2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T4b0,Despite the promise of immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC), mediators of response are poorly understood. To address this, here we analyzed oropharyngeal HNSCCs treated with neoadjuvant durvalumab (anti-PDL1) alone or in combination with tremelimumab (anti-CTLA4) from the CIAO clinical trial ( NCT03144778 ). We found that only the total abundance of intratumoral bacteria predicted ICB response, which was validated in multiple independent cohorts. High intratumoral bacteria abundance was associated with an immunosuppressive tumor microenvironment, characterized by an accumulation of neutrophils coupled with depletion of T cells and other adaptive immune cells. Experimental elevation or reduction in intratumoral bacteria abundance in orthotopic models of HNSCC in female mice recapitulated immunological associations observed in participant tumors. Increasing intratumoral bacteria abundance was sufficient to induce resistance to anti-PDL1 ICB, irrespective of bacterial species tested. Together, these findings demonstrate that high intratumoral bacteria abundance is a key suppressor of antitumor immunity and promotes immunotherapy resistance.31:T5e0,Abstract Despite the promise of immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC), mediators of response are poorly understood. To address this, here we analyzed oropharyngeal HNSCCs treated with neoadjuvant durvalumab (anti-PDL1) alone or in combination with tremelimumab (anti-CTLA4) from the CIAO clinical trial ( NCT03144778 ). We found that only the total abundance of intratumoral bacteria predicted ICB response, which was validated in multiple independent cohorts. High intratumoral bacteria abundance was associated with an immunosuppressive tumor microenvironment, characterized by an accumulation of neutrophils coupled with depletion of T cells and other adaptive immune cells. Experimental elevation or reduction in intratumoral bacteria abundance in orthotopic models of HNSCC in female mice recapitulated immunological associations observed in participant tumors. Increasing intratumoral bacteria abundance was sufficient to induce resistance to anti-PDL1 ICB, irrespective of bacterial species tested. Together, these findings demonstrate that high intratumoral bacteria abundance is a key suppressor of antitumor immunity and promotes immunotherapy resistance. 32:T5d0,T.A.C. is a cofounder of Gritstone Oncology and holds equity. T.A.C. holds equity in An2H. T.A.C. acknowledges grant funding from Bristol-Myers Squibb, AstraZeneca, Illumina, Pfizer, An2H and Eisai. T.A.C. has served as an advisor for Bristol-Myers, MedImmune, Squibb, Illumina, Eisai, AstraZeneca and An2H. T.A.C. is an inventor on intellectual property held by Memorial Sloan Kettering Cancer Center on using TMB to predict immunotherapy response, with a pending patent, which has been licensed to PGDx. E.J.S. consults for Siren Biotechnology and has immunotherapy patent applications under option to license agreements with iOncologi. N.G. reports grants or contracts and personal or consulting fees from Regeneron Pharmaceuticals, personal or consulting fees from DragonFly Therapeutics, Intuitive Surgical, Merck, Replimune and Sanofi/Genzyme US Companies and support for other professional activities from PDS Biotechnology Corporation outside the submitted work. R.F. reports consulting or advisory roles for Regeneron, Sanofi, Ayala Pharmaceuticals, Prelude Therapeutics, Elevar Therapeutics, G1 Therapeutics, Guidepoint, Expert Connect, Remix, Eisai and Bioatlas in the past 24 months and research funds from Prelude, Ayala, Merck, Genentech, Pfizer, Rakuten, Nanobiotix, EMD Serono, ISA, Viracta and Gilead in the past 24 months. D.J.M. holds intellectual property for transcriptional signatures to predict response to ICB. The other authors declare no competing interests.33:T9ef,Older adults with head and neck squamous cell carcinoma (HNSCC) are underrepresented in clinical trials, limiting evidence-based treatment decisions. Artificial neural networks (ANNs) have demonstrated the ability to personalize treatment recommendations using patient-specific characteristics. To develop and externally validate ANNs for overall survival (OS) and progression-free survival (PFS) in older adults with HNSCC undergoing definitive chemoradiation. This international cohort study included retrospective clinical data from 19 academic cancer centers across Germany, Switzerland, Czech Republic, Cyprus, and the US from the SENIOR registry. ANNs were developed and validated using data from patients 65 years and older with locoregionally advanced HNSCC treated with definitive chemoradiation. Exclusion