Dana-Farber Research Publication, 9.1.2021

Cancer Cell Recovery of Cancer Screening Tests and Possible Associated Disparities After the First Peak of the COVID-19 Pandemic Labaki C, Bakouny Z, Schmidt A, Lipsitz SR, Rebbeck TR, Trinh QD, Choueiri TK Following the pandemic onset, a dramatic decrease in the number of cancer screening tests and ensuing diagnoses was observed. The consequent delays in diagnosis are expected to result in adverse oncologic outcomes. It is unknown to what extent screening pathways adapted during the pandemic, enabling the recovery of missed diagnoses.

Cancer Discovery CARM1 Inhibition Enables Immunotherapy of Resistant Tumors by Dual Action on Tumor Cells and T Cells Kumar S, Zeng Z, Bagati A, Tay RE, Ito Y, Abderazzaq F, Hatchi E, Jiang P, Cartwright ANR, Olawoyin O, Mathewson ND, Pyrdol JW, Li MZ, Doench JG, Booker MA, Tolstorukov MY, Elledge SJ, Liu XS, Wucherpfennig KW A number of cancer drugs activate innate immune pathways in tumor cells but unfortunately also compromise antitumor immune function. We discovered that inhibition of CARM1, an epigenetic enzyme and cotranscriptional activator, elicited beneficial antitumor activity in both cytotoxic T cells and tumor cells. In T cells, Carm1 inactivation substantially enhanced their antitumor function and preserved memory-like populations required for sustained antitumor immunity. In tumor cells, Carm1 inactivation induced a potent type 1 interferon response that sensitized resistant tumors to cytotoxic T cells. Substantially increased numbers of dendritic cells, CD8 T cells, and natural killer cells were present in Carm1-deficient tumors, and infiltrating CD8 T cells expressed low levels of exhaustion markers. Targeting of CARM1 with a small molecule elicited potent antitumor immunity and sensitized resistant tumors to checkpoint blockade. Targeting of this cotranscriptional regulator thus offers an opportunity to enhance immune function while simultaneously sensitizing resistant tumor cells to immune attack. SIGNIFICANCE: Resistance to cancer immunotherapy remains a major challenge. Targeting of CARM1 enables immunotherapy of resistant tumors by enhancing T-cell functionality and preserving memory-like T-cell populations within tumors. CARM1 inhibition also sensitizes resistant tumor cells to immune attack by inducing a tumor cell-intrinsic type 1 interferon response.This article is highlighted in the In This Issue feature, p. 1861.

Cancer Discovery Intrinsic Immunogenicity of Small Cell Lung Carcinoma Revealed by Its Cellular Plasticity Mahadevan NR, Knelson EH, Wolff JO, Vajdi A, Saigi M, Campisi M, Hong D, Thai TC, Piel B, Han S, Reinhold BB, Duke-Cohan JS, Poitras MJ, Taus LJ, Lizotte PH, Portell A, Quadros V, Santucci AD, Kitajima S, Akitsu A, Reardon B, Gokhale PC, Paweletz CP, Awad MM, Van Allen EM, Hong F, Sholl LM, Tolstorukov MY, Pfaff K, Jänne PA, Rodig S, Reinherz EL, Oser MG, Barbie DA Small cell lung carcinoma (SCLC) is highly mutated, yet durable response to immune checkpoint blockade (ICB) is rare. SCLC also exhibits cellular plasticity, which could influence its immunobiology. Here we discover that a distinct subset of SCLC uniquely upregulates MHC I, enriching for durable ICB benefit. In vitro modeling confirms epigenetic recovery of MHC I in SCLC following loss of neuroendocrine differentiation, which tracks with derepression of STING. Transient EZH2 inhibition expands these nonneuroendocrine cells, which display intrinsic innate immune signaling and basally restored antigen presentation. Consistent with these findings, murine nonneuroendocrine SCLC tumors are rejected in a syngeneic model, with clonal expansion of immunodominant effector CD8 T cells. Therapeutically, EZH2 inhibition followed by STING agonism enhances T-cell recognition and rejection of SCLC in mice. Together, these data identify MHC I as a novel biomarker of SCLC immune responsiveness and suggest novel immunotherapeutic approaches to co-opt SCLC's intrinsic immunogenicity. SIGNIFICANCE: SCLC is poorly immunogenic, displaying modest ICB responsiveness with rare durable activity. In profiling its plasticity, we uncover intrinsically immunogenic MHC Ihi subpopulations of nonneuroendocrine SCLC associated with durable ICB benefit. We also find that combined EZH2 inhibition and STING agonism uncovers this cell state, priming cells for immune rejection.This article is highlighted in the In This Issue feature, p. 1861.

