PURPOSE Rituximab and lenalidomide is effective for previously untreated and relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). However, long-term survival and predictive biomarkers are not well-described. METHODS We conducted two phase 2 open-label trials involving 60 patients with previously untreated and R/R advanced stage iNHL. Patients received lenalidomide and rituximab induction followed by continuous lenalidomide until disease progression or unacceptable toxicity. The primar...
PURPOSE Although tumor infiltrating lymphocytes (TIL) assessment has been acknowledged to have both prognostic and predictive importance in triple negative breast cancer (TNBC), it is subject to inter and intra-observer variability that has prevented widespread adoption. Here we constructed a machine-learning based breast cancer TIL scoring approach and validated its prognostic potential in multiple TNBC cohorts. EXPERIMENTAL DESIGN Using the QuPath open source software, we built a neural-networ...
Last. Alexander Drilon(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 56
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PURPOSE We report the intracranial efficacy of selpercatinib, a highly potent and selective RET inhibitor, approved in the US for RET fusion-positive non-small cell lung cancers (NSCLCs). EXPERIMENTAL DESIGN In the global phase 1/2 LIBRETTO-001 trial (NCT03157128) in advanced RET-altered solid tumors, selpercatinib was dosed orally (160mg twice/day) in 28-day cycles. Patients with baseline intracranial metastases had MRI/CT scans every 8-weeks for 1 year (12-weeks thereafter). In this pre-planne...
PURPOSE We recently reported the development of a cell-free DNA (cfDNA) targeted methylation (TM)-based sequencing approach for multi-cancer early detection (MCED) and cancer signal origin prediction. Here, we evaluated the prognostic significance of cancer detection by the MCED test using longitudinal follow-up data. EXPERIMENTAL DESIGN As part of a Circulating Cell-free Genome Atlas (CCGA) substudy, plasma cfDNA samples were sequenced using TM, and machine learning classifiers predicted cancer...
#1Theodora Pappa(Brigham and Women's Hospital)H-Index: 1
#2Sara Ahmadi(Brigham and Women's Hospital)H-Index: 7
Last. Inigo Landa(Brigham and Women's Hospital)H-Index: 1
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PURPOSE The extent to which routine genomic sequencing can identify relevant secondary genomic alterations among BRAFV600E -mutant papillary thyroid carcinoma (PTC) is unknown. Such markers would prove highly valuable for prognostic purposes. EXPERIMENTAL DESIGN We reviewed clinicopathological data of 225 patients with BRAFV600E -mutant PTC and integrated them with genomic data derived from targeted next generation sequencing on tumor specimens. We defined patient subgroups based on bona fide se...
PURPOSE Circulating tumor DNA (ctDNA) has been suggested as a major prognostic factor in resected stage III colon cancer. We analyzed ctDNA of patients randomized in the phase III IDEA-France trial. EXPERIMENTAL DESIGN ctDNA was tested for WIF1 and NPY by droplet digital PCR with method developed and validated for colorectal cancer. Disease-free survival (DFS) and overall survival (OS) were analyzed via multivariable analysis in patients with ctDNA samples and in sub-groups according to treatmen...
Neoadjuvant immunotherapy is gathering pace, particularly in melanoma. A recent study of pembrolizumab and HDI not only further supports the safety and activity of neoadjuvant anti-PD-1 based immunotherapy but also highlights neoadjuvant therapy as a solid platform for drug development that is likely to become a standard-of-care in the near future.
Last. Alexander W. Wyatt(UBC: University of British Columbia)H-Index: 35
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PURPOSE Cross-resistance renders multiple lines of androgen receptor (AR) signaling inhibitors increasingly futile in metastatic castration-resistant prostate cancer (mCRPC). We sought to determine acquired genomic contributors to cross-resistance. EXPERIMENTAL DESIGN We collected 458 serial plasma cell-free DNA samples at baseline and progression timepoints from 202 mCRPC patients receiving sequential AR signaling inhibitors (abiraterone and enzalutamide) in a randomized phase II clinical trial...
Last. Steven J. Lemery(CDER: Center for Drug Evaluation and Research)H-Index: 14
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The Food and Drug Administration (FDA) approved pembrolizumab on June 16, 2020, for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [greater than or equal to 10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. FDA granted the approval based on a clinically important overall response rate (29%...
PURPOSE Patient-derived organoids (PDOs) of lung cancer has been recently introduced, reflecting the genomic landscape of lung cancer. However, clinical relevance of advanced lung adenocarcinoma organoids remains unknown. Here, we examined the ability of PDOs to predict clinical responses to targeted therapies in individual patients and to identify effective anti-cancer therapies for novel molecular targets. EXPERIMENTAL DESIGN Eighty-four organoids were established from patients with advanced l...