criteria included induction or adjuvant chemotherapy, history of head and neck cancer, and metastatic disease at treatment initiation. Data were collected from January 2021 to December 2023, and data were analyzed from December 2023 to April 2025. All patients received definitive radiotherapy with concurrent systemic therapy between 2005 and 2019. OS and PFS were predicted using 2 separate ANN models. Patients were classified as high or low risk based on median prediction thresholds. Model performance was assessed with receiver operating characteristic (ROC) area under the curve (AUC) and precision recall AUC. Model explainability was assessed with Shapley additive explanations values. Of 898 patients included in the OS analysis (738 in training cohort and 160 in testing cohort), 665 (74.1%) were male, and the median (IQR) age was 71 (68-76) years. Of 945 included in the PFS analysis (770 in training cohort and 175 in testing cohort), 696 (73.7%) were male, and the median (IQR) age was 71 (68-76) years. The OS ANN stratified patients into high-risk and low-risk groups with significantly different survival, achieving an ROC-AUC of 0.68 (95% CI, 0.60-0.76). The PFS ANN showed similar discrimination, with an ROC-AUC of 0.64 (95% CI, 0.56-0.72). Human papillomavirus status, kidney function (estimated glomerular filtration rate), Eastern Cooperative Oncology Group Performance Status score, and nodal classification were among the most predictive features. In this study, ANN-based models using routine clinical data effectively stratified older adults with HNSCC into prognostic groups. Integration of ANNs into clinical workflows could support personalized treatment decisions for this vulnerable population.34:Tec3, Importance Older adults with head and neck squamous cell carcinoma (HNSCC) are underrepresented in clinical trials, limiting evidence-based treatment decisions. Artificial neural networks (ANNs) have demonstrated the ability to personalize treatment recommendations using patient-specific characteristics. Objective To develop and externally validate ANNs for overall survival (OS) and progression-free survival (PFS) in older adults with HNSCC undergoing definitive chemoradiation. Design, Setting, and Participants This international cohort study included retrospective clinical data from 19 academic cancer centers across Germany, Switzerland, Czech Republic, Cyprus, and the US from the SENIOR registry. ANNs were developed and validated using data from patients 65 years and older with locoregionally advanced HNSCC treated with definitive chemoradiation. Exclusion criteria included induction or adjuvant chemotherapy, history of head and neck cancer, and metastatic disease at treatment initiation. Data were collected from January 2021 to December 2023, and data were analyzed from December 2023 to April 2025. Exposures All patients received definitive radiotherapy with concurrent systemic therapy between 2005 and 2019. Main Outcomes and Measures OS and PFS were predicted using 2 separate ANN models. Patients were classified as high or low risk based on median prediction thresholds. Model performance was assessed with receiver operating characteristic (ROC) area under the curve (AUC) and precision recall AUC. Model explainability was assessed with Shapley additive explanations values. Results Of 898 patients included in the OS analysis (738 in training cohort and 160 in testing cohort), 665 (74.1%) were male, and the median (IQR) age was 71 (68-76) years. Of 945 included in the PFS analysis (770 in training cohort and 175 in testing cohort), 696 (73.7%) were male, and the median (IQR) age was 71 (68-76) years. The OS ANN stratified patients into high-risk and low-risk groups with significantly different survival, achieving an ROC-AUC of 0.68 (95% CI, 0.60-0.76). The PFS ANN showed similar discrimination, with an ROC-AUC of 0.64 (95% CI, 0.56-0.72). Human papillomavirus status, kidney function (estimated glomerular filtration rate), Eastern Cooperative Oncology Group Performance Status score, and nodal classification were among the most predictive features. Conclusions and Relevance In this study, ANN-based models using routine clinical data effectively stratified older adults with HNSCC into prognostic groups. Integration of ANNs into clinical workflows could support personalized treatment decisions for this vulnerable population. 