Cell Stem Cell Race to the Bottom: Darwinian Competition in Early Intestinal Tumorigenesis Shivdasani RA Mutant oncogenes could enable clonal dominance by cell-intrinsic means or by suppressing nearby wild-type stem cells. Reporting recently in Nature, three groups demonstrate potent neighborhood effects, both within intestinal crypts (Flanagan et al., 2021; van Neerven et al., 2021) and across crypts through intermediary sub-epithelial trophocytes (Yum et al., 2021).

Journal of Clinical Oncology Amivantamab: Treating EGFR Exon 20-Mutant Cancers with Bispecific Antibody-Mediated Receptor Degradation Köhler J, Jänne PA Insertions in exon 20 of the epidermal growth factor (EGF) receptor (EGFR Ex20ins) represent the third and most common type of activating EGFR mutations in non-small-cell lung cancer (NSCLC). With some geographical variation, they are detected in up to 4% of all advanced NSCLC and in 4%-12% of EGFR mutation-positive NSCLC. EGFR Ex20ins are more common in tumors amoung never smokers, but unlnike common Exon19 deletions or Exon21 L858R poing mutations, most of the Ex20ins mutations (except for EGFR A763_Y764FQEA) exhibit de novo resistance to the currently approved first-line EGFR tyrosine kinase inhibitors (TKIs): erlotinib, gefitinib, afatinib, and Osimertinib. Therefore, chemotherapy represents the mainstay treatment option. Mechanisms of TKI resistance are multifactorial including steric hinderance, similar TKI affinities to Exon20ins-mutation EGFR, and unchanged ATP binding of mutant compared with wild-type EGFR.

Journal of Clinical Oncology Final Overall Survival Analysis of the TOURMALINE-MM1 Phase III Trial of Ixazomib, Lenalidomide, and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma Richardson PG, Laubach JP PURPOSE: The double-blind, placebo-controlled, phase III TOURMALINE-MM1 study demonstrated a statistically significant improvement in progression-free survival with ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd in patients with relapsed or refractory multiple myeloma. We report the final analyses for overall survival (OS). PATIENTS AND METHODS: Patients were randomly assigned to ixazomib-Rd (n = 360) or placebo-Rd (n = 362), stratified by number of prior therapies (1 v 2 or 3), previous proteasome inhibitor (PI) exposure (yes v no), and International Staging System disease stage (I or II v III). OS (intent-to-treat population) was a key secondary end point. RESULTS: With a median follow-up of 85 months, median OS with ixazomib-Rd versus placebo-Rd was 53.6 versus 51.6 months (hazard ratio, 0.939; P = .495). Lower hazard ratios, indicating larger magnitude of OS benefit with ixazomib-Rd versus placebo-Rd, were seen in predefined subgroups: refractory to any (0.794) or last (0.742) treatment line; age > 65-75 years (0.757); International Staging System stage III (0.779); 2/3 prior therapies (0.845); high-risk cytogenetics (0.870); and high-risk cytogenetics and/or 1q21 amplification (0.862). Following ixazomib-Rd versus placebo-Rd, 71.7% versus 69.9% of patients received 1 anticancer therapy, of whom 24.7% versus 33.9% received daratumumab and 71.8% versus 76.9% received PIs (next-line therapy: 47.5% v 55.8%). Rates of new primary malignancies were similar with ixazomib-Rd (10.3%) and placebo-Rd (11.9%). There were no new or additional safety concerns. CONCLUSION: Median OS values in both arms were the longest reported in phase III studies of Rd-based triplets in relapsed or refractory multiple myeloma at the time of this analysis; progression-free survival benefit with ixazomib-Rd versus placebo-Rd did not translate into a statistically significant OS benefit on intent-to-treat analysis. OS benefit was greater in subgroups with adverse prognostic factors. OS interpretation was confounded by imbalances in subsequent therapies received, especially PIs and daratumumab.

