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Dana-Farber Research Publication 11.1.2022

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November 1, 2022

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:

Annals of Oncology

Dissecting the Clinicopathologic, Genomic, and Immunophenotypic Correlates of KRAS(G12D)-Mutated Non-Small-Cell Lung Cancer

Ricciuti B, Alessi JV, Wang X, Li YY, Vaz VR, Gupta H, Pecci F, Barrichello A, Lamberti G, Nguyen T, Lindsay J, Sharma B, Felt K, Rodig SJ, Nishino M, Sholl LM, Barbie DA, Cherniack AD, Meyerson M, Jänne PA, Awad MM, Luo J

BACKGROUND: Allele-specific KRAS inhibitors are an emerging class of cancer therapies. KRAS-mutant (KRASMUT) non-small-cell lung cancers (NSCLCs) exhibit heterogeneous outcomes, driven by differences in underlying biology shaped by co-mutations. In contrast to KRASG12C NSCLC, KRASG12D NSCLC is associated with low/never-smoking status and is largely uncharacterized.

PATIENTS AND METHODS: Clinicopathologic and genomic information were collected from patients with NSCLCs harboring a KRAS mutation at the Dana-Farber Cancer Institute (DFCI), Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, and Imperial College of London. Multiplexed immunofluorescence for CK7, programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), Foxp3, and CD8 was carried out on a subset of samples with available tissue at the DFCI. Clinical outcomes to PD-(L)1 inhibition chemotherapy were analyzed according to KRAS mutation subtype.

RESULTS: Of 2327 patients with KRAS-mutated (KRASMUT) NSCLC, 15% (n = 354) harbored KRASG12D. Compared to KRASnon-G12D NSCLC, KRASG12D NSCLC had a lower pack-year (py) smoking history (median 22.5 py versus 30.0 py, P < 0.0001) and was enriched in never smokers (22% versus 5%, P < 0.0001). KRASG12D had lower PD-L1 tumor proportion score (TPS) (median 1% versus 5%, P < 0.01) and lower tumor mutation burden (TMB) compared to KRASnon-G12D (median 8.4 versus 9.9 mt/Mb, P < 0.0001). Of the samples which underwent multiplexed immunofluorescence, KRASG12D had lower intratumoral and total CD8+PD1+ T cells (P < 0.05). Among 850 patients with advanced KRASMUT NSCLC who received PD-(L)1-based therapies, KRASG12D was associated with a worse objective response rate (ORR) (15.8% versus 28.4%, P = 0.03), progression-free survival (PFS) [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.45-2.00, P = 0.003], and overall survival (OS; HR 1.45, 1.05-1.99, P = 0.02) to PD-(L)1 inhibition alone but not to chemo-immunotherapy combinations [ORR 30.6% versus 35.7%, P = 0.51; PFS HR 1.28 (95%CI 0.92-1.77), P = 0.13; OS HR 1.36 (95%CI 0.95-1.96), P = 0.09] compared to KRASnon-G12D.

CONCLUSIONS: KRASG12D lung cancers harbor distinct clinical, genomic, and immunologic features compared to other KRAS-mutated lung cancers and worse outcomes to PD-(L)1 blockade. Drug development for KRASG12D lung cancers will have to take these differences into account.


Avapritinib for Advanced Systemic Mastocytosis

DeAngelo DJ

Avapritinib, a highly selective inhibitor of KIT D816V, was approved by the Food and Drug Administration in 2021 for treatment of advanced systemic mastocytosis (AdvSM) and by the European Medicines Agency in 2022 for AdvSM after prior systemic therapy. The phase 1 EXPLORER and phase 2 PATHFINDER trials demonstrated that avapritinib can elicit complete and durable clinical responses and molecular remission of KIT D816V. Key management challenges relate to the complex mutational landscape of AdvSM, often found with an associated hematologic neoplasm.

Correction: Due to a PubMed error, we inadvertently omitted a senior author (Munshi NC) from the following listing in the last issue of Research News. The corrected listing is below.


