tbuckley/cabot-search huggingface dataset:
Assessing impact of postoperative outcomes and quality of life on decisional regret after resection of pancreatic ductal adenocarcinoma.
Authors: Judy Li, Thomas M Li, Adam Geffner, Sophie Neugarten, Camilo Correa, Umut Sarpel, Daniel M Labow, Ganesh Gunasekaran, Myron E. Schwartz, Parissa Tabrizian, Spiros P Hiotis, James O Park, Noah A Cohen
Journal: Journal of Clinical Oncology (2025)

699 Background: Surgery is potentially curative for patients with localized pancreatic ductal adenocarcinoma (PDAC). Given the high rate of complications, decline in quality of life (QoL) postoperatively, and high rates of recurrence, clear preoperative communication and expectation setting is critical. This study investigates clinical outcomes that affect postoperative decisional regret (DR) in patients with PDAC. Methods: This mixed-methods study investigates the impact of clinical outcomes and QoL on the degree of DR in patients with PDAC who have undergone curative-intent resection at least 6 months prior to study recruitment. Patients completed validated surveys assessing DR and QoL by the European Organization for Research and Treatment of Cancer (EORTC). Groups are stratified by presence or absence of DR, assessed by the Decisional Regret Scale (DRS). Characteristics and survey scores were compared by chi-square, independent t-test, and median test. Narrative responses were thematically analyzed. Given significant findings, results of this interim analysis are reported below. Results: 45 patients met inclusion criteria and completed all questionnaires. 19 (42.2%) patients expressed regret about their decision to pursue curative-intent surgery, with 5 patients expressing moderate to severe regret (DRS ≥ 25). There was no significant difference in median postoperative timing of survey completion between groups (56 months in DR group vs 34 months, P=0.465). Baseline characteristics, medical treatments, and operative approaches were similar. Both groups had similar recurrence rates at time of survey completion. While 30 and 90 day readmission rates were similar, a greater proportion of the DR group had 30 day complications (42.1% vs 15.4%, P=0.045). Those expressing regret reported poorer physical functional status (mean score 79.30 ± 18.84 vs 92.31 ± 10.27, P=0.011) and greater impact on social activities (mean score 67.54 ± 33.55 vs 84.67 ± 19.19, P=0.038). Thematic analysis of narrative responses revealed that a majority of patients expressed a strong desire to have a greater focus on potential QoL changes during preoperative discussions. Conclusions: Patients expressing postoperative DR experienced more 30 day complications, and still report lasting effects on their current physical status and social activities. This emphasizes the importance of thorough preoperative counseling on surgical risks and potential changes in postoperative QoL so that patients may make the best informed decision.
Management trends and outcomes of appendiceal cancers: A National Cancer Database study.
Authors: Ali Esparham, Jennifer Whittington, George Agriantonis, Zahra Shafaee
Journal: Journal of Clinical Oncology (2025)

810 Background: Appendiceal tumors encompass a variety of histological types that exhibit different behaviors. The current study aimed to investigate and compare overall survival, predictive factors for overall survival, and management of histological variations of appendiceal tumors. Methods: The National Cancer Data Bank (NCDB) database (2004–2020) was evaluated to include patients with appendiceal tumors histologies including goblet cell adenocarcinoma (GCA), neuroendocrine neoplasm (NEN), non-mucinous adenocarcinoma (NMA), and mucinous adenocarcinoma (MA). Univariate and multivariable analyses were conducted. Results: The GCA, MA, NEN, and NMA groups consist of 6,111, 16,471, 19,199, and 11,065 patients, respectively. The NMA and NEN groups had significantly lowest and higher overall survival compared to other types (p&lt;0.001 for both) (GCC: 143.27 (140.23-146.30), MA: 111.91 (109.996-113.832), NEN: 170.88 (168.56-173.20), and NMA: 101.399 (99.132-103.666) months). The independent predicting factors of worse overall survival were age (HR: 1.03 (1.03-1.04)), black race (HR: 1.24 (1.08-1.43), ref: white race), fourth median income (HR: 0.84 (0.74-0.96), ref: first median), Charleson index comorbidity score (HR: 1.3 (1.22-1.38)), lymphovascular invasion (HR: 1.28 (1.15-1.42)), pathologic stage 2 (HR: 1.32 (1.12-1.57)), stage 3 (HR: 1.99 (1.66-2.40)), stage 4 (HR: 4.20 (3.47-5.07)), ref: stage 1, intraoperative systemic therapy (HR: 0.52 (0.39-0.70)), positive surgical margin (1.55 (1.39-1.73)), number of positive lymph nodes (HR:1.06 (1.05-1.07)), moderately differentiated tumors (HR:1.43 (1.25-1.63)), poorly differentiated (HR: 1.94 (1.69-2.24)), undifferentiated (HR: 1.48 (1.14-1.91)), ref: well differentiated, and NMA type (HR:1.30 (1.10-1.55)). Furthermore, in terms of type of surgery, significantly higher patients of GCA (54.6%) and NMA (55.2%) groups underwent subtotal colectomy compared to other groups. Regarding systemic therapy, significantly higher patients of MA group received intraoperative, and both neoadjuvant and adjuvant therapy compared to other groups. Also, NEN group had significantly higher patients who underwent surgery with laparoscopic approach compared to others. Conclusions: This study reveals that different types of appendiceal tumors have distinct characteristics in regard to overall survival outcomes and treatment approaches. NENs showed the highest survival rates, while NMAs had the lowest. These results underscore the need for personalized treatment strategies for each tumor type to improve patient outcomes.
