A5026202651- Prostate Cancer Treatment and Research
- Cancer Immunotherapy and Biomarkers
- Cancer, Lipids, and Metabolism
- Estrogen and related hormone effects
- Peptidase Inhibition and Analysis
- Renal cell carcinoma treatment
- Advanced Breast Cancer Therapies
- Acute Myeloid Leukemia Research
- Bladder and Urothelial Cancer Treatments
- Adenosine and Purinergic Signaling
- Chronic Myeloid Leukemia Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- MRI in cancer diagnosis
- Immune Cell Function and Interaction
- Hepatocellular Carcinoma Treatment and Prognosis
- Prostate Cancer Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Pancreatic and Hepatic Oncology Research
- Renal and related cancers
- Ovarian cancer diagnosis and treatment
- Ferroptosis and cancer prognosis
The University of Texas MD Anderson Cancer Center
2019-2025
Scripps MD Anderson Cancer Center
2023
Georgetown University Medical Center
2020
Georgetown University
2020
Whether dosimetric advantages of proton beam therapy (PBT) translate to improved clinical outcomes compared with intensity-modulated radiation (IMRT) remains unclear. This randomized trial total toxicity burden (TTB) and progression-free survival (PFS) between these modalities for esophageal cancer.This phase IIB randomly assigned patients PBT or IMRT (50.4 Gy), stratified histology, resectability, induction chemotherapy, stage. The prespecified coprimary end points were TTB PFS. TTB, a...
Significance A substantial portion of cancer patients treated by immune checkpoint (IC) therapy develop immune-related adverse events (irAEs), which result in significant morbidity and mortality. We sought to understand the mechanisms these irAEs identify biomarkers predict maximize clinical benefits IC therapy. screened plasma samples from who developed therapy-induced hypophysitis or pneumonitis against a cDNA expression library brain lungs directly identified autoimmune antibodies...
The safety and efficacy of combining the isocitrate dehydrogenase-1 (IDH1) inhibitor ivosidenib (IVO) with BCL2 venetoclax (VEN; IVO + VEN) ± azacitidine (AZA; VEN AZA) were evaluated in four cohorts patients IDH1-mutated myeloid malignancies (n = 31). Most (91%) adverse events grade 1 or 2. maximal tolerated dose was not reached. Composite complete remission AZA versus 90% 83%. Among measurable residual disease (MRD)-evaluable (N 16), 63% attained MRD--negative remissions; IDH1 mutation...
Low–tumor mutational burden prostate tumors express neoantigens that elicit T cell responses associated with favorable clinical outcomes to ipilimumab.
Methylthioadenosine phosphorylase, an essential enzyme for the adenine salvage pathway, is often deficient (MTAPdef) in tumors with 9p21 loss and hypothetically renders susceptible to synthetic lethality by antifolates targeting de novo purine synthesis. Here we report our single arm phase II trial (NCT02693717) that assesses pemetrexed MTAPdef urothelial carcinoma (UC) primary endpoint of overall response rate (ORR). Three 7 enrolled patients show (ORR 43%). Furthermore, a historic cohort...
Importance Appendiceal adenocarcinoma is a rare tumor, and given the inherent difficulties in performing prospective trials such disease, there are currently minimal high-quality data to guide treatment decisions, highlighting need for more preclinical clinical investigation this disease. Objective To prospectively evaluate effectiveness of fluoropyrimidine-based systemic chemotherapy patients with inoperable low-grade mucinous appendiceal adenocarcinoma. Design, Setting, Participants This...
Surgical removal of primary tumors reverses tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery the setting modulates responses patients, especially context checkpoint therapy (ICT), is not understood. We report first prospective, pilot, non-comparative clinical trial (NCT02210117) to evaluate feasibility, benefits, and immunologic changes combining three different ICT-containing strategies or biopsy for patients clear cell...
Abstract Purpose: Clear cell renal carcinoma (ccRCC) is frequently associated with inactivation of the von Hippel–Lindau tumor suppressor, resulting in activation HIF-1α and HIF-2α. The current paradigm, established using mechanistic cell-based studies, supports a promoting role for HIF-2α, suppressor HIF-1α. However, few studies have comprehensively examined clinical relevance this paradigm. Furthermore, hypoxia-associated factor (HAF), which regulates HIFs, has not been evaluated ccRCC....
