2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/2iy5wruuedsh6.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/00yc7rcvua6a7.js","/_next/static/immutable/chunks/37ktb71aq3480.js","/_next/static/immutable/chunks/2d50b-7eu4558.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/2d6noqpp6ehas.js","/_next/static/immutable/chunks/1sx186c93bpzg.js","/_next/static/immutable/chunks/3dc-1n866s65i.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2w1bvggzb0ga8.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T7bf,TAR-200 is a first-in-class intravesical drug-releasing system designed to provide sustained delivery of gemcitabine in the bladder. TAR-200 alone or in combination with cetrelimab (PD-1 inhibitor) could improve outcomes in patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC) ineligible for or refusing radical cystectomy. In this phase IIb parallel cohort study, patients with BCG-unresponsive carcinoma in situ (CIS) with/without papillary disease received TAR-200 monotherapy (Cohort 2 [C2]), TAR-200 plus cetrelimab (C1), or cetrelimab monotherapy (C3). Patients with BCG-unresponsive high-risk papillary disease-only NMIBC received TAR-200 monotherapy (C4). TAR-200 was dosed through month 24 and cetrelimab through month 18. Primary end points were centrally confirmed overall complete response (CR) rate (C1-3) or disease-free survival (DFS) rate (C4) (ClinicalTrials.gov number: NCT04640623). At data cutoff (March 31, 2025), 53, 85, 28, and 52 patients were treated in C1-4, respectively. In C2, CR rate and median duration of response were 82.4% (95% CI, 72.6 to 89.8) and 25.8 months (95% CI, 8.3 to not estimable), respectively. In C4, 6-, 9-, and 12-month DFS rates were 85.3% (95% CI, 71.6 to 92.7), 81.1% (95% CI, 66.7 to 89.7), and 70.2% (95% CI, 51.6 to 82.8), respectively. In C1 and C3, CR rates were 67.9% (95% CI, 53.7 to 80.1) and 46.4% (95% CI, 27.5 to 66.1), respectively. Rates of grade ≥3 treatment-related adverse events (AEs) were 12.9%, 13.5%, 37.7%, and 7.1% in C2, C4, C1, and C3, respectively, and of serious treatment-related AEs, 5.9%, 5.8%, 15.1%, and 3.6%. No treatment-related deaths occurred. TAR-200 monotherapy was well tolerated, with a high CR rate, durable responses, and prolonged DFS in patients with BCG-unresponsive high-risk NMIBC. TAR-200 monotherapy offered a more favorable risk-benefit profile versus TAR-200 plus cetrelimab or cetrelimab alone in BCG-unresponsive CIS.31:Tb02, PURPOSE TAR-200 is a first-in-class intravesical drug-releasing system designed to provide sustained delivery of gemcitabine in the bladder. TAR-200 alone or in combination with cetrelimab (PD-1 inhibitor) could improve outcomes in patients with bacillus Calmette-Guérin (BCG)–unresponsive high-risk non–muscle-invasive bladder cancer (NMIBC) ineligible for or refusing radical cystectomy. METHODS In this phase IIb parallel cohort study, patients with BCG-unresponsive carcinoma in situ (CIS) with/without papillary disease received TAR-200 monotherapy (Cohort 2 [C2]), TAR-200 plus cetrelimab (C1), or cetrelimab monotherapy (C3). Patients with BCG-unresponsive high-risk papillary disease–only NMIBC received TAR-200 monotherapy (C4). TAR-200 was dosed through month 24 and cetrelimab through month 18. Primary end points were centrally confirmed overall complete response (CR) rate (C1-3) or disease-free survival (DFS) rate (C4) (ClinicalTrials.gov number: NCT04640623 ). RESULTS At data cutoff (March 31, 2025), 53, 85, 28, and 52 patients were treated in C1-4, respectively. In C2, CR rate and median duration of response were 82.4% (95% CI, 72.6 to 89.8) and 25.8 months (95% CI, 8.3 to not estimable), respectively. In C4, 6-, 9-, and 12-month DFS rates were 85.3% (95% CI, 71.6 to 92.7), 81.1% (95% CI, 66.7 to 89.7), and 70.2% (95% CI, 51.6 to 82.8), respectively. In C1 and C3, CR rates were 67.9% (95% CI, 53.7 to 80.1) and 46.4% (95% CI, 27.5 to 66.1), respectively. Rates of grade ≥3 treatment-related adverse events (AEs) were 12.9%, 13.5%, 37.7%, and 7.1% in C2, C4, C1, and C3, respectively, and of serious treatment-related AEs, 5.9%, 5.8%, 15.1%, and 3.6%. No treatment-related deaths occurred. CONCLUSION TAR-200 monotherapy was well tolerated, with a high CR rate, durable responses, and prolonged DFS in patients with BCG-unresponsive high-risk NMIBC. TAR-200 monotherapy offered a more favorable risk-benefit profile versus TAR-200 plus cetrelimab or cetrelimab alone in BCG-unresponsive CIS. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"gemcitabine: generic Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on gemcitabine (generic). Clinician-written summaries and actionable practice insights. 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the strength of the clinical validation is difficult to assess without sample size data.","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.08.003","tag_type":"warning","value":"'practice_changing' impact flag applied with caution: findings are translational/correlative and have not been confirmed in a prospective or interventional trial.","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.08.003","tag_type":"warning","value":"Study design label is ambiguous — this combines lab-based resistance modeling with retrospective cohort analysis rather than fitting a single canonical design category.","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.08.003","tag_type":"warning","value":"The study design mixes in vitro resistance modeling with retrospective human cohort analysis — causality in the clinical findings remains unproven.","value_numeric":null}],"summaries":{"what_studied":"This study examined whether gemcitabine-cisplatin (GC) chemotherapy reduces Nectin-4 expression and causes cross-resistance to enfortumab vedotin (EV) in bladder cancer, using patient-derived in vitro models and two independent human cohorts (matched pre/post-neoadjuvant and primary/metastatic specimens).","key_result":"In vitro GC-resistance consistently downregulated membranous Nectin-4 and induced EV cross-resistance; this Nectin-4 loss was validated in both human cohorts and was linked to an EMT-like transcriptional shift, with TGF-β signaling emerging as a potential druggable vulnerability.","limitations":"In vitro resistance models may not fully replicate the tumor microenvironment; cohort sizes for clinical validation are not specified in the abstract; causality between EMT reprogramming and Nectin-4 loss in patients remains correlative.","practice_takeaway":"In postplatinum settings, consider assessing membranous Nectin-4 expression before initiating EV therapy, as prior GC chemotherapy may reduce target expression and blunt EV efficacy. TGF-β pathway inhibition may warrant further investigation as a salvage strategy in GC-resistant bladder cancer."}},{"doi":"10.1038/s43018-026-01225-z","pmid":"42675216","title":"l-Glutamine in combination with first-line gemcitabine and nab-paclitaxel in advanced pancreatic ductal adenocarcinoma: an open-label, single-arm, phase 1 GlutaPanc trial","journal_title":"Nature Cancer","journal_issn":"2662-1347","published_at":"2026-08-31T00:00:00.000Z","url":"https://doi.org/10.1038/s43018-026-01225-z","source_score":30,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-06T06:23:04.218Z","updated_at":"2026-09-06T06:23:04.218Z","tags":[{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"brand","value":"Abraxane","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"brand","value":"Endari","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"condition","value":"Pancreatic Ductal Adenocarcinoma","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"generic","value":"L-glutamine","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"generic","value":"nab-paclitaxel","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"modality","value":"Amino Acid Supplement","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"modality","value":"Nucleoside Analog","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"modality","value":"Taxane","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"sample_size","value":"n=16","value_numeric":16},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"study_design","value":"Phase 1 Single-Arm Trial","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"warning","value":"Historical comparison to the MPACT trial (GA alone) is informal and not adjusted for patient selection differences; the claimed doubling of ORR and tripling of OS should be interpreted cautiously.","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"warning","value":"Single-center study (Cedars-Sinai Medical Center) with n=16; results may not generalize to broader PDAC