Skip to main content

Dana-Farber Research News 04.01.2025

Welcome to Dana-Farber's Research News

View Archive Newsletters

April 1, 2025

This twice-monthly newsletter highlights recently published research where Dana-Farber faculty are listed as first or senior authors. The information is pulled from PubMed and this issue notes papers published from March 1 through March 15.

If you are a Dana-Farber faculty member and you think your paper is missing from Research News, please let us know by emailing dfciresearchnews@dfci.harvard.edu.

Blood

Large-Scale Dependency and Drug Screens Characterize the Therapeutic Vulnerabilities of Multiple Myeloma with 1q

Sklavenitis-Pistofidis R, Lightbody ED, Reidy M, Tsuji J, Alberge JB, Aranha MP, Heilpern-Mallory DL, Roweth HG, Huyng D, Chong SJF, Chung AY, Zhang J, Hackett L, Haradhvala NJ, Wu T, Su NK, Berrios B, Belkin S, Dutta AK, Davids MS, Getz G, Ghobrial IM

The development of targeted therapy for patients with multiple myeloma (MM) is hampered by the low frequency of actionable genetic abnormalities. Gain or amplification of chromosome 1q (1q+) is the most frequent arm-level copy number gain in patients with MM and is associated with higher risk of progression and death despite recent therapeutic advances. Thus, developing targeted therapy for MM patients with 1q+ stands to benefit a large portion of patients in need of more effective management. Here, we employed large-scale dependency screens and drug screens to systematically characterize the therapeutic vulnerabilities of MM with 1q+ and displayed increased sensitivity to MCL1 and PI3K inhibitors. Using single-cell RNA sequencing, we compared subclones with and without 1q+ within the same patient tumors and demonstrated that 1q+ is associated with higher levels of MCL1 and the PI3K pathway. Furthermore, by isolating isogenic clones with different copy number profiles for part of the chromosome 1q arm, we observed increased sensitivity to MCL1 and PI3K inhibitors with arm-level gain. Lastly, we demonstrated synergy between MCL1 and PI3K inhibitors and dissected their mechanism of action in MM with 1q+, uncovering a cytostatic effect. In conclusion, this study highlights that MM with 1q+ may present enhanced sensitivity to MCL1 and PI3K inhibitors, enabling their use at lower doses without sacrificing efficacy, and may thus accelerate the development of targeted therapy for patients with MM and 1q+.

 

Blood

Over 4 Decades, French Children Teach About LCH

Degar BA, Rollins BJ

In this issue of Blood, Thalhammer and colleagues describe the characteristics and outcomes of 331 children with Langerhans cell histiocytosis (LCH), out of a total of 2313 enrolled in the French National Histiocytosis Registry, who had features of hematologic involvement (HI). The study, which includes patients enrolled over 4 decades between 1983 and 2023, reflects the power of forethought, patience, and meticulous record keeping. Prior to 2010, the fundamental nature of LCH was a mystery. It had long been recognized that although the tumors of patients with LCH share histopathologic features, patients’ clinical courses can vary dramatically. A subset of patients, usually babies and very young children, experience an aggressive multisystem disease. This entity, first described in the early 20th century and dubbed Letterer-Siwe disease, typically features pancytopenia and hepatosplenomegaly. In 1975, Lahey identified HI as an important adverse feature in childhood LCH and defined it as hemoglobin <10 g/dL (<9 g/dL in infants) not due to other causes, leukocytes <4000/?L, and platelets <100 G/L. The identification of prognostic factors, including involvement of the hematopoietic system, liver, and/or spleen (so-called risk organs), created the opportunity to risk-stratify treatment. Beginning in the LCH-II clinical trial (1996-2001), the Histiocyte Society adopted a risk-stratification algorithm and showed that, in comparison with LCH-I, intensified treatment improved outcomes in risk organ–positive patients. But since 1975, the definition of HI has not been refined and initial treatment of patients with HI who are at highest risk of treatment failure also has not changed. Nor have additional risk factors been established.

