Publications by authors named "Hedy Kindler"

Purpose: To provide evidence-based recommendations to practicing physicians and others on the management of pleural mesothelioma (PM).

Methods: ASCO convened an Expert Panel of medical oncology, thoracic surgery, radiation oncology, pathology, cancer genetics, and advocacy experts to conduct an updated literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2016 through 2024. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life.

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Purpose: The BRCA1-associated protein 1 () gene is of great interest because somatic () mutations are the most common alteration associated with pleural mesothelioma (PM). Further, germline mutation of the gene has been linked to the development of PM. This study aimed to explore the potential of radiomics on computed tomography scans to identify somatic gene mutations and assess the feasibility of radiomics in future research in identifying germline mutations.

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The Peritoneal Surface Oncology Group International (PSOGI) previously issued a recommendation endorsing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for treating diffuse malignant peritoneal mesothelioma (DMPM). However, broader acceptance of this approach, particularly within some segments of medical oncology, remains limited. To address this, PSOGI initiated a multisociety consensus effort, involving multidisciplinary International Societies, to strengthen and expand the endorsement of CRS-HIPEC for DMPM.

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Article Synopsis
  • The study analyzed how different probability thresholds affect the accuracy of tumor delineations for pleural mesothelioma using a convolutional neural network (CNN) on CT scans.
  • Results showed that a lower probability threshold reduced the difference in tumor volume estimated by the CNN compared to a radiologist's contours.
  • However, no single optimal threshold was found that worked well for both tumor volume accuracy and spatial overlap, highlighting the need to evaluate both metrics when assessing CNN performance.
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Purpose: The mesothelin-targeting antibody-drug conjugate anetumab ravtansine was evaluated in combination with the programmed cell death-1 (PD-1) inhibitor pembrolizumab based on the common expression of mesothelin and reports of activity in mesothelioma.

Patients And Methods: A phase 1 safety run-in of the combination of anetumab ravtansine (6.5 mg/kg iv q3weeks) and pembrolizumab (200 mg, IV q3weeks) was conducted, followed by a phase 2 randomization to the combination or pembrolizumab alone at medical centers across the United States and Canada in the National Cancer Institute's Experimental Therapeutics Clinical Trials Network.

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Introduction: The International Association for the Study of Lung Cancer developed a global multicenter database to propose evidence-based revisions for the ninth edition of the TNM classification of pleural mesothelioma (PM). This study analyzes the M category to validate eighth edition M category recommendations.

Methods: Cases were submitted electronically or by transfer of existing institutional databases for patients with histologically or cytologically confirmed PM.

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Background: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms.

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Article Synopsis
  • The International Association for the Study of Lung Cancer created an international database to assess the need for updates to the TNM classification of diffuse pleural mesothelioma (PM) based on clinical and pathologic N categories from 2013 to 2022.
  • After analyzing 3,598 cases, the study found that the existing eighth edition N categories performed adequately, with patients classified as N0 showing better overall survival compared to N1 patients.
  • The results indicate no necessary changes to the N categories for the ninth edition of the PM staging system, as the findings support continuing the current classification.
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Introduction: The eighth edition of the TNM classification of pleural mesothelioma (PM) saw substantial changes in T and N components and stage groupings. The International Association for the Study of Lung Cancer collected data into a multinational database to further refine this classification. This ninth edition proposal incorporates changes proposed in the clinical (c)T component but not the pathologic T component, to include size criteria, and further refines TNM stage groupings for PM.

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Background: Imaging of peritoneal malignancies using conventional cross-sectional imaging is challenging, but accurate assessment of peritoneal disease burden could guide better selection for definitive surgery. Here we demonstrate feasibility of high-resolution, high-contrast magnetic resonance imaging (MRI) of peritoneal mesothelioma and explore optimal timing for delayed post-contrast imaging.

Methods: Prospective data from inpatients with malignant peritoneal mesothelioma (MPM), imaged with a novel MRI protocol, were analyzed.

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Introduction: The primary tumor (T) component in the eighth edition of pleural mesothelioma (PM) staging system is based on pleural involvement and extent of invasion. Quantitative assessment of pleural tumor has been found to be prognostic. We explored quantitative and qualitative metrics to develop recommendations for T descriptors in the upcoming ninth edition of the PM staging system.

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Introduction: Venous thromboembolism (VTE) is a common complication in patients with abdominal malignancies. Despite known associations between pleural mesothelioma and increased VTE risk, the characteristics of VTE in patients with peritoneal mesothelioma (PeM) remain undescribed.

Methods: Patients treated for PeM were retrospectively identified from our institutional database.

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Importance: Arginine deprivation using ADI-PEG20 (pegargiminase) combined with chemotherapy is untested in a randomized study among patients with cancer. ATOMIC-Meso (ADI-PEG20 Targeting of Malignancies Induces Cytotoxicity-Mesothelioma) is a pivotal trial comparing standard first-line chemotherapy plus pegargiminase or placebo in patients with nonepithelioid pleural mesothelioma.

Objective: To determine the effect of pegargiminase-based chemotherapy on survival in nonepithelioid pleural mesothelioma, an arginine-auxotrophic tumor.