35:T405,STAT3 is an oncogenic transcription factor that activates cancer cell signaling and induces an immunosuppressive immune environment, making it an attractive therapeutic target. Transcription factors are exceptionally challenging targets and there are no Food and Drug Administration-approved STAT3 inhibitors. We previously reported positive pharmacodynamics of a linear STAT3 decoy oligonucleotide administered intratumorally in a phase 0 trial in patients with head and neck cancer squamous cell carcinoma (HNSCC). Here, we describe the anti-tumor and immune effects of a systemically administered cyclic STAT3 decoy (CS3D) in immunocompetent HNSCC murine models and the safety and efficacy of CS3D in a clinical trial in pet cats with HNSCC. Responders in the clinical trial (35% disease control rate) showed significant differences in selected peripheral blood immune parameters as well as elevated PD-1 expression in the tumors compared with non-responders. These findings support a clinical trial of CS3D in HNSCC patients.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Head and Neck Squamous Cell Carcinoma: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Head and Neck Squamous Cell Carcinoma (condition). Clinician-written summaries and actionable practice insights. 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The RVS group (n=42) achieved 2-year DFS of 90% (95% CI, 77%–96%) with 100% laryngeal preservation in laryngeal/hypopharyngeal cancers, while the SVS group (n=5) had 2-year DFS of only 20% (95% CI, 0.8%–58%). Grade 3 AEs occurred in 16% (NAICT-related) and 15% (surgery-related); no grade 4–5 AEs were recorded.","limitations":"- Single-arm phase II design with no randomized comparator limits causal inference.\n- Small SVS subgroup (n=5) makes outcomes in poor responders highly uncertain.\n- Restricted to HPV-negative LA-HNSCC, limiting generalizability to HPV-positive disease.","practice_takeaway":"For HPV-negative LA-HNSCC patients who achieve ≥50% tumor regression after neoadjuvant immunochemotherapy, response-adapted reduced-volume surgery appears feasible and yields high laryngeal preservation rates with manageable toxicity. These results should be considered hypothesis-generating; phase III validation is needed before adopting this de-escalation approach."}},{"doi":"10.1001/jamaoto.2026.2259","pmid":"42593779","title":"Pathologic Response After Neoadjuvant Chemoimmunotherapy in Head and Neck Squamous Cell Carcinoma","journal_title":"JAMA Otolaryngology–Head & Neck Surgery","journal_issn":"2168-6181","published_at":"2026-08-13T00:00:00.000Z","url":"https://doi.org/10.1001/jamaoto.2026.2259","source_score":37,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-17T13:33:04.181Z","updated_at":"2026-08-17T13:33:04.181Z","tags":[{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"category","value":"Surgery","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"condition","value":"Head and Neck Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"modality","value":"Chemoimmunotherapy","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"modality","value":"Immunotherapy","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"modality","value":"Neoadjuvant Chemotherapy","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"sample_size","value":"n=86","value_numeric":86},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"warning","value":"Patients with locoregional recurrence were included alongside treatment-naive patients, which may introduce heterogeneity in the study population.","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied cautiously given this is a retrospective single-center study — prospective confirmation is explicitly called for by the authors.","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"warning","value":"The specific immunotherapy and chemotherapy agents used are not named in the abstract; brand/generic drug tags could not be assigned.","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2259","tag_type":"warning","value":"The upper bound of the adjusted OR confidence interval (274.7) is extremely wide, indicating low precision; results should be interpreted with caution.","value_numeric":null}],"summaries":{"what_studied":"This single-center retrospective cohort study compared pathologic response rates between neoadjuvant immunotherapy alone (NAI) and neoadjuvant chemoimmunotherapy (NACI) in 86 adults with resectable HNSCC of the aerodigestive tract, treated at a tertiary academic center from July 2024 to March 2026.","key_result":"Deep pathologic response (pCR or MPR) occurred in 39/58 NACI recipients (67%) vs. 1/28 NAI recipients (3.6%); propensity score-adjusted OR for pCR or MPR with NACI was 29.1 (95% CI, 6.7–274.7). Overall, 25 patients (29%) achieved pCR and 15 (17%) achieved MPR. Treatment was generally well tolerated with few adverse event-related surgical delays.","limitations":"- Single-center retrospective design with a small sample (n=86) limits generalizability and statistical precision.