Publications by authors named "Hedy L Kindler"

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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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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  • 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: 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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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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  • 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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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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Background: The phase 3 POLO study demonstrated a significant progression-free survival (PFS) benefit and preserved health-related quality of life (HRQOL) for active maintenance treatment with olaparib vs placebo in patients with metastatic pancreatic cancer and a germline BRCA mutation. Here, we present a post hoc analysis of the patient-centered outcomes: time without significant symptoms of disease progression or toxicity (TWiST) and quality-adjusted TWiST (Q-TWiST).

Methods: Patients were randomized 3:2 to maintenance olaparib (300 mg tablets twice daily) or placebo.

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Purpose: Guidelines recommend all patients with pancreatic ductal adenocarcinoma (PDAC) undergo germline genetic testing (GT). Rates of recommendation and completion of GT among diverse patients with PDAC are not known. The aim was to determine rates of recommendation and completion of point-of-care GT in diverse patients with PDAC.

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Purpose: Primary mesothelioma of the tunica vaginalis (TVM) is a rare and poorly understood malignancy with insufficient population-level data to guide management decisions.

Materials And Methods: A retrospective analysis of TVM cases recorded in the National Cancer Database from 2004 to 2015 was performed. Cases were identified using International Classification of Diseases for Oncology histology codes.

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Purpose: The phase III POLO study demonstrated significant progression-free survival (PFS) benefit for active olaparib maintenance therapy versus placebo for patients with metastatic pancreatic adenocarcinoma and a germline BRCA mutation. Here, we report the final analysis of overall survival (OS) and other secondary end points.

Patients And Methods: Patients with a deleterious or suspected deleterious germline BRCA mutation whose disease had not progressed after ≥ 16 weeks of first-line platinum-based chemotherapy were randomly assigned 3:2 to active maintenance olaparib (300 mg twice daily) or placebo.

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Background: Patients with cancer were excluded from phase 3 COVID-19 vaccine trials, and the immunogenicity and side effect profiles of these vaccines in this population is not well understood. Patients with cancer can be immunocompromised from chemotherapy, corticosteroids, or the cancer itself, which may affect cellular and/or humoral responses to vaccination. PD-1 is expressed on T effector cells, T follicular helper cells and B cells, leading us to hypothesize that anti-PD-1 immunotherapies may augment antibody or T cell generation after vaccination.

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The most common malignancies that develop in carriers of BAP1 germline mutations include diffuse malignant mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and less frequently, breast cancer, several types of skin carcinomas, and other tumor types. Mesotheliomas in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. Some BAP1 carriers have asymptomatic mesothelioma that can be followed by close clinical observation without apparent adverse outcomes: they may survive many years without therapy.

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Article Synopsis
  • This study looked at a new treatment called anetumab ravtansine for patients with a serious type of lung cancer called malignant pleural mesothelioma who didn't get better from previous treatments.
  • Researchers wanted to see if this new drug worked better than an existing one called vinorelbine.
  • They tested 248 patients in a fair way, where some got anetumab ravtansine and others got vinorelbine, to find out how long they could survive without the cancer getting worse.
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Purpose: Imaging of the peritoneum and related pathology is a challenge. Among peritoneal diseases, malignant peritoneal mesothelioma (MPeM) is an uncommon tumor with poor prognosis. To date, there are no specific guidelines or imaging protocols dedicated for the peritoneum and MPeM.

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Importance: The American Cancer Society and American Institute for Cancer Research recommend that cancer survivors limit intake of red and processed meats. This recommendation is based on consistent associations between red and processed meat intake and cancer risk, particularly risk of colorectal cancer, but fewer data are available on red and processed meat intake after cancer diagnosis.

Objectives: To examine whether intake of unprocessed red meat or processed meat is associated with risk of cancer recurrence or mortality in patients with colon cancer.

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