tbuckley/cabot-search huggingface dataset:
A single-arm, multi-center phase II study of tislelizumab combined with lenvatinib and GEMOX as conversion therapy in potentially resectable locally advanced biliary tract cancer (ZSAB-TransGOLP): A primary analysis.
Authors: Jia Fan, Jian Zhou, Guoming Shi, Xiaoyong Huang, Qiang Gao, Xiaowu Li, Yuan Ji, Fei Liang, Yi Chen, Pinxiang Lu, Shuangjian Qiu, Ning Ren, Yinghao Shen, Yongfeng Xu, Zhenbin Ding, Xiaodong Zhu, Huichuan Sun, Yinghong Shi, Xiaoying Wang, Yong Yi
Journal: Journal of Clinical Oncology (2024)

488 Background: We have previously reported that GEMOX combined with lenvatinib and PD-1 antibody (GOLP regimen) showed promising efficacy as first-line treatment for advanced intrahepatic cholangiocarcinoma (iCCA), indicating that GOLP regimen may be an ideal conversion therapy for patients (pts) with potentially resectable advanced biliary tract cancer (BTC). This phase II trial explored the efficacy and safety of GOLP as conversion therapy in potentially resectable and locally advanced BTC. Methods: Patients with potentially resectable locally advanced BTC were enrolled and received tislelizumab (200mg, Q3W) and lenvatinib (8mg, QD) and GEMOX chemotherapy (Q3W) including gemcitabine 1000mg/m 2 on day 1, 8 and oxaliplatin 85mg/m 2 on day 1. Tumor responses were evaluated every 9 weeks according to RECIST v1.1, and the resectability was simultaneously discussed by MDT. For pts who were eligible for surgery, capecitabine alone was administered as adjuvant therapy after radical surgery. Pts who was not suitable for surgery continued to the original treatment regimen until progression or intolerable toxicity. The primary endpoint was R0 resection rate, and secondary endpoints included ORR, DCR, PFS, OS, CPR, MPR, RFS. Results: From December 2021 to July 2023, 41 pts were enrolled, 21 males and 20 females with a mean age of 57 years. 87.8% pts had iCCA, 7.3% had perihilar bile duct cancer and 4.9% had gallbladder cancer. TNM stage was II, IIIA, IIIB and IIIC for 2.4%, 34.1%, 58.5% and 4.9% of pts respectively. At cut-off date (September 10, 2023), the mean follow-up was 7.7 months, 39 pts completed at least three cycles of conversion therapy and 7 pts still administered with scheduled conversion therapy. The ORR was 43.9% (18/41) and the DCR was 87.8% (36/41). The median duration of therapy before surgery was 2.9 months (95%CI 2.6-4.6), R0 resection rate was 48.8% (20/41), and 2 pts underwent R1 resection. 9.1% (2/22) pts had a pCR and 22.7% (5/22) had an MPR. The most common grade 3/4 treatment-related adverse events (TRAEs) included neutropenia (31.7%), increased GGT (19.5%), leukopenia (12.2%). No grade 5 AEs occurred. Conclusions: This study demonstrates the high effectiveness and manageable safety of GOLP regimen as conversion therapy for potentially resectable locally advanced BTC. Survival data will continue to be followed up. Clinical trial information: NCT05156788 .
Prognostic factors for overall survival in patients with advanced digestive neuroendocrine carcinoma treated with first-line cisplatin-based chemotherapy: A post-hoc analysis of JCOG1213.