populations.","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"warning","value":"The full text provided is primarily the clinical trial protocol (version 3, dated September 2021), not the final published results paper. Efficacy outcomes (ORR 44%, CR 12.5%, PFS 8.5 months, OS 22 months) and the 66.7% grade ≥3 adverse event rate are cited only in the abstract; detailed results tables and patient-level data are not present in the provided text.","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01225-z","tag_type":"warning","value":"The paper is dated 2026-08-31 (Nature Cancer), but today's date is September 6, 2026—this is a very recently published article and has not yet undergone broad post-publication scrutiny.","value_numeric":null}],"summaries":{"what_studied":"Single-arm, open-label phase 1 trial (GlutaPanc) evaluating oral FDA-approved L-glutamine (0.1–0.3 g/kg twice daily) added to standard-dose gemcitabine and nab-paclitaxel (GA) as first-line therapy in 16 treatment-naive adults with advanced PDAC, using an adaptive Bayesian (EWOC) dose-escalation design over 28-day cycles.","key_result":"The RP2D was established at the maximum doses of both L-glutamine (0.3 g/kg BID) and GA. Tumor shrinkage occurred in 94% of evaluable subjects; ORR was 44% (including 12.5% complete responses). Median PFS was 8.5 months (95% CI 6–NR) and median OS was 22 months (95% CI 11–NR)—roughly double the ORR and triple the OS compared to historical GA alone (MPACT trial: ORR 23%, median OS 8.5 months). Grade ≥3 treatment-related adverse events occurred in 66.7%, primarily attributed to GA.","limitations":"Very small sample size (n=16) at a single center limits generalizability. No randomized comparator arm; historical comparisons are indirect and confounded. Efficacy data are preliminary secondary endpoints only—no formal hypothesis testing was powered.","practice_takeaway":"These early phase 1 data suggest adding oral L-glutamine to gemcitabine/nab-paclitaxel is feasible and may meaningfully improve response and survival in advanced PDAC, but results must be confirmed in a randomized trial before practice change. The RP2D of L-glutamine 0.3 g/kg BID with full-dose GA supports design of a phase 2/3 study."}},{"doi":"10.1001/jamasurg.2026.3716","pmid":"42647021","title":"Neoadjuvant Chemotherapy With or Without Radiotherapy in Resected Pancreatic Ductal Adenocarcinoma","journal_title":"JAMA Surgery","journal_issn":"2168-6254","published_at":"2026-08-26T00:00:00.000Z","url":"https://doi.org/10.1001/jamasurg.2026.3716","source_score":11,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-01T06:21:00.987Z","updated_at":"2026-09-01T06:21:00.987Z","tags":[{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"category","value":"Surgery","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"condition","value":"Pancreatic Ductal Adenocarcinoma","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"generic","value":"fluorouracil","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"generic","value":"irinotecan","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"generic","value":"leucovorin","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"generic","value":"nab-paclitaxel","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"generic","value":"oxaliplatin","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"modality","value":"Chemotherapy","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"modality","value":"Radiotherapy","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"sample_size","value":"n=800","value_numeric":800},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"warning","value":"Patients who did not proceed to surgery after neoadjuvant treatment were excluded, which may introduce survivorship bias favoring both groups.","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"warning","value":"Propensity score matching was applied retrospectively; unmeasured confounders (e.g., performance status, radiation technique/dose heterogeneity) may persist.","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.3716","tag_type":"warning","value":"The study is limited to two referral centers; results may not generalize to community or lower-volume settings.","value_numeric":null}],"summaries":{"what_studied":"This retrospective propensity score-matched cohort study evaluated whether adding preoperative radiotherapy to neoadjuvant chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel) improved oncologic outcomes in 800 patients undergoing curative-intent resection for pancreatic ductal adenocarcinoma at 2 high-volume centers (2015–2023), with a median follow-up of 44 months.","key_result":"Adding radiotherapy improved pathologic markers (R0 resection: 85.0% vs 52.2%; node-negative disease: 61.5% vs 33.6%; pCR: 6.6% vs 4.4%), but did not improve event-free survival (HR 1.10; 95% CI 0.88–1.37; P=.38), overall survival (HR 1.02; 95% CI 0.79–1.32; P=.84), or locoregional recurrence rates (subdistribution HR 0.90; 95% CI 0.53–1.54; P=.71). Distant recurrence was the dominant first failure in both groups (~50%).","limitations":"- Retrospective design with inherent selection bias, despite propensity matching.\n- Two-center study limits generalizability; radiotherapy techniques and doses may vary.\n- Patients who progressed on chemotherapy and never reached surgery were excluded, potentially enriching for favorable biology in both groups.","practice_takeaway":"Adding radiotherapy to neoadjuvant chemotherapy before pancreatic resection improves pathologic response but does not translate into survival benefit — systemic control remains the priority. Routine use of preoperative radiotherapy in resectable or borderline-resectable pancreatic cancer should not be adopted outside of clinical trials."}},{"doi":"10.1001/jamasurg.2026.2988","pmid":"42525419","title":"Maximal Ablative Irradiation Because of Encasement for Patients With Locally Advanced Pancreatic Cancer","journal_title":"JAMA Surgery","journal_issn":"2168-6254","published_at":"2026-07-29T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13420186/","source_score":6,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-04T18:17:40.930Z","updated_at":"2026-08-04T18:17:40.930Z","tags":[{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"category","value":"Surgery","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"condition","value":"Locally Advanced Pancreatic Cancer","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"condition","value":"Pancreatic Adenocarcinoma","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"generic","value":"capecitabine","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"generic","value":"fluorouracil","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"generic","value":"irinotecan","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"generic","value":"leucovorin","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"generic","value":"nab-paclitaxel","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"generic","value":"oxaliplatin","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"modality","value":"Ablative Radiation Therapy","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"modality","value":"Chemotherapy","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"sample_size","value":"n=48","value_numeric":48},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"study_design","value":"Phase 2 Non-Randomized Clinical Trial","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"warning","value":"Full text is under PMC embargo until July 29, 2027; structured data extracted from abstract and results section only — subgroup analyses and full toxicity tables are not available for review.","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"warning","value":"Median age of 67 years with a range of 50–80 skews toward older adults; findings may not apply to younger patients or those with different performance status.","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2988","tag_type":"warning","value":"No comparator arm was included; observed survival rates cannot be attributed to A-RT over induction chemotherapy alone without a randomized comparison.","value_numeric":null}],"summaries":{"what_studied":"Phase 2 single-arm trial (NCT03523312) at Memorial Sloan Kettering evaluated hypofractionated ablative radiation therapy (A-RT: 67.5 Gy/15 fractions or 75 Gy/25 fractions) with capecitabine, followed by surgical evaluation, in 48 patients with LAPC remaining unresectable after ≥3 months of induction chemotherapy (94% mFOLFIRINOX).","key_result":"27% of patients (13/48) achieved resection; 2-year overall survival was 38% for the full cohort, 54% (95% CI, 33%–89%) in resected patients vs. 31% (95% CI, 19%–51%) in unresected patients. Two-year local progression rates were low (11–15%), though 2-year distant metastasis reached 73%. No 90-day postoperative deaths occurred; grade III+ late RT toxicity affected 26.1% of participants.","limitations":"Single-arm, non-randomized design at a single high-volume center limits generalizability and precludes causal inference. Small sample size (n=48) reduces statistical precision. High distant metastasis rate (73% at 2 years) suggests systemic disease remains the dominant failure mode regardless of local control.","practice_takeaway":"For LAPC patients with extensive vascular encasement after induction chemotherapy, hypofractionated A-RT can convert ~27% to resectability without increasing surgical morbidity and provides durable local control even in unresected patients. Clinicians should weigh this approach against the high distant metastasis risk and refer patients to high-volume centers experienced with ablative dose regimens."