Dana-Farber Cancer Institute

Prognostic Significance of Contrast Enhancement in Newly Diagnosed Grade 2 IDH-mutant Glioma

Abstract Background Contrast enhancement is generally considered an adverse prognostic feature in adult glioma. However, its significance in newly diagnosed grade 2 IDH-mutant glioma remains uncertain, with important implications for use of the mutant IDH inhibitor vorasidenib. W...

Cullin-5 RING E3 ligase limits CD8⁺ T-cell persistence and effector responses during chronic antigen stimulation

Abstract T-cell exhaustion limits durable antitumor responses and remains a barrier to adoptive cell therapies (ACT) in solid tumors. To identify regulators of T-cell persistence, we performed genome-wide CRISPR knockout screens in primary human CD8⁺ T cells expressing an NY-ESO-...

Human-in-the-loop large language model framework for identification of cutaneous immune-related adverse events

This study evaluated a retrieval-augmented, multi-agent large language model (LLM)–driven, human-in-the-loop framework for detecting cutaneous immune-related adverse events (cirAEs) from clinical notes. Compared with the unassisted manual-review group, the LLM-assisted group demo...

Cohesin Mutations in Cancer and Development

Cohesin is a ring-shaped protein complex that wraps around DNA and is crucial for sister chromatid cohesion, chromatin organization, gene regulation, replication, and DNA damage repair. In somatic cells, it consists of the core ring subunits SMC1A, SMC3, and RAD21 and one of two...

Next-generation CDK inhibitors in HR+/HER2– breast cancer

Cell-cycle dysregulation is a central driver of breast cancer progression and a major therapeutic vulnerability, particularly in hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR + /HER2 – ) disease. The clinical success of cyclin-dependent kinase (C...

A randomized phase II study of fulvestrant with or without ganetespib in patients with endocrine resistant metastatic breast cancer

Abstract Background Patients with endocrine-resistant hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC) have limited effective treatment options. Heat shock protein 90 (HSP90) regulates estrogen receptor stability and function; its inhibition has been...

Proton Radiotherapy Decreases Incidence of Radiation‐Induced Second Malignant Neoplasms Compared to Photon Radiotherapy in Patients With Retinoblastoma

Retinoblastoma is the most common primary intraocular neoplasm in children. Use of radiotherapy has decreased due to the incidence of second malignant neoplasms (SMNs). In our study, photon (n = 42) and proton (n = 66) radiotherapy cohorts had median follow-up of 28.7 and 18.2 ye...

Delays in breast cancer presentation, diagnosis, and treatment in young women

BACKGROUND: Breast cancer (BC) in young patients is often identified at later stages, which can result in poor prognosis. It is important to investigate the factors influencing care delays and how delays affect outcomes. METHODS: This study included women aged ≤40 years at diagno...

A study to learn how well HER3-DXd (patritumab deruxtecan) works and how safe it is in people with previously treated non-small-cell lung cancer that has a mutation in the EGFR gene: a plain language summary of the HERTHENA-Lung01 study

Plain Language SummaryWhat is this summary about?This is a summary of the publication about the HERTHENA-Lung01 study, which was published in the Journal of Clinical Oncology in September 2023. The study included 277 adults with non-small-cell lung cancer (NSCLC) that had a mutat...

Predicting the clinical course of advanced systemic mastocytosis on treatment with avapritinib or midostaurin

Abstract Advanced systemic mastocytosis (AdvSM) is driven by KIT D816V in approximately 95% of cases. Accurate assessment and prediction of clinical course and disease outcome before and during treatment with the KIT inhibitors midostaurin and avapritinib may facilitate optimizat...

Validation of the International Working Group 2023 response criteria for higher risk myelodysplastic syndromes/neoplasms using the International Consortium for Myelodysplastic Syndromes VALIDATE database and a randomized phase III trial

Response assessment criteria in patients with higher-risk myelodysplastic syndromes/neoplasms (HR-MDS) have been updated in the 2023 International Working Group (IWG) criteria. However, validation of these criteria has been limited to date. We analyzed overall survival (OS) by be...

INCREASED PREVALENCE OF PANCREATIC CYSTS IN NONSECRETOR (FUT2 NULL) INDIVIDUALS UNDER PANCREATIC SURVEILLANCE

Abstract Background: Pancreatic surveillance commonly detects pancreatic cysts, most of which are presumed intraductal papillary mucinous neoplasms (IPMN). FUT2, the gene responsible for secretor status, has been implicated in IPMN development, although not with pancreatic cancer...

Development and Validation of a Tool to Measure Documented Health Care Encounter Time

Importance Time toxicity, defined as the time patients spend receiving cancer treatment and interacting with health care systems, is an emerging treatment-related burden. Existing studies typically quantify time toxicity using health care contact days, which may inadequately capt...

21-Gene recurrence score assay in pN2-3 Early-Stage breast cancer: a national cancer database study

BACKGROUND: The clinical utility of the 21-gene recurrence score (RS) for guiding adjuvant chemotherapy in patients with pN2-3 early-stage breast cancer (eBC) has not been evaluated in prospective trials. This study aims to assess adjuvant chemotherapy benefit in patients with pN...

Pancreatic Reirradiation: A Multi-Institutional Retrospective Analysis of Feasibility, Tolerability, and Clinical Outcomes

Objectives: With improvements in systemic therapy for pancreatic cancer (PC), the role of radiation therapy (RT) to optimize local control has increased. While the tolerability and outcomes for RT for PC are well described, limited data exist on the feasibility and clinical impac...

Mitochondrial carrier SLC25A34 links clock, diet, and temperature control of adipocyte lipid cycling

Adipocyte lipid metabolism is coordinated by circadian rhythms, diet, and environmental temperature, but how these diverse signals are molecularly integrated remains unknown. We showed that these cues converge on the orphan mitochondrial transporter SLC25A34 to orchestrate lipid...

Hearts too small for body size after doxorubicin for childhood acute lymphoblastic leukemia: Grinch Syndrome

Cardiovascular disease is a major cause of morbidity and mortality in childhood cancer survivors. We assessed the very long-term cardiac structure and function of adult survivors of childhood leukemia treated with anthracycline-based therapy. One hundred fifteen patients with hig...

A Versatile DNA‐Encoded Library Platform for the Discovery of Highly Cooperative Chemical Inducers of Proximity

ABSTRACT Chemical‐induced proximity, particularly via molecular glues, represents a rapidly advancing therapeutic paradigm. Expanding the scope of proximity‐based therapeutics requires generalizable discovery platforms that can be easily tailored to diverse presenter proteins. He...

Top Ten Tips Palliative Care Clinicians Should Know About Collaborating with Consultation-Liaison Psychiatry

Palliative care (PC) and consultation-liaison (CL) psychiatry are complementary clinical disciplines that frequently care for the same patients facing serious illness complicated by psychiatric symptoms, psychological distress, neuropsychiatric syndromes, and high-stakes medical...

Positive selection screen identifies natural product β-catenin inactivators

Many genetically validated targets in cancer, including the transcription factor β-catenin (β-cat), have historically been viewed as undruggable. Cell-based phenotypic screening of chemical compounds can reveal unanticipated biological and pharmacological principles. Natural prod...