22,542 results match your criteria: "a Massachusetts General Hospital Cancer Center; Harvard Medical School ; Charlestown[Affiliation]"

Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C).

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Biotherapeutics are among the therapeutics that have revolutionized standard inflammatory bowel disease (IBD) treatment, which was previously limited to mesalamine, 5-aminosalicylic acid, corticosteroids, and classical immunosuppressants. Self-administrable biotherapeutics for IBD would enable home-based treatment and reduce the burden on medical infrastructure. Self-administration is made possible through subcutaneous injectable, oral, and rectal dosage forms.

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Huntington's disease (HD) is caused by a CAG repeat expansion in the HTT gene, leading to altered gene expression. However, the mechanisms leading to disrupted RNA processing in HD remain unclear. Here we identify TDP-43 and the N6-methyladenosine (m6A) writer protein METTL3 to be upstream regulators of exon skipping in multiple HD systems.

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Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

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Homozygous MTAP deletion occurs in ~15% of cancers, making them vulnerable to decreases in the concentration of S-adenosylmethionine (SAM). AG-270/S095033 is an oral, potent, reversible inhibitor of methionine adenosyltransferase 2 A (MAT2A), the enzyme primarily responsible for the synthesis of SAM. We report results from the first-in-human, phase 1 trial of AG-270/S095033 as monotherapy in patients with advanced malignancies (ClinicalTrials.

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Objectives: Radiotherapy manages pancreatic cancer in various settings; however, the proximity of gastrointestinal (GI) luminal organs-at-risk (OAR) poses challenges to conventional radiotherapy. Proton beam therapy (PBT) may reduce toxicities compared to photon therapy. This consensus statement summarizes PBT's safe and optimal delivery for pancreatic tumors.

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High-dose methotrexate (MTX) results in high rates of acute kidney injury (AKI), neutropenia, and hepatotoxicity. Glucarpidase is a recombinant enzyme that cleaves MTX, but clinical data supporting its use are scarce. We examined the association between glucarpidase administration and outcomes in adults with MTX-AKI from 28 cancer centers across the U.

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Purpose: Despite its high cost-effectiveness, radiation oncology faces the greatest prior authorization (PA) burden of any medical specialty. Insurance denials and resulting treatment delays have been documented across several treatment modalities, including stereotactic body radiation, intensity modulated radiation, and proton therapy. Although insurance companies suggest that PA is intended to control health care spending and ensure the implementation of evidence-based practice, the number of radiation treatment plans reviewed by the PA process that result in changes is quite low.

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Medical school offers comprehensive education and career development both in the classroom and clinical spaces. Much of the literature surrounding optimizing and navigating clinical rotations is directed towards faculty, such as clerkship directors. However, as advisors for medical students, we notice a large gap exists in peer-reviewed content focused on teaching medical students concrete skills of navigating clinical years.

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Members of the genus including Jurona virus (JURV) have emerged as promising immunotherapeutic agents, characterized by their tumor selectivity, fast kinetics, low seroprevalence, and minimal toxicity in humans. Here, we demonstrate that the administration of JURV leads to tumor regression in both hepatocellular carcinoma (HCC) xenograft and syngeneic models. Furthermore, our findings indicate that combining JURV and anti-PD-1 therapy reduced tumor burden and improved survival rates over JURV or anti-PD-1 alone in an orthotopic HCC model.

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Advances and challenges in precision imaging.

Lancet Oncol

January 2025

Department of Radiology and Center for Systems Biology, Massachusetts General Brigham, Boston, MA, USA; Department of Systems Biology, Harvard Medical School, Boston, MA, USA. Electronic address:

Technological innovations in genomics and related fields have facilitated large sequencing efforts, supported new biological discoveries in cancer, and spawned an era of liquid biopsy biomarkers. Despite these advances, precision oncology has practical constraints, partly related to cancer's biological diversity and spatial and temporal complexity. Advanced imaging technologies are being developed to address some of the current limitations in early detection, treatment selection and planning, drug delivery, and therapeutic response, as well as difficulties posed by drug resistance, drug toxicity, disease monitoring, and metastatic evolution.

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Background: Belzutifan, a first-in-class HIF-2α inhibitor, has shown antitumour activity as monotherapy and in combination with cabozantinib in patients with previously treated advanced kidney cancer. The phase 2 LITESPARK-003 study was designed to determine the antitumour activity and safety of belzutifan in combination with cabozantinib in patients with advanced clear-cell renal cell carcinoma that was previously untreated (cohort 1) or previously treated with immunotherapy (cohort 2). Here, we report results from cohort 1 of this clinical trial.

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Emerging Novel Combined CAR-NK Cell Therapies in Cancer Treatment: Finding a Dancing Partner.

Mol Ther

January 2025

Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of California, Irvine, CA; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA. Electronic address:

In recent decades, immunotherapy with chimeric antigen receptors (CAR) has revolutionized cancer treatment and given hope where other cancer therapies have failed. CAR-NK cells are NK cells that have been engineered ex vivo with a CAR on the cell membrane with high specificity for specific target antigens of tumor cells. The impressive results of several studies suggest that CAR-NK cell therapy has significant potential and successful performance in cancer treatment.