Journal of the National Cancer Institute Defining Multimorbidity and Its Impact in Older United States Veterans Newly Treated for Multiple Myeloma Fillmore NR, DuMontier C, Yildirim C, La J, Cheng D, Cirstea D, Abel GA, Gaziano JM, Kim DH, Munshi NC, Driver JA BACKGROUND: Traditional count-based measures of comorbidity are unlikely to capture the complexity of multiple chronic conditions (multimorbidity) in older adults with cancer. We aimed to define patterns of multimorbidity and their impact in older United States veterans with multiple myeloma (MM). METHODS: We measured 66 chronic conditions in 5076 veterans aged 65 years and older newly treated for MM in the national Veterans Affairs health-care system from 2004 to 2017. Latent class analysis was used to identify patterns of multimorbidity among these conditions. These patterns were then assessed for their association with overall survival, our primary outcome. Secondary outcomes included emergency department visits and hospitalizations. RESULTS: Five patterns of multimorbidity emerged from the latent class analysis, and survival varied across these patterns (log-rank 2-sided P <.001). Older veterans with cardiovascular and metabolic disease (30.9%, hazard ratio [HR] = 1.33, 95% confidence interval [CI] = 1.21 to 1.45), psychiatric and substance use disorders (9.7%, HR = 1.58, 95% CI = 1.39 to 1.79), chronic lung disease (15.9%, HR = 1.69, 95% CI = 1.53 to 1.87), and multisystem impairment (13.8%, HR = 2.25, 95% CI = 2.03 to 2.50) had higher mortality compared with veterans with minimal comorbidity (29.7%, reference). Associations with mortality were maintained after adjustment for sociodemographic variables, measures of disease risk, and the count-based Charlson Comorbidity Index. Multimorbidity patterns were also associated with emergency department visits and hospitalizations. CONCLUSIONS: Our findings demonstrate the need to move beyond count-based measures of comorbidity and consider cancer in the context of multiple chronic conditions.

Nature Phenotype, Specificity and Avidity of Antitumour CD8(+) T Cells in Melanoma Oliveira G, Stromhaug K, Klaeger S, Kula T, Frederick DT, Le PM, Forman J, Huang T, Li S, Zhang W, Cieri N, Clauser KR, Shukla SA, Neuberg D, Carr SA, Fritsch EF, Hacohen N, Sade-Feldman M, Livak KJ, Boland GM, Ott PA, Keskin DB, Wu CJ Interactions between T cell receptors (TCRs) and their cognate tumour antigens are central to antitumour immune responses1-3; however, the relationship between phenotypic characteristics and TCR properties is not well elucidated. Here we show, by linking the antigenic specificity of TCRs and the cellular phenotype of melanoma-infiltrating lymphocytes at single-cell resolution, that tumour specificity shapes the expression state of intratumoural CD8+ T cells. Non-tumour-reactive T cells were enriched for viral specificities and exhibited a non-exhausted memory phenotype, whereas melanoma-reactive lymphocytes predominantly displayed an exhausted state that encompassed diverse levels of differentiation but rarely acquired memory properties. These exhausted phenotypes were observed both among clonotypes specific for public overexpressed melanoma antigens (shared across different tumours) or personal neoantigens (specific for each tumour). The recognition of such tumour antigens was provided by TCRs with avidities inversely related to the abundance of cognate targets in melanoma cells and proportional to the binding affinity of peptide-human leukocyte antigen (HLA) complexes. The persistence of TCR clonotypes in peripheral blood was negatively affected by the level of intratumoural exhaustion, and increased in patients with a poor response to immune checkpoint blockade, consistent with chronic stimulation mediated by residual tumour antigens. By revealing how the quality and quantity of tumour antigens drive the features of T cell responses within the tumour microenvironment, we gain insights into the properties of the anti-melanoma TCR repertoire.