Abstract Cryoablation in combination with immune checkpoint therapy was previously reported to improve anti-tumor responses pre-clinical studies. Here we report a pilot study of anti-CTLA-4 (tremelimumab) (n = 15) or without 14) cryoablation patients metastatic renal cell carcinoma (NCT02626130), 18 clear and 11 non-clear histologies. The primary endpoint is safety, secondary endpoints include objective response rate, progression-free survival, monitoring Safety data indicate ≥ grade 3...
Immune checkpoint therapy (ICT) has low response rates in patients with metastatic castration-resistant prostate cancer (mCRPC), part due to few T cells the tumor microenvironment (TME). Anti-cytotoxic lymphocyte-associated protein 4 (CTLA-4) promotes intratumoral cell infiltration but induces upregulation of PD-1 and programmed death ligand-1 (PD-L1) within TME. Combined anti-CTLA-4 plus anti-PD-1 can partly overcome this adaptive resistance was recently shown augment responses mCRPC...
Abstract Purpose: Despite the prognostic importance of immune infiltrate in colorectal cancer, immunotherapy has demonstrated limited clinical activity refractory metastatic proficient mismatch-repair (pMMR) cancer. This study explores combining anti–CTLA-4 and an anti–PD-L1 therapy preoperative management resectable cancer liver metastases with intent to improve responses this disease setting. Patients Methods: liver-only received one dose tremelimumab durvalumab preoperatively followed by...
Objective: To characterize associations between carbohydrate antigen 19–9 (CA19–9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC). Background: Although normalization of CA19–9 NT is associated improved outcomes following PDAC resection, we hypothesize that can improve prognostication. Methods: Characteristics undergoing (July 2011–October 2018) ≥3 results (bilirubin<2mg/dL) were collected grouped by dynamics. Nonproducers...
TPS614 Background: Complete response (CR) is a rare event in advanced clear cell renal carcinoma (ccRCC). The combination of nivolumab plus cabozantinib was recently approved for first-line treatment ccRCC, demonstrating improved progression-free survival (PFS) and objective rate (ORR) comparison to sunitinib. However, CR only 9%. Drugs that could synergize with T anti-tumor activity can improve rates. Radiation-induced DNA damage activate the cGAS-STING pathway promising mechanism. 177...
TPS612 Background: While metastatic renal cell carcinoma (mRCC) is known to be immunogenic, and there have been several recent advances with combinations of immunotherapy, the disease often progresses immunotherapy resistance mechanisms remain unclear. For patients mRCC refractory checkpoint inhibitors (ICIs), further treatment options are not curative improvements needed. Proprotein convertase subtilisin/kexin type 9 (PCSK9) directs MHC-I molecules lysosome, inhibition PCSK9 improves...
Abstract MTAP-deficiency in urothelial cancer is associated with poor clinical outcomes but correlates sensitivity to antifolate chemotherapy. This single-arm phase 2 trial (N=15) assessed the and biological effects of a sequential combination therapy using immune modulating agent pemetrexed anti-PD-L1 avelumab patients advanced resistant prior chemotherapy and/or immunotherapy. The regimen treatment resulted an overall response rate (ORR) 20% (95% CI: 5%, 42%), disease control (DCR) 47%...
While TKI are the preferred first-line treatment for chronic phase (CP) CML, alloHCT remains an important consideration. The aim is to estimate residual life expectancy (RLE) patients initially diagnosed with CP CML based on timing of or continuation in various settings: CP1 CP2 + [after transformation accelerated (AP) blast (BP)], AP, BP. Non-transplant cohort included single-institution initiating and switched due failure. CIBMTR transplant who underwent HLA sibling matched (MRD) unrelated...
Background The prostate tumor microenvironment (TME) is immunosuppressive, with few effector T cells and enrichment of inhibitory immune populations, leading to limited responses treatments such as checkpoint therapies (ICTs). composition the TME differs across soft tissue bone, most common site treatment-refractory metastasis. Understanding immunosuppressive mechanisms specific TMEs will enable rational immunotherapy strategies generate effective antitumor responses. Daratumumab (anti-CD38...
Abstract Purpose: To determine the efficacy and safety of risk-adapted combinations androgen signaling inhibitors inform disease classifiers for metastatic castration–resistant prostate cancers. Patients Methods: In a modular, randomized phase II trial, 192 men were treated with 8 weeks abiraterone acetate, prednisone, apalutamide (AAPA; module 1) then allocated to modules 2 or 3 based on satisfactory (≥50% PSA decline from baseline &lt;5 circulating tumor cell/7.5 mL) versus...