tbuckley/cabot-search huggingface dataset:
Unraveling the role of interferon-stimulated neutrophils: A promising biomarker for immunotherapy efficacy and prognosis in gastric adenocarcinoma.
Authors: Hongda Pan, Fenglin Liu
Journal: Journal of Clinical Oncology (2025)

472 Background: Despite significant advancements in immunotherapy, the identification of effective predictive biomarkers for treatment response in gastric adenocarcinoma (GAC) remains a critical challenge. Discovering such biomarkers could enhance patient stratification and improve therapeutic outcomes. Methods: We conducted a comprehensive analysis of 18 specimens obtained from 10 GAC patients, both prior to and following immunotherapy. Utilizing single-cell RNA sequencing, we compared the cellular composition and functional phenotypes of these specimens, with particular emphasis on tumor-infiltrating immune cells and the identification of previously uncharacterized neutrophil subclusters. Results: Our analysis identified eight distinct neutrophil subclusters, including Neu01_S100A12, Neu02_VEGF, Neu03_CCL3_CCL4, Neu04_IL1β, Neu05_CXCR4, Neu06_IFN-Stimulated, Neu07_Proliferative, and Neu08_B-cell_related. Notably, the presence of IFN-Stimulated neutrophils was positively correlated with the efficacy of immunotherapy in GAC, a finding that was further validated through analyses of public datasets and in-house cohort studies employing multiplex immunohistochemistry. Additionally, IFN-Stimulated neutrophils served as prognostic indicators across multiple datasets. Investigations revealed that these cells engage in significant cellular communication with other immune components within the tumor microenvironment, including CD8+ T cells, macrophages, and B cells, thereby promoting a pro-inflammatory and anti-tumor phenotype. Importantly, pan-cancer analyses demonstrated the consistent prognostic and immunotherapy efficacy-predicting potential of IFN-Stimulated neutrophils across various cancer types. Conclusions: IFN-Stimulated neutrophils represent a promising biomarker for predicting immunotherapy response and patient prognosis in GAC. Our findings offer novel insights into the underlying mechanisms of immunotherapy and highlight potential avenues for personalized treatment strategies in the management of GAC.
Observational study of the extent of lymph node metastasis among patients who underwent pancreatoduodenectomy for non-ampullary duodenal cancer using the National Clinical Database in Japan.
Authors: Yasuhiro Kodera, Masamichi Hayashi, Hiroyuki Yamamoto, Keisuke Kurimoto, Haruyoshi Tanaka, Hideki Takami, Yoshihiro Kakeji
Journal: Journal of Clinical Oncology (2025)

798 Background: Non-ampullary duodenal cancer (NPDC) is a rare cancer that occurs in 0.3% of all cancers of the gastrointestinal tract. The first Japanese guidelines for this entity were published in 2021, and resection by pancreatoduodenectomy was weakly recommended as a standard treatment. Although presence of regional lymph node metastasis was identified as a prognostic factor among patients who underwent resection with curative intent, the recommendation concerning the optimal extent of lymphadenectomy based on big data was lacking. Methods: We conducted an observational study of patients who underwent pancreatoduodenectomy for NPDC between 2018 and 2021 in Japan, using the National Clinical Data (NCD) database. The NCD database is web-based, is linked with the board certification systems of several domestic surgical societies and covers &gt;95% of the operations carried out by surgeons at 5,728 institutions in Japan. All cases of pancreatoduodenectomy for NPSC were retrieved from the NCD database after rigorously checking appropriateness of the patient selection, and surgeons in charge of these patients were invited by e-mails to fill in some additional data for this study during a time slot of Oct 2022 ~March 2023. Data thus obtained were the analyzed with particular focus on the incidence of metastases to each lymph node station, stratified by the tumor location in relation to the papilla. In addition, safety of surgery was compared between high-volume (institutions conducting ≥30 major hepatobiliary-pancreatic surgery) and low-volume (&lt;30) hospitals. The study was funded in part by the Japanese Ministry of Health, Labor and Welfare as a project to create guidelines for rare cancers. Results: Data of 881 patients from 600 institutions were obtained for the analysis. Male constituted 68% and the median age was 70 years. The depth of invasion and presence of nodal metastasis were significant prognostic factors. The median number of lymph node retrieval was similar between the high-volume and low-volume hospitals (19: 95%CI 12~27 versus 18: 95% CI 11~25). Distribution of metastatic nodes depended on the location of tumor. Incidence of nodal metastasis exceeded 10% in lymph node station Nos. 5, 6, 7, 8 and 9 in cancers located on the oral side of the papilla. Thus, stomach-conserving pancreatoduodenectomy was considered appropriate only for cancers located distal to the papilla. The incidences of Grade IIIb~IVb complications (4% versus 7.1%), Grade V complications (0.4% versus 1.9%), and mortality within 30 days (0.4% versus 2.6%) were lower in high-volume hospitals. Conclusions: Stomach-preserving pancreatoduodenectomy is recommended only for NDPC located distal to the papilla. Centralization of surgery may be desirable.