Cancer Cell

Effective Targeting of PDGFRA-Altered High-Grade Glioma with Avapritinib

Mayr L, Neyazi S, Trissal M, Labelle J, Eder SK, Marques JG, de Biagi-Junior CAO, Lo Cascio C, Hack O, Nascimento A, Nguyen CM, Castellani S, Rozowsky JS, Groves A, Panditharatna E, Cruzeiro GAV, Haase RD, Tabatabai K, Supko J, Baumgartner A, Clark LM, Cameron A, Nguyen QD, Wakimoto H, Dubois F, Greenwald NF, Bandopadhayay P, Beroukhim R, Ligon K, Filbin MG

PDGFRA is crucial to tumorigenesis and frequently genomically altered in high-grade glioma (HGG). In a comprehensive dataset of pediatric HGG (n = 261), we detect PDGFRA mutations and/or amplifications in 15% of cases, suggesting PDGFRA as a therapeutic target. We reveal that the PDGFRA/KIT inhibitor avapritinib shows (1) selectivity for PDGFRA inhibition, (2) distinct patterns of subcellular effects, (3) in vitro and in vivo activity in patient-derived HGG models, and (4) effective blood-brain barrier penetration in mice and humans. Furthermore, we report preliminary clinical real-world experience using avapritinib in pediatric and young adult patients with predominantly recurrent/refractory PDGFRA-altered HGG (n = 8). Our early data demonstrate that avapritinib is well tolerated and results in radiographic response in 3/7 cases, suggesting a potential role for avapritinib in the treatment of HGG with specific PDGFRA alterations. Overall, these translational results underscore the therapeutic potential of PDGFRA inhibition with avapritinib in HGG.

 

Journal of Clinical Oncology

Phase II Study of Acalabrutinib, Venetoclax, and Obinutuzumab in a Treatment-Naïve Chronic Lymphocytic Leukemia Population Enriched for High-Risk Disease

Davids MS, Ryan CE, Lampson BL, Ren Y, Tyekucheva S, Fernandes SM, Crombie JL, Kim AI, Weinstock M, Montegaard J, Walker HA, Greenman C, Patterson V, Jacobson CA, LaCasce AS, Armand P, Fisher DC, Arnason JE, Ahn IE, Brown JR

PURPOSE: The AMPLIFY trial recently established fixed-duration acalabrutinib, venetoclax, and obinutuzumab (AVO) as a new standard-of-care option for patients with previously untreated chronic lymphocytic leukemia (CLL) with wild-type TP53; however, due to the chemoimmunotherapy control arm, AMPLIFY excluded patients with high-risk TP53 aberration, for whom current standards of care are continuous Bruton tyrosine kinase inhibitor therapy or alternatively fixed-duration venetoclax-based doublets. AVO has not previously been evaluated in patients with CLL with TP53 aberration.

METHODS: This investigator-sponsored, multicenter, phase II study enrolled patients with treatment-naïve CLL enriched for high-risk CLL, defined by TP53 aberration (ClinicalTrials.gov identifier: NCT03580928). Patients received acalabrutinib, obinutuzumab, and then venetoclax, with each treatment introduced sequentially and in combination, with the duration guided by measurable residual disease (MRD). Patients who achieved undetectable MRD (uMRD) after either 15 or 24 cycles could discontinue treatment. The primary end point was complete remission (CR) with bone marrow uMRD (BM-uMRD) at the start of cycle 16.

RESULTS: Seventy-two patients were accrued, including 45 patients with TP53 aberration. The CR with BM-uMRD rates at the start of cycle 16 were 42% in patients with TP53 aberration and 42% in all-comers, and the BM-uMRD rates were 71% and 78%, respectively. Hematologic toxicities were mainly low grade, and cardiovascular toxicities and bleeding complications were infrequent. After a median follow-up of 55.2 months, 10 patients had progressed, including four with transformation, and three patients died. Four-year progression-free survival and overall survival for patients with or without TP53 aberration were 70%/96% and 88%/100%, respectively.

CONCLUSION: AVO was highly active and well tolerated in patients with previously untreated high-risk CLL, supporting its use as a new standard-of-care treatment option.

 

Journal of Clinical Oncology

Pooled Long-Term Outcomes with Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients with Advanced Melanoma

Hodi FS

PURPOSE: Nivolumab (NIVO) + ipilimumab (IPI) combination and NIVO monotherapy have demonstrated durable clinical benefit in patients with unresectable/metastatic melanoma. This analysis describes long-term overall survival (OS) with the combination or monotherapy pooled across all major company-sponsored trials, as well as clinical factors associated with survival, in patients with immune checkpoint inhibitor (ICI) treatment-naïve unresectable/metastatic melanoma.