Nature Cell Biology ASTE1 Cutting to Block DNA End Resection He YJ, Chowdhury D Double-strand DNA breaks (DSBs) are repaired by two major mechanistically distinct pathways, homologous recombination (HR) and non-homologous end-joining (NHEJ). The relative contributions of the competing DSB repair pathways differ across cell types and throughout the cell cycle, and this balance is critical for maintaining genomic stability. A decisive factor in the choice between DSB repair pathways is the competition between DNA end protection, which is necessary for NHEJ, and DNA end resection, which is necessary for HR. DSB end resection must be appropriately restricted to S and G2 phases of the cell cycle, as HR requires the presence of an intact sister chromatid. Depletion of NHEJ-promoting factors such as 53BP1 allows DNA end resection in the G1 phase, thereby impairing DSB repair and causing genomic instability. Conversely, loss of BRCA1, an HR protein that is critical for end resection initiation, allows the error-prone NHEJ pathway to dominate throughout the cell cycle, potentially leading to tumourigenesis. Loss of BRCA1 provides a therapeutic opportunity in these tumours, as they become sensitive to inhibitors of the DNA repair protein poly(ADP-ribose) polymerase (PARP) and to platinum-based drugs. Surprisingly, loss of 53BP1 or associated factors (e.g., RIF1, shieldin complex) in BRCA1-depleted tumours renders them insensitive to PARP inhibitors (PARPi), as DNA end resection and the subsequent steps of the HR pathway are restored. Therefore, factors that regulate the processing of DNA ends are crucial for pathway choice and may have tremendous relevance in cancer biology. In this issue of Nature Cell Biology, Zhao, Kim et al. report that ASTE1, a previously uncharacterised XPG family DNA endonuclease, functions as a downstream effector of 53BP1-shieldin in promoting NHEJ, thereby regulating the balance of DSB repair pathways.

Nature Communications The Conformational Stability of Pro-Apoptotic BAX is Dictated by Discrete Residues of the Protein Core Bloch NB, Prew MS, Levy HR, Walensky LD BAX is a pro-apoptotic member of the BCL-2 family, which regulates the balance between cellular life and death. During homeostasis, BAX predominantly resides in the cytosol as a latent monomer but, in response to stress, transforms into an oligomeric protein that permeabilizes the mitochondria, leading to apoptosis. Because renegade BAX activation poses a grave risk to the cell, the architecture of BAX must ensure monomeric stability yet enable conformational change upon stress signaling. The specific structural features that afford both stability and dynamic flexibility remain ill-defined and represent a critical control point of BAX regulation. We identify a nexus of interactions involving four residues of the BAX core ?5 helix that are individually essential to maintaining the structure and latency of monomeric BAX and are collectively required for dimeric assembly. The dual yet distinct roles of these residues reveals the intricacy of BAX conformational regulation and opportunities for therapeutic modulation.

Nature Communications Topological Isolation of Developmental Regulators in Mammalian Genomes Stamenova EK, Meissner A, Michor F Precise control of mammalian gene expression is facilitated through epigenetic mechanisms and nuclear organization. In particular, insulated chromosome structures are important for regulatory control, but the phenotypic consequences of their boundary disruption on developmental processes are complex and remain insufficiently understood. Here, we generated deeply sequenced Hi-C data for human pluripotent stem cells (hPSCs) that allowed us to identify CTCF loop domains that have highly conserved boundary CTCF sites and show a notable enrichment of individual developmental regulators. Importantly, perturbation of such a boundary in hPSCs interfered with proper differentiation through deregulated distal enhancer-promoter activity. Finally, we found that germline variations affecting such boundaries are subject to purifying selection and are underrepresented in the human population. Taken together, our findings highlight the importance of developmental gene isolation through chromosomal folding structures as a mechanism to ensure their proper expression.

Nature Genetics Genome-Scale Screens Identify Factors Regulating Tumor Cell Responses to Natural Killer Cells Sheffer M, Lowry E, Borah M, Amara SN, Mader CC, Roth JA, Tsherniak A, Freeman SS, Dashevsky O, Gandolfi S, Bender S, Bryan JG, Zhu C, Wang L, Tariq I, Simoes RM, Dhimolea E, Yu C, Hu Y, Giannakis M, Fraenkel E, Golub T, Romee R, Culhane AC, Mitsiades CS To systematically define molecular features in human tumor cells that determine their degree of sensitivity to human allogeneic natural killer (NK) cells, we quantified the NK cell responsiveness of hundreds of molecularly annotated 'DNA-barcoded' solid tumor cell lines in multiplexed format and applied genome-scale CRISPR-based gene-editing screens in several solid tumor cell lines, to functionally interrogate which genes in tumor cells regulate the response to NK cells. In these orthogonal studies, NK cell-sensitive tumor cells tend to exhibit 'mesenchymal-like' transcriptional programs; high transcriptional signature for chromatin remodeling complexes; high levels of B7-H6 (NCR3LG1); and low levels of HLA-E/antigen presentation genes. Importantly, transcriptional signatures of NK cell-sensitive tumor cells correlate with immune checkpoint inhibitor (ICI) resistance in clinical samples. This study provides a comprehensive map of mechanisms regulating tumor cell responses to NK cells, with implications for future biomarker-driven applications of NK cell immunotherapies.