Safety and efficacy of anti-HER2 agents in the treatment of biliary tract cancers: A systematic review.
Authors: Nikolas Naleid, Omkar Pawar, Sakti Chakrabarti, Zhaohui Jin, Ankit Mangla, Amit Mahipal
Journal: Journal of Clinical Oncology (2025)

639 Background: Limited treatment options exist for patients with locally advanced or metastatic biliary tract cancers (BTCs). Recently, several clinical trials provided preliminary evidence for human epidermal growth factor receptor-2 (HER2) as a new target for patients with HER2 expressing BTC. We conducted a systematic review and pooled analysis of the safety and efficacy of anti-HER2 agents in patients with advanced BTC. Methods: A comprehensive search of PubMed/MEDLINE and EMBASE was performed to identify phase 1, 2, or 3 clinical trials published between January 2019 and March 2024 that evaluated anti-HER2 therapy in locally advanced or metastatic BTC. Primary endpoints included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Secondary endpoints included the incidence of treatment-related adverse events (TRAEs), rate of treatment discontinuation, and death. Forest plots were generated to summarize the results and demonstrate the effect size estimates for each study, along with their confidence intervals and the pooled estimate from the random-effects model. The random-effects models were configured to use the Restricted Maximum Likelihood method for estimating between-study variance for all analyses. Results: After excluding duplicate and irrelevant articles, data extraction and analysis were performed on eight selected clinical trials. The analysis included 368 patients with a median age of 64 (range 49-68), with 55% being female. Patients were treated with several anti-HER2 agents, including zanidatamab, pertuzumab plus trastuzumab, tucatinib plus trastuzumab, trastuzumab deruxtecan, trastuzumab plus chemotherapy, trastuzumab-pkrb plus chemotherapy and neratinib. The pooled ORR and DCR were 34% (95% CI 24-44) and 64% (95% CI 51-77) respectively. The pooled weighted PFS and median OS survival were 4.8 and 9.4 months, respectively. The pooled duration of response was 5.0 months. In our subset analysis, which included only patients who had received ≥1 prior therapy, the pooled ORR was 30% (95% CI 22-39), the pooled DCR was 62% (95% CI 48-75), and the pooled median PFS was 4.4 months. In the study cohort, 82.6% of patients experienced any adverse event, and 32.1% experienced a grade 3-4 adverse event. Only 5.7% of the patients discontinued treatment secondary to TRAEs. Conclusions: In patients with HER2 expressing BTCs, anti-HER2 therapies demonstrated preliminary signals of efficacy with manageable toxicities, particularly in the second-line setting.
Phase Ib/II study of fruquintinib plus 5-fluorouracil/leucovorin after progression on fruquintinib monotherapy in metastatic colorectal cancer.