}},{"doi":"10.1056/nejmoa2601486","pmid":"42485627","title":"Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer","journal_title":"New England Journal of Medicine","journal_issn":"0028-4793","published_at":"2026-07-22T00:00:00.000Z","url":"https://doi.org/10.1056/nejmoa2601486","source_score":148,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-31T13:37:02.697Z","updated_at":"2026-07-31T13:37:02.697Z","tags":[{"paper_doi":"10.1056/nejmoa2601486","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"brand","value":"Keytruda","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"brand","value":"Padcev","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"condition","value":"Muscle-Invasive Bladder Cancer","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"generic","value":"cisplatin","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"generic","value":"enfortumab vedotin","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"generic","value":"pembrolizumab","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"modality","value":"Antibody-Drug Conjugate","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"modality","value":"PD-1 Inhibitor","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"modality","value":"Platinum-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"sample_size","value":"n=808","value_numeric":808},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"warning","value":"Brand name 'Padcev' assigned based on known enfortumab vedotin branding; not explicitly stated in the source text.","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"warning","value":"Cisplatin eligibility criteria used for enrollment are not specified in the abstract; generalizability to borderline-eligible patients is uncertain.","value_numeric":null},{"paper_doi":"10.1056/nejmoa2601486","tag_type":"warning","value":"The perioperative design (neoadjuvant + adjuvant EV+pembro vs. neoadjuvant cisplatin-gemcitabine only) means the survival benefit cannot be attributed solely to the neoadjuvant phase; the adjuvant component may contribute substantially.","value_numeric":null}],"summaries":{"what_studied":"Phase 3 open-label RCT (KEYNOTE-B15/EV-304) comparing perioperative enfortumab vedotin + pembrolizumab (neoadjuvant × 4 cycles → cystectomy → adjuvant × up to 18 cycles) vs. neoadjuvant cisplatin-gemcitabine (×4 cycles) → cystectomy in 808 cisplatin-eligible adults with muscle-invasive bladder cancer; median follow-up 33.6 months.","key_result":"At 2 years, EV+pembro improved event-free survival (79.4% vs. 66.2%; HR 0.53, 95% CI 0.41–0.70; P<0.001) and overall survival (86.9% vs. 81.3%; HR 0.65, 95% CI 0.48–0.89; P=0.006), with a pathological complete response rate of 55.8% vs. 32.5% (P<0.001); grade ≥3 adverse events were more frequent with EV+pembro (75.7% vs. 67.2%).","limitations":"- Open-label design may introduce bias in outcome assessment.\n- Adjuvant EV+pembro was given only in the experimental arm, making it impossible to isolate the neoadjuvant contribution alone.\n- Median follow-up of ~34 months may be insufficient to capture late recurrences or long-term OS differences.","practice_takeaway":"For cisplatin-eligible patients with muscle-invasive bladder cancer, perioperative EV + pembrolizumab offers meaningfully better survival and pathological response than cisplatin-gemcitabine, but clinicians should counsel patients on a higher rate of serious adverse events (75.7% vs. 67.2% grade ≥3). This regimen represents a strong candidate to replace cisplatin-based neoadjuvant chemotherapy as the new standard of care."}},{"doi":"10.1158/2159-8290.cd-25-1627","pmid":"41891402","title":"Senescent Cancer-Associated Fibroblasts Drive Early-Stage Lymph Node Metastasis in Pancreatic Cancer through Lactate-Mediated Metabolic–Epigenetic Rewiring","journal_title":"Cancer Discovery","journal_issn":"2159-8274","published_at":"2026-07-08T00:00:00.000Z","url":"https://doi.org/10.1158/2159-8290.cd-25-1627","source_score":38,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-14T13:24:16.512Z","updated_at":"2026-07-14T13:24:16.512Z","tags":[{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"brand","value":"Abraxane","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"condition","value":"Lymph Node Metastasis","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"condition","value":"Pancreatic Ductal Adenocarcinoma","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"generic","value":"chidamide","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"generic","value":"nab-paclitaxel","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"modality","value":"Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"modality","value":"Chemotherapy","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"modality","value":"HDAC Inhibitor","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"modality","value":"Senolytic Agent","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"study_design","value":"Translational Research (Preclinical + Early-Phase Clinical Trial)","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"warning","value":"Sample size for the clinical trial cohort is not reported in the abstract; the sample_size tag has been omitted accordingly.","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"warning","value":"Study design is mixed (preclinical mechanistic work + a preliminary clinical trial); level of evidence reflects the early-phase clinical component. Final clinical trial outcomes (survival, response rates) are not yet reported.","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"warning","value":"Study was published July 8, 2026; today is July 14, 2026 — this is a very recently published paper and peer review status should be independently verified.","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-1627","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously — the clinical findings are preliminary and the trial is ongoing as of publication.","value_numeric":null}],"summaries":{"what_studied":"This study examined how senescent cancer-associated fibroblasts (senCAFs) drive lymph node metastasis (LNM) in early-stage pancreatic ductal adenocarcinoma (PDAC), and whether selectively clearing senCAFs with chidamide could improve chemo-immunotherapy outcomes.","key_result":"senCAFs promoted lymphatic remodeling and LNM by boosting lactate production, which triggered lactylation-mediated serine metabolism to shield lymphatic endothelial cells from oxidative stress; CCR4+ Tregs also accumulated around lymphatic vessels to form an immunosuppressive niche. High-throughput drug screening identified chidamide as a selective senolytic agent; a clinical trial combining chidamide with nab-paclitaxel/gemcitabine plus anti-PD-1/CTLA-4 in metastatic PDAC patients showed preliminary promising results.","limitations":"Clinical trial results are preliminary only (no final efficacy/survival data reported); the study focuses on early-stage LNM but the clinical trial enrolled metastatic PDAC patients, limiting direct translational alignment; mechanistic findings are largely preclinical.","practice_takeaway":"Senescent CAF clearance with chidamide may enhance chemo-immunotherapy efficacy in PDAC — a clinical trial combining chidamide with nab-paclitaxel/gemcitabine and dual checkpoint blockade (anti-PD-1/CTLA-4) is underway and warrants close monitoring for mature results."