\n- Wide confidence intervals (especially in the adjusted OR: 6.7–274.7) reflect limited statistical power and residual confounding despite propensity score adjustment.\n- No survival outcomes reported; pathologic response is a surrogate endpoint whose link to OS in this context remains unconfirmed.","practice_takeaway":"NACI produced dramatically higher deep pathologic response rates than NAI alone in resectable HNSCC (67% vs. 3.6%), without apparent excess surgical delays. Clinicians should consider combination chemoimmunotherapy in the neoadjuvant setting, while awaiting prospective trial data on survival benefit."}},{"doi":"10.1001/jamaoto.2026.2124","pmid":"42560690","title":"Combined Positive Score and Cost-Effectiveness of Perioperative Pembrolizumab for Head and Neck Cancer","journal_title":"JAMA Otolaryngology–Head & Neck Surgery","journal_issn":"2168-6181","published_at":"2026-08-06T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13448835/","source_score":10,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-12T13:26:07.961Z","updated_at":"2026-08-12T13:26:07.961Z","tags":[{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"brand","value":"Keytruda","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"category","value":"Surgery","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"condition","value":"Head and Neck Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"generic","value":"cisplatin","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"generic","value":"pembrolizumab","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"modality","value":"PD-1 Inhibitor","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"modality","value":"Platinum-Based Chemotherapy","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"study_design","value":"Economic Evaluation (Cost-Effectiveness Analysis)","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"warning","value":"Cost inputs are US-specific (CMS/HCUP); cost-effectiveness conclusions may not generalize internationally.","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"warning","value":"Sample size is not reported in the abstract or results — the model simulates the KEYNOTE-689 cohort but the exact N used in the model is not stated.","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"warning","value":"Study design is labeled 'economic evaluation' rather than a standard clinical trial design; level of evidence assigned accordingly.","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.2124","tag_type":"warning","value":"The CPS 1–10 subgroup data were mathematically derived (not directly reported in KEYNOTE-689), which introduces additional modeling uncertainty.","value_numeric":null}],"summaries":{"what_studied":"This economic evaluation used a partitioned survival model to assess the cost-effectiveness of perioperative pembrolizumab added to standard of care (surgery, cisplatin, radiation) for locally advanced HNSCC, stratified by PD-L1 combined positive score (CPS >10 vs. CPS 1–10), based on KEYNOTE-689 trial data.","key_result":"For CPS >10 patients, pembrolizumab yielded ~1.35 additional QALYs at an incremental cost of $181,900 (ICER $134,700/QALY; 57% probability of cost-effectiveness at $150,000 WTP). For CPS 1–10 patients, it added only ~0.08 QALYs at $166,500 incremental cost (ICER $2,179,400/QALY; 11% probability of cost-effectiveness at $150,000 WTP).","limitations":"- Model inputs for QALYs were borrowed from a different trial (CheckMate 141), not directly from KEYNOTE-689 patients.\n- CPS 1–10 subgroup data were mathematically derived from two reported subgroups rather than directly observed.\n- The 57% cost-effectiveness probability for CPS >10 reflects substantial residual uncertainty.","practice_takeaway":"Consider PD-L1 CPS testing before offering perioperative pembrolizumab for locally advanced HNSCC — the drug appears cost-effective only in patients with CPS >10. Routine use in CPS 1–10 patients is not supported on value-based grounds at current pricing."}},{"doi":"10.1001/jamaoto.2026.1527","pmid":"42313403","title":"Pembrolizumab Plus Quad-Shot Radiotherapy for Recurrent, Unresectable, or Metastatic Head and Neck Cancer","journal_title":"JAMA Otolaryngology–Head & Neck Surgery","journal_issn":"2168-6181","published_at":"2026-06-18T00:00:00.000Z","url":"https://doi.org/10.1001/jamaoto.2026.1527","source_score":7,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-23T13:25:09.612Z","updated_at":"2026-06-23T13:25:09.612Z","tags":[{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"brand","value":"Keytruda","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"category","value":"Surgery","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"condition","value":"Head and