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The International Association for the Study of Lung Cancer collaborated with the International Mesothelioma Interest Group to propose the first TNM stage classification system for diffuse pleural mesothelioma in 1995, accepted by the Union for International Cancer Control and the American Joint Committee on Cancer for the sixth and seventh edition stage classification manuals. The International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Mesothelioma Domain developed and analyzed an international registry of patients with pleural mesothelioma and updated TNM descriptors for the eighth edition of the stage classification system. To inform revisions for the forthcoming ninth edition of the TNM stage classification system, data submission was solicited for patients diagnosed between 2013 and 2022 with expanded data elements on the basis of the first project's exploratory analyses, including pleural thickness measurements, updated surgical nomenclature, and molecular markers.

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Article Synopsis
  • This study identified protein quantitative trait loci (pQTL) related to angiogenic and inflammatory proteins in patients with metastatic colorectal cancer (mCRC) using genetic and protein data from a large clinical trial.
  • The analysis revealed a new pQTL associated with TGF-2 protein levels, validated in additional cancer patient datasets, and confirmed previously reported associations with VEGF-A and other protein markers.
  • The findings enhance our understanding of how genetic variants influence protein levels in mCRC, potentially guiding future cancer treatments and research.
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Aim: Diagnosis of mesothelioma in situ (MIS) is historically controversial and, until recently, specific features defining the entity have not been well characterized. Most reported cases of MIS occurred in the pleura; peritoneal MIS is very rare. This study investigates the morphologic features and results of ancillary testing in peritoneal MIS.

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Article Synopsis
  • Malignant pleural mesothelioma (MPM) is primarily caused by asbestos exposure, and its treatment response is assessed through tumor measurements from CT scans, with tumor volume being the more accurate metric.
  • The study tested the effectiveness of deep learning methods, specifically a CNN model, to automatically segment MPM tumors, comparing its results with those from a radiologist using varying probability thresholds.
  • Results indicated that while CNN segmentations generally yielded smaller tumor volumes than radiologist contours, no optimal threshold was found suitable for both tumor volume and the Dice Similarity Coefficient, highlighting the need to balance multiple performance metrics in evaluating AI-generated tumor segmentations.
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Tebotelimab, a bispecific PD-1×LAG-3 DART molecule that blocks both PD-1 and LAG-3, was investigated for clinical safety and activity in a phase 1 dose-escalation and cohort-expansion clinical trial in patients with solid tumors or hematologic malignancies and disease progression on previous treatment. Primary endpoints were safety and maximum tolerated dose of tebotelimab when administered as a single agent (n = 269) or in combination with the anti-HER2 antibody margetuximab (n = 84). Secondary endpoints included anti-tumor activity.

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We assessed the efficacy and safety of combining bevacizumab with temsirolimus in patients with advanced extra-pancreatic neuroendocrine tumors. This NCI-sponsored multicenter, open-label, phase II study (NCT01010126) enrolled patients with advanced, recurrent, or metastatic extra-pancreatic neuroendocrine tumors. All patients were treated with temsirolimus and bevacizumab until disease progression or unacceptable toxicity.

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Introduction: The International Association for the Study of Lung Cancer developed an international pleural mesothelioma database to improve staging. Data entered from 1995 to 2009 (training data set) were analyzed previously to evaluate supplemental prognostic factors. We evaluated these factors with new clinical data to determine whether the previous models could be improved.

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Importance: Patients with mesothelioma often have next-generation sequencing (NGS) of their tumor performed; tumor-only NGS may incidentally identify germline pathogenic or likely pathogenic (P/LP) variants despite not being designed for this purpose. It is unknown how frequently patients with mesothelioma have germline P/LP variants incidentally detected via tumor-only NGS.

Objective: To determine the prevalence of incidental germline P/LP variants detected via tumor-only NGS of mesothelioma.

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Objectives: Mesothelioma is a lethal disease that arises from the serosal lining of organ cavities. Several recurrent alterations have been observed in pleural and peritoneal -mesotheliomas, including in BAP1, NF2, and CDKN2A. Although specific histopathologic parameters have been correlated with prognosis, it is not as well known whether genetic alterations correlate with histologic findings.

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Pancreatic cancer is one of the few cancer types in the US with incidence and death rates continuing to rise. As the disease threatens to become the second leading cause of cancer-related deaths in the country, it is imperative to review the best practices currently available to extend and improve patient lives. To provide a roadmap for healthcare professionals detecting, diagnosing, and caring for patients with pancreatic cancer as a supplement to national guidelines focused on recommended treatment regimens, the Pancreatic Cancer Action Network (PanCAN)'s Scientific and Medical Affairs staff and expert Scientific and Medical Advisory Board have created a series of position statements.

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Background: This study aimed to investigate if peritoneal mesothelioma (PM) patients with germline mutations (GM) have distinct surgical characteristics when compared to those without GM.

Methods: PM patients were selected from an ongoing prospective study that conducts germline testing of 82 susceptibility genes. Germline status was correlated with surgical data obtained from a prospectively collected database using univariate, multivariate, and receiver operating characteristic (ROC) analyses.

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