Publications by authors named "Douglas Donnelly"

There is currently no targeted therapy to treat NF1-mutant melanomas. In this study, we compared the genomic and transcriptomic signatures of NF1-mutant and NF1 wild-type melanoma to reveal potential treatment targets for this subset of patients. Genomic alterations were verified using qPCR, and differentially expressed genes were independently validated using The Cancer Genome Atlas data and immunohistochemistry.

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Image-based analysis as a method for mutation detection can be advantageous in settings when tumor tissue is limited or unavailable for direct testing. In this study, we utilize two distinct and complementary machine-learning methods of analyzing whole-slide images for predicting mutated BRAF. In the first method, whole-slide images of melanomas from 256 patients were used to train a deep convolutional neural network to develop a fully automated model that first selects for tumor-rich areas (area under the curve = 0.

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Article Synopsis
  • Recent studies hint at a potential benefit when combining immune checkpoint inhibitors (ICI) with anticoagulation (AC), but this research analyzed their effects in advanced cancer patients to see if the combination leads to better outcomes.
  • The study included 728 cancer patients over a decade, comparing those on AC during ICI treatment with those who weren't, assessing various clinical outcomes like response rates and survival.
  • Results showed no significant improvement in treatment efficacy for patients on AC, while they faced a higher risk of bleeding, leading to a conclusion that combining AC with immunotherapy lacks enough supporting evidence for future trials.
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Background: Recent research suggests that baseline body mass index (BMI) is associated with response to immunotherapy. In this study, we test the hypothesis that worsening nutritional status prior to the start of immunotherapy, rather than baseline BMI, negatively impacts immunotherapy response.

Methods: We studied 629 patients with advanced cancer who received immune checkpoint blockade at New York University.

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Purpose: Several biomarkers of response to immune checkpoint inhibitors (ICI) show potential but are not yet scalable to the clinic. We developed a pipeline that integrates deep learning on histology specimens with clinical data to predict ICI response in advanced melanoma.

Experimental Design: We used a training cohort from New York University (New York, NY) and a validation cohort from Vanderbilt University (Nashville, TN).

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Article Synopsis
  • Immune checkpoint inhibition (ICI) improves survival for cancer patients but can cause immune-related side effects, including skin toxicity (ST), which may correlate with better treatment response.
  • The study analyzed advanced cancer patients to explore the relationship between the severity of ST and survival outcomes, categorizing ST as none, mild, or severe.
  • Findings showed that while mild and severe ST were initially linked to better survival rates, severe ST lost its association with improved outcomes when factoring in the timing of these events, suggesting time and severity should be considered in future analyses.
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The outbreak of the novel coronavirus disease 2019 (COVID-19) and consequent social distancing practices have disrupted essential clinical research functions worldwide. Ironically, this coincides with an immediate need for research to comprehend the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the pathology of COVID-19. As the global crisis has already led to over 15,000 deaths out of 175,000 confirmed cases in New York City and Nassau County, NY alone, it is increasingly urgent to collect patient biospecimens linked to active clinical follow up.

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Background: The American Joint Committee on Cancer (AJCC) maintains that the eighth edition of its Staging Manual (AJCC8) has improved accuracy compared with the seventh (AJCC7). However, there are concerns that implementation may disrupt analysis of active clinical trials for stage III patients. We used an independent cohort of melanoma patients to test the extent to which AJCC8 has improved prognostic accuracy compared with AJCC7.

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Despite major improvements in combatting metastatic melanoma since the advent of immunotherapy, the overall survival for patients with advanced disease remains low. Recently, there is a growing number of reports supporting an "obesity paradox," in which patients who are overweight or mildly obese may exhibit a survival benefit in patients who received immune checkpoint inhibitors. We studied the relationship between body mass index and progression-free survival and overall survival in a cohort of 423 metastatic melanoma patients receiving immunotherapy, enrolled and prospectively followed up in the NYU Interdisciplinary Melanoma Cooperative Group database.

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In the recent decade, cutting edge molecular and proteomic analysis platforms revolutionized biomarkers discovery in cancers. Melanoma is the prototype with over 51,100 biomarkers discovered and investigated thus far. These biomarkers include tissue based tumor cell and tumor microenvironment biomarkers and circulating biomarkers including tumor DNA (cf-DNA), mir-RNA, proteins and metabolites.

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