Publications by authors named "Digumarthy S"

Article Synopsis
  • Approximately 10% of lung adenocarcinomas (LUAD) have mucinous histology (LUADMuc), which is linked to a lighter/absent smoking history and a higher prevalence of KRAS mutations compared to LUAD without this histology (LUADnon-muc).
  • A study analyzed features and treatment outcomes of LUADMuc and LUADnon-muc patients, revealing LUADMuc patients had less aggressive disease characteristics and a poorer response to current therapies, especially immunotherapy.
  • Overall, LUADMuc showed lower objective response rates, shorter progression-free and overall survival compared to LUADnon-muc, highlighting a need for more effective treatment strategies for this subgroup.
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Introduction: Anaplastic lymphoma kinase rearranged (ALK + ) lung cancers often develop ALK-independent resistance mechanisms that reactivate the mitogen-activated protein kinase pathway signaling pathway. We therefore evaluated alectinib combined with the MEK inhibitor cobimetinib in metastatic ALK + lung cancer.

Materials And Methods: This phase Ib study employed a 3 + 3 design.

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Purpose: Temozolomide plus PARP inhibition has shown promise in small cell lung cancer (SCLC). We previously reported outcomes from the first 50 patients (cohort 1) of a phase I/II trial of olaparib/temozolomide in recurrent SCLC. In this study, we report a final analysis of this trial, including a second cohort with an alternate dosing strategy and an exploratory analysis of central nervous system (CNS)-specific outcomes.

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Arsenic is associated with lung disease and experimental models suggest that arsenic-induced degradation of the chloride channel CFTR (cystic fibrosis transmembrane conductance regulator) is a mechanism of arsenic toxicity. We examined associations between arsenic exposure, sweat chloride concentration (measure of CFTR function), and pulmonary function among 285 adults in Bangladesh. Participants with sweat chloride ≥ 60 mmol/L had higher arsenic exposures than those with sweat chloride < 60 mmol/L (water: median 77.

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Article Synopsis
  • Dual immune checkpoint blockade (ICB) using CTLA4 and PD-(L)1 inhibitors shows improved anti-tumor effectiveness and immune toxicity compared to PD-(L)1 inhibitors alone in advanced non-small-cell lung cancer (NSCLC) patients.
  • Patients with mutations in STK11 and/or KEAP1 genes benefit more from the combination treatment compared to those receiving only PD-(L)1 inhibitors, as shown in the POSEIDON trial.
  • The loss of KEAP1 serves as a strong predictor for the success of dual ICB, as it leads to a more favorable outcome by changing the tumor's immune environment to better engage CD4 and CD8 T cells for anti-tumor activity. *
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Purpose: To assess the ability of the Annalise Enterprise CXR Triage Trauma (Annalise AI Pty Ltd, Sydney, NSW, Australia) artificial intelligence model to identify vertebral compression fractures on chest radiographs and its potential to address undiagnosed osteoporosis and its treatment.

Materials And Methods: This retrospective study used a consecutive cohort of 596 chest radiographs from four US hospitals between 2015 and 2021. Each radiograph included both frontal (anteroposterior or posteroanterior) and lateral projections.

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The opportunistic use of radiological examinations for disease detection can potentially enable timely management. We assessed if an index created by an AI software to quantify chest radiography (CXR) findings associated with heart failure (HF) could distinguish between patients who would develop HF or not within a year of the examination. Our multicenter retrospective study included patients who underwent CXR without an HF diagnosis.

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Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions.

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Introduction: Central nervous system (CNS) metastases remain a common challenge in patients with ALK-positive NSCLC. We previously reported reinduction of CNS responses using dose-intensified alectinib in two patients with CNS progression on standard-dose alectinib. Nevertheless, this strategy has not been assessed in larger cohorts.

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Introduction: Interventions and surgical procedures are common for nonmalignant lung lesions detected on lung cancer screening (LCS). Inadvertent surgical resection of benign nodules with a clinical suspicion of lung cancer can occur, can be associated with complications, and adds to the cost of screening. The objective of this study is to assess the characteristics of surgically resected benign nodules detected on LCS computed tomography which were presumed to be lung cancers.

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Rationale And Objectives: To assess differences in radiomics derived from semi-automatic segmentation of liver metastases for stable disease (SD), partial response (PR), and progressive disease (PD) based on RECIST1.1 and to assess if radiomics alone at baseline can predict response.

Materials And Methods: Our IRB-approved study included 203 women (mean age 54 ± 11 years) with metastatic liver disease from breast cancer.

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Acquired drug resistance remains a major problem across oncogene-addicted cancers. Elucidation of mechanisms of resistance can inform rational treatment strategies for patients relapsing on targeted therapies while offering insights into tumor evolution. Here, we report acquired MET amplification as a resistance driver in a ROS1-rearranged lung adenocarcinoma after sequential treatment with ROS1 inhibitors.