}},{"doi":"10.1016/j.jhep.2026.06.033","pmid":"42409321","title":"Ivonescimab plus gemcitabine and cisplatin as first-line therapy for advanced biliary tract cancer: a multicenter, open-label phase 2 trial","journal_title":"Journal of Hepatology","journal_issn":"0168-8278","published_at":"2026-07-06T00:00:00.000Z","url":"https://doi.org/10.1016/j.jhep.2026.06.033","source_score":12,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-11T13:33:01.939Z","updated_at":"2026-07-11T13:33:01.939Z","tags":[{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"brand","value":"Ivonescimab","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"condition","value":"Biliary Tract Cancer","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"condition","value":"Extrahepatic Cholangiocarcinoma","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"condition","value":"Gallbladder Cancer","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"condition","value":"Intrahepatic Cholangiocarcinoma","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"generic","value":"cisplatin","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"generic","value":"ivonescimab","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"modality","value":"Bispecific Antibody (PD-1/VEGF Inhibitor)","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"modality","value":"Platinum-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"sample_size","value":"n=30","value_numeric":30},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"study_design","value":"Phase 2 Single-Arm Trial","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"warning","value":"Ivonescimab is currently approved in China for NSCLC indications only; its use in BTC remains investigational.","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"warning","value":"MAP2K7 biomarker findings are entirely post-hoc and exploratory—p values are unadjusted and the evaluable biomarker cohort was only n=15.","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"warning","value":"The ORR and OS results are notably higher than historical controls, but cross-trial comparisons are unreliable due to small sample size, single-arm design, absence of early deaths (suggesting possible selection bias), and a predominantly Chinese patient population with limited extrahepatic cholangiocarcinoma representation (n=1).","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.033","tag_type":"warning","value":"Two separate trial registration numbers (NCT05214482 and NCT06048289) are listed; the paper reports results from a subset arm of a broader multi-cohort study, which may affect interpretation of the sample size and enrollment rationale.","value_numeric":null}],"summaries":{"what_studied":"This multicenter, open-label phase 2 trial evaluated ivonescimab (a bispecific anti-PD-1/VEGF antibody, 20 or 30 mg/kg Q3W) combined with gemcitabine (1000 mg/m²) and cisplatin (25 mg/m²) for up to 8 cycles, then ivonescimab maintenance, in 30 treatment-naive adults with unresectable locally advanced or metastatic biliary tract cancer (BTC). A post-hoc proteomic analysis explored MAP2K7 as a resistance biomarker.","key_result":"ORR was 66.7% (95% CI: 47.2–82.7; 1 CR + 19 PR), DCR was 100%, median PFS was 8.5 months (95% CI: 7.6–10.5), and median OS was 16.8 months (95% CI: 11.1–22.5). All patients had TRAEs; most common were anemia (83.3%), decreased neutrophil count (76.7%), decreased WBC (73.3%), and decreased platelets (73.3%). No treatment-related deaths occurred. MAP2K7 was upregulated in non-responders, and its knockdown enhanced ivonescimab-mediated T-cell activity in co-culture models.","limitations":"- Single-arm design with only 30 patients (all enrolled in China, nearly all intrahepatic cholangiocarcinoma or gallbladder cancer), limiting generalizability and preventing causal inference.\n- No blinded independent central review of efficacy; response assessed by investigators only.\n- Proteomic and MAP2K7 biomarker analyses were post-hoc, non-prespecified, and unadjusted for multiplicity, making all biomarker findings hypothesis-generating only.","practice_takeaway":"Ivonescimab plus gemcitabine/cisplatin showed an ORR of 66.7% and median OS of 16.8 months in advanced BTC—well above historical benchmarks with PD-1/L1 inhibitor plus chemotherapy—but these are single-arm phase 2 data requiring confirmation in an ongoing randomized phase 3 trial (NCT06591520) before practice change. Clinicians may note MAP2K7 expression as a potential future biomarker for patient selection, though it remains investigational."}},{"doi":"10.1016/j.jhep.2026.06.025","pmid":"42402265","title":"Durvalumab with gemcitabine-based chemotherapy regimens in advanced biliary tract cancer: primary results from the phase IIIb TOURMALINE study","journal_title":"Journal of Hepatology","journal_issn":"0168-8278","published_at":"2026-07-06T00:00:00.000Z","url":"https://doi.org/10.1016/j.jhep.2026.06.025","source_score":28,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-09T13:35:55.787Z","updated_at":"2026-07-09T13:35:55.787Z","tags":[{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"brand","value":"Imfinzi","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"condition","value":"Biliary Tract Cancer","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"generic","value":"cisplatin","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"generic","value":"durvalumab","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"modality","value":"Antimetabolite Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"modality","value":"Platinum-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"sample_size","value":"n=142","value_numeric":142},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"study_design","value":"Phase IIIb Non-Randomized Open-Label Trial","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"warning","value":"Median follow-up of ~11.6 months is relatively short; OS and PFS estimates may mature with longer follow-up.","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"warning","value":"Seven different chemotherapy backbones were used across participants; subgroup-level efficacy and safety data per regimen are not reported in the abstract, limiting interpretation of individual combination outcomes.","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"warning","value":"The DOI and publication date (2026-07-06) appear to be future-dated relative to today (2026-07-09); this is flagged but accepted as provided.","value_numeric":null},{"paper_doi":"10.1016/j.jhep.2026.06.025","tag_type":"warning","value":"TOURMALINE is a single-arm phase IIIb study without a randomized comparator; efficacy data (PFS, OS, ORR) are descriptive and cannot establish superiority or non-inferiority vs. standard gem-cis plus durvalumab.","value_numeric":null}],"summaries":{"what_studied":"The phase IIIb TOURMALINE study evaluated the safety and efficacy of first-line durvalumab (1500 mg IV) combined with one of seven investigator-chosen gemcitabine-based chemotherapy regimens in 142 adults with advanced biliary tract cancer (aBTC), including those with poor prognosis, over a median follow-up of ~11.6 months.","key_result":"Grade 3/4 possibly related AEs occurred in 50.7% of participants (95% CI 42.19–59.19) within 6 months, with no treatment-related deaths from serious AEs of special interest. Median PFS was 7.39 months, median OS was 13.50 months, and ORR was 33.1% (95% CI 25.44–41.48).","limitations":"Single-arm design with no comparator group limits causal inference; the 142-participant cohort is relatively small and interim in nature; real-world generalizability is constrained by the investigator's-choice regimen design, which introduces heterogeneity across seven different chemotherapy backbones.","practice_takeaway":"Durvalumab can be combined with a range of gemcitabine-based regimens beyond the standard gem-cis doublet with a manageable safety profile, even in aBTC patients with less favorable disease characteristics. The abbreviated 30-minute durvalumab infusion did not increase infusion-related reactions, supporting its practical use in busy oncology settings."