Authors: Wenwei Yang, Xiu Liu, Qi Wang, Lizhen Gao, Kai Ou, Xiaoting Ma, Lin Yang
Journal: Journal of Clinical Oncology (2025)

128 Background: Fruquintinib is a standard third-line treatment in metastatic colorectal cancer (mCRC). However, no standard therapeutic regimen is available for mCRC patients who progressed on third-line therapy. Preclinical experiments supported a rationale for combining antiangiogenic therapy and 5-fluorouracil (5FU) in refractory mCRC with evidence for synergy. This open-label phase Ib/II study was designed to determine the safety and efficacy of fruquintinib plus 5-fluorouracil/leucovorin for mCRC patients who progressed on fruquintinib monotherapy. Methods: The enrolled patients would receive fruquintinib at a fixed dose of 4mg once daily (three weeks on, one week off) and 5FU at two dose levels (1800mg/m 2 and 2400mg/m 2 ) CIV 46 hours on day one and day 15, with leucovorin 400mg/m 2 iv 2 hours before 5FU. Treatments were repeated every 28 days. The primary endpoint was determining the recommended phase II dose (R2PD) of 5FU in phase Ib and the six-month OS rate in phase II. Secondary endpoints for phase II included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and safety. Planned enrollment was 39 patients. Results: No dose-limiting toxicities occurred in the phase Ib dose-escalation study, and the R2PD of 5FU was 2400mg/m 2 . Between April 2020 and June 2024, 24 patients were enrolled in the phase II stage. The median age was 57.5 years old (from 35 to 68), and 58.33% were female. Left-sided colorectal cancer patients accounted for 75%. Sixteen (66.7%) patients harbored KRAS mutation, and one (4%) had BRAF V600E mutation. Regarding the number of lines of systemic therapy, 83.3% received this study regimen as fourth-line therapy and 16.7% as fifth-line or later therapy. As of June 30, 2024, efficacy was assessed in all 24 patients with a DCR of 62.5% (15 stable disease, nine progression disease). The median follow-up time was 16.5 months (95% CI:12.553-20.447). The primary endpoint six-month OS rate was 91.3%, the median PFS was 4.4 months (95% CI: 1.243-7.557), and the median OS was 17.3 months (95% CI: 12.892-21.708). The most common TRAEs were nausea (25%), hand-foot syndrome (16.7%), abnormal liver function (8.3%), and proteinuria (8.3%). One patient experienced grade 3 mucositis. No treatment-related death occurred. Conclusions: Fruquintinib plus 5-fluorouracil/leucovorin regimen preliminarily demonstrated promising efficacy with a tolerable safety profile for mCRC patients despite progression on prior fruquintinib monotherapy. Further investigation into this possible later-line regimen in mCRC is warranted. Clinical trial information: ChiCTR2000032640 .
Utilization of <i>SDC2</i> gene in conjunction with <i>SEPTIN9</i> gene methylation analysis for the diagnosis and efficacy assessment of colorectal cancer.
Authors: Rongjia Xie, Zhuqing Liu, Xiaolan Yin, Min Yuan, Xinpei Luo, Qing Xu
Journal: Journal of Clinical Oncology (2025)

240 Background: SDC2 gene encodes the transmembrane proteoglycan molecule Syndecan-2. Syndecan-2 protein affects the proliferation, migration and invasion of colorectal cancer cells by participating in the regulation of cell adhesion, tissue differentiation and angiogenesis. Plasma methylated SEPTIN9 gene has been shown to be a sensitive and specific biomarker for the detection of CRC, which is involved in apoptosis, pseudopod projection, tumor cell migration and invasion. The aim of this study is to validate the value of SDC2 and S9 gene methylation detection in the diagnosis and efficacy evaluation of CRC. Methods: A total of 102 patients were enrolled in the study. The methylation levels of fecal SDC2 gene and blood SEPTIN9 gene were detected by fluorescence PCR. The clinical diagnostic accuracy of SDC2 kit was evaluated by patients with benign gastrointestinal lesions, gastrointestinal tumors and healthy subjects. Combined detection of SDC2 and S9 to improve the detection rate of CRC. SDC2m levels were analyzed in 26 patients with partial remission or stable disease after palliative treatment and 32 patients with complete remission after radical surgery. Results: The detection rate of SDC2 in patients was 0.0% for UC and CD, 66.7% for AA and 60.0% for NA, 25.0% for HOP. For 8 healthy subjects with negative colonoscopies, the true negative rate was 100%. The detection rates of GC and EC were 50.0% and 0.0%, respectively. Data from 72 patients with CRC were evaluated, with a sensitivity of 89.1% (41/46,95%CI 0.798-0.985) for patients with untreated CRC. The sensitivity of SDC2 was 46.2% (12/26,95%CI 0.256-0.667) in patients with partial response or stable disease after palliative treatment. The difference was statistically significant (P &lt; 0.001). The sensitivity of S9 for CRC detection was 88.2% (15/17, 95%CI 0.712-1.053). By two tests, 94.1%(16/17, 95%CI 0.816-1.066) of CRC cases could be detected.The sensitivity was 89.1% (41/46 95%CI 0.798-0.985) in untreated CRC and 46.2% (12/26 95%CI 0.256-0.667) in patients with PR and SD after chemotherapy/radiotherapy/targeted/immunotherapy. The difference rate of SDC2m between two groups was statistically significant (P &lt; 0.001). Among 46 untreated patients with CRC, 32 patients with positive SDC2m underwent radical surgery, of which 30 CR patients turned SDC2m test negative after surgery. We found reduced SDC2m in stool from patients with clinical benefit (CR+PR+SD). Conclusions: Detection of SDC2m in untreated CRC patients has high sensitivity and has the potential to become a non-invasive diagnostic tool for CRC. Combination of S9 and fecal SDC2 could improve the detection rate of SDC2 in non-dominant population. The methylation level of SDC2 may be helpful for postoperative follow-up of CRC after radical surgery, prediction of recurrence, and monitoring the efficacy of a series of palliative treatments for CRC.
