Publications by authors named "Alexis D Leal"

This study aimed to evaluate the role of pathological features beyond tumor size in the risk of lymph node metastasis in appendiceal neuroendocrine tumors. Analyzing data from the national cancer database, we found that among 5353 cases, 18.8% had lymph node metastasis.

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Background: Modulation of glucocorticoid receptor (GR) activity in tumor cells enhances chemotherapy efficacy. We evaluated the selective GR modulator relacorilant plus nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who had received at least 2 prior therapy lines.

Patients And Methods: In this open-label, single-arm, phase III study, patients received once-daily oral relacorilant (100 mg, titrated to 150 mg in 25 mg increments/cycle) and nab-paclitaxel (80 mg/m2) on days 1, 8, and 15 of 28-day cycles.

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  • * The study involved 50 patients who had not responded to at least two previous treatments, resulting in an objective response rate (ORR) of 12%, which was statistically better than historical data.
  • * While the combination treatment showed a high disease control rate and acceptable side effects, it did not achieve the primary goal of improving ORR compared to historical controls.
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  • - The study investigated the safety and effectiveness of combining alisertib and sapanisertib in patients with difficult-to-treat solid tumors, focusing on pancreatic adenocarcinoma.
  • - A total of 31 patients were treated, and while similar side effects to previous studies were noted, only one patient with breast cancer showed a significant improvement, and pancreatic cancer patients had modest treatment responses.
  • - The findings suggest that targeting proteins involved in cell cycle regulation (Aurora A kinase) and tumor growth (mTOR) had limited overall clinical impact, but responses varied based on tumor characteristics and patient treatment history.
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  • Pancreatic ductal adenocarcinoma (PDAC) is difficult to treat due to its late-stage diagnosis and resistance to most therapies, with Wnt signaling playing a significant role in tumor growth and treatment resistance.
  • *Research using patient-derived organoids (PDOs) revealed distinct growth dependencies and responses to Wnt inhibitors, particularly the drug ETC-159, in combination with chemotherapy agents like paclitaxel and gemcitabine.
  • *In vivo studies with xenografts showed that the combination of ETC-159 and paclitaxel was more effective at reducing tumor growth than either treatment alone, indicating potential for targeted therapies based on Wnt signaling pathways in pancreatic cancer.
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Pancreatic and colorectal cancers are often KRAS mutated and are incurable when tumor DNA or protein persists or recurs after curative intent therapy. Cancer vaccine ELI-002 2P enhances lymph node delivery and immune response using amphiphile (Amph) modification of G12D and G12R mutant KRAS (mKRAS) peptides (Amph-Peptides-2P) together with CpG oligonucleotide adjuvant (Amph-CpG-7909). We treated 25 patients (20 pancreatic and five colorectal) who were positive for minimal residual mKRAS disease (ctDNA and/or serum tumor antigen) after locoregional treatment in a phase 1 study of fixed-dose Amph-Peptides-2P and ascending-dose Amph-CpG-7909; study enrollment is complete with patient follow-up ongoing.

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  • - The study investigates how pancreatic ductal adenocarcinoma (PDAC) cells release CSF-1, leading to NLRP3 activation in immune cells, which contributes to an immune-tolerant microenvironment that facilitates tumor growth and drug resistance.
  • - Higher NLRP3 expression was observed in PDAC patients, correlating with increased inflammation driven by IL1β, which suppresses CD8+ T-cell activation and promotes tumor expansion.
  • - The study highlights the potential of using NLRP3 inhibitors in combination with gemcitabine chemotherapy to enhance immune response and reduce tumor growth, suggesting a new therapeutic target for PDAC treatment.
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We conducted a dose escalation Phase 1 study of autologous PBMCs loaded by microfluidic squeezing (Cell Squeeze technology) with HPV16 E6 and E7 antigens (SQZ-PBMC-HPV), in HLA-A*02+ patients with advanced/metastatic HPV16+ cancers. Preclinical studies in murine models had shown such cells resulted in stimulation and proliferation of antigen specific CD8+ cells, and demonstrated antitumor activity. Administration of SQZ-PBMC-HPV was every 3 weeks.

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Purpose: Guanylyl cyclase C (GCC) is highly expressed in several gastrointestinal malignancies and preclinical studies suggest that it is a promising target for antibody-based therapeutics. This phase I trial assessed the safety and tolerability of TAK-164, an investigational, anti-GCC antibody-drug conjugate (NCT03449030).

Methods: Thirty-one patients with GCC-positive, advanced gastrointestinal cancers received intravenous TAK-164 on day 1 of 21-day cycles.

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  • Scientists found that a medicine called cabozantinib can help a type of cancer called MSS-CRC work better with another medicine, nivolumab, which usually only helps a different type, MSI-high CRC.
  • They tested this combination on special mice with human immune systems and saw that it made the tumors grow slower in most of their experiments.
  • The study suggests that this combination might be worth trying in real-life tests with cancer patients who have MSS-CRC to see if it helps them too!
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  • AZD0156, an oral ATM inhibitor, was tested in combination with irinotecan and 5-fluorouracil (5FU) to see if it enhances the effectiveness of chemotherapy in treating colorectal cancer (CRC).
  • In vitro studies showed that the combination led to increased cell death and G2/M phase cell cycle arrest, suggesting improved anti-cancer effects compared to single-agent treatments.
  • Results from patient-derived xenograft models indicated that this combination therapy resulted in greater tumor growth inhibition, although the effectiveness varied across different models.
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Pancreatic adenocarcinoma is one of the deadliest malignancies worldwide and its incidence is rising in the United States. The only potential curative treatment for this disease is surgical resection, however, due to the lack of an effective screening strategy, the majority of patients present with advanced or metastatic disease which preclude resectability. Further, the best clinical outcomes occur in those patients that receive multimodality treatment with surgical resection combined with chemotherapy with or without the addition of radiation therapy.