}},{"doi":"10.1097/ju.0000000000005179","pmid":"42330429","title":"Phase 2 Trial of Intravesical Gemcitabine and Docetaxel as First-Line Treatment of Bacillus Calmette-Guérin‒Naïve Nonmuscle-Invasive Urothelial Carcinoma: Updated, 3-Year Outcomes","journal_title":"Journal of Urology","journal_issn":"0022-5347","published_at":"2026-06-22T00:00:00.000Z","url":"https://doi.org/10.1097/ju.0000000000005179","source_score":23,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-14T06:23:22.291Z","updated_at":"2026-09-14T06:23:22.291Z","tags":[{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"condition","value":"Non-Muscle-Invasive Bladder Cancer","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"condition","value":"Urothelial Carcinoma","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"generic","value":"docetaxel","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"modality","value":"Intravesical Chemotherapy","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"sample_size","value":"n=25","value_numeric":25},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"study_design","value":"Phase 2 Single-Arm Trial","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"warning","value":"No randomized comparator arm (e.g., BCG) was included, so comparative efficacy cannot be established.","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"warning","value":"Sex distribution and detailed patient demographics (e.g., age range, performance status) are not reported in the abstract or available full text, limiting full characterization of the cohort.","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005179","tag_type":"warning","value":"Very small sample size (n=25) limits statistical power; confidence intervals are wide and results should be interpreted with caution.","value_numeric":null}],"summaries":{"what_studied":"This prospective, single-arm, open-label phase 2 trial evaluated intravesical gemcitabine plus docetaxel (Gem/Doce) as first-line therapy in 25 BCG-naïve high-risk (HR) NMIBC patients (64% HGT1, 32% HGTa, 36% with CIS), with 6-week induction followed by monthly maintenance for 2 years and a median follow-up of 50 months.","key_result":"High-grade recurrence-free survival (HG-RFS) was 84% at 24 months (21/25; 95% CI 63%–94%) and 80% at 36 months (20/25; 95% CI 58%–91%); no patients progressed during Gem/Doce, and only 2 (8%) required cystectomy. Grade 3 adverse events occurred in 5 patients (20%), including hematuria and UTI.","limitations":"Very small cohort (n=25) from a single-arm trial without a BCG comparator arm limits generalizability and causal inference. Single-institution design with no randomization may introduce selection bias.","practice_takeaway":"For BCG-naïve HR NMIBC patients, intravesical Gem/Doce appears durable at 3 years with an 80% HG-RFS and a manageable safety profile. It may serve as a viable alternative when BCG is unavailable or contraindicated, though larger randomized trials are needed."}},{"doi":"10.1182/bloodadvances.2026019764","pmid":"42269085","title":"Glofitamab plus gemcitabine and oxaliplatin for relapsed/refractory DLBCL: 3-year follow-up of STARGLO","journal_title":"Blood Advances","journal_issn":"2473-9529","published_at":"2026-06-10T00:00:00.000Z","url":"https://doi.org/10.1182/bloodadvances.2026019764","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-06T13:22:15.187Z","updated_at":"2026-08-06T13:22:15.187Z","tags":[{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"brand","value":"Columvi","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"condition","value":"Diffuse Large B-Cell Lymphoma","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"generic","value":"glofitamab","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"generic","value":"oxaliplatin","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"generic","value":"rituximab","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"modality","value":"Bispecific Antibody","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"modality","value":"Chemotherapy","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"warning","value":"Phase 3 classification is confirmed, but the abstract does not specify randomization ratio or blinding status, which may affect bias assessment.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"warning","value":"The brand name 'Columvi' is glofitamab's approved proprietary name but is not explicitly stated in the abstract — clinicians should verify current regulatory labeling.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019764","tag_type":"warning","value":"The paper abstract does not report the total sample size (N); the sample_size tag has been omitted as the value could not be confirmed from the available text.","value_numeric":null}],"summaries":{"what_studied":"The phase 3 STARGLO trial (NCT04408638) evaluated glofitamab plus gemcitabine-oxaliplatin (Glofit-GemOx) vs rituximab plus GemOx (R-GemOx) in ASCT-ineligible patients with relapsed/refractory DLBCL, with a 3-year follow-up (median OS follow-up 35.1 months; data cutoff May 1, 2025).","key_result":"Glofit-GemOx showed superior OS vs R-GemOx (median 25.5 vs 12.5 months; HR 0.60, 95% CI 0.4–0.8), superior PFS (14.4 vs 3.3 months; HR 0.41, 95% CI 0.3–0.6), and a higher complete response rate (58.5% vs 25.3%); in the 2L setting, the 36-month OS rate was 54.6% with Glofit-GemOx vs not reported for R-GemOx, and among 2L patients with primary refractory disease or early treatment failure, 36-month OS was 46.1% vs 16.5%.","limitations":"- Trial enrolled only ASCT-ineligible patients, limiting generalizability to transplant-eligible populations.\n- Subgroup analyses (e.g., 2L vs 3L+, age ≥75) are likely underpowered for definitive conclusions.\n- No new safety signals were noted, but the abstract does not provide granular adverse event data for full safety appraisal.","practice_takeaway":"For ASCT-ineligible R/R DLBCL patients, fixed-duration Glofit-GemOx offers a meaningful OS benefit over R-GemOx, with the strongest gains seen in the second-line setting and in early-relapsing or primary refractory disease — including older patients (≥75 years). Clinicians should consider Glofit-GemOx as an off-the-shelf option with curative potential in this population."}},{"doi":"10.1200/jco-26-00788","pmid":"42223137","title":"Pemigatinib for Unresectable or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor–2 Rearrangement: Results From the Phase III FIGHT-302 Trial","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-06-01T00:00:00.000Z","url":"https://doi.org/10.1200/jco-26-00788","source_score":23,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-19T06:28:59.171Z","updated_at":"2026-08-19T06:28:59.171Z","tags":[{"paper_doi":"10.1200/jco-26-00788","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"brand","value":"Pemazyre","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"condition","value":"Cholangiocarcinoma","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"generic","value":"cisplatin","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"generic","value":"pemigatinib","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"modality","value":"FGFR Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"modality","value":"Platinum-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"sample_size","value":"n=167","value_numeric":167},{"paper_doi":"10.1200/jco-26-00788","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"warning","value":"High crossover rate (n=42 of 84 chemotherapy patients received second-line pemigatinib) substantially confounds the OS analysis.","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"warning","value":"The brand name 'Pemazyre' is listed as an assumed tag; the paper does not explicitly state the brand name.","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"warning","value":"The comparator arm (gemcitabine-cisplatin without immunotherapy) may no longer reflect current standard of care, which in many regions now includes durvalumab or pembrolizumab combinations, reducing direct applicability.","value_numeric":null},{"paper_doi":"10.1200/jco-26-00788","tag_type":"warning","value":"The trial was closed early (n=167 enrolled vs. a presumably larger planned sample) due to a change in the standard of care; this limits power for OS and secondary endpoints, and the nominal P-value for PFS should be interpreted cautiously.","value_numeric":null}],"summaries":{"what_studied":"First-line pemigatinib (13.5 mg once daily) vs gemcitabine-cisplatin chemotherapy in adults with unresectable or metastatic FGFR2-rearranged cholangiocarcinoma; primary endpoint was PFS (phase III FIGHT-302 trial, NCT03656536).","key_result":"Pemigatinib improved median PFS (8.3 vs 6.8 months; HR 0.58 [95% CI, 0.39–0.87]; P = .0078) and ORR (47% vs 15%), with longer median duration of response (14.2 vs 6.3 months); however, median OS was similar (24.4 vs 25.0 months). In the crossover group (n = 42), second-line pemigatinib yielded a median PFS of 8.1 months.","limitations":"- Trial closed early (n = 167 of planned enrollment) due to a change in standard of care, limiting statistical power for OS and other secondary endpoints.\n- Crossover from chemotherapy to pemigatinib (n = 42) likely confounded OS comparison.