tbuckley/cabot-search huggingface dataset:
Impact of combined resection of pancreas on long-term survival in patients with gastric cancer.
Authors: Taku Hattori, Masanori Terashima, Kyota Takahashi, Yosuke Matsumoto, Yusuke Koseki, Kenichiro Furukawa, Keiichi Fujiya, Yutaka Tanizawa, Etsuro Bando
Journal: Journal of Clinical Oncology (2025)

359 Background: In patients with advanced gastric cancer invading adjacent organs, extended multivisceral resection is required to achieve R0 resection. However, the survival benefit of combined resection of pancreas remains controversial. We investigated the safety and efficacy of combined pancreatic resection in gastric cancer. Methods: This study included 64 patients who underwent gastrectomy with pancreatectomy (pancreaticoduodenectomy (PD) or distal pancreatectomy with splenectomy (PS)) for primary gastric cancer with invasion to the pancreas by primary tumor or lymph node metastasis and invasion to the duodenum. Patients who underwent R2 resection were excluded. Short- and long-term outcomes were assessed. Results: PD was performed in 18 patients (28.1%) and PS in 46 patients (71.9%). Macroscopic invasion to the pancreas by primary tumor was observed in 47 patients (73.4%), by lymph node in 13 patients (20.3%), and the invasion to the duodenum by primary lesion was in 4 patients (6.3%). Pathologically, pancreatic invasion was confirmed in 27 out of 47 patients (57.4%). Postoperative intra-abdominal infectious complications (PIIC) of Clavien-Dindo (CD) Grade III or higher were observed in 33 patients (51.6%). The most common postoperative complication was pancreatic fistula, which was observed in 31 patients (48.4%). There was no mortality within 30 days after surgery. Univariate analysis revealed that invasion the duodenum was highly associated with PIIC (p=0.038). Twelve patients (18%) resulted in R1 resection due to positive peritoneal cytology in 11 patients and positive surgical margin in one patient. The 5-year overall survival (OS) rate was 42.9%, which was 53.6% in R0 resection and 0% in R1 resection. Multivariate analysis revealed R1 resection was an independent prognostic factor for OS (HR:5.315, p&lt;0.001). The 5-year recurrence-free survival (RFS) rate was 44.5%. The 5-year RFS rate was significantly worse in patients with PIIC (28.7%) than in patients without it (58.7%). Multivariate analysis revealed that PIIC was an independent prognostic factor for RFS (HR:2.345, p=0.036). Conclusions: Pancreatic resection for gastric cancer is considered safe and effective when R0 resection is possible. However, surgeon should pay particular attention to avoid the postoperative complications.
Real-world analysis of the impact of timing of biomarker testing on first-line treatment choice in patients with metastatic colorectal cancer in British Columbia.
Authors: Tae Hoon Lee, Tharani Krishnan, Sharlene Gill
Journal: Journal of Clinical Oncology (2025)

253 Background: The treatment landscape for metastatic colorectal cancer (mCRC) has evolved significantly, shifting from chemotherapy alone to more personalized approaches that include immune checkpoint inhibitors and targeted therapies. Treatment decisions in mCRC are driven by molecular characteristics, and current guidelines recommend a minimum standard of biomarker testing, such as mismatch repair (MMR) status, and RAS and BRAF mutations, at the time of metastatic disease diagnosis to guide treatment selection. This study aimed to assess the real-world implementation of biomarker testing in a contemporary cohort of mCRC patients in British Columbia (BC) and its impact on treatment decisions by medical oncologists. Methods: We conducted a retrospective chart review of patients who received first-line systemic therapy for mCRC in BC between January 2022 and December 2023. Patient demographics, tumour characteristics, and treatment details were obtained from the BC Cancer provincial pharmacy database. Medical oncology documentation and pathology reports were reviewed to determine the availability of biomarkers, including MMR status, and RAS and BRAF mutations (OncoPanel), at the time of initial medical oncology consultation, and to assess how these results influenced treatment plan. Results: To date, 71 eligible patients have been identified, with data collection ongoing. Of these, 82% had proficient MMR status, 17% had deficient MMR status, and 1% had incomplete data. RAS mutations were present in 55% of cases, while BRAF mutations were found in 21% (Table). At the time of the initial medical oncology consultation, MMR status was unavailable in 14 patients (20%), two of whom were later found to have deficient MMR status. OncoPanel results were unavailable for 63 patients (88%) at the time of the initial consultation, and in 16 of these cases (25%), the systemic therapy plan was modified once the results were received. Conclusions: Even in contemporary practice with publicly funded biomarker testing, the results for RAS and BRAF mutations were not available at the time of initial medical oncology consultation for most patients. Biomarker testing is an essential tool for guiding therapeutic decisions in mCRC. This subsequently led to treatment plan changes in one-quarter of cases after results were received. These findings highlight the importance of timely biomarker testing to ensure optimal and efficient treatment decision-making for all mCRC patients. Metastatic colorectal cancer biomarker testing. Proficient/WT Deficient/Mutated Incomplete MMR 58 12 1 RAS 29 39 3 BRAF 53 15 3
Safety and efficacy of first-line nivolumab plus chemotherapy for HER2-negative advanced gastric cancer in real-world patients: Updated analysis.
