tbuckley/cabot-search huggingface dataset:
Enhancing appendiceal cancer care: Towards evidence-based practice and continuous education for healthcare providers.
Authors: Sulin Wu, Jenna Nimer, Rushabh Gujarathi, Varun Vivek Bansal, Chih-Yi Liao, Manik A. Amin, Janet Chin, Mecker Moller, Ryan P Merkow, Oliver S. Eng, Blase N. Polite, Kiran Turaga, Ardaman Shergill
Journal: Journal of Clinical Oncology (2024)

e16377 Background: Appendiceal cancers (AC) are a set of rare and histologically diverse malignancies with distinct biological features and treatment implications. Despite surgical advances, there are gaps in the standardization of systemic therapies for AC. Hence, there is a pressing need to understand the current practice patterns amongst oncologists to facilitate unifying management strategies. Methods: A cross-sectional survey was distributed electronically among GI oncology specialists between April – October 2023 to map current practices in AC care. The survey contained 18 questions structured in three sections— participant demographics, treatment experiences, and management preferences for hypothetical cases. The analysis focused on response frequencies informing the need to develop targeted educational and research initiatives. Results: Most of the respondents (N = 104; response rate 22%), primarily from academic (86%) and urban settings (77%), manage up to 10 AC patients annually. Despite over five years of practice experience for 80% of respondents, high confidence in treating AC was modest (38%). The majority (83%) cited lack of guidelines and standardized treatments as a concern. The NCCN guidelines were commonly referred to, but only 13% were satisfied with AC education. For intermediate and high-grade AC, 63% and 53%, respectively, of respondents reported using perioperative chemotherapy with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. 40% opted for systemic therapy for low-grade neoplasms. 5FU/Capecitabine and oxaliplatin were the most common regimens of choice, whereas irinotecan, anti-VEGF, and anti-EGFR agents were used less frequently. Surveillance primarily involved serum CEA (91%) and CT scans (99%), with PET, MRI, and ctDNA used by 20-30% of the respondents. Free-text comments noted deficient evidence and educational needs to guide clinical practice. Conclusions: Our study is the first to describe physician attitudes and practice patterns in the management of AC. The survey highlights that even experienced providers feel underconfident when treating AC patients and supports the need for better evidence and data for systemic therapies. About 40% of the respondents noted offering chemotherapy to low grade neoplasms – a disease that is not thought to respond to systemic therapy, highlighting the need for education and clinical trials to guide evidence-based decision-making in this disease. In addition, multidisciplinary, multi-institutional efforts to unify treatment approaches and enhance patient outcomes are needed.
Durvalumab plus gemcitabine/cisplatin/nab-paclitaxel in resectable biliary tract cancer: A phase II, single-arm, open-label study (DurGAP).
Authors: Rentao Li, Yang Liu, Yayue Liu, Linlin Fu, Qi Qi, Xihao Zhang, Yunlong Cui, Wei Lu, Huikai Li
Journal: Journal of Clinical Oncology (2024)

e16260 Background: Biliary tract cancer (BTC) presents a formidable challenge, marked by its aggressive nature and dismal prognosis. While surgical resection remains the lone potentially curative option, 5-year survival rates have plateaued below 50%, largely due to high rates of recurrences and metastases. Given these sobering statistics, the imperative for neoadjuvant therapy to enhance outcomes is evident. Building upon the success of the TOPAZ-1 trial, which established durvalumab in combination with gemcitabine and cisplatin as a standard regimen for advanced BTC, this study seeks to assess the safety and efficacy of incorporating neoadjuvant durvalumab alongside gemcitabine, cisplatin, and Nab-paclitaxel for resectable BTC. Methods: Resectable, treatment-naïve BTC patients (pts) were enrolled and administered 3 cycles of neoadjuvant durvalumab (1000mg, iv, d1, q3w) + GAP (gemcitabine 1000mg/m 2 , cisplatin 25mg/m 2 , Nab-paclitaxel 100mg/m 2 , d1, d8, 21d cycle). Primary endpoints included assessing Adverse Events (AEs) and Objective Response Rate (ORR). Secondary endpoints comprised R0 resection rate, Recurrence-Free Survival (RFS), Overall Survival (OS). Results: Between Feb, 2023 to Jan, 2024, a total of 24 patients were enrolled, 12 (50.0%) were male, all with ECOG 0 and 18 (75.0%) presenting with N1 status. Median age: 65 years. Primary sites: intrahepatic (50.0%), extrahepatic (33.3%), gallbladder (16.7%). Median follow-up: 8.75 months; all pts received ≥2 neoadjuvant cycles. The ORR was 62.5%, with all 15 pts demonstrating partial responses (PR). The DCR was 87.5% with 15 PR and 6 stable disease (SD) responses. The most common treatment-related adverse events (TRAEs) were increased ALT/AST (28.6%), anemia (21.8%), hypoalbuminemia (16.0%). Grade ≥3 TRAEs occurred in 2 (8.3%) pts. 13 pts underwent resection, achieving R0 resection in 12 (92.3%) of cases, comprising 10 PR, 2 SD, and 1 pt deemed eligible for surgery post-assessment despite a PD response. 11 pts did not undergo resection, with reasons including patient refusal (4 PR, 1 SD), not meeting resection criteria (2 PD), lost to follow-up (1 PR, 1 SD), and still under active follow-up (2 SD). Conclusions: Neoadjuvant durvalumab combined with gemcitabine/cisplatin/Nab-paclitaxel demonstrated a promising ORR and DCR, with a tolerable safety profile, warranting further investigations in a larger cohort. Clinical trial information: NCT05640791 .