\n- Standard of care shifted during the trial, reducing generalizability to current treatment landscapes that may include immunotherapy.","practice_takeaway":"In patients with FGFR2-rearranged advanced cholangiocarcinoma, first-line pemigatinib significantly improves PFS and response rates over gemcitabine-cisplatin, though OS benefit was not demonstrated—likely due to early closure and high crossover rates. Clinicians should weigh these results in the context of evolving first-line standards."}},{"doi":"10.1038/s43018-026-01165-8","pmid":"42185478","title":"Gemcitabine and nab-paclitaxel with or without the VDR agonist paricalcitol for metastatic pancreatic cancer: a randomized, multiarm, run-in phase trial","journal_title":"Nature Cancer","journal_issn":"2662-1347","published_at":"2026-05-25T00:00:00.000Z","url":"https://doi.org/10.1038/s43018-026-01165-8","source_score":57,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-29T13:23:16.655Z","updated_at":"2026-05-29T13:23:16.655Z","tags":[{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"condition","value":"Metastatic Pancreatic Cancer","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"generic","value":"nab-paclitaxel","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"generic","value":"paricalcitol","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"modality","value":"Chemotherapy","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"modality","value":"Vitamin D Receptor Agonist","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"sample_size","value":"n=36","value_numeric":36},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"warning","value":"Level of evidence assigned as '2' for a randomized run-in phase trial; this trial was not powered for efficacy, so clinical conclusions should be interpreted cautiously.","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"warning","value":"No brand name for nab-paclitaxel (Abraxane) was explicitly mentioned in the abstract; brand tag omitted to avoid assumption.","value_numeric":null},{"paper_doi":"10.1038/s43018-026-01165-8","tag_type":"warning","value":"The full text pages appear to contain encoding artifacts and minimal readable content; all structured data were extracted from the abstract only.","value_numeric":null}],"summaries":{"what_studied":"A randomized, multiarm, run-in phase trial (NCT03520790) evaluated the safety and pharmacodynamics of adding the VDR agonist paricalcitol (IV or oral) to first-line gemcitabine plus nab-paclitaxel (GA) in 36 patients with metastatic pancreatic cancer, with pre- and on-treatment tumor biopsies.","key_result":"Paricalcitol was safely combined with GA; however, 5/12 (42%) patients on oral paricalcitol developed grade 2–4 hypercalcemia requiring dose reduction. On-treatment biopsies in paricalcitol arms showed decreased αSMA+ fibroblasts, altered fibroblast VDR activation signatures, and increased CD8+ T-cell density and spatial colocalization with tumor cells. Tumor VDR expression was predictive of response in the paricalcitol arms.","limitations":"Very small sample size (n=36, ~12 per arm) limits statistical power and generalizability. This was a run-in safety/pharmacodynamic trial, not powered for efficacy endpoints. Nuclear VDR protein expression was heterogeneous, complicating patient selection.","practice_takeaway":"IV paricalcitol can be added to gemcitabine/nab-paclitaxel without prohibitive toxicity, but oral paricalcitol carries a meaningful risk of hypercalcemia (42% grade 2–4). VDR expression on tumor biopsy may help select patients most likely to benefit, warranting further study in a larger efficacy trial."}},{"doi":"10.20892/j.issn.2095-3941.2025.0748","pmid":"41992753","title":"Poor prognosis outcome tumors, bacteria-infected tumors and nanodrugs: current evidence and hypotheses towards a paradigm change for treatment","journal_title":"Cancer Biology & Medicine","journal_issn":"2095-3941","published_at":"2026-04-15T00:00:00.000Z","url":"https://doi.org/10.20892/j.issn.2095-3941.2025.0748","source_score":131,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-16T13:22:36.268Z","updated_at":"2026-05-16T13:22:36.268Z","tags":[{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"condition","value":"Bacteria-Infected Tumors","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"condition","value":"Biliary Tract Cancer","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"condition","value":"Colorectal Carcinoma","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"condition","value":"Pancreatic Ductal Adenocarcinoma","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"generic","value":"ciprofloxacin","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"generic","value":"doxorubicin","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"modality","value":"Antibiotic Therapy","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"modality","value":"Chemotherapy","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"modality","value":"Nanoparticulate Drug Delivery","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"sample_size","value":"n=2589","value_numeric":2589},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"warning","value":"Publication date (April 15, 2026) is in the future relative to most cited literature; the paper is a perspective/hypothesis article and has not yet undergone prospective clinical validation.","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"warning","value":"Some data points in Figure 2 were collected with AI-assisted literature mining (DeepSeek/ChatGPT); authors state foundational references were manually verified, but this method introduces potential selection bias.","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"warning","value":"The paper presents hypotheses and a narrative synthesis, not a systematic review or meta-analysis; the impact_flag 'practice_changing' reflects the paradigm shift proposed, but the clinical evidence base is preclinical and retrospective.","value_numeric":null},{"paper_doi":"10.20892/j.issn.2095-3941.2025.0748","tag_type":"warning","value":"The sample size tag (n=2,589) refers only to the cited doxorubicin meta-analysis subset, not the overall study population of this review.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates whether intratumoral bacteria contribute to poor prognosis outcome tumors (PPO-tumors) — including pancreatic ductal adenocarcinoma, colorectal carcinoma, and biliary tract cancers — and whether carrier-free antibiotic/chemotherapeutic combinations (e.g., ciprofloxacin + gemcitabine) could re-sensitize these tumors compared to nanoparticulate drug delivery strategies.","key_result":"Three hypotheses are advanced and judged plausible: (1) all PPO-tumors are bacterially infected; (2) bacterial infection enhances vascular permeability (EPR effect) in human PPO-tumors; and (3) all PPO-tumors should be treated upfront with carrier-free antibiotic + chemotherapeutic combinations. Supporting animal data show that carrier-free ciprofloxacin + gemcitabine significantly inhibited E. coli-infected colorectal tumor growth, with results comparable to stimuli-responsive dual-loaded liposomes — yet >80% of nanoparticulate doses still miss the tumor even in rodent models, and a meta-analysis of 14 trials (n=2,589) found no significant efficacy difference between liposomal and free doxorubicin in humans.","limitations":"- No clinically validated method exists to diagnose intratumoral bacterial infection in vivo, so bacterial causation vs. correlation cannot be confirmed.\n- Evidence supporting the hypotheses relies heavily on rodent models and post-resection/post-mortem data, limiting direct clinical translation.\n- The review does not account for antibiotic resistance risks at scale or individual microbiome disruption from empiric antibiotic use.","practice_takeaway":"Clinicians treating PPO-tumors (e.g., pancreatic, colorectal, biliary cancers) may consider adding an approved antibiotic (e.g., ciprofloxacin) to standard chemotherapy from the outset, given that many of these patients already receive antibiotics during treatment and preclinical data suggest this combination can restore chemosensitivity. Retrospective clinical validation of this approach is proposed as a pragmatic next step, given the urgency and high mortality of this patient population."