Abdominal Radiology Robustness and Performance of Radiomic Features in Diagnosing Cystic Renal Masses Könik A, Miskin N, Guo Y, Shinagare AB, Qin L

American Journal of Emergency Medicine Digital Health Innovation to Integrate Palliative Care During the COVID-19 Pandemic Lai L, Sato R, Ouchi K, Landman AB, Zhang HM

Annals of Surgical Oncology ASO Visual Abstract: Racial and Socioeconomic Disparities in Breast Cancer Outcomes within the AJCC Pathologic Prognostic Staging System Kantor O, Wang ML, Freedman RA, Chavez-MacGregor M, King TA, Mittendorf EA

Blood Advances Clonal Hematopoiesis in Patients Receiving Chimeric Antigen Receptor T-Cell Therapy Miller PG, Sperling AS, Brea EJ, Leick MB, Fell GG, Jan M, Gohil SH, Tai YT, Munshi NC, Wu CJ, Neuberg DS, Maus MV, Jacobson C, Gibson CJ, Ebert BL

British Journal of Cancer Communication Around Palliative Care Principles and Advance Care Planning Between Oncologists, Children with Advancing Cancer and Families Mack JW

British Journal of Cancer Essential Role of the Histone Lysine Demethylase KDM4A in the Biology of Malignant Pleural Mesothelioma (MPM) Lapidot M, Case AE, Weisberg EL, Meng C, Garg S, Ni W, Hung YP, Carrasco RD, Knott A, Gokhale PC, Frank DA, Griffin JD, Saladi SV, Bueno R, Sattler M

British Journal of Cancer Phase 1 Study of the ATR Inhibitor Berzosertib in Combination with Cisplatin in Patients with Advanced Solid Tumours Shapiro GI

British Journal of Haematology Bone Marrow Involvement and Subclonal Diversity Impairs Detection of Mutated CXCR4 by Diagnostic Next-Generation Sequencing in Waldenström Macroglobulinaemia Gustine JN, Xu L, Yang G, Liu X, Kofides A, Tsakmaklis N, Munshi M, Demos M, Guerrera ML, Meid K, Patterson CJ, Sarosiek S, Branagan AR, Hunter ZR, Castillo JJ, Treon SP

British Journal of Haematology Plasmablastic Lymphoma Transformation in a Patient with Waldenström Macroglobulinemia Treated with Ibrutinib Castillo JJ, LaMacchia J, Flynn CA, Sarosiek S, Pozdnyakova O, Treon SP

Breast Who are the Women Who Enrolled in the POSITIVE Trial: A Global Study to Support Young Hormone Receptor Positive Breast Cancer Survivors Desiring Pregnancy Partridge AH, Niman SM, Gelber RD

Breast Cancer Research Comparing Syngeneic and Autochthonous Models of Breast Cancer to Identify Tumor Immune Components that Correlate with Response to Immunotherapy in Breast Cancer Lal JC, Townsend MG, Mehta AK, Oliwa M, Sotayo A, Cheney E, Mittendorf EA, Letai A, Guerriero JL

Breast Cancer Research and Treatment Chemotherapy-Related Amenorrhea (CRA) After Adjuvant Ado-Trastuzumab Emtansine (T-DM1) Compared to Paclitaxel in Combination with Trastuzumab (TH) (TBCRC033: ATEMPT Trial) Zheng Y, Tayob N, Hu J, Isakoff SJ, Faggen MG, Mulvey TM, Sella T, Constantine M, Briccetti FM, Rosenberg S, DeMeo MK, Burstein HJ, Winer EP, Krop IE, Partridge AH, Tolaney SM

Breast Cancer Research and Treatment Factors Associated with Late Risks of Breast Cancer-Specific Mortality in the SEER Registry Leone JP, Hassett MJ, Graham N, Tayob N, Freedman RA, Tolaney SM, Winer EP, Lin NU

Breast Cancer Research and Treatment Tumor Subtypes and Survival in Male Breast Cancer Freedman RA, Lin NU, Tolaney SM, Winer EP, Leone JP

Breast Cancer Research and Treatment Utilization and Predictors of Postmastectomy Radiation Receipt in an Oncology Center in Zimbabwe Chipidza FE, Iyer HS, Bellon JR, Elmore SN

