Publications by authors named "Overman M"

Background: Physical activity (PA) and dexamethasone (Dex) when used independently have modest benefits for cancer-related fatigue (CRF) in patients with advanced cancer. In this study we aimed to determine the feasibility (adherence, safety, and satisfaction) of combining PA with Dex versus PA with placebo (PBO) for CRF, and to explore the effects of PA+Dex and PA+PBO on CRF.

Patients And Methods: In this phase II, randomized, double-blind controlled trial, eligible patients had advanced cancer and a CRF score of ≥4 on the Edmonton Symptom Assessment Scale (ESAS) for fatigue (0-10 scale).

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Introduction: Colorectal cancer (CRC) incidence and mortality before 50 have been rising alarmingly in the recent decades.

Methods: Using a cohort of 10,000 patients, this study investigates the clinical, mutational, and co-mutational features of CRC in early-onset (EOCRC, < 50 years) compared to late-onset (LOCRC, ≥ 50 years).

Results: EOCRC was associated with a higher prevalence of Asian and Hispanic patients, rectal or left-sided tumors (72% vs.

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Purpose: overexpression/amplification in wild-type (WT) metastatic colorectal cancer (mCRC; human epidermal growth factor receptor 2 [HER2]-positive mCRC) appears to be associated with limited benefit from anti-EGFR antibodies and promising responses to dual-HER2 inhibition; however, comparative efficacy has not been investigated. We conducted a randomized phase II trial to evaluate efficacy and safety of dual-HER2 inhibition against standard-of-care anti-EGFR antibody-based therapy as second/third-line treatment in HER2-positive mCRC.

Methods: Patients with -WT mCRC after central confirmation of HER2 positivity (immunohistochemistry 3+ or 2+ and in situ hybridization amplified [HER2/CEP17 ratio >2.

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Background: Immune checkpoint inhibitors (ICIs) are recommended to treat patients with deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). Pivotal trials have fixed a maximum ICI duration of 2 years, without a compelling rationale. A shorter treatment duration has the potential to improve patients' quality of life and reduce both toxicity and cost without compromising efficacy.

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Depression and anxiety are associated with deficits in adjusting learning behaviour to changing outcome contingencies. This is likely to drive and maintain symptoms, for instance, by perpetuating negative biases or a sense of uncontrollability. Normalising such deficits in adaptive learning might therefore be a novel treatment target for affective disorders.

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Purpose: Appendiceal adenocarcinoma (AA) is a rare malignancy with distinct histopathologic subtypes and a natural history with metastasis primarily limited to the peritoneum. Little is known about the molecular pathogenesis of AA relative to common tumors.

Experimental Design: We analyzed molecular data for patients within the Guardant Health database with appendix cancer (n = 718).

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Purpose: Mismatch repair deficient (dMMR) tumors have demonstrated favorable responses to immune checkpoint inhibition targeting PD-1. However, more in-depth identification of predictors of response could further refine patient selection for immunotherapy treatment.

Experimental Design: We undertook integrated evaluation performed on samples collected from 28 of 42 patients enrolled on the NCI-MATCH arm Z1D trial that evaluated PD-1 inhibition treatment with nivolumab in patients with non-colorectal dMMR tumors.

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Article Synopsis
  • PD-1 inhibition shows effectiveness in treating patients with mismatch repair deficient (dMMR) solid tumors; however, routine testing for dMMR using immunohistochemistry (IHC) is not common across different tumor types.
  • A study involving over 15,000 solid tumor patients demonstrated that next-generation sequencing (NGS) can help identify mutations in MMR genes, revealing a correlation with IHC results in those tested.
  • The findings indicate that patients with MMR mutations showed a significant rate of dMMR, highlighting the potential benefits of employing IHC testing on patients with identified MMR mutations to optimize treatment options.
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Background: Immune checkpoint blockade (ICB) has revolutionized treatment of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). However, there is no evidence on the optimal treatment duration. We aimed to compare outcomes of different immunotherapy durations.

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Importance: Disparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown.

Objective: To quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall survival among patients with colorectal cancer.

Design, Setting, And Participants: This single-center cohort study was conducted at a tertiary-level cancer center using relevant data on all patients diagnosed with colorectal cancer from January 1, 1973, to March 1, 2023.