A MIR17HG-Derived Long Noncoding RNA Provides an Essential Chromatin Scaffold for Protein Interaction and Myeloma Growth

Morelli E, Fulciniti M, Samur MK, Wert-Lamas L, Gulla A, Aktas Samur A, Talluri S, Bianchi G, Johnstone M, Liu N, Gramegna D, Maisano D, Tai YT, Chauhan D, Hideshima T, Shammas MA, Anderson KC, Novina CD, Munshi NC

Long noncoding RNAs (lncRNA) can drive tumorigenesis and are susceptible to therapeutic intervention. Here, we used a large-scale CRISPR interference viability screen to interrogate cell growth dependency to lncRNA genes in multiple myeloma (MM), and identified a prominent role for the miR-17-92 cluster host gene (MIR17HG). We show that a MIR17HG-derived lncRNA, named lnc-17-92, is the main mediator of cell growth dependency acting in a microRNA- and DROSHA- independent manner. Lnc-17-92 provides a chromatin scaffold for the functional interaction between c-MYC and WDR82, thus promoting the expression of ACACA, which encodes the rate-limiting enzyme of de novo lipogenesis acetyl-coA carboxylase 1 (ACC1). Targeting MIR17HG pre-RNA with clinically applicable antisense molecules disrupts the transcriptional and functional activities of lnc-17-92, causing potent anti-tumor effects both in vitro and in vivo in three pre-clinical animal models, including a clinically relevant PDX-NSG mouse model. This study establishes a novel oncogenic function of MIR17HG and provides potent inhibitors for translation to clinical trials.

Cancer Cell

Ancestry-Driven Recalibration of Tumor Mutational Burden and Disparate Clinical Outcomes in Response to Immune Checkpoint Inhibitors

Nassar AH, Adib E, Abou Alaiwi S, El Zarif T, Groha S, Akl EW, Nuzzo PV, El-Khoury H, Labban M, Labaki C, Xu W, Sonpavde G, Haddad RI, Mouw KW, Giannakis M, Hodi FS, MacConaill LE, Ananda G, Kwiatkowski DJ, Choueiri TK, Gusev A

The immune checkpoint inhibitor (ICI) pembrolizumab is US FDA approved for treatment of solid tumors with high tumor mutational burden (TMB-high; 10 variants/Mb). However, the extent to which TMB-high generalizes as an accurate biomarker in diverse patient populations is largely unknown. Using two clinical cohorts, we investigated the interplay between genetic ancestry, TMB, and tumor-only versus tumor-normal paired sequencing in solid tumors. TMB estimates from tumor-only panels substantially overclassified individuals into the clinically important TMB-high group due to germline contamination, and this bias was particularly pronounced in patients with Asian/African ancestry. Among patients with non-small cell lung cancer treated with ICIs, those misclassified as TMB-high from tumor-only panels did not associate with improved outcomes. TMB-high was significantly associated with improved outcomes only in European ancestries and merits validation in non-European ancestry populations. Ancestry-aware tumor-only TMB calibration and ancestry-diverse biomarker studies are critical to ensure that existing disparities are not exacerbated in precision medicine.

Cancer Cell

MPS1 Inhibition Primes Immunogenicity of KRAS-LKB1 Mutant Lung Cancer

Kitajima S, Tani T, Springer BF, Campisi M, Haratani K, Chen M, Knelson EH, Mahadevan NR, Ritter J, Yoshida R, Köhler J, Ogino A, Sundararaman SK, Thai TC, Piel B, Kivlehan S, Obua BN, Purcell C, Barbie TU, Lizotte PH, Jänne PA, Paweletz CP, Gokhale PC, Barbie DA

KRAS-LKB1 (KL) mutant lung cancers silence STING owing to intrinsic mitochondrial dysfunction, resulting in T cell exclusion and resistance to programmed cell death (ligand) 1 (PD-[L]1) blockade. Here we discover that KL cells also minimize intracellular accumulation of 2'3'-cyclic GMP-AMP (2'3'-cGAMP) to further avoid downstream STING and STAT1 activation. An unbiased screen to co-opt this vulnerability reveals that transient MPS1 inhibition (MPS1i) potently re-engages this pathway in KL cells via micronuclei generation. This effect is markedly amplified by epigenetic de-repression of STING and only requires pulse MPS1i treatment, creating a therapeutic window compared with non-dividing cells. A single course of decitabine treatment followed by pulse MPS1i therapy restores T cell infiltration in vivo, enhances anti-PD-1 efficacy, and results in a durable response without evidence of significant toxicity.


Before You Call the Midwife

Glimcher LH, Petsko GA

The 2022 Lasker-DeBakey Clinical Medical Research Award is presented to Yuk Ming Dennis Lo of the Chinese University of Hong Kong for the discovery of fetal DNA in maternal blood, leading to development of noninvasive prenatal testing for Down syndrome.