Postoperative adjuvant hepatic arterial infusion chemotherapy combined with donafenib in hepatocellular carcinoma with solitary large tumor and microvascular invasion: A multicenter, prospective, single-arm, phase II trial.
Authors: Yin Long, Ziqi Huang, Xiaodong He, Jue Huang, Jianguo Liao, Yongyi Zeng, Yunqiang Tang, Lei Zhang
Journal: Journal of Clinical Oncology (2024)

e16227 Background: Hepatocellular carcinoma (HCC) with solitary large tumor (≥ 5 cm) and microvascular invasion (MVI) was associated with high 5-year recurrence rate and poor survival prognosis. Postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) was found to improve the recurrence-free survival (RFS) with acceptable safety profiles in HCC patients with MVI. However, the prognosis of HCC who received adjuvant HAIC after hepatectomy still remain far from satisfactory. Several studies have shown that the combination of HAIC and tyrosine kinase inhibitors (TKIs) could exhibit a synergistic anticancer effect and improve the survival outcomes of advanced HCC. Thus, the present study was conducted to explore the efficacy and safety of adjuvant HAIC plus the novel multikinase inhibitor donafenib in HCC with solitary tumor ≥ 5 cm and MVI. Methods: This prospective, single-arm phase II study was conducted in three medical centers in China. HCC patients with both solitary tumor ≥ 5 cm and MVI, no evidence of recurrence at radiological follow-up at 4-8 weeks after hepatectomy, no previous treatment for HCC other than hepatectomy, Child-Pugh score A or B7 were enrolled. Eligible patients received one cycle of HAIC with oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX4), and followed by donafenib (200 mg orally twice daily) for up to 1 year until disease recurrence or unacceptable toxicity. The primary endpoint was 1-year recurrence-free survival rate (1-year RFS rate). Secondary endpoints included RFS, overall survival (OS) and safety. Results: A total of 18 patients were included for analysis. The median age was 59 years (range, 28–75), the median maximum tumor size was 7.0 cm (interquartile range [IQR], 6.2–7.8), 88.9% had low-risk MVI, 61.1% had Edmondson-Steiner grade III-IV and 44.4% had incomplete tumour capsule. As of November 27, 2023, 4 of 18 patients (22.2%) recurrenced and no deaths occurred with a median follow-up of 15.0 months (95% confidence interval [CI], 5.1–19.1). The 1-year RFS rate was 64.9% (95%CI, 39.2%–100%), and current immature median RFS was 14.3 months (95%CI, not available [NA], 11.2–NA). The most common treatment-related adverse events (TRAEs) were hand-foot skin reaction (72.2%), diarrhea (38.9%), decreased platelet count (22.2%), hypoalbuminemia (22.2%), and alopecia (22.2%). Grade 3 TRAEs occurred in 6 patients (33.3%), and no grade 4 or 5 TRAEs occurred. Conclusions: In this prospective study, the preliminary data indicated that HAIC combined with donafenib is an encouraging adjuvant therapy with well-tolerated safety profiles for HCC patients with solitary tumor ≥ 5 cm and MVI. Clinical trial information: NCT04962958 .
A randomized, multicenter, open-label, phase 2 study of TRK-950 in combination with ramucirumab and paclitaxel as second-line therapy in patients with Caprin-1 positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.