Authors: Hidekazu Hirano, Kenro Hirata, Yoshitaka Honma, Chigusa Morizane, Nozomu Machida, Ken Kato, Takuji Okusaka, Narikazu Boku, Shigeki Sekine, Nobuyoshi Hiraoka, Gakuto Ogawa, Yusuke Sano, Yuichi Shibuya, Masanobu Takahashi, Nao Fujimori, Motoo Nomura, Yuichiro Doki, Makoto Ueno, Takaki Yoshikawa, HIROYA TAKEUCHI
Journal: Journal of Clinical Oncology (2024)

594 Background: Advanced digestive neuroendocrine carcinoma (ADNEC) is a rare and aggressive malignancy without evidence of prognostic factors assessed in prospective studies. We aimed to evaluate prognostic factors in patients with ADNEC receiving first-line cisplatin-based chemotherapy. Methods: This is a post-hoc analysis of JCOG1213, which is a phase 3 randomized trial showing equivalent overall survival (OS) for cisplatin plus etoposide versus cisplatin plus irinotecan as first-line chemotherapy for patients with ADNEC. The primary endpoint of JCOG1213 was OS. For this post-hoc analysis of prognostic factors, patients who had ineligible histology based on the central pathological review or who lacked the necessary clinical data for analysis were excluded. A Cox proportional hazard model was used to assess the effect of independent variables on OS. Priori variables selected on previous reports (performance status (PS), Ki-67 index, and serum LDH level), as well as variables that remained at a level of p-value &lt;0.20 by backward stepwise selection, were incorporated in the final model of OS. Results: Among 170 patients enrolled in JCOG1213, a total of 129 patients with ADNEC were included in this analysis. In multivariable analysis, serum LDH level (&gt; upper normal limit vs. normal) was identified as a significant prognostic factor for OS (HR = 1.721, 95% CI: 1.144–2.589, p = 0.009). Other clinicopathological factors were not found to be significant, including PS (1 vs. 0; HR = 0.784, 95% CI: 0.507–1.214, p = 0.276), Ki-67 (≥ 55% vs. &lt; 55%; HR = 1.475, 95% CI: 0.588–3.698, p = 0.407), liver metastasis (present vs. absent; HR = 1.434, 95% CI: 0.968–2.124, p = 0.072), sex (female vs. male; HR = 1.387, 95% CI: 0.937–2.053, p = 0.102), and serum ALP level (&gt; upper normal limit vs. normal; HR = 0.948, 95% CI: 0.639–1.406, p = 0.789). OS of patients with elevated serum LDH levels was shorter than those with normal serum LDH levels (median: 9.5 months vs. 15.6 months, p = 0.0019). No statistically significant differences were observed between the two groups regarding objective response rate (58.8% vs. 54.1%, p = 0.594) and progression-free survival (median: 4.5 months vs. 5.9 months, p = 0.141). A numerically lower proportion of patients with elevated serum LDH levels received second-line chemotherapy than those with normal serum LDH levels (76.5% vs. 88.3%). Conclusions: Serum LDH level may serve as a prognostic factor in the daily practice of patients with ADNEC and as a risk stratification factor in future randomized clinical trials. Clinical trial information: UMIN000014795 .
Real-world <sup>177</sup>Lu-DOTATATE peptide receptor radionuclide therapy: Treatment outcomes with dosing variations and in non-midgut neuroendocrine tumors.
Authors: Hwan Lee, Sarit Kipnis, Sophia O'Brien, Jennifer Rachel Eads, Bryson W. Katona, Daniel A. Pryma
Journal: Journal of Clinical Oncology (2024)

593 Background: Peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE has been used for neuroendocrine tumors (NETs) since its approval in the United States based on demonstrated progression-free survival benefit in grade 1-2 midgut NETs. The recommended dosing is 7.4 GBq (200 mCi) every 8 weeks for 4 doses in total. We examined the post-PRRT outcomes with dosing variations and in patients with non-midgut NETs. Methods: The medical records of 108 PRRT-naïve NET patients who received at least one cycle of PRRT at a single academic institution were reviewed. Among the patients with Ki-67 index ≤ 20%, progression-free survival (PFS) and overall survival (OS) were compared between midgut and non-midgut NETs. Among the patients who did not develop disease progression or mortality during the treatment course, PFS and OS were compared based on dosing variations. Dosing variations were defined as "reduced” (50% of 7.4 GBq/cycle), “delayed” (&gt;12 weeks between cycles), or “fewer” (&lt;4 cycles) doses. Kaplan-Meier survival analysis with log-rank test was used for statistical analysis. Results: Median clinical follow-up was 18.7 months, during which disease progression and death occurred in 54 (50%) and 20 (18%) patients, respectively. Among the 98 patients with Ki-67 index ≤ 20%, those with non-midgut tumors (n=55) showed significantly shorter PFS compared to those with midgut tumors (n=43) with the hazard ratio of 2.0 ( P=0.014, median of 15.6 vs. 26.9 mo.). No difference in OS was found between the two groups ( P=0.83). Among the 93 patients who did not develop disease progression or mortality during the course of PRRT, dosing variations were used in 23 patients. The types of dosing variations were “reduced” in 4 (17%) patients, “delayed” in 16 (70%) patients, and “fewer” in 7 (30%) patients. The reasons for dosing variations were hematologic in 9 (39%) patients, hepatic in 2 (9%) patients, renal in 1 (4%) patient, other medical in 3 (13%) patients, functional in 3 (13%) patients, and logistical in 6 (26%) patients. No difference in PFS ( P=0.20) or OS ( P=0.24) was found based on the presence or absence of dosing variations. Conclusions: Patients with non-midgut NETs show approximately twice the rate of disease progression over time following PRRT than those with midgut NETs. Administering reduced, delayed, or fewer doses of PRRT may still offer comparable benefit compared to the recommended dosing.