METHODS: Data were pooled from six CheckMate studies in ICI treatment-naïve patients receiving NIVO + IPI (NIVO 1 mg/kg + IPI 3 mg/kg or NIVO 3 mg/kg + IPI 1 mg/kg) or NIVO monotherapy (3 mg/kg). OS was assessed for each treatment, as well as in select subgroups. Cox proportional multivariate analysis (MVA) and classification and regression tree (CART) analyses were performed within treatment arms.

RESULTS: Median follow-up for OS was 45.0 months for patients treated with NIVO + IPI (n = 839) and 35.8 months for patients treated with NIVO (n = 536). OS was longer with NIVO + IPI versus NIVO monotherapy (hazard ratio, 0.78 [95% CI, 0.67 to 0.91]), with 6-year OS rates of 52% versus 41%, respectively. Consistent benefit was observed in BRAF-mutant and BRAF-wild-type patients and those with normal and elevated lactate dehydrogenase (LDH). Numerical difference in OS was also observed across PD-L1 expression levels, although more pronounced with no/low PD-L1 expression. Clinical factors associated with decreased survival in both the MVA and CART analyses were LDH > upper limit of normal with either treatment, age ?65 years with NIVO + IPI, and the presence of liver metastases with NIVO monotherapy.

CONCLUSION: In this large, pooled nonrandomized retrospective analysis, we observed that NIVO + IPI provides longer OS than NIVO in patients with ICI treatment-naïve advanced melanoma and identifies clinical factors that appear to be associated with survival for each treatment, which may assist with treatment decision making.

 

JAMA

Atezolizumab in High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial

Haddad R

IMPORTANCE: Treating locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) involves any combination of surgery, radiation, and chemotherapy, followed by routine monitoring for local recurrence or distant metastases. Given the poor patient outcomes, a significant unmet clinical need for improved treatment options remains.

OBJECTIVE: To evaluate efficacy and safety of maintenance atezolizumab in patients with LA SCCHN at high risk of disease progression after multimodal definitive treatment.

DESIGN, SETTING, AND PARTICIPANTS: IMvoke010 was a phase 3, global, double-blind, randomized clinical trial. Patients were recruited at 128 sites in 23 countries between April 3, 2018, and February 14, 2020 (clinical cutoff date: September 27, 2023). Eligible patients had LA SCCHN (stage IVa/IVb involving the oral cavity, larynx, hypopharynx, or human papillomavirus-negative oropharynx, or stage III human papillomavirus-positive oropharynx [AJCC Cancer Staging Manual, eighth edition]) without disease progression after multimodal definitive treatment.

INTERVENTION: Patients were randomized (1:1) to receive atezolizumab 1200 mg or placebo every 3 weeks for 1 year or until disease recurrence, disease progression, unacceptable toxicity, or consent withdrawal.

MAIN OUTCOMES AND MEASURES: The primary end point was investigator-assessed event-free survival. Other end points included overall survival and safety.

RESULTS: Overall, 406 patients were randomized to receive atezolizumab (n?=?203) or placebo (n?=?203); baseline demographics were balanced between both treatment groups (<65 years, 142 [70.0%] vs 155 [76.4%]; male, 168 [82.8%] vs 174 [85.7%]; Asian, 68 [35.6%] vs 61 [31.0%]; Black, 1 [0.5%] vs 1 [0.5%]; and White, 121 [63.4%] vs 135 [68.5%], respectively). At clinical cutoff (median follow-up, 46.5 months), median investigator-assessed event-free survival was 59.5 months (95% CI, 46.8 to not estimable) with atezolizumab vs 52.7 months (95% CI, 41.4 to not estimable) with placebo (hazard ratio, 0.94; 95% CI, 0.70-1.26; P?=?.68). There was no difference in overall survival between atezolizumab and placebo (24-month overall survival, 82.0% vs 79.2%, respectively). No new or unexpected safety signals were identified.

CONCLUSIONS AND RELEVANCE: In this study, atezolizumab did not improve clinical outcomes in patients with LA SCCHN at high risk of disease progression after multimodal definitive treatment. These data contribute to evidence on the limited activity of checkpoint inhibitors in the global population of this disease setting. Overall, the role of immunotherapy for patients with LA SCCHN remains to be determined.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03452137.

