Publications by authors named "Christopher Lieu"

Article Synopsis
  • The study explores how body compassion—viewing one's body with kindness and mindfulness—may help colorectal cancer (CRC) patients adjust psychosocially to their condition and improve their quality of life (QOL).
  • Fifty-four CRC patients completed surveys measuring body compassion, distress, loneliness, resilience, and QOL, validating a new measure called the Body Compassion Scale (BCS) with strong reliability (α = 0.94).
  • Results indicated that patients with metastatic cancer and those currently in treatment reported lower body compassion, while higher body compassion correlated with reduced distress and loneliness, and increased resilience and QOL, especially linked to specific BCS subscales like defusion.
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Purpose: Precision oncology relies on accurate and interpretable reporting of testing and mutation rates. Focusing on the mutations in advanced colorectal carcinoma, non-small-cell lung carcinoma, and cutaneous melanoma, we developed a platform displaying testing and mutation rates reported in the literature, which we annotated using an artificial intelligence (AI) and natural language processing (NLP) pipeline.

Methods: Using AI, we identified publications that likely reported a testing or mutation rate, filtered publications for cancer type, and identified sentences that likely reported rates.

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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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Purpose: Rising rates of early-onset colon cancer (EOCC) present challenges in deciding how to optimally treat patients. Although standard of care for stage II CC is surgical resection, adding chemotherapy for high-risk disease, evidence suggests treatment selection may differ by age. We investigated whether adjuvant chemotherapy (AC) administration rates differ between patients with early- and later-onset stage II CC.

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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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Purpose: Treatment of metastatic pancreatic neuroendocrine tumors (pancNETs), particularly grade 2 (G2) and grade 3 (G3), often presents a dilemma in choosing from multiple similarly efficacious therapies. Data on targeted therapies for these tumor types is limited, and this report presents BRAF-targeted therapy as a therapeutic option for metastatic pancNET G3.

Methods: This is a case report of a patient with G3 pancNET metastatic to the liver, lung, lymph node, and scalp (soft tissue) treated with dabrafenib/trametinib (D/T) in the presence of a BRAF V600E mutation detected in tumor tissue.

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Importance: Early-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes.

Objective: To report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation.

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Background: The phase 1b KEYNOTE-651 study evaluated pembrolizumab plus chemotherapy in microsatellite stable or mismatch repair-proficient metastatic colorectal cancer.

Patients And Methods: Patients with microsatellite stable or mismatch repair-proficient metastatic colorectal cancer received pembrolizumab 200 mg every 3 weeks plus 5-fluorouracil, leucovorin, oxaliplatin (previously untreated; cohort B) or 5-fluorouracil, leucovorin, irinotecan (previously treated with fluoropyrimidine plus oxaliplatin; cohort D) every 2 weeks. Primary end point was safety; investigator-assessed objective response rate per RECIST v1.

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Cibisatamab is a bispecific antibody-based construct targeting carcinoembryonic antigen (CEA) on tumour cells and CD3 epsilon chain as a T-cell engager. Here we evaluated cibisatamab for advanced CEA-positive solid tumours in two open-label Phase 1 dose-escalation and -expansion studies: as a single agent with or without obinutuzumab in S1 (NCT02324257) and with atezolizumab in S2 (NCT02650713). Primary endpoints were safety, dose finding, and pharmacokinetics in S1; safety and dose finding in S2.