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ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Nat Genet

January 2025

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

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Recent progress in deep learning (DL) is producing a new generation of tools across numerous clinical applications. Within the analysis of brain tumors in magnetic resonance imaging, DL finds applications in tumor segmentation, quantification, and classification. It facilitates objective and reproducible measurements crucial for diagnosis, treatment planning, and disease monitoring.

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Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.

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Radionuclides used for imaging and therapy can show high molecular specificity in the body with appropriate targeting ligands. We hypothesized that local energy delivered by molecularly targeted radionuclides could chemically activate prodrugs at disease sites while avoiding activation in off-target sites of toxicity. As proof of principle, we tested whether this strategy of radionuclide-induced drug engagement for release (RAiDER) could locally deliver combined radiation and chemotherapy to maximize tumor cytotoxicity while minimizing off-target exposure to activated chemotherapy.

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Article Synopsis
  • CheckMate 204 study found that the combination of nivolumab and ipilimumab resulted in high intracranial objective response rates (icORRs) for patients with melanoma brain metastases (MBMs), prompting a need for standardized response criteria.
  • Different assessment criteria (like mRECIST and volumetric measurements) showed higher icORRs and stronger correlations with progression-free survival (icPFS) and overall survival (OS) compared to RANO-BM and RECIST.
  • The analysis suggests that mRECIST and volumetric criteria are reliable scales for future MBM trials, and response can be effectively measured even in patients with small lesions (<10 mm).
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AI-assisted Total Body Dermoscopic Evaluation of Changes in Melanocytic Nevi during Pregnancy: A Prospective, Comparative Study of 2,799 Nevi.

Acta Derm Venereol

January 2025

Department of Dermatology, University Hospital of Basel, Basel, Switzerland; Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, Switzerland.

Pregnancy-associated changes in melanocytic nevi (MN), apart from size increase on the trunk, remain a topic of debate. We conducted the first prospective study to investigate dermoscopic changes in MN comparing pregnant with non-pregnant women on all body parts using a market-approved convolutional neural network (CNN). We included 25 pregnant and 25 non-pregnant women from Basel, Switzerland, who underwent standard skin cancer screenings and whose MN > 2 mm were digitally recorded and analysed by a CNN.

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Background: The cornerstone of low anterior resection syndrome (LARS) treatment is self-management, which requires patient engagement. Colorectal surgeons and nurses may use patient-generated health data (PGHD) to help guide patients in their use of self-management strategies for LARS. However, the perspectives of LARS experts on the use of PGHD remain largely unexplored.

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Background: Patient navigation is an evidence-based intervention for reducing delays in cancer care for underserved populations. There are limited economic evaluations of patient navigation in the US health care system and few have considered costs at various phases along the implementation spectrum. Having economic data, including costs and cost savings, can support sustainability of patient navigation programs.

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Colorectal cancer (CRC) is the third most common cancer among men and women combined, and the second leading cause of cancer death in the US. The revised USPSTF CRC screening recommendations increased CRC screening needs across health systems, which may create particular challenges for community health centers (CHCs) given their resource constraints. The objective of our study is to assess CRC screening rates across 10 CHCs in Massachusetts and estimate the additional increase in the number of average-risk screening-eligible individuals after the revision in guidelines.

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Circulating Tumor Cells (CTCs) in blood encompass DNA, RNA, and protein biomarkers, but clinical utility is limited by their rarity. To enable tumor epitope-agnostic interrogation of large blood volumes, we developed a high-throughput microfluidic device, depleting hematopoietic cells through high-flow channels and force-amplifying magnetic lenses. Here, we apply this technology to analyze patient-derived leukapheresis products, interrogating a mean blood volume of 5.

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Context: Approximately 11% of cancer survivors smoke post-diagnosis.

Objective: Understanding the relationship between smoking and perceived cancer-related symptoms may inform tobacco treatment interventions for this population.

Methods: From 2017-2021, 740 adults in 9 ECOG-ACRIN trials provided baseline data.

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Interview Results from a Telehealth Hospice Intervention for Children and Young Adults with Cancer.

J Pain Symptom Manage

December 2024

Aflac Cancer & Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA; Emory University School of Medicine, Department of Pediatrics, Emory University, Atlanta, GA.. Electronic address:

Background And Aims: Surveyed families of children and young adults with cancer who participated in a pilot study of three coordinated telehealth visits (triad of patient/family, hospital clinician, and hospice nurse) during the first month of hospice enrollment found telehealth feasible and were highly satisfied with hospice care. The aim of this study is to further explore adult patient and caregiver perspectives on telehealth, specifically the benefits of telehealth, trade-offs with in-person appointments, and the impact on patient care and family end-of-life preparations.

Methods: This is a single-arm prospective pilot study of patients aged 0-29-with cancer initiating hospice care between 2021-2022 and their caregivers.

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