Role of cfDNA and DNA integrity index (DII) in colon cancer in response to surgery.
Authors: Vipul Goyal, Chandramohan Krishnana Nair, Madhu Muralee, Mira Wagh
Journal: Journal of Clinical Oncology (2025)

236 Background: Colorectal cancer diagnosis requires new biomarkers for improved detection and monitoring. cfDNA has shown potential in detecting minimal residual disease, evaluating treatment response, and providing prognostic information. Recent studies highlight cfDNA as a promising molecular marker for early disease detection and progression monitoring. This study aims to evaluate the role of cfDNA and DII in assessing surgical response in CRC patients. The primary objective is to assess cfDNA levels pre- and post-curative resection. Secondary objectives include identifying factors influencing baseline cfDNA levels, evaluating factors affecting DII, and comparing cfDNA and CEA levels in response to surgery. Statistical analyses included descriptive statistics, ROC curve, Student T tests and Fisher's exact test. Methods: The study was designed as a prospective investigation conducted over a period from September 2022 to April 2024 at the Regional Cancer Centre. Forty pathologically proven non metastatic colonic carcinoma planned for primary surgery were included and patients with sepsis and chronic diseases were excluded from the study. Blood samples (10 ml) were collected pre-surgery and at four weeks post-surgery. Plasma cfDNA was extracted, quantified, and analyzed via quantitative real-time PCR using human β-actin as a reference. The DII was calculated as the ratio of 394 bp to 99 bp amplicons of β-actin. Results: The mean age was 62.15 years (range 39-85), with 55% over 60 years. High-risk features included poor differentiation (4.2%), preoperative CEA &gt;5 ng/ml (17.5%), LVI (20.8%), and PNI (6.3%). Surgical approaches included 10 laparoscopic, 29 open, and 1 converted from laparoscopic to open due to excessive bleeding. Overall stage grouping showed 18 patients in Stage III, and 11 each in Stage I and II. Median pre- and postoperative cfDNA levels were 24.2 ng/μl and 29.6 ng/μl (p=0.83), and median DNA integrity index levels were 1.1 and 1.0 (p=0.95). Preoperative cfDNA levels averaged 24.2 ng/μl and postoperative levels 29.6 ng/μl (p = 0.83); DII levels were 1.1 preoperatively and 1.0 postoperatively (p = 0.95). Postoperative cfDNA levels decreased in 21 patients and increased in 19, while DII decreased in 20 and increased in 20. Significant associations were noted for cfDNA changes with surgery type and high-risk features. ROC analysis revealed cfDNA cut-off at 275 ng/μl, DII at 1.5, and CEA at 4 µg/L. Sensitivities for cfDNA and DII were 66.67% and 100%, respectively, with combined sensitivity reaching 100%. Conclusions: Persistent high cfDNA levels post-surgery suggest potential minimal residual disease despite radical resection. The residual disease is a harbinger of systemic failure. Monitoring cfDNA and DII can identify patients at risk for recurrence, guiding intensified adjuvant therapy. Further studies with extended follow-up are recommended to validate these findings. Clinical trial information: CTRI/2023/10/058468 .
Factors and timing of decreased adherence to S-1 in postoperative docetaxel + S-1 therapy for gastric cancer.
Authors: Kazuyoshi Kawakami, Yuka Kimura, Masashi Nakamura, Takashi Yokokawa, Kazuo Kobayashi, Takeshi Aoyama, Wataru Suzuki, Masahiro Hatori, Hisanori Shimizu, Makoto Hiraide, Kenichi Suzuki, Daisuke Takahari, Kensei Yamaguchi, Masakazu Yamaguchi
Journal: Journal of Clinical Oncology (2025)

403 Background: The combination of docetaxel + S-1 (DS) therapy in postoperative adjuvant treatment for gastric cancer has proven to be effective and has become a standard therapy. Clarification of factors involved in and the timing of S-1 non-adherence is important to minimize non-adherence. Methods: Among 92 patients who started DS treatment as postoperative adjuvant chemotherapy for gastric cancer between November 1, 2015 and April 30, 2021 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 90 were eligible for this study. The S-1 adherence rate per cycle was defined as the number of times a patient took S-1 divided by 28. In this study, adherence to S-1 was assessed through pill counts and by asking patients about reasons for non-adherence in interviews at a pharmaceutical outpatient clinic. Elicited reasons for non-adherence were categorized and analyzed. Results: Percentage of remaining S-1 was 3.9% in the first cycle, 7.4% in the second cycle, and 2.0% in the seventh cycle. Median relative dose intensity of S-1 was 80.9%. As reasons for non-adherence, patients most commonly cited nausea/vomiting (18.9%), missed dose (17.6%), and diarrhea (9.9%). From the first to the seventh course, the highest percentage of remaining S-1 was in the second course. Conclusions: Nausea/vomiting, missed dose, and diarrhea were identified as the most common factors for decreased adherence to S-1 in postoperative DS therapy for gastric cancer. Between the first and seventh courses, S-1 adherence decreased the most during the second course, when docetaxel was started. Using this information, we intend to develop methods to improve S-1 adherence in the future.