A phase II study of fruquintinib plus sintilimab as a second-line therapy for advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC): Updated results.
Authors: Min Jin, Shengli Yang, Junli Liu, Jieying Zhang, Lei Zhao, Dandan Yu, Zhenyu Lin, Pindong Li, Jing Wang, Jun Xue, Hong Ma, Jianli Hu, Tao Zhang, Hongli Liu
Journal: Journal of Clinical Oncology (2025)

407 Background: Preliminary results of the open-label, single-arm phase II study (NCT05625737) had demonstrated the combination of fruquintinib and sintilimab as a second-line therapy had a promising anti-tumor activity and an acceptable safety profile in pts with advanced GC/GEJC (ASCO-GI 2024. Poster 332). Here, we update the results with a focus on subgroup analyses. Methods: Patients (pts) aged 18-75 years who were HER2-negative and had failed first-line standard treatment were enrolled. Eligible pts received 4mg of fruquintinib orally once daily on days 1-14 and 200 mg of sintilimab intravenously on day 1, with treatment repeated every 3 weeks. An optimal Simon two-stage design was employed. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: At data cut-off (August 25, 2024), 29 pts (7 in the first stage; 22 in the second stage) with median age 51 (range 33–73) years old had been enrolled. 41.4% were male, 37.9% had ECOG PS 1, 69% had lymph node metastasis and 72.4% had previously received immunotherapy. Among the 24 efficacy evaluable pts, the ORR was 33.3% (95% CI 15.6–55.3) and DCR was 66.7% (95% CI 44.7–84.4). After a median follow-up of 13.14 months, the median PFS was 5.13 (95% CI: 2.73–7.03) months and OS result was pending maturity. Pts who had lymph node metastasis exhibited higher ORR compared to pts without lymph node metastasis (ORR-47.1 vs 0%). In particular, pts without prior immunotherapies were more likely to achieve higher response rate (37.5 vs 33.3%) and had an obvious trend for longer PFS than pts with prior immunotherapies (9.00 vs 5.13 months). Majority of treatment-emergent adverse events (TEAEs) were grade 1-2 and the most frequently reported ones (≥20%) were white blood cell decreased (33%), hypertriglyceridemia (25%), lymphocyte count decreased (21%), abdominal pain (21%) and decreased appetite (21%). Grade 3/4 TEAEs occurred in only one patient, consisting of increased blood bilirubin levels, aspartate transaminase elevation, and alanine transaminase elevation. Conclusions: Fruquintinib combined sintilimab was well tolerated, with encouraging antitumor activity as second-line treatment for advanced GC/GEJC, especially in pts without prior immunotherapies. Further studies in larger cohorts to validate these findings are warranted. Clinical trial information: NCT05625737 .
Efficacy and safety of durvalumab plus tremelimumab for unresectable hepatocellular carcinoma in Thailand: A real-world multicenter observational study.