Western-Style Diet, Pks Island-Carrying Escherichia coli, and Colorectal Cancer: Analyses from Two Large Prospective Cohort Studies

Arima K, Zhong R, Ugai T, Zhao M, Haruki K, Akimoto N, Lau MC, Okadome K, Mehta RS, Väyrynen JP, Kishikawa J, Twombly TS, Shi S, Fujiyoshi K, Kosumi K, Wang F, Wu K, Song M, Zhang X, Willett WC, Giovannucci EL, Meyerhardt JA, Garrett WS, Huttenhower C, Chan AT, Nowak JA, Giannakis M, Ogino S

BACKGROUND & AIMS: Evidence supports a carcinogenic role of Escherichia coli carrying the pks island that encodes enzymes for colibactin biosynthesis. We hypothesized that the association of the Western-style diet (rich in red and processed meat) with colorectal cancer incidence might be stronger for tumors containing higher amounts of pks+E coli.

METHODS: Western diet score was calculated using food frequency questionnaire data obtained every 4 years during follow-up of 134,775 participants in 2 United States-wide prospective cohort studies. Using quantitative polymerase chain reaction, we measured pks+E coli DNA in 1175 tumors among 3200 incident colorectal cancer cases that had occurred during the follow-up. We used the 3200 cases and inverse probability weighting (to adjust for selection bias due to tissue availability), integrated in multivariable-adjusted duplication-method Cox proportional hazards regression analyses.

RESULTS: The association of the Western diet score with colorectal cancer incidence was stronger for tumors containing higher levels of pks+E coli (Pheterogeneity = .014). Multivariable-adjusted hazard ratios (with 95% confidence interval) for the highest (vs lowest) tertile of the Western diet score were 3.45 (1.53-7.78) (Ptrend = 0.001) for pks+E coli-high tumors, 1.22 (0.57-2.63) for pks+E coli-low tumors, and 1.10 (0.85-1.42) for pks+E coli-negative tumors. The pks+E coli level was associated with lower disease stage but not with tumor location, microsatellite instability, or BRAF, KRAS, or PIK3CA mutations.

CONCLUSIONS: The Western-style diet is associated with a higher incidence of colorectal cancer containing abundant pks+E coli, supporting a potential link between diet, the intestinal microbiota, and colorectal carcinogenesis.

Journal of Clinical Oncology

Building on More Than 20 Years of Progress in Pancreatic Cancer Surveillance for High-Risk Individuals

Yurgelun MB

The vast majority of patients with pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) are diagnosed in the unresectable and/or metastatic setting where 5-year survival is < 5%, although long-term cure is possible when PDAC is detected early. Individuals with inherited PDAC risk are thus ideal candidates in whom to study/develop surveillance strategies. Studies have shown that 4%-20% of individuals with PDAC harbor pathogenic germline variants (PGVs) in PDAC susceptibility genes Approximately 10% of individuals with PDAC have significant clustering of PDAC diagnoses in their family (usually without identifiable PGVs), which has been labeled familial pancreatic cancer.

Journal of Clinical Oncology

Impact of RxPONDER and monarchE on the Surgical Management of the Axilla in Patients with Breast Cancer

Mittendorf EA, King TA, Tolaney SM

Results of the RxPONDER and monarchE trials have informed systemic therapy recommendations for hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)–negative breast cancer. RxPONDER looked at the utility of the Oncotype DX Recurrence Score (RS) in determining chemotherapy benefit for patients with HR+ breast cancer and 1-3 positive nodes.1 The monarchE trial evaluated the cyclin-dependent kinase 4/6 inhibitor abemaciclib in the adjuvant setting for patients with high-risk early-stage HR+ disease.2 High-risk was defined as ? 4 pathologically positive axillary nodes or 1-3 positive nodes and at least one of the following: tumor size ? 5 cm, histologic grade 3 disease, or Ki?67 ? 20%. Given the importance of the extent of nodal disease in these studies, surgical management of the axilla has resurfaced as a question asked at multidisciplinary tumor boards. Specifically, do these patients require axillary lymph node dissection (ALND) to determine total nodal burden to inform systemic therapy recommendations?

Journal of Clinical Oncology

My White Coat Doesn't Fit

Duma N

There I was, crying once again all the way from the hospital's parking lot to my apartment, into the shower, and while trying to fall asleep. This had become the norm during my internal medicine residency. For years, I tried hard every day to be someone else in order to fit in. It started with off-hand comments like “Look at her red shoes,” “You are so colorful,” and “You are so Latina.” These later escalated to being interrupted during presentations with comments about my accent, being told that my medical school training in my home country was inferior to my US colleagues, and being assigned all Spanish-speaking patients because “They are your people.” Some of those comments and interactions were unintentionally harmful but led to feelings of isolation, and over time, I began to feel like an outsider.