 

JAMA

Bridging Medicine and Society-A Call to Expand the Pipeline of Physician-Social Scientists

Walensky LD, Mather RV, Meng EX

Health care crises, whether sparked by natural disaster or human action, have underscored the urgent need for leaders who can navigate the social dimensions of modern medicine. From inequities in delivery to barriers in public trust, today’s health care challenges require more than medical or scientific expertise—they demand a deeper understanding of societal forces to achieve transformative interventions. Physician-scientists trained in the social sciences and humanities (SSH) are positioned to tackle these issues, combining clinical insight with unique perspectives from a broad range of disciplines, including health policy, economics, anthropology, history, epidemiology, and bioethics. Despite their critical contributions—from founding nongovernmental organizations to leading national and international institutions—SSH physician-scientists remain a minority in the physician-scientist workforce. Traditional training pathways and funding mechanisms have prioritized basic and translational science, leaving SSH MD-PhD students to navigate fewer training sites, limited funding opportunities, and numerous logistical barriers. Expanding the pipeline of SSH physician-scientists is essential to meeting the growing demand for leaders who can fully integrate medicine and society.

 

JAMA Oncology

Persistent Prostate-Specific Antigen Following Radical Prostatectomy for Prostate Cancer and Mortality Risk

D'Amico AV

IMPORTANCE: Whether the conventional 1.5-month to 2.0-month time interval following radical prostatectomy (RP) for prostate cancer (PC) is sufficient to accurately document a persistent prostate-specific antigen (PSA) remains unanswered.

OBJECTIVE: To evaluate the time necessary to accurately document a persistent PSA level after RP.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study evaluated whether a significant interaction existed between (1) a pre-RP PSA level greater than 20 ng/mL vs 20 ng/mL or less and (2) persistent PSA vs undetectable PSA after RP on PC-specific mortality (PCSM) risk and all-cause mortality (ACM) risk, adjusting for known PC prognostic factors, age at RP, year of RP, and the time-dependent use of post-RP radiation therapy (RT) and androgen deprivation therapy (ADT). Whether an increasing persistent PSA level was associated with a worse prognosis was also investigated. Patients with T1N0M0 to T3N0M0 PC treated with RP between 1992 and 2020 at 2 academic centers were included. Follow-up data were collected until November 2023. Data were analyzed from July 2024 to January 2025.

EXPOSURE: RP.

MAIN OUTCOMES AND MEASURES: Adjusted hazard ratio (aHR) of ACM and PCSM risk.

RESULTS: Of 30?461 patients included in the discovery cohort, the median (IQR) age was 64 (59-68) years; of 12?837 patients included in the validation cohort, the median (IQR) age was 59 (54-64) years. Compared with patients with undetectable PSA, among patients with persistent PSA, a pre-RP PSA level greater than 20 ng/mL vs 20 ng/mL or less was significantly associated with reduced ACM risk (aHR, 0.69; 95% CI, 0.51-0.91; P?=?.01; P for interaction?<?.001) and PCSM risk (aHR, 0.41; 95% CI, 0.25-0.66; P?<?.001; P for interaction?=?.02). This result remained after adjustment for prostate volume and was confirmed in the validation cohort for PCSM risk and may represent a higher proportion of patients with a pre-RP PSA greater than 20 ng/mL vs 20 ng/mL or less who could have reached an undetectable PSA level if additional time for PSA assessment occurred before initiating post-RP therapy for presumed persistent PSA. Notably, there was more frequent and a shorter median time to post-RP RT plus ADT or ADT use in patients with a pre-RP PSA greater than 20 ng/mL (244 of 446 [54.7%] at a median [IQR] of 2.68 [1.51-4.40] months) vs 20 ng/mL or less (338 of 972 [34.8%] at a median [IQR] of 3.30 [2.00-5.39] months). These treatment times were shorter than the times to an undetectable PSA in observed patients (median [IQR] of 2.96 [1.84-3.29] months vs 3.37 [2.35-4.09] months, respectively). Increasing persistent PSA level was associated with an increased ACM risk (aHR, 1.14; 95% CI, 1.04-1.24; P?=?.004) and PCSM risk (aHR, 1.27; 95% CI, 1.12-1.45; P?<?.001).