Authors: Ronan Joseph Kelly, Dani Ran Castillo, Kensei Yamaguchi, Ken Kato, Toshihiro Kudo, Zev A. Wainberg, Sun Young Rha, Jeeyun Lee, Min-Hee Ryu, Fumiyoshi Okano, Kohei Shitara
Journal: Journal of Clinical Oncology (2024)

TPS4181 Background: Caprin-1 is strongly expressed on the cell membrane of many cancer types including G/GEJ and on cancer stem cells. High expression is associated with enhanced in vitro colony-forming activity and in vivo tumorigenicity. TRK-950 is a first in class humanized antibody targeting CAPRIN-1 1) . In the phase I study (NCT02990481), TRK-950 was well tolerated as monotherapy with no DLTs and MTD not reached at doses of 3-30mg/kg IV weekly. Subsequently the Phase 1b study demonstrated that TRK-950 was well tolerated with a high potential for synergistic anti-tumor activity when used in combination with standard of care treatment(s) in selected advanced solid tumors (NCT03872947). Specifically, Regimen D which evaluated TRK-950 in combination with Ramucirumab and Paclitaxel in G/GEJ showed a DCR of 100% in all nine patients receiving 10 mg/kg and partial responses were seen in 5/9 (55%) patients. Caprin-1 strong expression was observed in 4/9 patients and an ORR of 100% was seen in those patients 2) . A Phase II clinical trial in gastric/GEJ cancer patients with strong Caprin-1 expressions is now enrolling patients. Methods: The phase II study is a multi-national, open-label, randomized, multicenter study evaluating the efficacy of TRK-950 in combination with ramucirumab (Ram) + paclitaxel (PTX ) as compared with Ram + PTX treatment alone in patients with previously treated metastatic G/GEJ adenocarcinoma (NCT06038578). Patients enrolled across 10 sites in Japan, South Korea and the United States are randomized 1:1:1 by the permuted block method to (arm A) TRK-950 5mg/kg plus Ram + PTX, (arm B) TRK-950 10mg/kg plus Ram + PTX or (arm C) Ram + PTX alone. Inclusion criteria include patients with Caprin-1 positive (cutoff; 30% at ≥ 2+ staining) advanced/metastatic G/GEJ adenocarcinoma who have received first line therapy. Key exclusion criteria include HER2 positive disease. The primary endpoint is progression free survival (PFS) based on Independent Central Review (ICR) assessment per RECIST v1.1. Key secondary and exploratory endpoints include overall survival (OS), ORR, DoR, and biomarker evaluation. An interim analysis will be performed after 105 patients are randomized in stage 1 to determine the optimal dose of TRK-950 (5mg/kg or 10mg/kg) that will be evaluated in arm stage 2. In total 146 patients will be enrolled (40 patients in one arm and each 53 patients in two arms). This study opened in September 2023. 1. Okano F, et al. Cancer Res Commun. 2023 Apr 18;3(4):640-658. 2. Cassier P, et al. J Clin Oncol. 2023 Vol. 41, No. 4, suppl. Clinical trial information: NCT06038578 .
PD-1 blockade plus chemotherapy followed by concurrent SBRT with SIB as preoperative therapy for patients with potentially resectable pancreatic cancer: A single-arm phase 2 study.
Authors: Juan Du, Jiayao Ni, Yi Sun, Hui-zi Sha, Fan Tong, Liang Mao, Weiwei Kong, Shanshan Shen, Qing Gu, Lei Wang, Yudong Qiu, Baorui Liu
Journal: Journal of Clinical Oncology (2024)

e16312 Background: Pancreatic cancer has 10% low rate of early diagnosis and resection due to its insidious onset and poor prognosis. We aimed to assess the safety and efficacy of a new mode of preoperative therapy for patients with Potentially Resectable Pancreatic Cancer. Methods: This is a single arm clinical trial (NCT05634564). Gemcitabine (1000 mg/m2) and nabpaclitaxel (125 mg/m2; AG) were administered to patients with LAPC or BRPC on days 1 and 8, along with tislelizumab (200 mg) on day 1 intravenously (IV) every three weeks. Concurrently, the patients underwent stereotactic body radiotherapy (SBRT) with simultaneous integrated boost (SIB)during the third cycle of treatment. Surgical intervention was reassessed after four cycles of treatment. Objective response rate (ORR) was the primary endpoint and Disease control rate (DCR), R0 resection rate, median overall survival (mOS), median progression free survival (mPFS) rate, time to progression (TTP) and safety were analyzed as secondary endpoints. Results: Between May 2020 and April 2023, 62 patients with LAPC or BRPC were enrolled. Until the last follow-up time (January 30, 2024) ,56 of them included in the intention-to-treat (ITT) analysis who completed at least three cycles of tislelizumab plus AG and underwent concurrent radiotherapy. The median age in intention-to-treat analysis was 65 years. 25 patients had a best response of partial response, the ORR was 44.6%, DCR was 100%. Thirty-one patients met the criteria for surgical resection after treatment, 9 of whom refused surgery and continued conservative treatment. 22 patients underwent resection, and the R0 resection rate was 95.45%. Two of the 22 resected patients achieved pathologic complete response (pCR) and five patients achieved major pathological response (MPR). The pathologic complete response rate was 9.10% and significant pathological response rate was 31.82%. The TTP was 19.38 months (95% CI: 12.8%-27.9%), and the mOS was 21.32 months (95% CI:15.9%-NR). The 12-months PFS rate and 12-months OS rate were 59.9% (95% CI:45.2%-71.8%) and 74.4% (95% CI:59.9%-84.3%), respectively. Grade 5 adverse events were not observed. The most common grade 3-4 hematological and non-hematological toxicities were leukopenia (17.9%), neutropenia (16.1%), anemia (8.9%), thrombocytopenia (7.1%), rash: dermatitis (7.1%), Peripheral neuropathy (3.6%). Conclusions: Anti-PD-1 inhibitor tislelizumab plus AG chemotherapy followed by concurrent SBRT with SIB significantly prolonged mPFS rate, as well as R0 resection rate of surgical patients, and also improved the major pathological response rate. Clinical trial information: NCT05634564 .