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  • Ampullary adenocarcinoma (AA) shows clinical and genetic diversity, and a new genomic classifier may improve patient classification beyond traditional methods, but it needs validation before being widely used.
  • A study involving 192 patients with AA assessed the accuracy of this genomic classifier against standard histology to see if it could predict survival outcomes.
  • Results indicated a 55% agreement between genomic and histological classifications; however, while histological subtypes did not predict survival, the genomic scores did correlate with survival probabilities, suggesting the genomic approach might be more effective.
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  • The study explores the use of a CD73 inhibitor (oleclumab) combined with durvalumab and chemotherapy in treating pancreatic ductal adenocarcinoma (PDAC), targeting immune surveillance evasion.
  • Conducted across multiple centers, the trial included patients with metastatic PDAC in two cohorts, assessing safety and response rates with various treatment combinations for the chemotherapy regimens.
  • While safety results were acceptable, the trial did not achieve its main goal of demonstrating significant treatment efficacy, although some patients with high CD73 levels showed improved outcomes.
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Unlabelled: Secondary endpoints (SEP) provide crucial information in the interpretation of clinical trials, but their features are not yet well understood. Thus, we sought to empirically characterize the scope and publication rate of SEPs among late-phase oncology trials. We assessed SEPs for each randomized, published phase III oncology trial across all publications and ClinicalTrials.

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Background: Visuospatial neglect is a common consequence of stroke and is characterized by impaired attention to contralesional space. Currently, the extent and time course of recovery from neglect are not clearly established. This systematic review and meta-analysis aimed to determine the recovery trajectory of poststroke neglect with standard treatment.

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Background: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Secondary brain metastasis (Br-M) occurs in less than 1% of patients. Clinical characteristics and molecular alterations have not been characterized in this rare patients' subset.

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  • Colorectal cancer (CRC) ranks as the fourth most common cancer and the second deadliest in the U.S.
  • Treatment for advanced metastatic CRC includes multiple active drugs used alone or in combination, depending on patient-specific factors.
  • The paper reviews the systemic therapy recommendations for metastatic CRC as outlined in the NCCN Guidelines for Colon Cancer.
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Background: Programmed death-1 (PD-1) inhibitors, including nivolumab, have demonstrated long-term survival benefit in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (CRC). PD-1 and lymphocyte-activation gene 3 (LAG-3) are distinct immune checkpoints that are often co-expressed on tumor-infiltrating lymphocytes and contribute to tumor-mediated T-cell dysfunction. Relatlimab is a LAG-3 inhibitor that has demonstrated efficacy in combination with nivolumab in patients with melanoma.

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Background: POLE and POLD1 proofreading deficiency (POLE/D1pd) define a rare subtype of ultramutated metastatic colorectal cancer (mCRC; over 100 mut/Mb). Disease-specific data about the activity and efficacy of immune checkpoint inhibitors (ICIs) in POLE/D1pd mCRC are lacking and it is unknown whether outcomes may be different from mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRCs treated with ICIs.

Patients And Methods: In this global study, we collected 27 patients with mCRC harboring POLE/D1 mutations leading to proofreading deficiency and treated with anti-programmed cell death-ligand 1 alone +/- anti-cytotoxic T-lymphocyte antigen-4 agents.

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  • Traditional guidelines recommend preserving 700 cc of liver during radiation treatment to minimize the risk of liver failure, but this study explores using SPECT imaging to better identify and protect functional liver tissue in patients with diminished liver volume from previous treatments.
  • The phase I trial involved 12 patients with colorectal liver metastases, all having received prior chemotherapy, and assessed safety by monitoring for toxicities after high-dose liver-directed radiotherapy.
  • Results showed that incorporating SPECT imaging allowed for safe administration of higher radiation doses without dose-limiting toxicities, achieving a 57% in-field control rate and a 73% overall survival rate after one year.
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  • Appendiceal adenocarcinoma (AA) is a rare cancer with few treatment options, especially for patients who can't have surgery, leading researchers to test a combination therapy of atezolizumab and bevacizumab (Atezo+Bev).
  • In a phase II study, the Atezo+Bev treatment demonstrated a 100% disease control rate and significantly longer progression-free survival (18.3 months) compared to traditional chemotherapy for colorectal cancer (4.4 months).
  • The promising results suggest that Atezo+Bev could be an effective option for patients with unresectable AA, indicating a need for further research into this treatment approach.
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Objective: Investigate the cross-sectional association between the psychosocial status of mothers and fathers and the BMI z-scores of their 10 to 12-year-old children. Explore whether this association is mediated by children's diet, physical activity, screen time and sleep. Analyze the moderating effect of the educational levels of both the mother and father on the association.

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System dynamics approaches are increasingly addressing the complexity of public health problems such as childhood overweight and obesity. These approaches often use system mapping methods, such as the construction of causal loop diagrams, to gain an understanding of the system of interest. However, there is limited practical guidance on how such a system understanding can inform the development of an action programme that can facilitate systems changes.

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Importance: Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125) have been useful in the management of gastrointestinal and gynecological cancers; however, there is limited information regarding their utility in patients with appendiceal adenocarcinoma.

Objective: To assess the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes and pathologic and molecular features in patients with appendiceal adenocarcinoma.

Design, Setting, And Participants: This is a retrospective cohort study at a single tertiary care comprehensive cancer center.

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