Cancer Healthy Days at Home: A Population-Based Quality Measure for Cancer Patients at the End of Life Lam MB, Riley KE, Zheng J, Orav EJ, Burke LG

Cancer Impact of Fertility Concerns on Endocrine Therapy Decisions in Young Breast Cancer Survivors Sella T, Poorvu PD, Gelber SI, Peppercorn JM, Come SE, Partridge AH, Rosenberg SM

Cancer Prostate-Specific Antigen Nadir and Testosterone Level at Prostate-Specific Antigen Failure Following Radiation and Androgen Suppression Therapy for Unfavorable-Risk Prostate Cancer and the Risk of All-Cause and Prostate Cancer-Specific Mortality Bitterman DS, Loffredo M, D'Amico AV

Cancer Immunology, Immunotherapy Cytokine Changes During Immune-Related Adverse Events and Corticosteroid Treatment in Melanoma Patients Receiving Immune Checkpoint Inhibitors Tyan K, Baginska J, Brainard M, Giobbie-Hurder A, Severgnini M, Manos M, Haq R, Buchbinder EI, Ott PA, Hodi FS, Rahma OE

Cancer Immunology Research TMB and Inflammatory Gene Expression Associated with Clinical Outcomes Following Immunotherapy in Advanced Melanoma Hodi FS

Cancer Research Gene Fusions Create Partner and Collateral Dependencies Essential to Cancer Cell Survival Gillani R, Seong BKA, Crowdis J, Conway JR, Dharia NV, Haas BJ, Park J, Dietlein F, He MX, Imamovic A, Ma C, Boehm JS, Vazquez F, Gusev A, Liu D, Janeway KA, McFarland JM, Stegmaier K, Van Allen EM

Cancer Research The MCF10 Model of Breast Tumor Progression Puleo J, Polyak K

Chemical Society Reviews Chemoproteomic Methods for Covalent Drug Discovery Chan WC, Sharifzadeh S, Buhrlage SJ, Marto JA

Clinical Cancer Research Facts and Hopes in Multiple Myeloma Immunotherapy Sperling AS, Anderson KC

Clinical Cancer Research Oncogenic Mutations in PI3K/AKT/mTOR Pathway Effectors Associate with Worse Prognosis in BRAF(V600E) -Driven Papillary Thyroid Cancer Patients Pappa T, Ahmadi S, Marqusee E, Johnson HL, Nehs MA, Cho NL, Barletta JA, Lorch JH, Doherty GM, Lindeman NI, Alexander EK, Landa I

Clinical Cancer Research Prognostic Utility of Breast Cancer Index to Stratify Distant Recurrence Risk in Invasive Lobular Carcinoma Sella T, Sgroi DC, Metzger O

Clinical Cancer Research Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial Cote GM, Wen PY

Clinical Pharmacology in Drug Development Pharmacokinetics and Safety of PTC596, a Novel Tubulin-Binding Agent, in Subjects with Advanced Solid Tumors Shapiro GI

Current Opinion in Oncology Maintenance Therapies in Acute Myeloid Leukemia: The Renaissance of an Old Therapeutic Concept Stahl M

European Journal of Cancer Ripretinib Intrapatient Dose Escalation After Disease Progression Provides Clinically Meaningful Outcomes in Advanced Gastrointestinal Stromal Tumour George S

Gynecologic Oncology Rationale for Combination PARP Inhibitor and Antiangiogenic Treatment in Advanced Epithelial Ovarian Cancer: A Review Liu JF

Gynecologic Oncology The American Society of Clinical Oncology 2021 Annual (virtual) Meeting: A Review and Summary of Selected Abstracts Liu JF

HemaSphere Diagnostic Next-generation Sequencing Frequently Fails to Detect MYD88(L265P) in Waldenström Macroglobulinemia Kofides A, Hunter ZR, Xu L, Tsakmaklis N, Demos MG, Munshi M, Liu X, Guerrera ML, Leventoff CR, White TP, Flynn CA, Meid K, Patterson CJ, Yang G, Branagan AR, Sarosiek S, Castillo JJ, Treon SP, Gustine JN

Hematology/Oncology Clinics of North America Chronic Lymphocytic Leukemia: So Much Progress, Still Challenges Ahead Brown JR

Hematology/Oncology Clinics of North America The Evolving Use of Phosphatidylinositol 3-Kinase Inhibitors for the Treatment of Chronic Lymphocytic Leukemia Lampson BL, Brown JR

