


 

Hematology/Oncology Clinics of North America

Targeted Therapy for Non-Small Cell Lung Cancer: First Line and Beyond

Brea E, Rotow J


 

International Journal of Radiation Oncology, Biology, Physics

Modulation of Radiation Biomarkers in a Randomized Phase II Study of (131)I-MIBG with or without Radiation Sensitizers for Relapsed or Refractory Neuroblastoma

Campbell K, Armant M, Pal S, Haas-Kogan DA, DuBois SG


 

Journal of the American College of Radiology

Frequency and Clinical Utility of Alerts for Intra-Institutional Radiologist Discrepant Opinions

DiPiro PJ, Licaros A, Zhao AH, Glazer DI, Healey MJ, Curley PJ, Giess CS, Khorasani R


 

Journal of the American Geriatrics Society

Evaluation of Interdisciplinary Care Pathway Implementation in Older Elective Surgery Patients

Hu FY, Rowe KA, O'Mara LM, Bulger A, Bleday R, Groff MW, Cooper Z, Bernacki RE


 

Journal of Cancer Survivorship

Online Description of Services Provided in Adult Survivorship Programs Across U.S. Accredited Cancer Centers

Contreras-Chavez P, Nekhlyudov L


 

Journal of Experimental Medicine

PD-1 Blockade and CDK4/6 Inhibition Augment Nonoverlapping Features of T Cell Activation in Cancer

Ali LR, Garrido-Castro AC, Lenehan PJ, Bollenrucher N, Stump CT, Dougan M, Shapiro GI,
Tolaney SM, Dougan SK


 

Journal of Immunology

cIAP1/2 Antagonism Induces Antigen-Specific T Cell-Dependent Immunity

Ventre KS, Roehle K, Bello E, Bhuiyan AM, Biary T, Crowley SJ, Bruck PT, Heckler M, Lenehan PJ,
Ali LR, Stump CT, Lippert V, Clancy-Thompson E, Conce Alberto WD, Hoffman MT, Qiang L,
Dougan M, Dougan SK


 

Journal of Medicinal Chemistry

Catalytic Degraders Effectively Address Kinase Site Mutations in EML4-ALK Oncogenic Fusions

Gao Y, Jiang B, Kim H, Berberich MJ, Che J, Donovan KA, Hatcher JM, Huerta F, Kwiatkowski NP,
Liu Y, Liuni PP, Metivier RJ, Murali VK, Nowak RP, Fischer ES, Gray NS, Jones LH


 

Journal of Pain and Symptom Management

Measuring Palliative Care Communication via Telehealth: A Pilot Study

Tarbi EC, Durieux BN, Brain JM, Kwok A, Umeton R, Samineni S, Tulsky JA, Lindvall C


 

Journal of Palliative Medicine

Caring for People We Know: An Unrecognized Risk for Burnout?

Morris SE, Revette AC, Brandoff DE, Leiter RE, Sannes TS, Thomas JD


 

Journal of Palliative Medicine

Adaptations within Palliative Care Delivery Models Due to the COVID-19 Pandemic at a Tertiary Care Hospital

Jain N, Bernacki RE, Lee KA, Siegel JH, Yenulevich EG, Lally KM


 

Journal of Palliative Medicine

Concerns for Medical Neglect in Children with Complex or Serious Medical Conditions: What Pediatric Palliative Care Brings to the Table

Cleveland RW, Ullrich CK


 

Journal of Surgical Oncology

Non-Small Cell Lung Cancer Disparities in Stage at Presentation and Treatment for Asian American, Native Hawaiian, and Pacific Islander Women

Hong JH, Swami N, Lam MB


 

JAMA Surgery

Racial and Ethnic Disparities in Locoregional Recurrence Among Patients with Hormone Receptor-Positive, Node-Negative Breast Cancer: A Post Hoc Analysis of the TAILORx Randomized Clinical Trial

Kantor O, King TA, Freedman RA, Mayer EL, Mittendorf EA


 

JAMIA Open

Development of a Keyword Library for Capturing PRO-CTCAE-Focused "Symptom Talk" in Oncology Conversations

Durieux BN, Zverev SR, Tarbi EC, Kwok A, Sciacca K, Tulsky JA, Lindvall C


 

JCO Oncology Practice

Early Bereavement Psychosocial Outcomes in Parents of Children Who Died of Cancer with a Focus on Social Functioning

Snaman JM, Mazzola E, Feifer D, Morris SE, Wolfe J


 

JCO Oncology Practice

The Day One Talk, 20 Years Later: What Have We Learned?