Journal of Clinical Oncology

Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer

Bardia A, Tolaney SM

PURPOSE: Hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) endocrine-resistant metastatic breast cancer is treated with sequential single-agent chemotherapy with poor outcomes. Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer.

METHODS: In this global, randomized, phase III study, SG was compared with physician's choice chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine) in endocrine-resistant, chemotherapy-treated HR+/HER2- locally recurrent inoperable or metastatic breast cancer. The primary end point was progression-free survival (PFS) by blinded independent central review.

RESULTS: Patients were randomly assigned to receive SG (n = 272) or chemotherapy (n = 271). The median age was 56 years, 95% had visceral metastases, and 99% had a prior cyclin-dependent kinase 4/6 inhibitor, with three median lines of chemotherapy for advanced disease. Primary end point was met with a 34% reduction in risk of progression or death (hazard ratio, 0.66 [95% CI, 0.53 to 0.83; P = .0003]). The median PFS was 5.5 months (95% CI, 4.2 to 7.0) with SG and 4.0 months (95% CI, 3.1 to 4.4) with chemotherapy; the PFS at 6 and 12 months was 46% (95% CI, 39 to 53) v 30% (95% CI, 24 to 37) and 21% (95% CI, 15 to 28) v 7% (95% CI, 3 to 14), respectively. Median overall survival (first planned interim analysis) was not yet mature (hazard ratio, 0.84; P = .14). Key grade 3 treatment-related adverse events (SG v chemotherapy) were neutropenia (51% v 38%) and diarrhea (9% v 1%).

CONCLUSIONS: SG demonstrated statistically significant PFS benefit over chemotherapy, with a manageable safety profile in patients with heavily pretreated, endocrine-resistant HR+/HER2- advanced breast cancer and limited treatment options.

JAMA Oncology

Surrogacy of Pathologic Complete Response in Trials of Neoadjuvant Therapy for Early Breast Cancer: Critical Analysis of Strengths, Weaknesses, and Misinterpretations

De Pas T, Gelber RD

IMPORTANCE: The pathologic complete response (pCR) is supported by regulatory agencies as a surrogate end point for long-term patients' clinical outcomes in the accelerated approval process of new drugs tested in neoadjuvant randomized clinical trials (RCTs) for early breast cancer (BC). However, a meaningful association between pCR and patients' survival has been proven only at the patient level (ie, significantly better survival of patients who achieved pCR compared with those who did not), but not at trial level (ie, poor association between degree of improvement in pCR rate and survival reported across trials).

OBSERVATIONS: We critically discuss the potential reasons of such discrepancy between pCR surrogacy value at the patient and trial level, as well as the relevant implications for both clinical research and drug regulatory policy. We also describe alternative surrogate end points, including combined end points that jointly analyzed pathological response and event-free survival data, or the assessment of circulating tumor DNA (ctDNA). Such proposed surrogate end points could overcome limits of pCR and provide a reasonable trade-off between the 2 conflicting needs to have access to effective therapies rapidly, and to reliably assess patients' clinical benefit.

CONCLUSIONS AND RELEVANCE: Using surrogate end points to grant drug approvals is justified only when they can provide accurate prediction of a drug's effect on the long-term patient outcomes. Evidence currently available does not support pCR used alone as a reliable surrogate end point in regulatory neoadjuvant RCTs for BC. The surrogacy value at trial level of potentially more robust surrogate end points needs to be urgently tested.

Nature Biotechnology

A Proteome-Scale Map of the SARS-CoV-2-Human Contactome

Kim DK, Sheykhkarimli D, Knapp JJ, Spirohn K, Laval F, Lambourne L, Kishore N, Rayhan A, Pogoutse O, Li R, Coté AG, Hazelwood I, Liu BB, Nguyen M, Giuliana P, Hao T, Hill DE, Twizere JC, Vidal M, Calderwood MA, Roth FP

Understanding the mechanisms of coronavirus disease 2019 (COVID-19) disease severity to efficiently design therapies for emerging virus variants remains an urgent challenge of the ongoing pandemic. Infection and immune reactions are mediated by direct contacts between viral molecules and the host proteome, and the vast majority of these virus-host contacts (the 'contactome') have not been identified. Here, we present a systematic contactome map of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with the human host encompassing more than 200 binary virus-host and intraviral protein-protein interactions. We find that host proteins genetically associated with comorbidities of severe illness and long COVID are enriched in SARS-CoV-2 targeted network communities. Evaluating contactome-derived hypotheses, we demonstrate that viral NSP14 activates nuclear factor Œ?B (NF-?B)-dependent transcription, even in the presence of cytokine signaling. Moreover, for several tested host proteins, genetic knock-down substantially reduces viral replication. Additionally, we show for USP25 that this effect is phenocopied by the small-molecule inhibitor AZ1. Our results connect viral proteins to human genetic architecture for COVID-19 severity and offer potential therapeutic targets.