International Journal of Radiation Oncology, Biology, Physics Mean Heart Dose Is an Inadequate Surrogate for Left Anterior Descending Coronary Artery Dose and the Risk of Major Adverse Cardiac Events in Lung Cancer Radiation Therapy Atkins KM, Bitterman DS, Chaunzwa TL, Kozono DE, Baldini EH, Aerts HJWL, Hoffmann U, Nohria A, Mak RH

International Journal of Radiation Oncology, Biology, Physics Postmastectomy Bolus: Urban Legend or Sound Practice? Bellon JR

Investigational New Drugs A Phase Ib, Open Label, Dose Escalation Trial of the Anti-CD37 Monoclonal Antibody, BI 836826, in Combination with Ibrutinib in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Brown JR

Investigational New Drugs A Phase 1b Trial of the CXCR4 Inhibitor Mavorixafor and Nivolumab in Advanced Renal Cell Carcinoma Patients with No Prior Response to Nivolumab Monotherapy Choueiri TK, McDermott DF

Journal of Biological Chemistry Multifunctional Protein 4.1R Regulates the Asymmetric Segregation of Numb During Terminal Erythroid Maturation Huang SC, Vu LV, Yu FH, Nguyen DT, Benz EJ Jr

Journal of Medicinal Chemistry Structure-Guided Design of a "Bump-and-Hole" Bromodomain-Based Degradation Tag Nowak RP, Xiong Y, Kirmani N, Kalabathula J, Donovan KA, Eleuteri NA, Yuan JC, Fischer ES

Journal of Pain and Symptom Management Development, Implementation, and Outcomes of a Serious Illness Care Community of Practice Maloney FL, Hawrusik B, Paquette E, Takahashi K, Downey N, Paladino J, Bernacki RE

Journal of Pain and Symptom Management Naming the Problem: A Structural Racism Framework to Examine Disparities in Palliative Care Umaretiya P, Wolfe J, Bona K

Journal of Pain and Symptom Management Patterns of Specialty Palliative Care Utilization Among Patients Receiving Palliative Radiation Therapy Chen JJ, Rawal B, Krishnan MS, Hertan LM, Shi DD, Roldan CS, Huynh MA, Spektor A, Balboni TA

Journal of Palliative Medicine A Yet Unrealized Promise: Structured Advance Care Planning Elements in the Electronic Health Record Lakin JR, Gundersen DA, Lindvall C, Tulsky JA, Volandes A

Journal of Urology Editorial Comment Mantia CM, Sonpavde GP

Journal of Urology Editorial Comment Sonpavde GP

JAMA Network Open Polysymptomatology in Pediatric Patients Receiving Palliative Care Based on Parent-Reported Data Wolfe J

Leukemia and Lymphoma Clinical Application of Genomics in Waldenström Macroglobulinemia Branagan AR, Lei M, Treon SP, Castillo JJ

Leukemia Targeting Serine Hydroxymethyltransferases 1 and 2 for T-Cell Acute Lymphoblastic Leukemia Therapy Pikman Y, Ocasio-Martinez N, Alexe G, Dimitrov B, Kitara S, Robichaud AL, Conway AS, Ross L, Qi J, Vander Heiden MG, Stegmaier K

Leukemia Targeting Ubiquitin-Specific Protease-7 in Plasmacytoid Dendritic Cells Triggers Anti-Myeloma Immunity Ray A, Du T, Song Y, Buhrlage SJ, Chauhan D, Anderson KC

Molecular Cancer Research Genomic Landscape of Primary and Recurrent Anal Squamous Cell Carcinomas in Relation to HPV Integration, Copy-Number Variation, and DNA Damage Response Genes Aldersley J, Lorenz DR, Mouw KW, D'Andrea AD, Gabuzda D

Molecular Cancer Research Mutant KRAS Downregulates the Receptor for Leukemia Inhibitory Factor (LIF) to Enhance a Signature of Glycolysis in Pancreatic Cancer and Lung Cancer Liu S, Gandler HI, Tosic I, Ye DQ, Giaccone ZT, Frank DA

Molecular Cancer Therapeutics Gene Expression Signature Correlates with Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with Everolimus Alone or with a Vascular Disrupting Agent Nassar AH, Adib E, Jegede OA, Alaiwi SA, Braun DA, Zarei M, Du H, Sonpavde GP