Neck Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"generic","value":"pembrolizumab","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"modality","value":"Hypofractionated Radiotherapy","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"modality","value":"PD-1 Inhibitor","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"sample_size","value":"n=21","value_numeric":21},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"study_design","value":"Single-Arm Phase 2 Clinical Trial","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"warning","value":"Median OS for the full treated cohort (n=20) was not estimable at the upper confidence bound, indicating immature survival data at time of analysis.","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"warning","value":"Only 15 of 21 enrolled patients were evaluable for the primary endpoint; results may not reflect the full enrolled population.","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1527","tag_type":"warning","value":"The older adult age range extends to 86 years but the median is 61; subgroup outcomes by age are not reported.","value_numeric":null}],"summaries":{"what_studied":"This single-arm phase 2 trial evaluated pembrolizumab (200 mg every 3 weeks) combined with cyclic quad-shot radiotherapy (QSRT: 14.8 Gy in 4 fractions twice daily on 2 consecutive days) in 21 patients with recurrent, unresectable, or metastatic (RUM) head and neck squamous cell carcinoma (HNSCC) amenable to QSRT, enrolled February 2021–May 2024.","key_result":"Among 15 response-evaluable patients, the overall response rate was 47% (95% CI, 21%–73%). Median PFS was 11.5 months and median OS was 15.3 months for evaluable patients. Grade 3 and 4 adverse events occurred in 6 and 2 patients, respectively; patient-reported adverse events did not substantially worsen over time.","limitations":"- Single-arm, nonrandomized design at one academic center with no comparator arm limits causal inference.\n- Small evaluable population (n = 15 for primary endpoint) reduces statistical power and precision of estimates.\n- Eligibility required a QSRT-amenable site, limiting generalizability to the broader RUM HNSCC population.","practice_takeaway":"Pembrolizumab plus QSRT appears feasible and shows preliminary activity in RUM HNSCC, with a 47% response rate in evaluable patients. Clinicians should view these results as hypothesis-generating; a randomized trial is needed before adopting this combination as standard practice."}},{"doi":"10.1002/hed.70357","pmid":"42310965","title":"Current State and Future of Systemic Treatment for Elderly Patients With Head and Neck Cancer Undergoing Radiotherapy","journal_title":"Head & Neck","journal_issn":"1043-3074","published_at":"2026-06-17T00:00:00.000Z","url":"https://doi.org/10.1002/hed.70357","source_score":5,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-27T13:27:36.899Z","updated_at":"2026-06-27T13:27:36.899Z","tags":[{"paper_doi":"10.1002/hed.70357","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"category","value":"Surgery","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"condition","value":"Head and Neck Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"generic","value":"carboplatin","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"generic","value":"cetuximab","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"generic","value":"cisplatin","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"modality","value":"Chemoradiotherapy","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"modality","value":"Targeted Therapy","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"sample_size","value":"n=35","value_numeric":35},{"paper_doi":"10.1002/hed.70357","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"study_design","value":"Systematic Review","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"warning","value":"ICI efficacy findings are preliminary; the review flags the need for further research and biomarker identification before practice adoption.","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"warning","value":"Level of evidence is set to 3 (systematic review of heterogeneous, mostly non-RCT studies); the review explicitly notes study heterogeneity and limited trial representation of elderly patients, which may lower effective evidence quality.","value_numeric":null},{"paper_doi":"10.1002/hed.70357","tag_type":"warning","value":"The sample size tag reflects the number of included studies (n=35), not individual patients — total patient numbers are not reported in the abstract.","value_numeric":null}],"summaries":{"what_studied":"This systematic review evaluated systemic treatment options — chemotherapy, targeted therapy, and immune checkpoint inhibitors (ICIs) — in patients aged 65+ with HNSCC receiving definitive or adjuvant radiotherapy, drawing from 35 included studies.","key_result":"Cisplatin-based CRT was the most effective and tolerable option for fit elderly patients. In unfit patients, cetuximab and carboplatin showed variable results. Adding ICIs to radiotherapy appeared feasible and safe, but efficacy data and predictive biomarkers remain insufficient.","limitations":"- Elderly patients are underrepresented in trials, limiting the evidence base.