CONCLUSIONS AND RELEVANCE: PSA level assessed for at least 3 months after RP may minimize overtreatment, and in this study, a higher persistent PSA level was associated with a worse prognosis.

 

Molecular Cell

A Methyltransferase-Independent Role for METTL1 in tRNA Aminoacylation and Oncogenic Transformation

Ali RH, Orellana EA, Lee SH, Chae YC, Chen Y, Kennedy AL, Gutierrez AE, Papke DJ, Valenzuela M, Silverman B, Ficarro SB, Marto JA, Fletcher CDM, Perez-Atayde A, Alcindor T, Shimamura A, Prensner JR, Gregory RI, Gutierrez A

Amplification of chromosomal material derived from 12q13-15 is common in human cancer and believed to result in overexpression of multiple collaborating oncogenes. To define the oncogenes involved, we overexpressed genes recurrently amplified in human liposarcoma using a zebrafish model of the disease. We found several genes whose overexpression collaborated with AKT in sarcomagenesis, including the tRNA methyltransferase METTL1. This was surprising, because AKT phosphorylates METTL1 to inactivate its enzymatic activity. Indeed, phosphomimetic S27D or catalytically dead alleles phenocopied the oncogenic activity of wild-type METTL1. We found that METTL1 binds the multi-tRNA synthetase complex, which contains many of the cellular aminoacyl-tRNA synthetases and promotes tRNA aminoacylation, polysome formation, and protein synthesis independent of its methyltransferase activity. METTL1-amplified liposarcomas were hypersensitive to actinomycin D, a clinical inhibitor of ribosome biogenesis. We propose that METTL1 overexpression promotes sarcomagenesis by stimulating tRNA aminoacylation, protein synthesis, and tumor cell growth independent of its methyltransferase activity.

 

Nature

A Neoantigen Vaccine Generates Antitumour Immunity in Renal Cell Carcinoma

Braun DA, Chea V, McGregor BA, Blass E, Tu CR, Vanasse AP, Forman C, Forman J, Afeyan AB, Liu Y, Li S, Southard J, Chang SL, Hirsch MS, LeBoeuf NR, Olive O, Mehndiratta A, Greenslade H, Shetty K, Klaeger S, Sarkizova S, Mossanen M, Carulli I, Tarren A, Duke-Cohan J, Howard AA, Iorgulescu JB, Shim B, Simon JM, Signoretti S, Aster JC, Elagina L, Carr SA, Leshchiner I, Getz G, Gabriel S, Hacohen N, Oliveira G, Neuberg DS, Livak KJ, Shukla SA, Fritsch EF, Wu CJ, Keskin DB, Ott PA, Choueiri TK

Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens1-6. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient's tumour and result in clinical activity are largely unknown. These questions are of particular interest for patients who have tumours with a low mutational burden. Here we conducted a phase?I trial (ClinicalTrials.gov identifier NCT02950766) to test a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage?III or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2?months after surgery, none of the 9 participants enrolled in the study had a recurrence of RCC. No dose-limiting toxicities were observed. All patients generated T?cell immune responses against the PCV antigens, including to RCC driver mutations in VHL, PBRM1, BAP1, KDM5C and PIK3CA. Following vaccination, there was a durable expansion of peripheral T?cell clones. Moreover, T?cell reactivity against autologous tumours was detected in seven out of nine patients. Our results demonstrate that neoantigen-targeting PCVs in high-risk RCC are highly immunogenic, capable of targeting key driver mutations and can induce antitumour immunity. These observations, in conjunction with the absence of recurrence in all nine vaccinated patients, highlights the promise of PCVs as effective adjuvant therapy in RCC.

 

Nature

CD45-PET is a Robust, Non-Invasive Tool for Imaging Inflammation

Salehi Farid A, Rowley JE, Allen HH, Kruger IG, Tavakolpour S, Neeley K, Cong M, Shahbazian H, Dorafshani N, Berrada A, MacDonagh AC, Padera RF, Brugarolas P, Packard AB, Rosenbaum MW, Divakaran S, Di Carli MF, Rashidian M