Nature Communications

IgG-Like Bispecific Antibodies with Potent and Synergistic Neutralization Against Circulating SARS-CoV-2 Variants of Concern

Chang MR, Tomasovic L, Ke H, Coherd C, Nguyen K, Kamkaew M, Zhu Q, Marasco WA

Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern.

Nature Communications

The Design and Evaluation of Hybrid Controlled Trials that Leverage External Data and Randomization

Sands J, Wen PY, Rahman R, Alexander BM, Trippa L

Patient-level data from completed clinical studies or electronic health records can be used in the design and analysis of clinical trials. However, these external data can bias the evaluation of the experimental treatment when the statistical design does not appropriately account for potential confounders. In this work, we introduce a hybrid clinical trial design that combines the use of external control datasets and randomization to experimental and control arms, with the aim of producing efficient inference on the experimental treatment effects. Our analysis of the hybrid trial design includes scenarios where the distributions of measured and unmeasured prognostic patient characteristics differ across studies. Using simulations and datasets from clinical studies in extensive-stage small cell lung cancer and glioblastoma, we illustrate the potential advantages of hybrid trial designs compared to externally controlled trials and randomized trial designs.

Nature Genetics

Long-Range Phasing of Dynamic, Tissue-Specific and Allele-Specific Regulatory Elements

Battaglia S, Dong K, Wu J, Chen Z, Najm FJ, Zhang Y, Moore MM, Hecht V, Shoresh N, Bernstein BE

Epigenomic maps identify gene regulatory elements by their chromatin state. However, prevailing short-read sequencing methods cannot effectively distinguish alleles, evaluate the interdependence of elements in a locus or capture single-molecule dynamics. Here, we apply targeted nanopore sequencing to profile chromatin accessibility and DNA methylation on contiguous ~100-kb DNA molecules that span loci relevant to development, immunity and imprinting. We detect promoters, enhancers, insulators and transcription factor footprints on single molecules based on exogenous GpC methylation. We infer relationships among dynamic elements within immune loci, and order successive remodeling events during T cell stimulation. Finally, we phase primary sequence and regulatory elements across the H19/IGF2 locus, uncovering primate-specific features. These include a segmental duplication that stabilizes the imprinting control region and a noncanonical enhancer that drives biallelic IGF2 expression in specific contexts. Our study advances emerging strategies for phasing gene regulatory landscapes and reveals a mechanism that overrides IGF2 imprinting in human cells.

New England Journal of Medicine

GPRC5D-Targeted CAR T Cells for Myeloma

Carstens EJ, Russo D, Smith EL

BACKGROUND: B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell therapies have generated responses in patients with advanced myeloma, but relapses are common. G protein–coupled receptor, class C, group 5, member D (GPRC5D) has been identified as an immunotherapeutic target in multiple myeloma. Preclinical studies have shown the efficacy of GPRC5D-targeted CAR T cells, including activity in a BCMA antigen escape model.

METHODS: In this phase 1 dose-escalation study, we administered a GPRC5D-targeted CAR T-cell therapy (MCARH109) at four dose levels to patients with heavily pretreated multiple myeloma, including patients with relapse after BCMA CAR T-cell therapy.

RESULTS: A total of 17 patients were enrolled and received MCARH109 therapy. The maximum tolerated dose was identified at 150×106 CAR T cells. At the 450×106 CAR T-cell dose, 1 patient had grade 4 cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome (ICANS), and 2 patients had a grade 3 cerebellar disorder of unclear cause. No cerebellar disorder, ICANS of any grade, or cytokine release syndrome of grade 3 or higher occurred in the 12 patients who received doses of 25×106 to 150×106 cells. A response was reported in 71% of the patients in the entire cohort and in 58% of those who received doses of 25×106 to 150×106 cells. The patients who had a response included those who had received previous BCMA therapies; responses were observed in 7 of 10 such patients in the entire cohort and in 3 of 6 such patients who received 25×106 to 150×106 but not with tumor location, microsatellite instability, or BRAF, KRAS, or PIK3CA mutations.

CONCLUSIONS: The results of this study of a GPRC5D-targeted CAR T-cell therapy (MCARH109) confirm that GPRC5D is an active immunotherapeutic target in multiple myeloma. (Funded by Juno Therapeutics/Bristol Myers Squibb; number, NCT04555551. opens in new tab.)