\n- Study heterogeneity across the 35 included studies makes direct comparisons difficult.\n- Evidence in the adjuvant setting is especially sparse.","practice_takeaway":"Use a comprehensive geriatric assessment — not age alone — to guide systemic therapy decisions in older HNSCC patients. Fit elderly patients can receive cisplatin-based CRT, but treatment should be individualized given the heterogeneity of available data."}},{"doi":"10.1200/jco-26-01042","pmid":"42218660","title":"Amivantamab in Recurrent/Metastatic Head and Neck Squamous Cell Cancer After Checkpoint Inhibitor and Chemotherapy: Pivotal Results From the Phase Ib/II OrigAMI-4 Study","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-05-31T00:00:00.000Z","url":"https://doi.org/10.1200/jco-26-01042","source_score":167,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-24T06:18:26.590Z","updated_at":"2026-08-24T06:18:26.590Z","tags":[{"paper_doi":"10.1200/jco-26-01042","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-26-01042","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1200/jco-26-01042","tag_type":"brand","value":"Rybrevant","value_numeric":null},{"paper_doi":"10.1200/jco-26-01042","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-26-01042","tag_type":"condition","value":"Head and Neck Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1200/jco-26-01042","tag_type":"generic","value":"amivantamab","value_numeric":null},{"paper_doi":"10.1200/jco-26-01042","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1200/jco-26-01042","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1200/jco-26-01042","tag_type":"modality","value":"EGFR-MET Bispecific Antibody","value_numeric":null},{"paper_doi":"10.1200/jco-26-01042","tag_type":"sample_size","value":"n=102","value_numeric":102},{"paper_doi":"10.1200/jco-26-01042","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1200/jco-26-01042","tag_type":"study_design","value":"Phase Ib/II Single-Arm Trial","value_numeric":null},{"paper_doi":"10.1200/jco-26-01042","tag_type":"warning","value":"This is a single-arm phase Ib/II trial; ORR comparisons to cetuximab/paclitaxel are cross-trial and not head-to-head. Impact flag 'practice_changing' is provisional pending regulatory approval. The study enrolled only non-HPV (p16-negative) R/M HNSCC; results should not be extrapolated to HPV-positive disease. Sponsored by Janssen (Johnson & Johnson); multiple authors are employees or have financial relationships with the sponsor.","value_numeric":null}],"summaries":{"what_studied":"Subcutaneous amivantamab monotherapy (EGFR-MET bispecific antibody) given every 3 weeks was evaluated in 102 adults with non-HPV recurrent/metastatic HNSCC who had previously received anti-PD-(L)1 therapy and platinum-based chemotherapy; prior anti-EGFR therapy was exclusionary. The primary endpoint was RECIST v1.1 ORR by blinded independent central review (BICR) at a median follow-up of 11.8 months.","key_result":"BICR-confirmed ORR was 42% (95% CI, 32–52), including a 15% complete response rate. Median duration of response was not reached (95% CI, 6.9 months to NR); 56% of responders had DoR ≥6 months. Median PFS was 6.8 months (95% CI, 5.2–8.3) and median OS was 12.5 months (95% CI, 10.2–16.8), with 54% alive at 1 year. Treatment-related discontinuation rate was low at 8%.","limitations":"Single-arm design without a direct comparator limits causal inference. Biomarker subgroup analyses were underpowered due to small subgroup sizes. p16-positive oropharyngeal cancer was excluded, limiting generalizability to HPV-associated HNSCC.","practice_takeaway":"Subcutaneous amivantamab Q3W offers an ORR of 42% with a 15% complete response rate in previously ICI- and platinum-treated non-HPV R/M HNSCC — roughly double the ~21–24% ORR seen with cetuximab or paclitaxel in this setting. Clinicians should note the favorable subcutaneous administration profile (<10 minutes) and low discontinuation rate (8%), supporting its use as a later-line option pending regulatory approval."