Impact of adjuvant chemotherapy on outcomes after curative-intent surgery for biliary tract cancer: A 10-year retrospective single-center study.
Authors: Rachel Levy, Simon Zhen, Chenxin Zhang, Jee-Young Moon, Fernand Bteich, Chaoyuan Kuang
Journal: Journal of Clinical Oncology (2024)

e16273 Background: Surgical resection remains the mainstay of treatment for biliary tract cancers (BTCs). Although adjuvant capecitabine has been shown to reduce recurrence, the best adjuvant chemotherapy remains unclear and numerous practice differences exist. Methods: This study is a retrospective review of patients with BTCs who received curative-intent resection at one institution (Montefiore Medical Center) between 01/2014 and 04/2023. The primary outcome was relapse risk. Kaplan-Meier curves and Cox regression were used to analyze relapse-free and overall survival rates. Results: 146 patients met entry criteria. Median age was 72.2 years (IQR 62.4-77.9 months) and median follow-up time was 20 months (IQR 1-111 months). 35.6% of patients had gallbladder cancer and 64.4% cholangiocarcinoma. 57 patients (39%) relapsed and 30 patients (20.5%) died. 105 patients (71.9%) received adjuvant chemotherapy (41% single agent, 42.9% a double-agent regimen, and 16.2% triple-agent therapy). Examining individual factors (univariate analysis) revealed several linked to higher relapse risk. Patients with advanced cancer stages (III-IV vs I-II) had 2.1 times higher risk. Higher T stages also showed increased risk: 5.6 times greater for T2 and 6.7 times greater for T3 compared to T1. Additionally, positive lymph nodes (N+), elevated post-surgical CA19-9, and presence of lymphovascular or perineural invasion were all significantly associated with 1.88-2.78 times higher relapse risk. Surprisingly, receipt of adjuvant chemotherapy was associated with a higher relapse risk (HR 2.42, 95% CI 1.18, 4.95, p-value 0.015). The association between receipt of adjuvant chemotherapy and relapse remained significant (HR 2.41, 95% CI 1.09-5.35, p = 0.03), after adjusting for age, sex, residual CA19-9, and receipt of adjuvant radiation therapy. Higher overall stage (III-IV vs I-II) was identified as a significant predictor of poorer overall survival (OS) with a hazard ratio of 21.70 (2.94-27.70, p = 0.009). Node-positive disease (HR = 2.25, 1.05-4.80, p = 0.036) and relapse (HR = 3.61, 1.58-8.28, p = 0.002) were also independently associated with worse OS. Conclusions: Adjuvant chemotherapy is commonly given after curative-intent surgery for BTCs at our center. Numerous factors are associated with an increased risk of relapse. Receipt of adjuvant chemotherapy was associated with a higher relapse risk even after adjustment for multiple covariates; the reason for this association remains unclear. More studies are needed to better understand the role and best form of adjuvant chemotherapy in the treatment of BTCs.
Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from the JAVELIN Bladder 100 trial in patients (pts) with histological subtypes.