Advanced Healthcare Materials

Enhanced Tumor Accumulation of Multimodal Magneto-Plasmonic Nanoparticles Via an Implanted Micromagnet-Assisted Delivery Strategy

Panikkanvalappil SR, Bhagavatula SK, Deans K, Jonas O, Rashidian M, Mishra S

AJR American Journal of Roentgenology

Beyond the AJR: CT Radiomic Features of the Pancreas Predict Development of Pancreatic Cancer

Rosenthal MH, Schawkat K

Annals of Hematology

Anti-CD38 Antibody Therapy for Patients with Relapsed/Refractory Multiple Myeloma: Differential Mechanisms of Action and Recent Clinical Trial Outcomes

Richardson PG

Annals of Surgical Oncology

ASO Visual Abstract: Screening MRI Does Not Increase Cancer Detection or Result in Earlier Stage at Diagnosis in Patients with High-Risk Breast Lesions-A Propensity Score Analysis


Laws A, Katlin F, Hans M, Graichen M, Kantor O, Minami C, Bychkovsky BL, Pace LE, Scheib R, Garber JE, King TA


A Probabilistic Gene Expression Barcode for Annotation of Cell Types from Single-Cell RNA-Seq Data

Grabski IN, Irizarry RA


British Journal of Cancer

Adverse Prognostic Impact of the Loss of STAG2 Protein Expression in Patients with Newly Diagnosed Localised Ewing Sarcoma: A Report from the Children's Oncology Group


Shulman DS, Nag A, Thorner AR, Lessnick SL, Stegmaier K, Janeway KA, DuBois SG, Church AJ, Crompton BD

British Journal of Haematology

Lenalidomide, Bortezomib and Dexamethasone Induction Therapy for the Treatment of Newly Diagnosed Multiple Myeloma: A Practical Review

Richardson PG

British Journal of Haematology

Peripheral Blood CD3(+) T-Cell Gene Expression Biomarkers Correlate with Clinical Frailty in Patients with Haematological Malignancies

Fell G, Abel GA, Dumontier C, Higby KJ, Murillo A, Neuberg DS, Lane AA

Breast Cancer Research and Treatment

Breast Cancer Knowledge and Understanding Treatment Rationales Among Diverse Breast Cancer Survivors

Freedman RA, Lederman RI, Gagnon H, Gundersen DA, Revette AC, Odai-Afotey A, Kantor O, Keating NL


Incidence, Characteristics, and Management of Central Nervous System Metastases in Patients with Inflammatory Breast Cancer

Warren LEG, Niman SM, Remolano MC, Landry JM, Nakhlis F, Bellon JR, Aizer AA, Lin NU, Tolaney SM, Regan MM, Overmoyer BA, Lynce F

Cancer Immunology Research

Hippo Signaling Pathway Regulates Cancer Cell-Intrinsic MHC-II Expression

Zeng Z, Gu SS, Ouardaoui N, Tymm C, Yang L, Wong CJ, Li D, Wang X, Weirather JL, Rodig SJ, Hodi FS, Brown M, Liu XS

Cell Chemical Biology

Acute Pharmacological Degradation of ERK5 does not Inhibit Cellular Immune Response or Proliferation

Donovan KA, Krupnick NM, Boghossian AS, Rees MG, Ronan MM, Roth JA, Fischer ES

Cell Reports

MCL-1 is a Master Regulator of Cancer Dependency on Fatty Acid Oxidation

Prew MS, Adhikary U, Choi DW, Portero EP, Paulo JA, Gowda P, Gygi SP, Danial NN, Walensky LD

Clinical Cancer Research

Cediranib in Combination with Olaparib in Patients without a Germline BRCA1/2 Mutation and with Recurrent Platinum-Resistant Ovarian Cancer: Phase IIb CONCERTO Trial

Liu JF

Clinical Cancer Research

Clinical Efficacy and Whole Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Hormone Receptor-Positive Breast Cancer

Tsuji J, Li T, Grinshpun A, Coorens T, Russo D, Anderson L, Rees R, Nardone A, Patterson C, Lennon NJ, Cibulskis C, Leshchiner I, Tayob N, Tolaney SM, Tung N, Krop IE, Winer EP, Stewart C, Getz G, Jeselsohn R

Clinical Cancer Research

Facts and Hopes in the Relationship of EBV with Cancer Immunity and Immunotherapy

Zhang B

Clinical Lymphoma, Myeloma, and Leukemia

ALL-269 Safety and Pharmacokinetics of Calaspargase Pegol in Adults with Newly Diagnosed Philadelphia-Negative Acute Lymphoblastic Leukemia: A Phase 2/3 Study