Imaging inflammation holds immense potential for advancing the diagnosis, treatment and prognosis of many conditions1-3. The lack of a specific and sensitive positron emission tomography (PET) probe to detect inflammation is a critical challenge. To bridge this gap, we present CD45-PET imaging, which detects inflammation with exceptional sensitivity and clarity in several preclinical models. Notably, the intensity of the CD45-PET signal correlates robustly with the severity of disease in models of inflammatory lung and bowel diseases, outperforming 18F-fluorodeoxyglucose PET, the most widely used imaging modality for inflammation globally. Longitudinal CD45-PET imaging further enables precise monitoring of dynamic changes in tissue-specific inflammatory profiles. Finally, we developed a human CD45-PET probe for clinical translation that effectively detects human immune cells in a humanized mouse model. CD45-PET imaging holds substantial clinical promise, offering a tool for guiding diagnostic and therapeutic decisions for inflammatory diseases through a precise, whole-body assessment of the inflammation profiles of individual patients.

 

Nature Communications

Cultivated Autologous Limbal Epithelial Cell (CALEC) Transplantation for Limbal tem Cell Deficiency: A Phase I/II Clinical Trial of the First Xenobiotic-Free, Serum-Free, Antibiotic-Free Manufacturing Protocol Developed in the US

Jurkunas UV, Kaufman AR, Yin J, Johns LK, Parekh M, Li S, Gauthier A, Negre H, Shaw KL, Hernandez Rodriguez DE, Daley H, Dana R, Armant M, Ritz J

We developed a two-stage manufacturing process utilizing cultivated autologous limbal epithelial cells (CALEC), the first xenobiotic-free, serum-free, antibiotic-free protocol developed in the United States, to treat blindness caused by unilateral limbal stem cell deficiency (LSCD) and conducted a single-center, single-arm, phase I/II clinical trial. Primary outcomes were feasibility (meeting release criteria) and safety (ocular infection, corneal perforation, or graft detachment). Participant eligibility included male or female participants age 18 to <90 years old and ability to provide written informed consent with LSCD. Funding was provided by the National Eye Institute of the National Institutes of Health. CALEC grafts met release criteria in 14 (93%) of 15 participants at conclusion of trial. After first stage manufacturing, intracellular adenosine triphosphate levels correlated with colony forming efficiency (r?=?0.65, 95% CI [0.04, 0.89]). One bacterial infection occurred unrelated to treatment, with no other primary safety events. The secondary outcome was to investigate efficacy based on improvement in corneal epithelial surface integrity (complete success) or improvement in corneal vascularization and/or participant symptomatology as measured by OSDI and SANDI (partial success). 86%, 93%, and 92% of grafts resulted in complete or partial success at 3, 12, and 18 months, respectively. Our results provide strong support that CALEC transplantation is safe and feasible and further studies are needed to evaluate therapeutic efficacy. Clinicaltrials.gov registration: NCT02592330.

 

Nature Communications

Dissecting Tumor Cell Programs Through Group Biology Estimation in Clinical Single-Cell Transcriptomics

Johri S, Bi K, Titchen BM, Fu J, Conway J, Crowdis JP, Park J, Liu D, He MX, Van Allen EM

With the growth of clinical cancer single-cell RNA sequencing studies, robust differential expression methods for case/control analyses (e.g., treatment responders vs. non-responders) using gene signatures are pivotal to nominate hypotheses for further investigation. However, many commonly used methods produce a large number of false positives, do not adequately represent the patient-specific hierarchical structure of clinical single-cell RNA sequencing data, or account for sample-driven confounders. Here, we present a nonparametric statistical method, BEANIE, for differential expression of gene signatures between clinically relevant groups that addresses these issues. We demonstrate its use in simulated and real-world clinical datasets in breast cancer, lung cancer and melanoma. BEANIE outperforms existing methods in specificity while maintaining sensitivity, as demonstrated in simulations. Overall, BEANIE provides a methodological strategy to inform biological insights into unique and shared differentially expressed gene signatures across different tumor states, with utility in single-study, meta-analysis, and cross-validation across cell types.