Real-world survival differences in advanced biliary tract cancer patients with ctDNA detected IDH1 mutations and FGFR2 fusions receiving first-line gemcitabine-cisplatin with and without immunotherapy.
Authors: Richard D. Kim, Courtney Lewis, Adrian Bubie, Nicole Zhang, Keelia Clemens
Journal: Journal of Clinical Oncology (2025)

548 Background: Comprehensive genomic profiling (CGP) is recommended for patients (pts) with metastatic BTC (mBTC) given its aggressive, heterogeneous disease profile. Liquid biopsy is a rapid, non-invasive option with high concordance to tissue-based CGP. First-line (1L) therapy in mBTC is gemcitabine-cisplatin (GemCis) +/- durvalumab or pembrolizumab (IO) regardless of CGP results. However, data suggests pts with targetable alterations may have worse outcomes with addition of IO compared to all comers. We examined outcomes for mBTC pts receiving 1L GemCis vs. GemCis+IO following ctDNA-detected IDH1 mutation ( IDH1 +) or FGFR2 fusion ( FGFR2 +). Methods: Real-world data was sourced from GuardantINFORM, which comprises aggregated commercial payer health claims and de-identified records from pts with clinical ctDNA testing via Guardant360 (G360). Pts with mBTC and &gt;1 treatment claim after G360 results, and IDH+ or FGFR2+ between April 2019 and June 2024 were analyzed. Only pts treated with 1L GemCis +/- IO were included. Outcomes were assessed via real-world time to treatment discontinuation (rwTTD), real-world time to next treatment (rwTTNT), and real-world overall survival (rwOS), all in months with 95% confidence intervals. Log-rank test was used to compare Kaplan-Meier survival curves. Results: 412 pts were IDH1+ and 154 were FGFR2+ . In the IDH1 + cohort, 184 pts were treated with GemCis and 106 pts with GemCis+IO. Pts receiving GemCis demonstrated improved rwOS vs. GemCis+IO [27.2 (23.6-37.8) vs. 16 (13.6-19.9) mo.; HR=0.4 (95CI 0.27-0.59), p&lt;0.001]; there was no difference in rwTTNT [13 (10.8-14.3) vs. 10 (8.4-12.3); HR=0.85(95CI 0.6-1.22), p=0.4] or rwTTD [4.8 (4.1-5.5) vs. 6.6 (4.7-8.1); HR=1.17 (95CI 0.9-1.5), p=0.25]. Similarly, in the FGFR2 + cohort, pts receiving GemCis + IO (n=44) had worse rwOS than pts on GemCis (n=70) [NR (15.6-NR) vs. 43 (34.2-2.1); HR=0.37(95CI 0.18-0.74), p=0.005], with no difference in rwTTNT [8.9 (4.89-NR) vs. 13.78 (7.42-NR); HR=0.63 (95CI 0.36-1.1), p=0.1] or rwTTD [5.0 (3.1-7.8) vs. 4.2 (3.5-5.5); HR=1.08 (95CI 0.72-1.6), p=0.7]. Among all mBTC pts receiving GemCis+IO (n=1113), non- IDH1 + pts (n=1007) had numerically better rwOS compared to IDH1 + pts (n=106) [18.6 (17.2-21.3) vs. 16.0 (13.6-19.);HR=0.76 (95CI 0.6-1.03), p=0.075]. No survival difference was observed between IDH1+ (n=184) and non- IDH1 + (n=2333) pts receiving GemCis [27.2 (23.6-37.8) vs. 26.2 (24.5-28.2); HR=1.08 (95CI 0.88-1.32), p=0.4]. Conclusions: Addition of IO to GemCis in IDH1 + and FGFR2 + mBTC pts resulted in decreased rwOS. This data supports ctDNA CGP to inform clinical decision-making prior to 1L as well as at progression. Further studies in clinical cohorts are needed to confirm these findings.