DeAngelo DJ

Clinical Lymphoma, Myeloma, and Leukemia

AML-055 Outcomes Based on Sequential Use of Venetoclax Based Therapy and Targeted Therapy in Acute Myeloid Leukemia (AML)

Stahl M, Shimony S, DeAngelo DJ, Stone RM

Clinical Lymphoma, Myeloma, and Leukemia

CLL-115 First Interim Analysis of ALPINE Study: Results of a Phase 3 Randomized Study of Zanubrutinib vs Ibrutinib in Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Brown JR

Clinical Lymphoma, Myeloma, and Leukemia

EXABS-132-ALL Approach to Acute Lymphoblastic Leukemia in The Elderly

Luskin MR

Clinical Lymphoma, Myeloma, and Leukemia

EXABS-179-CLL DEBATE: Sequencing Small Molecules Is the Way to Go

Brown JR

Clinical Lymphoma, Myeloma, and Leukemia

IBCL-117 ASPEN: Long-Term Follow-Up Results of a Phase 3 Randomized Trial of Zanubrutinib vs Ibrutinib in Patients with Waldenström Macroglobulinemia

Castillo JJ

Critical Reviews in Oncology Hematology

Effect of Exercise on Tumor Markers - Is Exercise Anti-Tumorigenic in Humans?: A Scoping Review of Preliminary Clinical Investigations

Kang DW, Vander Heiden MG, Dieli-Conwright CM

Current Opinion in Neurobiology

Somatotopic Organization of Autonomic Reflexes by Acupuncture

Ma Q

Diagnostic and Interventional Imaging

The BUMPy Road of Peritoneal Metastases in Ovarian Cancer

Worley M, Shinagare AB


Emerging Targeted Therapies for Early Breast Cancer

Tarantino P, Morganti S, Lynce F, Trapani D, Mayer EL, Garrido-Castro AC, Waks A, Tolaney SM

European Journal of Cancer

HER2-Low Inflammatory Breast Cancer: Clinicopathologic Features and Prognostic Implications

Tarantino P, Niman SM, Erick TK, Priedigkeit N, Harrison BT, Giordano A, Nakhlis F, Bellon JR, Parker T, Strauss S, Jin Q, King TA, Overmoyer BA, Regan MM, Tolaney SM, Lynce F

Genetic Epidemiology

Statistical Methods for Mendelian Models with Multiple Genes and Cancers

Liang JW, Parmigiani G, Braun D

Genetics in Medicine

A Validation of Models for Prediction of Pathogenic Variants in Mismatch Repair Genes

Shyr C, Huang T, Ke J, Trippa L, Syngal S, Ukaegbu C, Uno H, Braun D, Parmigiani G

International Journal of Cancer

Detection of Circulating Tumor Human Papillomavirus DNA Before Diagnosis of HPV-Positive Head and Neck Cancer

Rettig EM, Faden DL, Sandhu S, Wong K, Faquin WC, Warinner C, Richmon JD, Uppaluri R, Varvares M, Sethi R, Hanna GJ, Sroussi H

JAMA Psychiatry

Potential Limitations for the Culturally Tailored Version of Internet-Delivered Cognitive Behavioral Therapy for Insomnia in Black Women-Reply

Zhou ES


Framework for Integrating Electronic Patient-Reported Data in Routine Cancer Care: An Oncology Intake Questionnaire

McCleary NJ, Haakenstad EK, Cleveland JLF, Manni M, Hassett MJ, Schrag D

JCI Insight

VRK1 as a Synthetic Lethal Target in VRK2 Promoter-Methylated Cancers of the Nervous System

So J, Mabe NW, Englinger B, Chow KH, Moyer SM, Yerrum S, Trissal MC, Marques JG, Kwon JJ, Shim B, Pal S, Panditharatna E, Quinn T, Schaefer DA, Jeong D, Mayhew DL, Beroukhim R, Ligon KL, Stegmaier K, Filbin MG, Hahn WC

JCO Oncology Practice

Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline Summary and Q&A

Ligibel JA

JCO Oncology Practice

Patient, Family, and Clinician Perspectives on Location of Death for Adolescents and Young Adults with Cancer

Odejide OO, Fisher L, Vega B, Rodrigues G, Buchanan S, Fasciano KM, Lakin JR, Lefebvre A, Wall CB, Mack JW

Journal of General Internal Medicine

ACO Spending and Utilization Among Medicare Patients at the End of Life: An Observational Study

Lam MB, Friend TH, Erfani P, Orav EJ, Figueroa JF

Journal of Investigative Dermatology

Merkel Cell Carcinoma Sensitivity to EZH2 Inhibition Is Mediated by SIX1 Derepression