 
 

American Journal of Clinical Dermatology

Individualized Neoantigen-Directed Melanoma Therapy

Khaddour K, Buchbinder EI

 

Annals of Surgical Oncology

Risk of Surgical Overtreatment in cN1 Breast Cancer Patients Who Become ypN0 After Neoadjuvant Chemotherapy: SLNB Versus TAD

Laws A, Vincuilla J, Parker T, Kantor O, Mittendorf EA, King TA

 

Blood Advances

Nivolumab to Restore T-Cell Fitness in CAR-T Refractory Multiple Myeloma

Waldschmidt JM, Sotudeh N, Arora S, Vijaykumar T, Anand P, Stuart H, Frede J, Munshi NC, Anderson KC, Yee AJ, Knoechel B, Lohr JG, Raje NS

 
 
 
 

Breast Care

Expert Discussion: ESMO 2024

Lin NU

 
 

Cancer

Clinician's Primer for Soft Tissue Sarcomas: Nuances of Histologic Subtypes

Wisdom AJ, Raut CP, Haddox CL, Hornick JL, Jagannathan JP, Painter CA, Baldini EH

 
 

Cancer Epidemiology, Biomarkers, and Prevention

Effects of Clinical Covariates on Serum miRNA Expression Among Women without Ovarian Cancer

Wollborn L, Webber JW, Alimena S, Mishra S, Sussman CB, Comrie CE, Williams M, Russell T, Fendler W, Chowdhury D, Elias KM

 
 

Cell Metabolism

RBM43 Controls PGC1? Translation and a PGC1?-STING Signaling Axis

Dumesic PA, Wilensky SE, Bose S, Van Vranken JG, Gygi SP, Spiegelman BM

 

Cell Reports Methods

A Sequence Context-Based Approach for Classifying Tumor Structural Variants without Paired Normal Samples

Chukwu W, Lee S, Crane A, Zhang S, Webster S, Dakhama O, Mittra I, Beroukhim R, Dubois F, Dalin S

 
 

Clinical Obstetrics and Gynecology

Female Sexual Health and Cancer

Bober SL, Falk SJ

 

European Urology

In Memory of Dr. Felix Feng

Beltran H

 

Fertility and Sterility

Contraception Use and Changes in Young Women with Newly Diagnosed Breast Cancer

Tesch ME, Sorouri K, Zheng Y, Emmons KM, Dutton MC, Partridge AH

 
 
 

Gynecologic Oncology

Role of Adjuvant Radiotherapy Modality on Clinical Outcomes for Early-Stage Uterine Carcinosarcoma

Tyan K, Liu KX, Smart AC, Feltmate CM, Horowitz NS, Muto MG, Worley MJ Jr, Elias KM, Liu JF, Wright AA, Konstantinopoulos PA, Campos SM, Matulonis UA, Franco I, Lee LJ, King MT, Dyer MA

 
 

International Journal of Cancer

Cohesin Mutations and Chromatin Changes in Cancer

Swett AD, Tothova Z

 

International Journal of Radiation Oncology, Biology, Physics

An Aggressive Approach for Mucinous Prostate Cancer

Moningi S, Orio PF 3rd

 

Journal of the American Academy of Dermatology

Blastic Plasmacytoid Dendritic Cell Neoplasm: Extensive Disease, Langer Lines, and Blood Burden in a Retrospective Study of 66 Cases

Fay CJ, Shimony S, Lane AA, LeBoeuf NR

 

Journal of Cancer Education

Brachytherapy as a Cancer Therapy Tool

Al Balushi MM, King MT

 

Journal of the European Academy of Dermatology and Venereology

Factors Predictive of Recurrence, Metastasis and Death in Node-Negative Penile Squamous Cell Carcinoma: A Retrospective Multicentre Cohort Study

O'Connell KA, Murad F, Zhou G, Mossanen M, Clinton TN, Schmults CD

 

Journal of Geriatric Oncology

Smartphone Application for Longitudinal Home Gait Speed Measurement in Older Adults with Blood Cancers: A Feasibility and Acceptability Study

Lee PA, DuMontier C, Groblewski N, Yu W, Zhou J, Hshieh T, Kim D, Travison T, Driver J, Lo OY, Manor B, Abel G

 

Journal of Geriatric Oncology

The Pervasive Impact of Frailty on Ovarian Cancer Care and the Role of Prehabilitation: Qualitative Perspectives of Key Stakeholders

Pozzar RA, Horowitz N, Feltmate C, Matulonis UA, Wright AA

 

Journal of Internal Medicine

Opportunistic Assessment of Steatotic Liver Disease in Lung Cancer Screening Eligible Individuals

Weiss J, Bernatz S, Johnson J, Thiriveedhi V, Mak RH, Fedorov A, Lu MT, Aerts HJWL

