Publications by authors named "Mark Knafl"

Background: Anti-PD-(L)1 antibodies are associated with responses in <25% of patients with metastatic human papillomavirus (HPV)-associated malignancies. VEGF signaling causes intratumoral immune evasion and immune suppression. We evaluated the anti-PD-L1 antibody atezolizumab and anti-VEGF antibody bevacizumab for patients with unresectable, advanced anal cancer.

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  • Triple-negative inflammatory breast cancer (TN-IBC) is the most aggressive form of breast cancer, and its specific genetic and immune characteristics are not well understood.
  • This study conducted extensive genomic analyses of TN-IBC tumors from a phase II clinical trial, comparing them to stage III triple-negative non-inflammatory breast cancer (TN-non-IBC) samples.
  • Key findings revealed that TN-IBC tumors have unique features, such as a lower mutation load and the presence of immune components that may hinder chemotherapy response, indicating a need for further research to identify potential biomarkers and treatment targets.
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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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Purpose: Dynamic operations platforms allow for cross-platform data extraction, integration, and analysis, although application of these platforms to large-scale oncology enterprises has not been described. This study presents a pipeline for automated, high-fidelity extraction, integration, and validation of cross-platform oncology data in patients undergoing treatment for rectal cancer at a single, high-volume institution.

Methods: A dynamic operations platform was used to identify patients with rectal cancer treated at MD Anderson Cancer Center between 2016 and 2022 who had magnetic resonance imaging (MRI) imaging and preoperative treatment details available in the electronic health record (EHR).

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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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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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The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.

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  • The study looked at how radiation therapy (RT) affects collecting certain blood cells from patients with multiple myeloma (MM) who need a stem cell transplant.
  • Researchers reviewed medical records of 732 patients who underwent RT between 1999 and 2017, focusing on 223 of them who had RT before collecting blood cells for the transplant.
  • They found that the amount of bone marrow treated with RT and the radiation dose didn't seem to impact the number of blood cells that could be collected for the transplant.
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Importance: Serum tumor markers CEA, CA19-9, & 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: Assessing the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes, pathologic, and molecular features in patients with appendiceal adenocarcinoma.

Design: This is a retrospective study with results reported in 2023.

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  • * Results showed that patients with specific mutations had significantly shorter median OS compared to those with wildtype tumors; median OS for mutated tumors ranged from 20 to 22 months, while wildtype patients had 38 months.
  • * A notable finding was that certain mutations were more common in metastatic tumors and well-differentiated tumors, and these trends were confirmed with an additional patient cohort (PanCAN's Know Your Tumor dataset).
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Purpose: Clinical management of patients receiving immune checkpoint inhibitors (ICIs) could be informed using accurate predictive tools to identify patients at risk of short-term acute care utilization (ACU). We used routinely collected data to develop and assess machine learning (ML) algorithms to predict unplanned ACU within 90 days of ICI treatment initiation.

Methods: We used aggregated electronic health record data from 7,960 patients receiving ICI treatments to train and assess eight ML algorithms.

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There is scant information on the clinical progression, end-of-life decisions, and cause of death of patients with cancer diagnosed with COVID-19. Therefore, we conducted a case series of patients admitted to a comprehensive cancer center who did not survive their hospitalization. To determine the cause of death, 3 board-certified intensivists reviewed the electronic medical records.

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Importance: Therapies for patients with advanced well-differentiated neuroendocrine tumors (NETs) have expanded but remain inadequate, with patients dying of disease despite recent advances in NET therapy. While patients with other cancers have seen long-term disease control and tumor regression with the application of immunotherapies, initial prospective studies of single-agent programmed cell death 1 inhibitors in NET have been disappointing.

Objective: To evaluate the response rate following treatment with the combination of the vascular endothelial growth factor inhibitor bevacizumab with the programmed cell death 1 ligand 1 inhibitor atezolizumab in patients with advanced NETs.

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Malignant peritoneal mesothelioma (MPeM) is a rare but aggressive malignancy with limited treatment options. VEGF inhibition enhances efficacy of immune-checkpoint inhibitors by reworking the immunosuppressive tumor milieu. Efficacy and safety of combined PD-L1 (atezolizumab) and VEGF (bevacizumab) blockade (AtezoBev) was assessed in 20 patients with advanced and unresectable MPeM with progression or intolerance to prior platinum-pemetrexed chemotherapy.

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