Mack JW


 

JCO Oncology Practice

A Three-Step Taxane Titration Protocol Decreases Hypersensitivity Reactions During First and Second Exposures

Lynch DM, Menon S, Mazzola E, Costa J, Jabaley T


 

JMIR Research Protocols

Improving Cognitive Function Through High-Intensity Interval Training in Breast Cancer Patients Undergoing Chemotherapy: Protocol for a Randomized Controlled Trial

Wilson R, Kang DW, Norris M, Uno H, Ligibel J, Guenette J, Christopher C, Dieli-Conwright C


 

Leukemia

A Phase 1b Study of Ibrutinib in Combination with Obinutuzumab in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia

Ryan CE, Tyekucheva S, Hackett LR, Collins MC, Fernandes SM, Ren Y, Zhou Y, McDonough MM, Walker HA, McEwan MR, Abramson JS, Jacobsen ED, LaCasce AS, Fisher DC, Brown JR, Davids MS


 

Molecular Cancer Research

Significance of RB Loss in Unlocking Phenotypic Plasticity in Advanced Cancers

Venkadakrishnan VB, Yamada Y, Weng K, Idahor O, Beltran H


 

Nature Reviews Cancer

Dynamics and Specificities of T Cells in Cancer Immunotherapy

Oliveira G, Wu CJ


 

Neuro-Oncology Practice

The Predictive Value of Partial MGMT Promoter Methylation for IDH-Wild-Type Glioblastoma Patients

Torre M, Wen PY, Iorgulescu JB


 

Oncologist

Avelumab Plus Axitinib as First-Line Therapy for Advanced Renal Cell Carcinoma: Long-Term Results from the JAVELIN Renal 100 Phase Ib Trial

McDermott D, Choueiri TK


 

Oncologist

Managing Ibrutinib-Intolerant Patients With B-Cell Malignancies

Sarosiek S, Castillo JJ


 

Pediatric Blood and Cancer

Primary Care Providers' Comfort in Caring for Cancer Survivors: Implications for Risk-Stratified Care

Nekhlyudov L, Snow C, Knelson LP, Dibble KE, Partridge AH


 

Scandinavian Journal of Medicine and Science in Sports

High-Intensity Interval Training Improves Metabolic Syndrome in Women with Breast Cancer Receiving Anthracyclines

Gonzalo-Encabo P, Christopher CN, Normann AJ, Yunker AG Norris MK, Dieli-Conwright CM


 

Science Immunology

You've got a fast CAR

Reyna ÁG, Griffin GK


 

Seminars in Radiation Oncology

Pharmacologic Pain Management: What Radiation Oncologists Should Know

Skarf LM, Jones KF, Meyerson JL, Abrahm JL


 

Statistics in Medicine

On Assessing Survival Benefit of Immunotherapy Using Long-Term Restricted Mean Survival Time

Horiguchi M, Uno H


 

Transplantation and Cellular Therapy

Paving the Road for Chimeric Antigen Receptor T Cells: American Society for Transplantation and Cellular Therapy 80/20 Task Force Consensus on Challenges and Solutions to Improving Efficiency of Clinical Center Certification and Maintenance of Operations for Commercially Approved Immune Effector Cell Therapies

Nikiforow S, Frigault MJ


 

Transplantation and Cellular Therapy

Clinical Features of AKI in the Early Post-Transplant Period Following Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation

Vergara-Cadavid J, Johnson PC, Kim HT, Yi A, Sise ME, Leaf DE, Hanna PE, Ho VT, Cutler CS,
Antin JH, Gooptu M, Kelkar A, Wells SL, Nikiforow S, Koreth J, Romee R, Soiffer RJ, Shapiro RM, Gupta S