<i>TP53</i> Y220C mutations in colorectal carcinoma (CRC): A genomic landscape study.
Authors: Deevyashali Parekh, Jeffrey S. Ross, Nimisha Srivastava, Tamara Jamaspishvili, Alina Basnet
Journal: Journal of Clinical Oncology (2025)

239 Background: Inactivating genomic alteration (GA) of the TP53 tumor suppressor gene leads to inactivation of p53 protein and is currently the most frequently associated GA across all cancers. Colorectal cancer is a common and lethal subtype of cancer, in the top 5 for incidence, prevalence and cancer-related deaths worldwide. TP53 is the second most frequent GA identified in clinically advanced CRC. It has been postulated that GA in TP53 not only affects the molecular biology of malignant cells but also impacts the tumor microenvironment in CRC. This GA is currently untargetable by approved drugs however, recently a novel approach designed to revert to wild type functioning of TP53 inactivated by Y220C base substitution has gained significant clinical interest. Methods: 67,301 cases of clinically advanced CRC underwent hybrid capture based comprehensive genomic profiling to assess all classes of GA. Cases were sequenced to a mean coverage depth of 650X with microsatellite instability (MSI) status and tumor mutation burden (TMB) determined from the sequencing data and PD-L1 expression measured by immunohistochemistry using the DAKO tumor proportional staining system (low positive set at 1-49% staining and high positive set at ≥50% staining). Results: 422 (0.6%) of the CRC featured the TP53 Y220C GA (Y220C+). When compared with the CRC that were TP53 Y220C negative (Y220C-), the Y220C+ cases were of similar age, gender and number of GA per tumor. The Y220C- cases has significantly higher frequencies of MSI status (6.1% vs 2.2%; p=.0007) and TMB levels greater &gt;10 mutations/Mb (8.7% vs 4.7%; p=.004). The Y220C+ featured lower frequencies of GA in PIK3CA (12.9% vs 18.6%; p=.002), BRAF (8.8% vs 10.1%; NS) and PTEN (7.4% vs 8.3%, NS) and a higher frequency of ERBB2 amplification (5.0% vs 2.7%; p=.004). GA in APC , KRAS , NRAS , BRCA2 , EGFR and MET were similar in both Y220C+ and Y220C- CRC. PD-L1 low expression was similarly infrequent (12.1% to 16.7% range) in both groups. Conclusions: The potentially targetable TP53 Y220C short variant mutation is uncommon in clinically advanced CRC but is associated with unique genomic and biomarker characteristics. Further research might elucidate subpopulations or CRC subtypes with a greater frequency of this mutation who might benefit from a novel targeted therapy. CRC TP53 Y220C+(422 Cases) CRC TP53 Y220C-(66,879 Cases) P Value Gender 41.2% F/ 58.8% M 44.4% F/55.6% M NS Median Age (range) 62 (23-89+) 61 (8-89+) NS GA/tumor 6.1 6.5 NS TP53 non-Y220C GA 16.1% 75.7% &lt;.0001 PIK3CA 12.9% 18.6% .002 ERBB2 6.2% (5.0% amp) 5.1% (2.7% amp) .004 (amp) MSI High 2.2% 6.1% .0007 TMB &gt; 10 mut/Mb 4.7% 8.7% .004 PD-L1 Low (1-49%TPS)/ PD-L1 High (&gt;50% TPS) 16.7% (132 cases)/2.3% 12.1% (20,759 cases)/1.4% NS
Total cost of care of immune-oncology treatments for unresectable hepatocellular carcinoma: A Singapore healthcare perspective analysis.