Authors: Keitaro Shimozaki, Koshiro Fukuda, Akira Ooki, Izuma Nakayama, Koichiro Yoshino, Shohei Udagawa, Shota Fukuoka, Hiroki Osumi, Mariko Ogura, Takeru Wakatsuki, Daisuke Takahari, Eiji Shinozaki, Keisho Chin, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2025)

341 Background: Based on the results of CheckMate-649 and ATTRACTION-4, nivolumab plus chemotherapy is the new standard of care as first-line treatment for patients with HER2-negative advanced gastric cancer (AGC) regardless of PD-L1 combined positive score (CPS) status in Japan. This study aimed to evaluate the safety and efficacy of this regimen in real-world patients with HER2-negative AGC with a longer follow-up. Methods: In this single-institutional retrospective study, patients with HER2-negative AGC who were treated with first-line nivolumab plus chemotherapy between September 2021 and April 2024 were consecutively enrolled and evaluated. Early tumor shrinkage (ETS) was defined as ≥20% tumor reduction at 8 ± 2 weeks. Results: Of 151 patients, median age was 66 years (range, 27–83); 58% were male; 81% had diffuse-type histology; the peritoneal metastasis was seen in 60%; PD-L1 CPS of &lt;1, 1≤/&lt;5, 5≤ was 30%/41%/29%; deficient mismatch repair and/or high microsatellite instability was 7%. At a median follow-up of 14.2 months, the median overall survival (OS) and progression-free survival (PFS) were 21.7 months (95% confidence interval [CI] 14.4–26.2) and 7.7 months (6.4–9.6), respectively. The median OS according to CPS subgroups (&lt;1, 1≤/&lt;5, 5≤) were 21.7 / not reached (NR) /25.0 months, respectively (log-rank P = 0.55). In patients with measurable lesions at baseline according to RECIST ver 1.1, the objective response rate and disease control rate were 62% and 87%, respectively, with a complete response rate of 10%. In the exploratory analysis by ETS, both median PFS and OS were significantly longer in the ETS group compared to the non-ETS group (PFS, NR vs. 6.2 months; hazard ratio [HR] 0.35; 95% CI 0.17–0.68; P = 0.001) (OS, 25.0 vs. 11.7 months; HR 0.44; 95% CI 0.20–0.93; P = 0.03). The immune-related adverse events (irAEs) of any grade were observed in 26% (grade 3–4 irAEs 12%), whereas no treatment-related death was documented. Conclusions: The updated analysis suggests that first-line nivolumab plus chemotherapy provides benefit in real-world patients with HER2-negative AGC regardless of PD-L1 status, and suggests that the magnitude of ETS may predict a significant impact on the duration of survival.
Risk of residual tumor following removal of a malignant colorectal polyp with high-risk features.