Defining ablative radiotherapy in patients with hepatocellular carcinoma: An expert consensus.
Authors: Ted K. Yanagihara, Joel E. Tepper, Andrew M Moon, Aisling S Barry, Meritxell Molla, Jinsil Seong, Ferrán Torres, Theodore Steven Lawrence, Maria Reig, Laura A. Dawson
Journal: Journal of Clinical Oncology (2024)

485 Background: External beam radiotherapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, there are many types of EBRT described in the literature with no formal definition of what constitutes “ablative.” Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC. Methods: A Steering Committee was convened to generate a series of Key Criteria (KC) that could be used to define ablative EBRT for HCC. KC were based on factors related to dose, fractionation, radiobiology, target identification, and delivery technique. An international panel of experts participated in a modified Delphi (mDelphi) process to independently answer questions for each KC. Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of ≥ 70% was used to define consensus for answers to each KC. Results: Invitations were sent to 40 individuals and 35 (88%) returned responses. In the first round of the mDelphi, 3 of 7 KC reached consensus. In the second round, 100% of participants returned responses and consensus was reached in 3 of the remaining 4 KC. Based on this mDelphi analysis, there was expert agreement that ablative EBRT for HCC should be defined as 1) a BED 10 ≥ 80 Gy, 2) daily imaging and multi-phasic contrast used for target delineation should be used, 3) treatment breaks (e.g., for adaptive EBRT) are allowed, but the total treatment time should be ≤ 6 weeks, 4) the equivalent dose when treating with protons should use a conversion factor of 1.1, and 5) there is no single conversion factor for carbon ions. In one KC, which questioned the expert’s opinion on the α/β ratio of HCC, consensus was not achieved. Conclusions: Using an mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empiric data are required to define the α/β of HCC.
Preliminary results of surufatinib (Suru) plus standard chemotherapy (ChT) as second line (2L) treatment of advanced gastric cancer (aGC): A single-arm, phase 2 clinical trial.
Authors: Ting Han, Xiaolin Lin, Meng Zhuo, Feng Jiao, Jiujie Cui, Xiaoxia Qiu, Xiuying Xiao
Journal: Journal of Clinical Oncology (2024)

353 Background: Limited options are available for aGC patients who have failed first line (1L) systemic treatment, and single-agent ChT with paclitaxel (Pac) or irinotecan (Iri) remains the mainstay. Recent studies have suggested improved efficacy with the combination of ChT and antiangiogenic agents in the 2L setting. Suru is a tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1 and CSF-1R. This trial is aimed to evaluate the efficacy and safety of Suru plus Pac or Iri as 2L treatment for aGC. Methods: This single-arm, single center, phase 2 trial was designed to enroll up to 35 histologically confirmed HER2-negative aGC patients with evaluable disease who failed 1L ChT with or without immunotherapy (IO). Eligible patients were administered 21-day cycles of Suru (250mg, po, qd) plus Pac (150mg/m 2 , iv, d1) or Iri (125mg/m 2 , iv, d1, d8) per investigator choice for 6 cycles, followed by Suru (250mg, po, qd) maintenance if no disease progression (PD), until intolerable toxicity, PD, or death. The primary endpoint was ORR (per RECIST v1.1), and secondary endpoints included DCR, PFS, OS, and safety. Results: As of Sep 11, 2023, 15 patients were enrolled, and 6 patients remained on treatment. The median follow-up time was 5.77 (95% CI: 3.37~10.13) months. Among all 15 patients, the median age was 66 (range: 33-76) years, 14 (93.3%) were male, and 14 (93.3%) had an ECOG PS of 1. Ten (66.7%) patients had received prior anti-PD-1 antibodies, and all 15 patients received Pac as the standard ChT. All 15 patients were evaluable for tumor response, with 5 PR, 9 SD, and 1 PD as their best overall response (BOR). The ORR and DCR were 33.3% and 93.3%, respectively. The median PFS was 5.23 months, while the OS data was immature yet. The ORR, DCR and PFS seemed comparable between patients with and without prior IO. In terms of safety, the combined treatment was generally well tolerated, treatment-related Grade 3/4 adverse events included neutropenia (6, 40%), leukopenia (1, 6.7%), lymphopenia (1, 6.7%), and proteinuria (1, 6.7%). There were no treatment-related serious adverse events or treatment-related deaths. Conclusions: These results suggested promising anti-tumor activity and a manageable safety profile of Suru plus standard ChT in 2L treatment of aGC. The trial is still ongoing, and more data will be disclosed in the future. Clinical trial information: ChiCTR2200063336 . [Table: see text]
Pembrolizumab plus FLOT vs FLOT as neoadjuvant and adjuvant therapy in locally advanced gastric and gastroesophageal junction cancer: Interim analysis of the phase 3 KEYNOTE-585 study.