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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with high incidences of p53 mutations. AZD1775 (adavosertib, previously MK-1775) is a small molecule WEE1 inhibitor that abrogates the G2M checkpoint and can potentially synergize with DNA damaging therapies commonly used in PDAC treatment. The purpose of this study was to identify combination partners for AZD1775, including standard chemotherapy or targeted agents, in PDAC preclinical models.

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The impact of radiation prescription dose on postoperative complications during standard of care trimodality therapy for operable stage II-III esophageal and gastroesophageal junction cancers has not been established. We retrospectively reviewed 82 patients with esophageal or gastroesophageal junction cancers treated between 2004 and 2016 with neoadjuvant chemoradiation followed by resection at a single institution. Post-operative complications within 30 days were reviewed and scored using the Comprehensive Complication Index (CCI).

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Introduction: Antibody drug conjugates (ADCs) represent a developing class of anticancer therapeutics which are designed to selectively deliver a cytotoxic payload to tumors, while limiting systemic toxicity to healthy tissues. There are several ADCs which are currently in various stages of clinical development for the treatment of gastrointestinal malignancies.

Areas Covered: We discuss the biologic rationale and review the clinical experience with ADCs in the treatment of gastrointestinal malignancies, summarizing the pre-clinical and phase I/II clinical trial data that have been completed or are ongoing.

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Prevention of chemotherapy-induced nausea and vomiting is essential to preserve quality of life in patients with cancer receiving highly emetogenic chemotherapy (HEC). Recently, new drugs (eg, fosaprepitant, and the newer neurokinin-1 receptor antagonists [NK1RAs] rolapitant and netupitant) and updated antiemetic guidelines have emerged. However, trends in real-world antiemetic use are understudied.

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Background: Treatment-related toxicity can vary substantially between chemotherapy regimens. In this study we evaluated the frequency of outpatient office visits among a cohort of early stage breast cancer survivors after completion of 4 different adjuvant chemotherapy regimens to better understand how differences in toxicities between regimens might affect health care use.

Materials And Methods: We analyzed administrative claims data from a US commercial insurance database (OptumLabs) to identify women who received adjuvant doxorubicin/cyclophosphamide (AC), AC followed or preceded by docetaxel or paclitaxel (AC-T), AC concurrent with docetaxel or paclitaxel (TAC), or docetaxel/cyclophosphamide (TC) between 2008 and 2014.

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This study was conducted to determine the incidence of inter-observer variability in Eastern Cooperative Oncology Group (ECOG) performance status (PS) rating between patients with leukemia and lymphoma and their physicians. ECOG PS was assessed at diagnosis by patients and their physicians and stratified by disease subtype, gender, age, disease stage and education. Association between patient- and physician-rated PS and overall survival (OS) was stratified by subtype and prognostic risk score.

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Purpose Molecular diagnostic testing has become an integral part of the evaluation of patients with metastatic colorectal cancer (CRC). Expanded mutational testing, such as next-generation sequencing (NGS), often identifies mutations with unclear clinical or prognostic implications. One such example is BRAF mutations that occur outside of codon 600 ( BRAF mutations).

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Background: Hormonal and reproductive history has been associated with risk of some hematologic malignancies, but their role in myeloproliferative neoplasms (MPN) is largely unknown.

Methods: Using a population-based cohort study, we evaluated the association of these factors with risk of MPN overall, and for essential thrombocythemia (ET) and polycythemia vera (PV) specifically. Incident MPN cases from 1993 to 2004 were identified via linkage to Medicare.

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Purpose: Fosaprepitant is an antiemetic used for chemotherapy-induced nausea and vomiting. We recently reported increased infusion site adverse events (ISAE) in a cohort of breast cancer patients receiving chemotherapy with doxorubicin and cyclophosphamide (AC). In this current study, we evaluated the venous toxicity of fosaprepitant use with non-anthracycline platinum-based antineoplastic regimens.

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There are few studies examining complementary and alternative medicine (CAM) use and beliefs among non-Hodgkin lymphoma (NHL) survivors. Seven hundred and nineteen patients with NHL from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource who completed the 3-year post-diagnosis questionnaire were included in this study. Altogether 636 (89%) reported ever using CAM, with 78% utilizing vitamins, 54% alternative therapies and 45% herbals.

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Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of taxane and platinum-based chemotherapy. Several studies have supported the potential benefit of glutathione for the prevention of platinum-induced CIPN. The current trial was designed to determine whether glutathione would prevent CIPN as a result of carboplatin/paclitaxel therapy.

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Classical myeloproliferative neoplasms (MPNs) are composed of essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF), the etiology of which is largely unknown. We investigated the role of anthropometric, medical and lifestyle factors with risk of MPN in a prospective cohort of 27,370 women aged 55-69 years at enrollment. After >250,000 person-years of follow-up, 257 cases of MPN were identified (172 ET, 64 PV, 21 MF).

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