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Article Synopsis
  • - 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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  • - The KEYNOTE-651 study assessed the combination of pembrolizumab and binimetinib, with or without chemotherapy, in patients with metastatic colorectal cancer that was microsatellite stable/mismatch repair-proficient.
  • - Cohorts showed varying levels of dose-limiting toxicities (DLTs), with the most significant occurring in cohort C at 33%, leading to a halt in dose escalation for that group and a dose reduction in cohort E.
  • - Overall, the study found binimetinib combined with pembrolizumab was tolerable in cohort A, but the objective response rates were low across all cohorts, with no significant additional benefit from adding binimetinib to pembrolizumab.
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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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  • Single-cell technologies allow detailed studies of how specific molecules define cell traits, but challenges like sparse data and cell differences make it tough to model biological variability.
  • SCORPION is introduced as a new tool that reconstructs gene regulatory networks from single-cell RNA-sequencing data, providing reliable comparisons across different populations.
  • In tests, SCORPION outperformed existing techniques and effectively identified differences in regulatory networks related to cancer, helping to reveal important factors that could affect patient survival.
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(1) Background: Histone deacetylases (HDACs) play a critical role in epigenetic signaling in cancer; however, available HDAC inhibitors have limited therapeutic windows and suboptimal pharmacokinetics (PK). This first-in-human phase I dose escalation study evaluated the safety, PK, pharmacodynamics (PDx), and efficacy of the oral Class I-targeting HDAC inhibitor bocodepsin (OKI-179). (2) Patients and Methods: Patients ( = 34) with advanced solid tumors were treated with OKI-179 orally once daily in three schedules: 4 days on 3 days off (4:3), 5 days on 2 days off (5:2), or continuous in 21-day cycles until disease progression or unacceptable toxicity.

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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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Background: There is a paucity of data on biomarker testing rates in rural populations with metastatic colorectal cancer (mCRC). To assess biomarker testing practices, oncologists in rural areas and urban clusters in the US were surveyed.

Materials And Methods: A web-based survey was administered to oncologists spending ≥40% of their time practicing in rural areas or urban clusters and who had treated ≥2 patients with stage IV mCRC in the prior month.

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Unlabelled: The incidence of esophageal cancer is increasing worldwide, with established risk factors explaining only a small fraction of cases. Currently, there are no established screening protocols in most countries, and treatment options are limited. The human microbiome has been implicated in carcinogenesis and the cancer treatment response.

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  • A study examined the outcomes of patients with isolated lung metastases after surgery for pancreatic ductal adenocarcinoma, hypothesizing that pulmonary metastasectomy could enhance survival with minimal risks.
  • Analyzing data from 39 patients, the researchers found that those who had pulmonary metastasectomy lived significantly longer after their recurrence (30.8 months) compared to those who didn't (18.6 months).
  • While overall survival rates were similar between groups, patients undergoing the procedure had higher survival rates at 3 years post-diagnosis (100% vs 64%) and 2 years post-recurrence (79% vs 32%), with only minor complications and no related deaths.
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Cancers in young adults (commonly described as early-onset [EO] cancer) represent a group of malignancies that have unique and challenging biology and genetic, treatment, social, and psychological implications. Even more concerning is a rising trend of EO cancers in multiple tumor types. Research and investigation in EO cancers will help elucidate mechanisms of carcinogenesis, differences in biology and response to treatment, and the need for multidisciplinary care to ensure comprehensive treatment and support for young patients.

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Christopher Lieu, co-director of gastrointestinal medical oncology and the associate director for clinical research at the University of Colorado Cancer Center (CO, USA) discusses the importance of biomarker testing in metastatic colorectal cancer to inform personalized patient care.

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Article Synopsis
  • The study investigates the effects of adjuvant chemotherapy on survival rates in rectal cancer patients who have achieved a pathologic complete response after neoadjuvant chemoradiotherapy and total mesorectal excision.
  • It included data from over 20,000 patients, focusing on those who received or did not receive adjuvant therapy, with findings indicating a significant survival advantage for those who underwent the additional treatment.
  • Results showed that patients who received adjuvant chemotherapy had a 5, 10, and 14-year survival rate of 93%, 85%, and 83%, respectively, compared to 87%, 67%, and 51% for those who did not receive it, suggesting a critical benefit
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Background/aims: Barrett's esophagus (BE), defined by the presence of intestinal metaplasia (IM) on histology, is thought to be the only identifiable precursor lesion for esophageal adenocarcinoma (EAC). Recent studies have suggested the possibility of an alternate, non-IM associated EAC that is a more aggressive form of EAC with worse survival. Among EAC patients, we aimed to compare survival of patients with and without IM at the time of diagnosis.

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Introduction: Patients newly diagnosed with cancer often seek information prior to being seen by a specialist. Little is known about the type of information desired and the sources used. We asked how patients find information about their new cancer diagnoses to improve information provision.

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