Authors: Salah-Eddin Al-Batran, Kohei Shitara, Gunnar Folprecht, Markus H. Moehler, Eray Goekkurt, Irit Ben-Aharon, Sara Lonardi, Stacey Stein, Ayala Hubert, Ian Chau, Moshe Mishaeli, Luis Villanueva, Petr Kavan, Xiao Fang, Chie-Schin Shih, Pooja Bhagia, Lucjan S. Wyrwicz
Journal: Journal of Clinical Oncology (2024)

247 Background: The phase 3 KEYNOTE-585 study (NCT03221426) evaluated neoadjuvant/adjuvant pembrolizumab (pembro) or placebo (pbo) + chemotherapy (chemo) followed by adjuvant pembro vs pbo in locally advanced, resectable gastric or gastroesophageal junction (G/GEJ) cancer. A separate cohort evaluated pembro + FLOT (FLOT cohort). We report results from safety and efficacy analyses of the FLOT cohort at third interim analysis. Methods: In the FLOT cohort, patients (pts) with untreated, locally advanced, resectable G/GEJ cancer were randomized 1:1 to neoadjuvant pembro 200 mg IV Q3W (pembro gp) or pbo (pbo gp) Q3W for 3 cycles + FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU) Q2W for 4 cycles. After surgery, pts received adjuvant pembro or pbo Q3W for 3 cycles + FLOT Q2W for 4 cycles, then adjuvant pembro or pbo Q3W for 11 cycles. Endpoints evaluated included safety, pathCR rate (BICR), EFS (RECIST 1.1, by investigator), and OS in the ITT. Data cut-off at third interim analysis was 09 Feb 2023. Results: A total of 203 pts were randomized (100 pembro + FLOT; 103 pbo + FLOT). Among these, 12 (6%) pts had cT1-T2, 161 (79%) had cT3, and 9 (4%) had cT4. 140 (69%) had N+ disease, and 79 (39%) had GEJ adenocarcinoma at baseline. Median follow-up was 31.6 months (mo) and 31.1 mo, respectively, at IA3. A total of 94 of 99 (95%) pts completed the neoadjuvant phase, 87 of 99 (87%) completed the surgery phase, and 45 of 77 (58%) completed adjuvant treatment. The R0-resection rate was 79% vs 80% in the pembro gp vs pbo gp, respectively. The pathCR rate was 17.0% (95% CI, 10.2-25.8) in the pembro gp and 6.8% (95% CI, 2.8-13.5) in the pbo gp, estimated difference (10.2% [95% CI, 1.3-19.7]). Median EFS was not reached (95% CI, 28.2-NR) in the pembro gp and 30.9 mo (22.8-NR) in the pbo gp (HR 0.79; 95% CI, 0.52-1.22). The 24-mo EFS rates were 66% and 57%, respectively. Median OS was not reached in either group (HR 1.04; 95% CI, 0.66-1.66). The 24-mo OS rates were 72% and 73%, respectively. Grade ≥ 3 drug-related AE rates in all phases combined were 76% and 63% in the pembro vs pbo gp, with serious drug-related AEs in 42% vs 20%, and surgery-related AEs in 20% vs 13%, respectively. A total of 3 (3%) vs 1 (1%) pt in the pembro vs pbo gp died due to a drug-related AE. Conclusions: Neoadjuvant/adjuvant pembro + FLOT was feasible with no new safety concerns. PathCR and EFS favored pembro + FLOT vs pbo + FLOT in pts with untreated, locally advanced resectable G/GEJ cancer. Clinical trial information: NCT03221426 .
Quality of surveillance in patients with completely resected gastroenteropancreatic neuroendocrine tumors.