Authors: Thikhamporn Tawantanakorn, Ayyuce Begum Bektas, Matthew Hill, Maria Widmar, Georgios Karagkounis, Iris H. Wei, Jesse Joshua Smith, Emmanouil Pappou, Garrett Michael Nash, Philip Paty, Julio Garcia-Aguilar, Mithat Gonen, Martin R. Weiser
Journal: Journal of Clinical Oncology (2025)

136 Background: National guidelines recommend surgery when pathology analysis of a colorectal polyp reveals high-risk features: positive margin/piecemeal resection (PM/PR), lymphovascular/perineural invasion (LVI/PNI), poor differentiation (PD), or tumor budding (TB). However, some patients choose to avoid surgery, with its morbidity and quality-of-life implications, despite the risk of residual disease. Methods: This single-center cohort study determined the rates of luminal or lymph node disease and distant metastasis in patients who underwent surgery and patients who underwent observation following removal of a malignant colorectal polyp with high-risk features between 2015 and 2022. Results: Of 336 patients who underwent a polypectomy for a malignant polyp in the colon (n = 226) or rectum (n = 110), 312 had a PM/PR, 96 had LVI/PNI, 47 had PD, and 45 had TB; 208 patients (62%) underwent surgery, and 128 (38%) underwent observation. Patients with a malignant polyp in the rectum were more likely to undergo observation than patients with a malignant polyp in the colon (79 [72%] vs. 49 [22%] patients; P &lt; 0.01). In the surgery group, 19 patients (9%) had residual luminal disease, 39 patients (19%) had lymph node disease, and 5 patients (2%) had distant metastasis. In the observation group, disease was identified in 14 patients (11%): regrowth in the lumen, 7 patients (9%); regrowth in lymph nodes, 5 patients (6%); distant metastasis, 1 patient (1%); regrowth with distant metastasis, 1 patient (1%). The 12 cases of regrowth were salvaged: resection, 4 patients; local excision, 2 patients; chemoradiotherapy, 6 patients. Conclusions: The risk of residual disease following removal of a malignant colorectal polyp with high-risk features is considerable. Patients concerned about the morbidity of surgery and postsurgery quality of life should be counseled about this risk, as well as the availability of effective salvage options. High-risk features (HRF) Surgery(n = 208) Observation (n = 128) Luminal/LN disease at surgery(n = 51; 25%) Luminal/LN regrowth during observation(n = 12; 9.4%) Distant metastasis(n = 7; 2.1%) PM/PR (n = 312; 93%) 193 119 49 (25%) 12 (10%) 7 (2.2%) LVI/PNI (n = 96; 29%) 56 40 16 (29%) 3 (7.5%) 3 (3.1%) PD (n = 47; 14%) 33 14 11 (33%) 0 1 (2.1%) TB (n = 45; 13%) 20 25 5 (25%) 1 (4.0%) 1 (2.2%) 1 HRF (n = 215; 64%) 141 74 31 (22%) 8 (11%) 4 (1.9%) 2 HRF (n = 78; 23%) 39 39 11 (28%) 4 (10%) 1 (1.3%) 3 HRF (n = 35; 10%) 25 10 8 (32%) 0 2 (5.7%) 4 HRF (n = 6; 1.8%) 2 4 1 (50%) 0 0
Beamion BCGC-1: A phase Ib/II trial of the HER2-selective tyrosine kinase inhibitor (TKI) zongertinib (BI 1810631) + trastuzumab deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1) for patients with metastatic breast cancer (mBC) and metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEAC).
Authors: Izuma Nakayama, David Berz, Sila Aykut Yazgili, Damijan Erzen, Kohei Shitara
Journal: Journal of Clinical Oncology (2025)

TPS509 Background: Approximately 15% of mGEAC tumors overexpress HER2. Currently, the HER2-targeted antibody-drug conjugate (ADC), T-DXd, is approved in mGEAC as a second-line or later-line treatment option following the failure of prior trastuzumab-containing therapy. Zongertinib (BI 1810631) is a novel, orally administered HER2-selective TKI that spares EGFR. In a Phase I trial (NCT04886804), zongertinib showed encouraging tolerability and efficacy in patients with HER2 aberration-positive advanced solid tumors, including mGEAC. Beamion BCGC-1 (NCT06324357) is a Phase Ib/II dose escalation/optimization trial investigating zongertinib plus T-DXd or T-DM1 in patients with HER2+ mGEAC or mBC. Here we focus on the mGEAC cohorts, in which patients will receive zongertinib in combination with T-DXd. Methods: Across the whole trial, approximately 240 patients will be enrolled from approximately 48 sites in 6 countries. In the mGEAC cohorts, approximately 80 patients with histologically/cytologically confirmed locally advanced/metastatic, unresectable, HER2-positive, pre-treated mGEAC will be enrolled. All patients must have investigator-assessed progression and documented HER2-positive disease (overexpressed and/or amplified; confirmed by immunohistochemistry and in situ hybridization). In Phase Ib, approximately 20 patients will receive escalating doses of zongertinib plus a fixed approved dose of T-DXd (6.4 mg/kg, once every 21 days). Dose escalation will be guided by a Bayesian Logistic Regression Model, with overdose control. In Phase Ib, the primary endpoint is the occurrence of dose-limiting toxicities (DLTs) during the maximum tolerated dose evaluation period (first 21-day cycle); secondary endpoints include objective response (RECIST v1.1), DLTs during the on-treatment period and pharmacokinetics. In Phase II, up to 60 patients with mGEAC will be randomized 1:1 to receive one of two zongertinib dose levels (dose levels informed by Phase Ib), plus a fixed approved dose of T-DXd. In Phase II, the primary endpoint is objective response; secondary endpoints include progression-free survival, disease control, treatment-emergent adverse events leading to dose reduction, pharmacokinetics and patient-reported outcomes. Patients will remain on treatment until disease progression, undue toxicity or any other protocol-defined stopping criterion. Enrollment is ongoing. Clinical trial information: NCT06324357 .