}},{"doi":"10.1200/jco-25-02027","pmid":"42102329","title":"Ficerafusp Alfa (BCA101) With Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Two-Year Results of an Expansion Cohort of a Phase I/Ib Trial","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-05-08T00:00:00.000Z","url":"https://doi.org/10.1200/jco-25-02027","source_score":80,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-16T13:22:35.422Z","updated_at":"2026-05-16T13:22:35.422Z","tags":[{"paper_doi":"10.1200/jco-25-02027","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"brand","value":"Keytruda","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"condition","value":"Head and Neck Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"generic","value":"ficerafusp alfa","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"generic","value":"pembrolizumab","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"modality","value":"Bispecific Fusion Protein (EGFR/TGF-β Inhibitor)","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"modality","value":"PD-1 Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"sample_size","value":"n=42","value_numeric":42},{"paper_doi":"10.1200/jco-25-02027","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"study_design","value":"Phase I/Ib Expansion Cohort","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"warning","value":"Efficacy-evaluable set (n=39) differs slightly from the safety population (n=42); all ORR/survival data are from the smaller efficacy set.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"warning","value":"HPV status subgroup analysis is exploratory and underpowered, especially for the HPV-positive group (n=11).","value_numeric":null},{"paper_doi":"10.1200/jco-25-02027","tag_type":"warning","value":"The 'practice_changing' impact flag is provisional — this is a small, single-arm phase I/Ib cohort without a randomized control arm; phase III confirmation is needed before practice change.","value_numeric":null}],"summaries":{"what_studied":"Phase I/Ib expansion cohort evaluating first-line ficerafusp alfa (1,500 mg weekly) plus pembrolizumab (200 mg Q3W) in 42 patients with PD-L1+ (CPS ≥1) recurrent or metastatic HNSCC, with a median follow-up of 26.3 months.","key_result":"In HPV-negative patients (n=28), confirmed ORR was 54% (CR in 21%), median DOR 21.7 months, median PFS 9.9 months, and median OS 21.3 months. In HPV-positive patients (n=11), ORR was 27%. Grade ≥3 TRAEs occurred in 45% of patients; most common were anemia (14%) and acneiform dermatitis (12%).","limitations":"Small single-arm expansion cohort (n=42) without a randomized comparator, limiting causal conclusions. HPV-positive subgroup was small (n=11), reducing reliability of that estimate. Phase I/Ib design is not powered for definitive efficacy.","practice_takeaway":"For HPV-negative R/M HNSCC — a group with poor outcomes on current immunotherapy — ficerafusp alfa plus pembrolizumab showed a 54% ORR and ~21-month median OS, suggesting this EGFR/TGF-β dual-targeting approach warrants further study. Clinicians should note the 14% rate of grade ≥3 anemia and 12% acneiform dermatitis when counseling patients."}},{"doi":"10.1001/jamaoto.2026.0369","pmid":"41989767","title":"Barriers and Facilitators to Timely Adjuvant Therapy for Head and Neck Cancer in Rural Care","journal_title":"JAMA Otolaryngology–Head & Neck Surgery","journal_issn":"2168-6181","published_at":"2026-04-16T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13087907/","source_score":26,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-14T13:34:44.455Z","updated_at":"2026-06-14T13:34:44.455Z","tags":[{"paper_doi":"10.1001/jamaoto.2026.0369","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.0369","tag_type":"category","value":"Surgery","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.0369","tag_type":"condition","value":"Head and Neck Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.0369","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.0369","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.0369","tag_type":"modality","value":"Radiation Therapy","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.0369","tag_type":"sample_size","value":"n=29","value_numeric":29},{"paper_doi":"10.1001/jamaoto.2026.0369","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.0369","tag_type":"study_design","value":"Qualitative Study","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.0369","tag_type":"warning","value":"No demographic data (age, sex, race/ethnicity) were collected, so population characteristics are incompletely described.","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.0369","tag_type":"warning","value":"Sample size (n=29) reflects only Partnership Academy and Community Engagement Studio participants; an additional 16 staff contributed during member checking but are not counted in the formal participant total—actual informant