Authors: John Fullarton, Serene Yap, Tania Krivasi, Barry Rodgers-Gray, Doreen Tay
Journal: Journal of Clinical Oncology (2025)

642 Background: Tremelimumab + durvalumab (STRIDE) and atezolizumab + bevacizumab are recommended first-line immune-oncology treatment options for unresectable hepatocellular carcinoma (uHCC). This study aimed to quantify the total economic burden to the Singapore healthcare system of treating patients with uHCC using STRIDE versus atezolizumab + bevacizumab. Methods: A model was developed to estimate the total cost of care of using STRIDE or atezolizumab + bevacizumab, which followed patients with uHCC eligible for first-line systemic therapy, considering direct medical costs. Costs considered in the model included treatment acquisition and administration, endoscopy, healthcare resource use, and cost for treating grade ≥3 treatment-emergent adverse events (TEAEs). Data on treatment regimens and TEAEs were taken from the HIMALAYA (STRIDE) and IMbrave150 (atezolizumab + bevacizumab) trials. Resource use rates were based on an average of 168 days treatment for both regimens. All costs were obtained from Singaporean sources. Results: The total cost of care for STRIDE and atezolizumab + bevacizumab was estimated at SGD$40,277 (USD$30,932) and SGD$43,605 (USD$33,487) per patient, respectively. This translates into an average cost savings of SGD$3,328 (USD$2,555]) per patient when treated with STRIDE compared to atezolizumab + bevacizumab. The main driver of cost savings was treatment acquisition and administration (-SGD$1,917 [-USD$1,472], -6%) though lower costs were also associated with resource use (-SGD$927 [-USD$712], -8%), endoscopy (-SGD$342 [-USD$263], -77%) and TEAE management (-SGD$141 [-USD$108], -74%). Assuming an incident population of 260 patients eligible for treatment, the total burden was estimated at SGD$10,489,604 (USD$8,055,696) when all patients were treated with STRIDE, and SGD$11,356,273 (USD$8,721,271) when treated with atezolizumab + bevacizumab (Table). The incremental cost offset to the health plan was SGD$866,669 (USD$665,575) when treated with STRIDE. Conclusions: This study suggests that STRIDE offers cost savings over atezolizumab + bevacizumab for uHCC treatment in the Singapore healthcare system. Additional real-world evidence studies are warranted to capture the long-term survival benefits and associated treatment costs. Annual cost of care based on 260 patients receiving first-line immune-oncology treatment. Category STRIDE Atezolizumab + Bevacizumab Incremental difference Endoscopy costs $26,358 $115,555 -$89,197 Resource Use costs* $2,607,000 $2,848,307 -$241,307 Adverse events costs $12,899 $49,716 -$36,817 Treatment acquisition and administration $7,843,347 $8,342,696 -$499,349 TOTAL $10,489,604 $11,356,273 -$866,669 All costs in SGD$. *Includes: physician visits; laboratory and radiological tests; and hospitalisation.
Comparison of efficacy and safety of PD-1 and PD-L1 antibodies in combination with hepatic arterial infusion chemotherapy and target therapy for unresectable intrahepatic cholangiocarcinoma: A multicenter retrospective study.
Authors: Xinhao Xiong, Qiaoxuan Wang, Wei Dai, Rongce Zhao, Jie Mei, Zehao Zheng, Junyu Gan, Longzhou Xu, Jibin Li, Lie Zheng, Wei Wei, Jian-Hong Zhong, Rongping Guo, Shaohua Li
Journal: Journal of Clinical Oncology (2025)

553 Background: Immune checkpoint inhibitors (ICIs) in combination with hepatic arterial infusion chemotherapy (HAIC) and target therapy have shown promising antitumor activity in unresectable intrahepatic cholangiocarcinoma (iCCA). The present study aimed to compare the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors in this setting. Methods: In this multicenter retrospective study, we included patients with iCCA who received ICIs + HAIC + target therapy from June 2018 to June 2023. Propensity score matching (PSM) was performed to reduce confounding factors. Patients were divided into two groups: those treated with PD-L1 antibody + HAIC + target therapy (Group A) and those treated with PD-1 antibody + HAIC + target therapy (Group B). Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were compared between the two groups. Adverse events were assessed according to CTCAE v5.0. Results: A total of 336 patients met the inclusion criteria and were enrolled for analysis. There were no significant differences in OS, PFS, or ORR between the two groups (median OS: 17.7 vs. 25.3 months, P=0.139; median PFS: 8.3 vs. 10.0 months, P=0.534; ORR: 48.4% vs. 31.1%, P=0.051). Following PSM (ratio = 3, caliper = 0.2), 30 patients in Group A and 83 patients in Group B were included. The ORR, according to the modified RECIST criteria, was significantly higher in Group A compared to Group B (50% vs. 28.9%, P=0.037). However, no significant difference in PFS (median 10.0 vs. 9.0 months, P=0.29) or OS (median 17.6 vs. 22.8 months, P=0.293) was observed between the two groups. Adverse events (AEs) occurred in all 113 patients (100%), wherein grade 3–4 AEs were reported for 12 (10.6%) patients in group A and 45 (39.8%) in group B. There was a tendency for Group A to have a lower incidence of grade 3–4 AEs compared to Group B (40.0% vs. 54.2%, P=0.182),although this difference was not statistically significant. Conclusions: This study found that in the treatment combining ICIs with HAIC and target therapy for unresectable iCCA, Group A demonstrated a superior tumor response and a more favorable safety profile.