}},{"doi":"10.1016/j.eururo.2026.02.016","pmid":"41945031","title":"Pembrolizumab in Combination With Gemcitabine and Concurrent Hypofractionated Radiation Therapy as Bladder-sparing Treatment for Muscle-invasive Urothelial Cancer of the Bladder: A Multicenter Phase 2 Trial","journal_title":"European Urology","journal_issn":"0302-2838","published_at":"2026-04-06T00:00:00.000Z","url":"https://doi.org/10.1016/j.eururo.2026.02.016","source_score":43,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-07T22:49:50.984Z","updated_at":"2026-05-07T22:49:50.984Z","tags":[{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"brand","value":"Keytruda","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"condition","value":"Muscle-Invasive Bladder Cancer","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"condition","value":"Urothelial Carcinoma","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"generic","value":"pembrolizumab","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"modality","value":"Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"modality","value":"Hypofractionated Radiation Therapy","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"modality","value":"PD-1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"sample_size","value":"n=54","value_numeric":54},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"study_design","value":"Phase 2 Single-Arm Trial","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"warning","value":"BIDFS of 60% is described as 'comparable to standard TMT' by the authors, but no direct historical control data is provided in the abstract to verify this claim.","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"warning","value":"Phase 3 trial results are pending; current findings should be interpreted as hypothesis-generating only.","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"warning","value":"Sex distribution is not explicitly reported in the abstract; 'mixed' is assumed based on typical MIBC trial populations.","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.02.016","tag_type":"warning","value":"The efficacy cohort (n=48) differs from total enrolled (n=54); reasons for exclusion of 6 patients are not detailed in the abstract.","value_numeric":null}],"summaries":{"what_studied":"This multicenter phase 2 trial evaluated the safety and efficacy of adding pembrolizumab to standard trimodality therapy (TMT) — maximal TURBT followed by concurrent gemcitabine and hypofractionated radiation — in patients with muscle-invasive bladder cancer (MIBC), with a 2-year follow-up period.","key_result":"2-year bladder-intact disease-free survival (BIDFS) was 60% (95% CI 45–73%) in 48 efficacy-evaluable patients; 2-year metastasis-free survival was 81% (95% CI 66–92%) and overall survival was 83% (95% CI 69–91%). Grade ≥3 treatment-related adverse events occurred in 25% of patients.","limitations":"Single-arm design without a comparator limits causal inference; modest sample size (n=54 enrolled, n=48 in efficacy cohort) reduces precision; no randomized control to distinguish pembrolizumab's contribution from standard TMT effects.","practice_takeaway":"Adding pembrolizumab to gemcitabine-based chemoradiation appears feasible with a manageable toxicity profile, and BIDFS rates are comparable to standard TMT. Clinicians should await results from ongoing phase 3 trials before adopting this regimen as routine practice."}},{"doi":"10.1200/jco-25-02199","pmid":"41671529","title":"Development and Validation of a Computational Histology Artificial Intelligence–Powered Predictive Biomarker for Selection of Chemotherapy in Advanced Pancreatic Cancer","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-02-11T00:00:00.000Z","url":"https://doi.org/10.1200/jco-25-02199","source_score":42,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-08T06:32:11.246Z","updated_at":"2026-09-08T06:32:11.246Z","tags":[{"paper_doi":"10.1200/jco-25-02199","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"condition","value":"Pancreatic Ductal Adenocarcinoma","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"generic","value":"fluorouracil","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"generic","value":"gemcitabine","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"modality","value":"Computational Pathology / AI Biomarker","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"modality","value":"Fluoropyrimidine-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"modality","value":"Gemcitabine-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"sample_size","value":"n=477","value_numeric":477},{"paper_doi":"10.1200/jco-25-02199","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"study_design","value":"Biomarker Development and Validation Study","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"warning","value":"Specific chemotherapy regimens within the F-chemo and G-chemo categories are not fully disaggregated in the abstract; heterogeneity within each class could affect interpretation.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"warning","value":"The G-pref subgroup showed a TNTD benefit with G-chemo but no OS benefit, which may limit the actionability of this biomarker arm.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02199","tag_type":"warning","value":"The validation cohort is observational (not a randomized trial), so residual confounding cannot be fully excluded even after propensity score weighting. The 'practice_changing' flag is applied cautiously — prospective RCT-level confirmation is still needed before routine clinical adoption.","value_numeric":null}],"summaries":{"what_studied":"The CHAI (Computational Histology AI) platform was used to develop and validate a histomorphology-based biomarker (GvF) from H&E-stained diagnostic biopsies to predict benefit from first-line fluoropyrimidine-based (F-chemo) vs. gemcitabine-based (G-chemo) chemotherapy in patients with advanced pancreatic ductal adenocarcinoma (PDAC), across a multi-institutional development cohort (n=178) and an independent prospective validation cohort (n=299, COMPASS and Know Your Tumor studies).","key_result":"In the validation cohort, F-pref patients treated with F-chemo had meaningfully better OS than those given G-chemo (14.4 vs. 11.7 months; P=.003); G-pref patients had superior TNTD with G-chemo (9.6 vs. 7.2 months; P=.038) but no significant OS difference (14.3 vs. 12.4 months; P=.5). Propensity score-weighted biomarker-treatment interaction was significant for both TNTD (P<.001) and OS (P=.005). RNA subtypes did not predict differential treatment effects (P=.3).","limitations":"- Retrospective/observational design in the validation cohort prevents ruling out selection bias, despite propensity score weighting.\n- The G-pref group showed no significant OS benefit with G-chemo, limiting clinical confidence for that subgroup.\n- Validation was drawn from specific prospective studies (COMPASS, Know Your Tumor), which may not represent all practice settings or treatment protocols.","practice_takeaway":"A one-time AI analysis of a standard H&E biopsy slide may reliably identify which advanced PDAC patients benefit more from fluoropyrimidine- vs. gemcitabine-based first-line therapy. Clinicians should consider this biomarker tool when choosing between FOLFIRINOX-based and gemcitabine-based regimens, particularly to favor F-chemo in F-pref patients where an OS advantage of ~2.7 months was observed."}},{"doi":"10.1200/jco-25-01651","pmid":"40737582","title":"TAR-200 for Bacillus Calmette-Guérin–Unresponsive High-Risk Non–Muscle-Invasive Bladder Cancer: Results From the Phase IIb SunRISe-1 Study","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2025-07-30T00:00:00.000Z","url":"https://doi.org/10.1200/jco-25-01651","source_score":338,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-11-18","doi":"10.1200/jco-25-01651","days":"30","issn":"0732-183X","rank":"5","field":"Clinical Medicine","score":"338","category":"Oncology","categories":["Oncology"],"_categories":["Oncology"]},"pubmed":{"doi":"10.1200/JCO-25-01651","title":"TAR-200 for Bacillus Calmette-Guérin-Unresponsive High-Risk Non-Muscle-Invasive Bladder Cancer: Results From the Phase IIb SunRISe-1 Study.","journal":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology","methods":"","results":"At data cutoff (March 31, 2025), 53, 85, 28, and 52 patients were treated in C1-4, respectively. In C2, CR rate and median duration of response were 82.4% (95% CI, 72.6 to 89.8) and 25.8 months (95% CI, 8.3 to not estimable), respectively. In C4, 6-, 9-, and 12-month DFS rates were 85.3% (95% CI, 71.6 to 92.7), 81.1% (95% CI, 66.7 to 89.7), and 70.2% (95% CI, 51.6 to 82.8), respectively. In C1 and C3, CR rates were 67.9% (95% CI, 53.7 to 80.1) and 46.4% (95% CI, 27.5 to 66.1), respectively. Rates of grade ≥3 treatment-related adverse events (AEs) were 12.9%, 13.5%, 37.7%, and 7.1% in C2, C4, C1, and C3, respectively, and of serious treatment-related AEs, 5.9%, 5.8%, 15.1%, and 3.6%. No treatment-related deaths occurred.","abstract":"$30","keywords":[],"pubmed_id":"40737582","conclusions":"TAR-200 monotherapy was well tolerated, with a high CR rate, durable responses, and prolonged DFS in patients with