A5075153453- Cancer Genomics and Diagnostics
- Statistical Methods in Clinical Trials
- Health Systems, Economic Evaluations, Quality of Life
- Breast Cancer Treatment Studies
- HER2/EGFR in Cancer Research
- Advanced Breast Cancer Therapies
- Glioma Diagnosis and Treatment
- Gene expression and cancer classification
- Multiple Myeloma Research and Treatments
- Advanced Causal Inference Techniques
- Statistical Methods and Inference
- Bayesian Methods and Mixture Models
- Radiomics and Machine Learning in Medical Imaging
- Optimal Experimental Design Methods
- Genetic factors in colorectal cancer
- Monoclonal and Polyclonal Antibodies Research
- Bioinformatics and Genomic Networks
- BRCA gene mutations in cancer
- Lung Cancer Treatments and Mutations
- Computational Drug Discovery Methods
- Cancer Immunotherapy and Biomarkers
- Cancer Treatment and Pharmacology
- Statistical Methods and Bayesian Inference
- Molecular Biology Techniques and Applications
- Chronic Lymphocytic Leukemia Research
Dana-Farber Cancer Institute
2016-2025
Boston University
2014-2025
Université de Montpellier
2024-2025
Assistance Publique – Hôpitaux de Paris
2024-2025
Institut de Recherche pour le Développement
2025
Sorbonne Université
2024-2025
Centre d'Immunologie et des Maladies Infectieuses
2024-2025
Inserm
2017-2025
Harvard University
2015-2024
Brigham and Women's Hospital
2015-2024
Significance Characterization of cellular heterogeneity and hierarchy are important tasks in developmental biology may help overcome drug resistance treatment cancer other diseases. Single-cell technologies provide a powerful tool for detecting rare cell types cell-fate transition events, whereas traditional gene expression profiling methods can be used only to measure the average behavior population. However, lack suitable computational single-cell data analysis has become bottleneck. Here...
Summary For a study with an event time as the endpoint, its survival function contains all information regarding temporal, stochastic profile of this outcome variable. The probability at specific point, say t, however, does not transparently capture temporal endpoint up to t. An alternative is use restricted mean (RMST) t summarize profile. RMST subjects in population followed and simply area under curve advantages using such quantification over rate have been discussed setting fixed-time...
Abstract Intratumor heterogeneity is postulated to cause therapeutic resistance. To prospectively assess the impact of HER2 (ERBB2) on response HER2-targeted therapy, we treated 164 patients with centrally confirmed HER2-positive early-stage breast cancer neoadjuvant trastuzumab emtansine plus pertuzumab. was assessed pretreatment biopsies from two locations each tumor. heterogeneity, defined as an area ERBB2 amplification in >5% but <50% tumor cells, or a HER2-negative by...
Abstract Purpose: Existing cell-free DNA (cfDNA) methods lack the sensitivity needed for detecting minimal residual disease (MRD) following therapy. We developed a test tracking hundreds of patient-specific mutations to detect MRD with 1,000-fold lower error rate than conventional sequencing. Experimental Design: compared our approach digital droplet PCR (ddPCR) in dilution series, then retrospectively identified two cohorts patients who had undergone prospective plasma sampling and clinical...
PURPOSE Smoldering multiple myeloma (SMM) is a precursor condition of (MM) with 10% annual risk progression. Various prognostic models exist for stratification; however, those are based on solely clinical metrics. The discovery genomic alterations that underlie disease progression to MM could improve current models. METHODS We used next-generation sequencing study 214 patients SMM. performed whole-exome 166 tumors, including 5 serial samples, and deep targeted 48 tumors. RESULTS observed...
The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients stage I human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC).Patients centrally confirmed HER2+ BC were randomly assigned 3:1 T-DM1 or TH received 3.6 mg/kg IV every 3 weeks for 17 cycles T 80 mg/m2 H once week × 12 (4 load →2 mg/kg), followed by...
For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis enhanced funding now permit randomized, controlled trials shortened-duration, all-oral treatments We conducted a phase 3, multinational, open-label, noninferiority trial compare standard therapy fluoroquinolone-susceptible, five 9-month oral regimens that included various combinations bedaquiline (B), delamanid (D),...