Gartin AK, Frost TC, Cushman CH, Leeper BA, Gokhale PC, DeCaprio JA

Journal of the National Comprehensive Cancer Network

Relationship Between Longitudinal Coping Strategies and Outcomes in Patients with Acute Myeloid Leukemia

Amonoo HL, Daskalakis E, Deary EC, Reynolds MJ, Nelson AM, Newcomb R, Dhawale TM, Yang D, Brunner A, Fathi AT, El-Jawahri A

Journal of Pain and Symptom Management

Natural Language Processing for Computer-Assisted Chart Review to Assess Documentation of Substance use and Psychopathology in Heart Failure Patients Awaiting Cardiac Resynchronization Therapy

Yusufov M, Pirl WF, Braun I, 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 Pediatric Hematology/Oncology Nursing

Oral Mercaptopurine Adherence in Pediatric Acute Lymphoblastic Leukemia: A Survey Study from the Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium

Stevenson K, Koch VB, Silverman LB, Bona K

Journal of Urology

Neoadjuvant Novel Hormonal Therapy Followed by Prostatectomy versus Up-Front Prostatectomy for High-Risk Prostate Cancer: A Comparative Analysis

Ravi P, Kwak L, Xie W, Kelleher K, Acosta AM, Kibel AS, Taplin ME

Nature Reviews Clinical Oncology

Is Early-Onset Cancer an Emerging Global Epidemic? Current Evidence and Future Implications

Ugai T, Sasamoto N, Lee HY, Ando M, Song M, Kawachi I, Giovannucci EL, Rebbeck TR, Ogino S

Nature Reviews Drug Discovery

Targeting Replication Stress in Cancer Therapy

da Costa AABA, Chowdhury D, Shapiro GI, D'Andrea AD, Konstantinopoulos PA


Brain Metastases: A Society for Neuro-Oncology (SNO) Consensus Review on Current Management and Future Directions

Aizer AA, Lamba N, Brastianos PK, Camidge DR, Huang RY, Lee EQ, Lin NU, Parsons M, Reardon DA, Wen PY


Characterizing the Biology of Primary Brain Tumors and Their Microenvironment via Single-Cell Profiling Methods

Gonzalez Castro LN, Liu I, Filbin M


Isocitrate Dehydrogenase (IDH) Mutant Gliomas: A Society for Neuro-Oncology (SNO) Consensus Review on Diagnosis, Management, and Future Directions

Miller JJ, Gonzalez Castro LN, Andronesi O, Bi WL, Cahill DP, Huang RY, Ligon KL, Reardon DA, Shi DD, Kaelin WG, Wen PY


Glioblastoma in Patients with Multiple Sclerosis

Berkman JM, Nakhate V, Gonzalez Castro LN

NPJ Precision Oncology

MatchMiner: An Open-Source Platform for Cancer Precision Medicine

Klein H, Mazor T, Siegel E, Trukhanov P, Ovalle A, Vecchio Fitz CD, Zwiesler Z, Kumari P, Marriott E, Hansel J, Yu J, Albayrak A, Barry S, Keller RB, MacConaill LE, Lindeman N, Johnson BE, Rollins BJ, Do KT, Beardslee B, Shapiro G, Hector-Barry S, Methot J, Sholl L, Lindsay J, Hassett MJ, Cerami E

Palliative and Supportive Care

Acceptability of a Serious Illness Conversation Guide to Black Americans: Results from a Focus Group and Oncology Pilot Study



Cost Effectiveness of Adding Pembrolizumab to Platinum and Fluoropyrimidine-Based Chemotherapy as First-Line Treatment for Advanced Esophageal Cancer: A US Healthcare Payer's Perspective

Enzinger PC


Invited Commentary: Pearls and Pitfalls in Imaging Evaluation of Lung Cancer Immunotherapy

Nishino M

Supportive Care in Cancer

Racial and Ethnic Disparities in Cancer Caregiver Burden and Potential Sociocultural Mediators

Fenton ATHR, Keating NL, Enzinger AC, Wright AA

Trends in Immunology

Does Delayed EBV Infection Contribute to Rising Childhood Cancers?

Zhang B, Panaampon J, Wang Z


Emergency Department-Based, Nurse-Initiated, Serious Illness Conversation Intervention for Older Adults: A Protocol for a Randomized Controlled Trial

Prachanukool T, Block SD, Lee RS, Rossmassler S, Hasdianda MA, Wang W, Schonberg MA, Tulsky JA, Ouchi K