Authors: Gordon Taylor Moffat, Aruz Mesci, Sami A. Chadi, Raymond Woo-Jun Jang, Lisa Avery, Carol-Anne Moulton, Paul C. Nathan, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2024)

591 Background: The incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasing worldwide. Surgery remains the only curative modality. Because of limited data on patterns of recurrence, real-world surveillance practices and duration vary widely. In 2018, the Commonwealth Neuroendocrine Tumour Research Collaboration (CommNETs) published consensus surveillance guidelines for patients with completely resected GEP-NETs. Our aim was to assess adherence to the CommNETs guidelines for surveillance practices for this patient population at our center. Methods: We conducted a retrospective cohort study of patients with GEP-NETs seen for a new patient appointment at Princess Margaret Cancer Centre (PMCC) from 2019-2022. Patients were included if they had a completely resected GEP-NET and followed on surveillance at our center. Demographic and tumor characteristics, surveillance practices, and clinical outcomes were abstracted. Summary statistics and a descriptive comparison of surveillance practices were completed. Results: Out of the 374 new patient appointments, 87 met the inclusion criteria. The main reasons for exclusion were metastatic disease at presentation (n=128), primary tumor not resected (n=58), and patients not followed at PMCC (n=49) so their surveillance practices cannot be determined from our records. The primary tumor sites were pancreatic (n=50, 57%), appendiceal (n=15, 17%), small bowel (n=11, 13%), rectal (n=10, 12%), and colon (n=1, 1%). Thirty-eight patients (44%) had stage 1 disease, 21 patients (24%) had stage 2, and 28 patients (32%) had stage 3. Forty-six patients (53%) had a WHO tumor grade of 1, 36 patients (41%) had grade 2, and 5 patients (6%) had grade 3. The median duration of follow-up was 18.2 months. Adherence to ordering the recommended surveillance investigations was 23% (20/87). Within the adherent cases, there was a higher number of appendiceal, WHO grade 1, and stage 1 tumors. Sixty-six patients (76%) had at least one test that was not recommended by the guidelines. The most frequent unnecessary tests were CT chest in all patient groups and CT pelvis in pancreatic NETs (Table). Six patients were lost to follow up and none discharged from surveillance. Conclusions: Adherence to the CommNETs consensus guidelines was low at our center, suggesting the guidelines had a minor impact on surveillance practices and providing an area for improvement in process of care and resource utilization. [Table: see text]
Safety and efficacy of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (Neo DCF) therapy for locally advanced esophageal cancer: Real world data analysis.
Authors: Mikako Tamba, Hiroki Osumi, Shota Fukuoka, Mariko Ogura, Akihiko Okamura, Jun Kanamori, Yu Imamura, Daisuke Takahari, Koichiro Yoshino, Shohei Udagawa, Takeru Wakatsuki, Eiji Shinozaki, Masayuki Watanabe, Kensei Yamaguchi, Keisho Chin, Akira Ooki
Journal: Journal of Clinical Oncology (2024)

365 Background: Neoadjuvant chemotherapy with docetaxel, cisplatin plus 5-FU (Neo DCF) is one of the standard treatments for locally advanced esophageal squamous cell carcinoma (ESCC) in Japan based on the results of the JCOG1109 NExT study. As Neo DCF is both highly effective and high rate of adverse events, it is important to confirm clinical outcomes in the clinical practice and to explore clinical factors that predict treatment efficacy and adverse events (AEs) for treatment optimization. Methods: ESCC patients who were treated with Neo DCF between July 2016 and May 2023, were enrolled. Three courses of DCF (DTX [day 1]: 70 mg/m2, CDDP [day 1]: 70 mg/m2, 5-FU [continuous infusion on days 1-5]: 750 mg/m2, every 3 weeks) were planned, and prophylactic antibiotics was administered on days 5-15. We retrospectively assessed disease free survival (DFS), pathological response, AEs. Pathological response was assessed according to the Becker’s Criteria. Subgroup analyses of clinical factors related to the pathological response and AEs were also performed. Results: In total, 91 patients (median age, 62.3 years) were enrolled. Clinical stages of this cohort were 8.8% (I),16.4% (II), 69.2% (III), and 5.5% (IVA), respectively. After Neo DCF treatment, 90 patients (98.9%) underwent curative surgery. Median DFS and 3-year DFS rate were not reached and 76.9%. The incidence of pathological complete response (pCR) and major pathological response (MPR) were 11.1% (10/90) and 35.6% (32/90), respectively. There were no cases of recurrence in patients with pCR and MPR. The most common grade 3 or 4 AEs were neutropenia (58/91, 63.7 %), diarrhea (15/91, 16.5%), and thrombosis (9/91, 9.9%), respectively. Febrile neutropenia occurred in 33 patient (36.2%). Clinical T stage was significantly associated with pCR (P = 0.033). Conclusions: Neo DCF was effective and tolerable in the real-world ESCC patients in Japan.