Abstract We sought a regimen that incorporates optimal novel agents and balances efficacy with toxicity in transplant‐ineligible multiple myeloma ( MM ) patients. Our study evaluated modified lenalidomide‐bortezomib‐dexamethasone RVD lite) this population was administered over 35‐day cycle. Lenalidomide 15 mg given orally on days 1–21; bortezomib 1·3 mg/m 2 weekly subcutaneously 1, 8, 22; dexamethasone 20 the day of after for 9 cycles followed by 6 consolidation lenalidomide bortezomib. The...
Multiple myeloma (MM) is a plasma-cell neoplasm that treated with high-dose chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. The presence of somatic mutations in the peripheral blood termed clonal hematopoiesis indeterminate potential (CHIP) associated adverse outcomes. Targeted sequencing product from 629 MM patients by ASCT at Dana-Farber Cancer Institute (2003-2011) detects CHIP 136/629 (21.6%). most commonly mutated genes are...
<h3>Importance</h3> Prior studies have shown that only a small proportion of patients with hormone receptor (HR)–positive metastatic breast cancer (MBC) experience benefit from programmed cell death 1 (PD-1)/programmed ligand (PD-L1) inhibitors given as monotherapy. There are data suggesting activity may be greater combination strategies. <h3>Objective</h3> To compare the efficacy eribulin plus pembrolizumab vs alone in HR-positive,<i>ERBB2 </i>(formerly<i>HER2</i>)–negative MBC. <h3>Design,...
To evaluate whether the use of Bayesian adaptive randomized (AR) designs in clinical trials for glioblastoma is feasible and would allow more efficient trials.
When several experimental treatments are available for testing, multi-arm trials provide gains in efficiency over separate trials. Including interim analyses allows the investigator to effectively use data gathered during trial. Bayesian adaptive randomization (AR) and multi-stage (MAMS) designs two distinct methods that patient outcomes improve ethics of AR allocates a greater proportion future patients have performed well; MAMS pre-specified stopping boundaries determine whether should be...
Abstract Motivation: Numerous competing algorithms for prediction in high-dimensional settings have been developed the statistical and machine-learning literature. Learning models they generate are typically evaluated on basis of cross-validation error estimates a few exemplary datasets. However, most applications, ultimate goal modeling is to provide accurate predictions independent samples obtained different settings. Cross-validation within datasets may not adequately reflect performance...
Waldenström macroglobulinemia (WM) is preceded by asymptomatic WM (AWM), for which the risk of progression to overt disease not well defined.We studied 439 patients with AWM, who were diagnosed and observed at Dana-Farber Cancer Institute between 1992 2014.During 23-year study period, a median follow-up 7.8 years, 317 progressed symptomatic (72%). Immunoglobulin M 4,500 mg/dL or greater, bone marrow lymphoplasmacytic infiltration 70% β2-microglobulin 4.0 albumin 3.5 g/dL less all identified...
502 Background: HER2 targeted therapy without chemotherapy may be insufficient to completely eradicate a HER2+ cancer in cases of significant intratumor heterogeneity (ITH-HER2). Methods: We conducted single-arm phase II study enrolling centrally confirmed breast cancer. Pts received 6 cycles T-DM1 plus Pertuzumab before surgery. Central ITH-HER2 was assessed on baseline ultrasound-guided core biopsies from 2 distinct areas each tumor (3 cores/site). defined as at least one the six...
Sacituzumab govitecan (SG), a novel antibody-drug conjugate (ADC) targeting TROP2, is approved for pre-treated metastatic triple-negative breast cancer (mTNBC). We conducted an investigator-initiated clinical trial evaluating neoadjuvant (NA) SG (NCT04230109), and report primary results.
Patients with precursors to multiple myeloma are dichotomised as having monoclonal gammopathy of undetermined significance or smouldering on the basis protein concentrations bone marrow plasma cell percentage. Current risk stratifications use laboratory measurements at diagnosis and do not incorporate time-varying biomarkers. Our goal was develop a stratification algorithm that utilised accessible, biomarkers model progression myeloma.