Authors: Yohann Loriot, Shilpa Gupta, Thomas Powles, Petros Grivas, Daniel P. Petrylak, Karin Tyroller, Natalia Jacob, Jason Hoffman, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2024)

4567 Background: Results from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) led international treatment guidelines to recommend avelumab 1L maintenance as a standard-of-care treatment for pts with aUC without progression after 1L platinum-based chemotherapy (PBC). Around 20% of UCs are mixed with other histological subtypes/variants; these tumors do not have specific treatment guidelines and represent an unmet treatment need. In the large real-world AVENANCE study (NCT04822350; N=594) of avelumab 1L maintenance in pts with aUC in France, outcomes in pts with histological subtypes were consistent with those in the overall population. Here, we report a post hoc analysis of long-term outcomes from JAVELIN Bladder 100 in pts with predominantly UC mixed with &lt;50% histological subtype component. Methods: Eligible pts had unresectable locally advanced or metastatic UC without progression after 1L PBC and were randomized 1:1 to receive avelumab + best supportive care (BSC) or BSC alone. The primary endpoint was overall survival (OS) measured from randomization; secondary endpoints included progression-free survival (PFS) and safety. This post hoc analysis was conducted in all pts with histological subtypes. Results: In the avelumab + BSC and BSC alone arms, respectively, 44/350 and 57/350 pts had histological subtypes. At efficacy data cutoff (June 4, 2021), median follow-up in both arms was ≥38.0 mo. In pts with histological subtypes, OS and PFS measured from randomization were prolonged with avelumab + BSC vs BSC alone (Table). Long-term safety (cutoff, April 6, 2023) in treated pts with histological subtypes was generally consistent with the overall safety population. Treatment-related adverse events (TRAEs) of any grade occurred in 36 pts (83.7%) in the avelumab + BSC arm vs 1 pt (1.8%) in the BSC alone arm; grade ≥3 TRAEs occurred in 9 pts (20.9%) and 0 pts, respectively. Conclusions: This exploratory analysis shows the long-term efficacy and safety of avelumab 1L maintenance in pts with histological subtypes in JAVELIN Bladder 100. No new safety concerns were identified. These results were consistent with those in the overall population and support the use of avelumab 1L maintenance in pts with aUC without progression following 1L PBC, including pts with predominantly UC mixed with &lt;50% histological subtype component. Clinical trial information: NCT02603432 . [Table: see text]
Potential impact of malnutrition on patients with hepatocellular carcinoma undergoing liver transplantation: A nationwide analysis.
Authors: Adham Obeidat, Nour Mansour, Ratib Mahfouz, Mohammad Aldiabat
Journal: Journal of Clinical Oncology (2024)

e16233 Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer mortality worldwide. Liver transplantation is the ideal treatment for HCC, and the Milan criteria, which has been the international gold standard, provided the opportunity for HCC patients to undergo liver transplantation with favorable outcomes. On the other hand, malnutrition is a prevalent condition, and carries a substantial burden on health and social-care systems. In this study, we aim to look at the potential impact of malnutrition on in-hospital mortality and other outcomes in HCC patients undergoing liver transplantation. Methods: The United States Nationwide Inpatient Sample (NIS) was used to extract hospitalization data of patients admitted between 2016 to 2018. Using ICD10 revision codes, we identified adults with a diagnosis of HCC, with or without cirrhosis, who underwent liver transplantation with concomitant malnutrition. The control group included HCC patients without malnutrition. The primary outcome was the in-hospital mortality. Secondary outcomes included length of stay (LOS), acute kidney injury (AKI) and hyponatremia. Multivariate logistic regression was used to adjust for relevant variables. Results: An estimated 33,321 patients were admitted with HCC during the study period. 503 of them underwent liver transplantation, and of those, 75 patients had the diagnosis of malnutrition. In this group of patients, the mean age was 60.3 years. 30% were females and 60% were Caucasians. When adjusted to other relevant variables, malnutrition was associated with increased in-hospital mortality (OR 2.42; P-value 0.033). It was also associated with increased chance of developing an AKI (OR 1.95; P-value 0.014). Moreover, it was associated with increased LOS (OR 1.18) and increased chance of liver transplant rejection (OR 1.47), however, these were not statistically significant. Other factors associated with increased in-hospital mortality in HCC patients undergoing liver transplantation are described in the table. Conclusions: Malnutrition is a potentially treatable condition, however, when untreated it may contribute to poor health and economic outcomes. In this study, HCC patients with malnutrition who underwent liver transplantation, have an increased chance of in-hospital mortality. Furthermore, they had an increased odds of developing an AKI which in turn can prolong the hospital length of stay and total charges. We recommend that clinicians pay more attention to identify patients with or at increased risk for malnutrition in order to treat and optimize them prior to liver transplantation, and therefore to prevent such complications. [Table: see text]