Adverse events (AEs) –derived biomarker in predicting clinical outcomes in patients with colorectal cancer (CRC) treated with immunotherapy (IC).
Authors: Dung-Tsa Chen, Rutika Mehta, Richard D. Kim, Jennifer B Permuth, Timothy I Shaw, Dae Won Kim
Journal: Journal of Clinical Oncology (2025)

132 Background: There are insufficient studies evaluating the role of AEs in CRC patients treated with IC. This study aims to transform AEs from traditional toxicity evaluation tools to informative biomarkers for assessing treatment efficacy by utilizing modern analytical strategies. Methods: We analyzed a single arm study of 51 mismatch repair proficient, refractory CRC patients (NCT03712943) treated with regorafenib and nivolumab. Data for analysis included CTCAE version 5 AE data, RECIST treatment response, progression-free survival (PFS), and overall survival (OS). Analytic approach leveraged multiple AE parameters to develop a set of innovative AE biomarkers. One AE biomarker of interest was treatment related low-grade early AEs (TR-LG-AE) which was defined as frequency of all TR-LG-AEs occurring between the 1st day and day 30 after the 1st treatment. Results: TR-LG-AE was associated with treatment response (p&lt;0.001 by ANOVA trend test). Patients with higher AE events tended to be a responder, compared to PD patients with a lower frequency of AE events. The TR-LG-AE also correlated with improved PFS and OS with hazard ratio of 0.83 (p=0.01) and 0.89 (p=0.03), respectively. Accordingly, patients were grouped into high versus low TR-LG-AE based on optimal cutoff of 6 events for further analysis. The dichotomized TR-LG-AE (high vs low) showed significant association with survival outcomes (median PFS: 15.3 vs 3.7 months; p&lt;0.001; median OS: 21.9 vs 9 months; p=0.02). Further interaction analysis showed patients with high TR-LG-AE had improved PFS regardless of occurrence of high-grade AE (HG-AE) (p=0.01), suggesting its independence of HG-AE. Individual AE analysis identified patients experienced with early low-grade rash maculo-papular, lipase increased, or hypertension had improved PFS (p&lt;0.001). In biomarker analysis, one key mutation biomarker, RAS, did not show significant association with survival outcomes (PFS: p=0.66; OS: p=0.81). In contrast, integration with TR-LG-AE led to remarkable improvement. Specifically, the TR-LG-AE was able to help improve RAS classification by identifying patients with better treatment benefit. Specifically, patients with RAS mutation and high TR-LG-AE experiences had a median PFS of 15.3 months compared to others (median PFS of 3.7 months; p=0.007), and a median OS of 21.9 months compared to others (median OS of 9.4 months; p=0.04). Conclusions: The study demonstrated utility of AE in predicting clinical outcomes in CRC, similar to our previous findings in lung cancer. Moreover, it discovered that integration of AE-derived biomarkers with molecular biomarkers could produce a more robust classifier than when considered individually. This analysis is the first of its kind to identify subgroups of CRC patients that benefit from IC treatment.
Effect of adjuvant radiotherapy after endoscopic resection of early esophagus cancer to prevent new intraluminal mucosal recurrence.