Neuro-Oncology Multimodal Platform for Assessing Drug Distribution and Response in Clinical Trials G C Lopez B, Du Z, Korsunsky I, Abdelmoula WM, Dai Y, Stopka SA, Gaglia G, Randall EC, Regan MS, Basu SS, Clark AR, Supko JG, Raychaudhuri S, Ligon KL, Wen PY, Alexander B, Lee EQ, Santagata S, Agar NYR

Neuro-Oncology Prognostication for Meningiomas: H3K27me3 to the Rescue? Santagata S, Ligon KL

Neuro-Oncology Report of National Brain Tumor Society Roundtable Workshop on Innovating Brain Tumor Clinical Trials: Building on Lessons Learned from COVID-19 Experience Lee EQ, Kvedar JC, Schwamm LH, Wen PY

Neuro-Oncology The Evolving Role of Systemic Therapy and Local, Brain-Directed Treatment in Patients with Melanoma and Brain Metastases Lamba N, Aizer AA

Neuro-Oncology The 2021 WHO Classification of Tumors of the Central Nervous System: Clinical Implications Wen PY

NPJ Precision Oncology Circulating Tumor Cell Heterogeneity in Neuroendocrine Prostate Cancer by Single Cell Copy Number Analysis Conteduca V, Ku SY, Beltran H

Oncoimmunology Association of PIK3CA Mutation and PTEN Loss with Expression of CD274 (PD-L1) in Colorectal Carcinoma Ugai T, Zhao M, Akimoto N, Shi S, Takashima Y, Zhong R, Lau MC, Haruki K, Arima K, Fujiyoshi K, Langworthy B, Masugi Y, da Silva A, Nosho K, Baba Y, Song M, Chan AT, Wang M, Meyerhardt JA, Giannakis M, Väyrynen JP, Nowak JA, Ogino S

Oncologist Impact of Cancer History on Outcomes Among Hospitalized Patients with COVID-19 Klein IA, Rosenberg SM, Reynolds KL, Zubiri L, Rosovsky R, Piper-Vallillo AJ, Gao X, Boland G, Bardia A, Gaither R, Freeman H, Kirkner GJ, Rhee C, Klompas M, Baker MA, Wadleigh M, Winer EP, Kotton CN, Partridge AH

Oncologist Prevalence and Tolerance of Prognostic Uncertainty Among Thoracic Oncologists Habib AR, Chen R, Magnavita ES, Jaung T, Awad MM, Odejide O, Abel GA

Oral Oncology A Phase II Trial of All-Trans Retinoic Acid (ATRA) in Advanced Adenoid Cystic Carcinoma Hanna GJ, ONeill A, Cutler JM, Flynn M, Vijaykumar T, Clark JR, Wirth LJ, Lorch JH, Park JC, Mito JK, Lohr JG, Zon LI, Haddad RI

Pediatric Blood and Cancer Broaching Goals-of-Care Conversations in Advancing Pediatric Cancer Mack JW

Protein Science A Structural Perspective on Targeting the RTK/Ras/MAP Kinase Pathway in Cancer Eck MJ

Radiotherapy and Oncology Second Malignancy Probabilities in Prostate Cancer Patients Treated with SBRT and Other Contemporary Radiation Techniques Dee EC, Muralidhar V, King MT, Martin NE, D'Amico AV, Mouw KW, Orio PF, Nguyen PL, Leeman JE

Supportive Care in Cancer Lessons Learned from the Delivery of Virtual Integrative Oncology Interventions in Clinical Practice and Research During the COVID-19 Pandemic Knoerl R, Phillips CS, Berfield J, Woods H, Acosta M, Tanasijevic A, Ligibel J

Transplantation and Cellular Therapy Novel Composite Endpoints after Allogeneic Hematopoietic Cell Transplantation Kim HT

Urologic Clinics of North America Clinical Multigene Testing for Prostate Cancer Berro T, Barrett E, AlDubayan SH

Urologic Oncology Decision Regret, Adverse Outcomes, and Treatment Choice in Men with Localized Prostate Cancer: Results From a Multi-Site Randomized Trial Berry DL, Hong F, Blonquist TM, Halpenny B, Xiong N, Chang P, Hayes JH, Trinh QD

Urology Clinical Characterization of Radiation-Associated Muscle-Invasive Bladder Cancer Sha ST, Dee EC, Mossanen M, Zaslowe-Dude C, Royce TJ, Hirsch MS, Preston MA, Nguyen PL, Mouw KW, Muralidhar V