BCG-unresponsive high-risk NMIBC. TAR-200 monotherapy offered a more favorable risk-benefit profile versus TAR-200 plus cetrelimab or cetrelimab alone in BCG-unresponsive CIS.","publication_date":"2025-07-30T00:00:00"},"crossref":{"DOI":"10.1200/jco-25-01651","URL":"https://doi.org/10.1200/jco-25-01651","ISSN":["0732-183X","1527-7755"],"link":[{"URL":"https://ascopubs.org/doi/pdfdirect/10.1200/JCO-25-01651","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"3578-3588","type":"journal-article","issue":"33","score":1,"title":["TAR-200 for Bacillus Calmette-Guérin–Unresponsive High-Risk Non–Muscle-Invasive Bladder Cancer: Results From the Phase IIb SunRISe-1 Study"],"author":[{"given":"Siamak","family":"Daneshmand","sequence":"first","affiliation":[{"name":"University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA"}]},{"given":"Michiel S.","family":"Van der Heijden","sequence":"additional","affiliation":[{"name":"Netherlands Cancer Institute, Amsterdam, the Netherlands"}]},{"given":"Joseph M.","family":"Jacob","sequence":"additional","affiliation":[{"name":"Upstate Medical University, Syracuse, NY"}]},{"given":"Felix","family":"Guerrero-Ramos","sequence":"additional","affiliation":[{"name":"Hospital Universitario 12 de Octubre, Madrid, Spain"}]},{"given":"Martin","family":"Bögemann","sequence":"additional","affiliation":[{"name":"Münster University Hospital, Münster, Germany"},{"name":"West German Cancer Center, Münster, Germany"}]},{"given":"Giuseppe","family":"Simone","sequence":"additional","affiliation":[{"name":"IRCCS 'Regina Elena' National Cancer Institute, Rome, Italy"}]},{"given":"Christopher M.","family":"Pieczonka","sequence":"additional","affiliation":[{"name":"Associated Medical Professionals of New York (an affiliate of US Urology Partners), Syracuse, NY"}]},{"given":"Nelson Canales","family":"Casco","sequence":"additional","affiliation":[{"name":"Hospital de Jerez de la Frontera y Punta Europa, Cádiz, Spain"}]},{"given":"Daniel","family":"Zainfeld","sequence":"additional","affiliation":[{"name":"Urology San Antonio, San Antonio, TX"}]},{"given":"Philipp","family":"Spiegelhalder","sequence":"additional","affiliation":[{"name":"Urologie Neandertal, Gemeinschaftspraxis für Urologie, Mettmann, Germany"}]},{"given":"Evanguelos","family":"Xylinas","sequence":"additional","affiliation":[{"name":"Bichat-Claude Bernard Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris Cité, Paris, France"}]},{"given":"David","family":"Cahn","sequence":"additional","affiliation":[{"name":"Colorado Urology, Lakewood, CO"}]},{"given":"Yair","family":"Lotan","sequence":"additional","affiliation":[{"name":"UT Southwestern Medical Center, Dallas, TX"}]},{"given":"Katie S.","family":"Murray","sequence":"additional","affiliation":[{"name":"NYU Langone Health, New York, NY"}]},{"given":"Takashi","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Yokohama City University Medical Center, Yokohama, Japan"}]},{"given":"Katharine","family":"Stromberg","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, Raritan, NJ"}]},{"given":"Jason","family":"Martin","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, High Wycombe, UK"}]},{"given":"Abhijit","family":"Shukla","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, Lexington, MA"}]},{"given":"Christopher J.","family":"Cutie","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, Lexington, MA"}]},{"given":"Kristi","family":"Bertzos","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, Horsham, PA"}]},{"given":"Shalaka","family":"Hampras","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, Raritan, NJ"}]},{"given":"Hussein","family":"Sweiti","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, Spring House, PA"}]},{"given":"Andrea","family":"Necchi","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Hospital, Milan, Italy"},{"name":"Vita-Salute San Raffaele University, Milan, Italy"}]},{"given":"Manish","family":"Patel","sequence":"additional","affiliation":[]},{"given":"Thierry","family":"Roumeguere","sequence":"additional","affiliation":[]},{"given":"Charles","family":"Van Praet","sequence":"additional","affiliation":[]},{"given":"Harm","family":"Arentsen","sequence":"additional","affiliation":[]},{"given":"Bart","family":"De Troyer","sequence":"additional","affiliation":[]},{"given":"Frederic","family":"Baekelandt","sequence":"additional","affiliation":[]},{"given":"Karel","family":"Decaestecker","sequence":"additional","affiliation":[]},{"given":"Girish","family":"Kulkarni","sequence":"additional","affiliation":[]},{"given":"Wassim","family":"Kassouf","sequence":"additional","affiliation":[]},{"given":"George","family":"Vrabec","sequence":"additional","affiliation":[]},{"given":"Sabrina","family":"Falkowski","sequence":"additional","affiliation":[]},{"given":"Geraldine","family":"Pignot","sequence":"additional","affiliation":[]},{"given":"Evanguelos","family":"Xylinas","sequence":"additional","affiliation":[]},{"given":"Morgan","family":"Roupret","sequence":"additional","affiliation":[]},{"given":"Marc","family":"Colombel","sequence":"additional","affiliation":[]},{"given":"Romain","family":"Mathieu","sequence":"additional","affiliation":[]},{"given":"Benoit","family":"Wolff","sequence":"additional","affiliation":[]},{"given":"Marc-Olivier","family":"Timsit","sequence":"additional","affiliation":[]},{"given":"Xavier","family":"Artignan","sequence":"additional","affiliation":[]},{"given":"Stephane","family":"Droupy","sequence":"additional","affiliation":[]},{"given":"Herve","family":"Lang","sequence":"additional","affiliation":[]},{"given":"Mathieu","family":"Roumiguie","sequence":"additional","affiliation":[]},{"given":"Frank","family":"Bladou","sequence":"additional","affiliation":[]},{"given":"Catherine","family":"Becht","sequence":"additional","affiliation":[]},{"given":"Martin","family":"Bögemann","sequence":"additional","affiliation":[]},{"given":"Phillipp","family":"Spiegelhalder","sequence":"additional","affiliation":[]},{"given":"Jorg","family":"Klier","sequence":"additional","affiliation":[]},{"given":"Tilman","family":"Toderhofer","sequence":"additional","affiliation":[]},{"given":"Eva","family":"Hellmis","sequence":"additional","affiliation":[]},{"given":"Petros","family":"Sountoulides","sequence":"additional","affiliation":[]},{"given":"Konstantinos","family":"Hatzimouratidis","sequence":"additional","affiliation":[]},{"given":"Giuseppe","family":"Simone","sequence":"additional","affiliation":[]},{"given":"Luca","family":"Galli","sequence":"additional","affiliation":[]},{"given":"Frederico","family":"Deho","sequence":"additional","affiliation":[]},{"given":"Andrea","family":"Minervini","sequence":"additional","affiliation":[]},{"given":"Andrea","family":"Necchi","sequence":"additional","affiliation":[]},{"given":"Takashi","family":"Kawahara","sequence":"additional","affiliation":[]},{"given":"Shuya","family":"Kandori","sequence":"additional","affiliation":[]},{"given":"Masao","family":"Tsujihata","sequence":"additional","affiliation":[]},{"given":"Shinji","family":"Urakami","sequence":"additional","affiliation":[]},{"given":"Taek Won","family":"Kang","sequence":"additional","affiliation":[]},{"given":"Ja Hyeon","family":"Ku","sequence":"additional","affiliation":[]},{"given":"Kang Su","family":"Cho","sequence":"additional","affiliation":[]},{"given":"Wonho","family":"Jung","sequence":"additional","affiliation":[]},{"given":"Ho Kyung","family":"Seo","sequence":"additional","affiliation":[]},{"given":"Jong Kil","family":"Nam","sequence":"additional","affiliation":[]},{"given":"Diederik","family":"Somford","sequence":"additional","affiliation":[]},{"given":"Michiel","family":"Van der 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TAR‑200 was dosed up to 24 months and cetrelimab up to 18 months; at the March 31, 2025 data cutoff, 218 patients were treated across four cohorts (C1 n=53; C2 n=85; C3 n=28; C4 n=52).","key_result":"In BCG‑unresponsive CIS, TAR‑200 monotherapy achieved a CR rate of 82.4% (95% CI 72.6–89.8) with median response duration 25.8 months (95% CI 8.3–not estimable), versus 67.9% (95% CI 53.7–80.1) with TAR‑200+cetrelimab and 46.4% (95% CI 27.5–66.1) with cetrelimab alone. In papillary-only disease, TAR‑200 yielded 6‑, 9‑, and 12‑month DFS rates of 85.3%, 81.1%, and 70.2%; grade ≥3 treatment‑related AEs were 12.9% (C2) and 13.5% (C4) versus 37.7% with the combination and 7.1% with cetrelimab alone; no treatment‑related deaths occurred.","practice_takeaway":"For BCG‑unresponsive CIS, TAR‑200 monotherapy produced a high and durable CR with fewer severe treatment‑related AEs than the combination and higher CR than PD‑1 monotherapy. 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