 

Journal of Pain and Symptom Management

Large Language Models to Identify Advance Care Planning in Patients with Advanced Cancer

Agaronnik ND, Davis J, Manz CR, Tulsky JA, Lindvall C

 

Journal of Thoracic Oncology

Corrigendum to 'MUC1-C Is a Common Driver of Acquired Osimertinib Resistance in NSCLC' [Journal of Thoracic Oncology 19 Issue 3 (2024) 434-450]

Haratake N, Ozawa H, Morimoto Y, Yamashita N, Daimon T, Bhattacharya A, Wang K, Nakashoji A, Isozaki H, Hata AN, Kufe D

 

JAMA Otolaryngology – Head and Neck Surgery

Current Progress and Future Directions of Immunotherapy in Head and Neck Squamous Cell Carcinoma: A Narrative Review

Sim ES, Nguyen HCB, Hanna GJ, Uppaluri R

 

JCO Oncology Practice

Subcutaneous vs Intravenous Trastuzumab/Pertuzumab: A Time and Motion Substudy of a Phase II Trial of Adjuvant Trastuzumab/Pertuzumab for Stage I HER2+ Breast Cancer (ADEPT Trial)

Waks AG, Chen EL, Graham N, Frey AM, Almeida K, Attaya V, Ryding C, Harvey C, Leth D, Faggen M, Sinclair N, Walsh J, Tung N, Chen WY, Leone JP, Schumer ST, Tayob N, Tolaney SM

 
 

JMIR Cancer

Usability, Acceptability, and Barriers to Implementation of a Collaborative Agenda-Setting Intervention (CASI) to Promote Person-Centered Ovarian Cancer Care: Development Study

Pozzar RA, Tulsky JA, Batista J, Barwick P, Lindvall CJ, Dykes PC, Manni M, Matulonis UA, McCleary NJ, Wright AA

 
 
 

Lung Cancer

Exercise Medicine for Individuals Diagnosed with Lung Cancer: A Systematic Review and Meta-Analysis of Health Outcomes

Ficarra S, Kang DW, Wilson RL, Gonzalo-Encabo P, Christopher CN, Normann AJ, Dieli-Conwright CM

 

Mediterranean Journal of Hematology and Infectious Diseases

Waldenström Macroglobulinemia - A State-of-the-Art Review: Part 2- Focus on Therapy

Sarosiek S, Castillo JJ

 

Molecular Cancer

BCL-2 Dependence is a Favorable Predictive Marker of Response to Therapy for Chronic Lymphocytic Leukemia

Chong SJF, Valentin R, Lehmberg TZ, Wang J, Zhu F, Fernandes SM, Zhang J, Herbaux C, Brown JR, Davids MS

 
 
 
 

NPJ Breast Cancer

Real-World Outcomes with Sacituzumab Govitecan Among Breast Cancer Patients with Central Nervous System Metastases

Grinda T, Morganti S, Hsu L, Yoo TK, Kusmick RJ, Aizer AA, Giordano A, Leone JP, Hughes M, Tolaney SM, Lin NU, Sammons SL

 
 

Pediatric Blood and Cancer

Treatment Approach for Metastatic Intracranial Germinoma: A Multi-Institutional Experience

Power PC, Liu KX, Chi SN, Wright KD, Marcus KJ, Haas-Kogan DA, Ioakeim-Ioannidou M, Sethi R, Elhalawani H, Ebb D, Yock TI, MacDonald SM, Yeo KK

 
 
 

Psycho-Oncology

Mental Health Challenges in Cancer Survivors from Diverse Backgrounds During COVID-19 Pandemic: Insights from the All of Us Research Program

Qian Z, Cho M, Zhangxu K, Onyeaka HK, Stelzl DR, Dagnino F, Zurl H, Korn SM, Cole AP, Amonoo HL

 

Psycho-Oncology

Interventions for Children of Parents with Cancer from the Time of Cancer Diagnosis Through Bereavement: Two Systematic Reviews

Malinowski PK, Pozo-Kaderman C, Muriel AC, Hanania J, Pirl WF, Dorste A, Rotman C, Jankauskaite G, Joyce EK, Morris SE

 
 
 

Trends in Cell Biology

Epigenetic Drivers of Metalloproteinases and Metastasis

Seehawer M, Polyak K