pool is larger.","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.0369","tag_type":"warning","value":"This is a pre-intervention qualitative discovery study; no clinical outcomes or effect sizes are reported. The level of evidence tag reflects the qualitative/exploratory design.","value_numeric":null}],"summaries":{"what_studied":"This qualitative study identified barriers and facilitators to timely postoperative radiotherapy (PORT) initiation—within 6 weeks of surgery—for head and neck squamous cell carcinoma (HNSCC) patients at two rural cancer clinics in northern New England (Dartmouth Health), using patient-, caregiver-, and staff-involved community-engaged research methods (November 2024–May 2025).","key_result":"Five barriers emerged: communication gaps, care coordination failures, limited dental care access, transportation challenges, and confronting negative emotions. Four facilitators were identified: key staff as central contacts, caregivers as advocates, rural culture of resilience, and leveraging pre-existing resources. Four solution-oriented themes highlighted the value of peer support, phased information delivery, and community-based organizations over health system–delivered resources.","limitations":"- Findings from only two rural clinics in northern New England limit generalizability to other regions or cultures.\n- No demographic data beyond participant role were collected due to regulatory constraints, preventing subgroup analysis.\n- Small, purposively sampled groups with potential selection bias; caregiver representation was notably limited.","practice_takeaway":"In rural HNSCC care, designating a named staff contact for PORT coordination and proactively connecting patients with community-based transportation and dental referral networks may reduce delays.\nPeer support programs and staged, just-in-time patient education should be considered as part of multilevel interventions targeting the 6-week PORT window."}},{"doi":"10.1038/s43018-025-01067-1","pmid":"41482523","title":"Intratumoral bacteria are immunosuppressive and promote immunotherapy resistance in head and neck squamous cell carcinoma","journal_title":"Nature Cancer","journal_issn":"2662-1347","published_at":"2026-01-03T00:00:00.000Z","url":"https://doi.org/10.1038/s43018-025-01067-1","source_score":170,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-05","doi":"10.1038/s43018-025-01067-1","days":"30","issn":"2662-1347","rank":"9","field":"Clinical Medicine","score":"170","category":"Oncology","categories":["Oncology"],"_categories":["Oncology"]},"pubmed":{"doi":"10.1038/s43018-025-01067-1","title":"Intratumoral bacteria are immunosuppressive and promote immunotherapy resistance in head and neck squamous cell carcinoma.","journal":"Nature cancer","methods":"","results":"","abstract":"$30","keywords":[],"pubmed_id":"41482523","conclusions":"","publication_date":"2026-01-03T00:00:00"},"crossref":{"DOI":"10.1038/s43018-025-01067-1","URL":"https://doi.org/10.1038/s43018-025-01067-1","ISSN":["2662-1347"],"link":[{"URL":"https://www.nature.com/articles/s43018-025-01067-1.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://www.nature.com/articles/s43018-025-01067-1","content-type":"text/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https://www.nature.com/articles/s43018-025-01067-1.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Intratumoral bacteria are immunosuppressive and promote immunotherapy resistance in head and neck squamous cell carcinoma"],"author":[{"given":"Natalie L.","family":"Silver","sequence":"first","affiliation":[]},{"given":"Jin","family":"Dai","sequence":"additional","affiliation":[]},{"given":"Travis D.","family":"Kerr","sequence":"additional","affiliation":[]},{"given":"Jessica","family":"Altemus","sequence":"additional","affiliation":[]},{"given":"Rekha","family":"Garg","sequence":"additional","affiliation":[]},{"given":"Hannah","family":"Simmons","sequence":"additional","affiliation":[]},{"given":"Tyler","family":"Alban","sequence":"additional","affiliation":[]},{"given":"Laura","family":"Noel-Romas","sequence":"additional","affiliation":[]},{"given":"Vladimir","family":"Makarov","sequence":"additional","affiliation":[]},{"given":"David J. 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Of 945 included in the PFS analysis (770 in training cohort and 175 in testing cohort), 696 (73.7%) were male, and the median (IQR) age was 71 (68-76) years. The OS ANN stratified patients into high-risk and low-risk groups with significantly different survival, achieving an ROC-AUC of 0.68 (95% CI, 0.60-0.76). The PFS ANN showed similar discrimination, with an ROC-AUC of 0.64 (95% CI, 0.56-0.72). 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