Authors: Krittiya Korphaisarn, Kosin Wirasorn, Suebpong Tanasanvimon, Kijjakom Thanasombunsukh, Kunlatida Maneenil, Jirawat Thanestada, Nattaya Teeyapun, Jarin Chindaprasirt, Chirawadee Sathitruangsak, Teerada Siripoon, Phannin Tiraswasdichai, Chanchai Charonpongsuntorn, Passakorn Wanchaijiraboon, Wannisa Laosuangkoon, Patrapim Sunpaweravong, Charuwan Akewanlop
Journal: Journal of Clinical Oncology (2025)

539 Background: Durvalumab plus tremelimumab (Durva/Treme) andatezolizumab plus bevacizumab are preferable first-line therapy for unresectable hepatocellular carcinoma (uHCC). This study aimed to evaluate the efficacy and safety of Durva/Treme in real world setting. Methods: Fifty patients with uHCC who enrolled in the expanded access program (EAP) for Durva/Treme as the first-line treatment from 12 centers in Thailand were included. Analysis was assessed for objective response rate (ORR), survival, and adverse events. We also compared data with the HIMALAYA study. Results: Median follow-up time was 9.8 months. There were 24 patients alive and 26 patients deceased. The median age was 62 years. Majority of the patients were male (80%). Hepatitis B, C and non-viral cause were identified in 44%, 30%, and 26%, respectively. Ninety-two percent of patients had Child-Pugh A, while 8% had Child-Pugh B(7). Macrovascular invasion was found in 24% of cases. The full data on efficacy and safety were summarized in table below. Conclusions: To date,this is the largest real-world data of Durva/Treme in the first-line treatment of uHCC. Our study demonstrated that Durva/Treme was effective but had lower ORR and higher liver toxicities than what reported in the HIMALAYA study. EAP (N=50) HIMALAYA (N=393) Response by RECIST1.1, n (%) CR PR SD PD Not evaluable 2(4)4(8)24(48)18(36)2(4) 12(3.1)67(17)157(39.9)157(39.9) - ORR (%) 12 20.1 DCR (%) 60 60.1 mPFS (range), mo 5.36(0.2-12.5) 3.78(3.7-5.3) mOS (range), mo NA 16.4 (14.2-19.6) Adverse events, n (%) A ny grade G rade &gt; 3 A ny grade G rade &gt; 3 Any AE Diarrhea Rash AST elevation ALT elevation Increase bilirubin Hypothyroidism Myocarditis Myositis 37(74) 3(6) 12(24) 23(46) 21(42) 8(16) 7(14) 1(2) 1(2) 12(24) 1(2) 0 6(12) 7(14) 4(8) 01(2) 1(2) 378(97.4)103(26.5) 87(22.4) 48(12.4) 36(9.3) 20(5.2) 47(12.1) -- 196(50.5)17(4.4) 6(1.5) 20(5.2) 10(2.6) 3(0.8) 02(0.5) 3(0.8)
Association of malnutrition at diagnosis with survival among older adults with pancreatic cancer.
Authors: Apoorva Doshi, Landon Martin, Grant Richard Williams, Smith Giri
Journal: Journal of Clinical Oncology (2025)

680 Background: Malnutrition is common among older adults newly diagnosed with pancreatic cancer. However, the implications of malnutrition among this vulnerable population are poorly understood. We sought to understand the association between malnourishment at diagnosis and overall survival (OS) among older adults with pancreatic cancer. Methods: We included adults aged ≥ 60 years with newly diagnosed pancreatic cancer, who were enrolled in the University of Alabama at Birmingham (UAB) Cancer and Aging Resilience Evaluation (CARE) registry between October 2017 and April 2024. To assess nutritional status, we administered an abridged version of the Patient-Generated Subjective Global Assessment (abPG-SGA) to patients at baseline prior to receiving chemotherapy. Using abPGSGA scores, we categorized patients as either normal (score ≤ 5) or malnourished (score ≥ 6). All participants were followed until death or until the cutoff date of July 10, 2024. We employed Kaplan-Meier survival analysis to estimate overall survival (OS) for both malnourished and non-malnourished groups and compared them using log-rank test. Additionally, we built multivariable Cox proportional hazards models to test the association between malnutrition and OS, while controlling for age at diagnosis, sex, race/ethnicity, and cancer stage. Results: A total of 274 patients were included; the median age at diagnosis was 70 (interquartile range, IQR: 65-75) years with 52% males, 75% non-Hispanic White and 52% with Stage IV disease at diagnosis. At baseline, 59% of patients were malnourished, and the median abPGSGA score was 8 (IQR 4-14). Patients who were malnourished had a similar demographic and clinical characteristics as compared to those without malnutrition. Over a median follow up of 36 months, a total of 202 patients (74 %) died. The median overall survival (OS) was significantly lower for malnourished patients at 13 months compared to 21 months for non-malnourished patients (log-rank test, p &lt; .001). After adjusting for potential age, sex, race/ethnicity and cancer stage, malnutrition at diagnosis remained independently associated with worse survival outcomes (adjusted HR: 1.762; 95% CI: 1.316–2.358; p &lt; .001). Conclusions: Our study reports that malnutrition at baseline is significantly associated with worse overall survival in older adults with pancreatic cancer. These findings underscore the importance of early nutritional assessment and intervention to enhance outcomes in this population.