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Introduction/background: Immune-related pneumonitis is a potentially fatal complication of treatment with immune checkpoint inhibitors (ICIs). Interstitial lung disease (ILD) is associated with increased risk for pneumonitis, but the impact of interstitial abnormalities (ILA) in the absence of ILD has not been extensively assessed. We examined the relationship between ILA on pretreatment chest computed tomography (CT) scans and risk of pneumonitis in patients with non-small-cell lung cancer (NSCLC).

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This article examines the intrathoracic applications for dual-energy computed tomography (DECT), focusing on lung cancer. The topics covered include the image data sets, methods for iodine quantification, and clinical applications. The applications of DECT are to differentiate benign and malignant lung nodules, determining the grade of lung cancer and expression of ki-67 expression.

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Article Synopsis
  • Guidelines suggest using CT scans for monitoring pleural mesothelioma, but there's debate on the need for regular imaging of distant areas.
  • A study analyzed patient data from Massachusetts General Hospital (1999-2022), finding that 44% developed extrathoracic metastases, with a median time of 11.5 months for these to appear.
  • Patients with extrathoracic metastases had significantly shorter survival rates, emphasizing the need for regular imaging to track potential spread beyond the chest.
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Article Synopsis
  • Amplification acts as a resistance mechanism in ALK+ lung cancer, and this study focuses on treatment outcomes for patients with this specific molecular profile.
  • A cohort of 12 patients receiving combined ALK and MET-targeting regimens showed partial responses in 42% of cases, highlighting some effectiveness but also significant side effects, such as peripheral edema.
  • The findings suggest that while there is moderate antitumor activity from combined therapy, further prospective studies are needed to better understand benefits and target suitable patients.
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Lung transplant is an established treatment for patients with end-stage lung disease. As a result, there is increased demand for transplants. Despite improvements in pretransplant evaluation, surgical techniques, and postsurgical care, the average posttransplant life expectancy is only around 6.

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Article Synopsis
  • Targeted therapy for patients with EGFR-mutant lung cancer is more effective than standard treatments, and timely detection of mutations can enhance management of the disease.
  • An intervention was developed to speed up the initiation of osimertinib treatment by integrating workflows across radiology, pathology, and pharmacy, significantly reducing the time to get testing results and start treatment.
  • The study showed that the new approach decreased the median time from biopsy to EGFR testing results and treatment initiation, allowing for quicker access to osimertinib for patients compared to traditional methods.
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Objective: To assess the effectiveness of low contrast volume (LCV) chest CT performed with multiple contrast agents on multivendor CT with varying scanning techniques.

Methods: The study included 361 patients (65 ± 15 years; M: F 173:188) who underwent LCV chest CT on one of the six 64-256 detector-row CT scanners using single-energy (SECT) or dual-energy (DECT) modes. All patients were scanned with either a fixed-LCV (LCVf, n = 103) or weight-based LCV (LCVw, n = 258) protocol.

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Article Synopsis
  • A study analyzed 424 patients with KRASG12C-mutant non-small cell lung cancer (NSCLC) and identified key genomic alterations (in KEAP1, SMARCA4, and CDKN2A) that lead to worse outcomes with KRASG12C inhibitors (KRASG12Ci).
  • These alterations allowed researchers to classify patients into different prognostic groups, indicating nearly 50% of those who experienced early disease progression.
  • The research suggests potential pathways not only associated with poor response (like PI3K/AKT/MTOR) but also hints that certain DNA damage response issues might improve KRASG12Ci effectiveness, paving the way for personalized treatment strategies.
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Anti-PD-1/PD-L1 agents have transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC). To expand our understanding of the molecular features underlying response to checkpoint inhibitors in NSCLC, we describe here the first joint analysis of the Stand Up To Cancer-Mark Foundation cohort, a resource of whole exome and/or RNA sequencing from 393 patients with NSCLC treated with anti-PD-(L)1 therapy, along with matched clinical response annotation. We identify a number of associations between molecular features and outcome, including (1) favorable (for example, ATM altered) and unfavorable (for example, TERT amplified) genomic subgroups, (2) a prominent association between expression of inducible components of the immunoproteasome and response and (3) a dedifferentiated tumor-intrinsic subtype with enhanced response to checkpoint blockade.

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Rationale And Objectives: Suboptimal chest radiographs (CXR) can limit interpretation of critical findings. Radiologist-trained AI models were evaluated for differentiating suboptimal(sCXR) and optimal(oCXR) chest radiographs.

Materials And Methods: Our IRB-approved study included 3278 CXRs from adult patients (mean age 55 ± 20 years) identified from a retrospective search of CXR in radiology reports from 5 sites.

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Article Synopsis
  • Osimertinib effectively treats a subset of non-small cell lung cancer (NSCLC) patients with atypical mutations, such as L861Q and G719X.
  • The study included 50 patients with uncommon mutations, revealing a median time to treatment discontinuation of 9.7 months and an overall objective response rate of 31.7%.
  • The efficacy of osimertinib varies significantly based on the specific atypical mutation present in the patients.
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