Authors: Hirofumi Fukushima, Awatsu Takahito, Shunsuke Adachi, Arisa Yuzawa, Takashi Murakami, Hiroya Ueyama, Tomoyoshi Shibuya, Mariko Hojo, Akihito Nagahara
Journal: Journal of Clinical Oncology (2025)

381 Background: Endoscopic resection (ER) is effective for treating T1a early esophageal squamous cell carcinoma (ESCC). Occasional distant metastasis and recurrence are inevitable invasion in depth of muscularis mucosa(MM). Additional surgical resection is an effective means for cure and prevent recurrence, but it imposes a heavy physical burden. Chemoradiation therapy (CRT) is a comparable alternative to surgery. Not all patients will want those additional treatment. Another problem is the occurrence of new esophagus intraluminal mucosal recurrence. After endoscopic treatment, there is an increased risk of scarring and deformity. But there are few reports of the effectiveness of additional RT in suppressing new lesions. This study was designed to verify the efficacy of not only curability but also suppressive effect the occurrence of new lesions additional treatment of T1a(MM) ESCC. Methods: This study was a retrospective study. We reviewed 71 consecutive patients who underwent ER followed by clinical stage I (T1a: MM) ESCC. We compared patients in the radiotherapy group or non-radiotherapy group after ER. Patients of radiotherapy group received radiation within 3 months after ER. All patients underwent regular follow-up. Recurrence, recurrence-free survival, cancer-specific survival, overall survival, and complications were evaluated. Results: There were 34 cases of radiotherapy group and 37 cases of non-radiotherapy group. 3 patients (8.9 %) in the radiotherapy group experienced intraluminal mucosal recurrence, and 2 patients (6.6 %) experienced local recurrence. On the other hand, in the non-radiotherapy group, 9 patients (24.3 %) experienced intraluminal mucosal recurrence, and 7 patients (18.9 %) experienced local recurrence (intraluminal mucosal recurrence: p&lt; 0.05, local recurrence p=0.14). The recurrent group received chemotherapy. The 3-year cumulative recurrence-free survival was 97 % in the radiotherapy group and 83.7 % in the non-radiotherapy group (p&lt; 0.05). No severe radiation toxicities were recorded. Conclusions: The radiotherapy after ESD reduced the risk of lymph nodes recurrence not only local lymph node recurrence but also new intraluminal mucosal recurrence, and safe and effective therapeutic strategy.
A single arm phase II trial of trastuzumab deruxtecan in patients with gastrooesophageal adenocarcinoma cancer who are ctDNA and HER2 positive: DECIPHER.
Authors: Elizabeth Catherine Smyth, Daniel Griffiths, Kelly Cozens, Richard C. Turkington, Rajarshi Roy, Sarah Ngan, Richard Owen, Kieran Foley, Robert Waugh, Ceri Steele, Dave Chuter, Chris Hurt, Gareth Owen Griffiths
Journal: Journal of Clinical Oncology (2025)

TPS512 Background: Oesophagogastric adenocarcinoma (OGA) is globally prevalent and frequently advanced at presentation. Less than 50% of patients with operable OGA are cured when treated with multimodality therapy. Patients in the UK with operable OGA, are treated with FLOT prior to and following surgery. However, patients who have circulating tumour DNA (ctDNA) in their blood after surgery have worse survival than ctDNA negative patients. Therefore, use of novel treatment approaches aiming to cure this micrometastatic disease are considered a rational and appropriate treatment approach. Trastuzumab deruxtecan (T-DXd), a novel HER2-targeting antibody drug conjugate, is licensed to treat advanced, previously treated HER2 positive OGA. Therefore, there is a need to evaluate T-DXd in resectable HER2 and ctDNA positive OGA, where options are limited. Methods: Co-ordinated by the Cancer Research UK Southampton Clinical Trials Unit, DECIPHER is a single arm, multicentre, phase II trial testing the effect of T-DXd on reducing micrometastatic disease burden in HER2 positive OGA patients who are ctDNA positive after chemotherapy and surgery. To be eligible, participants must have been treated with chemotherapy before surgery for at least 6 weeks and must have recovered from surgery with no evidence of metastatic disease on post-surgical imaging. HER2 positive patients are recruited to the tissue testing stage of the trial prior to surgery. Patients who are ctDNA positive after surgery will be treated with T-DXd at a dose of 6.4 mg/kg intravenously every 21 days for a maximum of 8 cycles or until disease recurrence. If required, patients may dose reduce, but no dose re-escalation will be permitted. A clinically validated, personalised, tumour-informed ctDNA assay (signatera, Natera, Inc.) will be utilised to detect ctDNA in patient plasma samples. The primary endpoint is the percentage of patients who are ctDNA negative after 4 cycles of treatment. Secondary endpoints include ctDNA clearance after each cycle, disease free survival, overall survival, quality of life and frequency of adverse events. DECIPHER (NCT05965479) opened in April 2024 and will run in approximately 15 UK secondary care hospitals with the aim of recruiting 25 evaluable patients (recruitment to the tissue testing stage is currently 27 on 23-Sep-2024). Clinical trial information: NCT05965479 .