Cancer最新文献

{"title":"The myeloma divide: How sex and age shape disease characteristics","authors":"Christin B. DeStefano MD, Wendy Cozen DO, MPH","doi":"10.1002/cncr.70365","DOIUrl":"10.1002/cncr.70365","url":null,"abstract":"","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teclistamab plus daratumumab significantly boosts survival for patients with early RRMM","authors":"Leah Lawrence","doi":"10.1002/cncr.70299","DOIUrl":"10.1002/cncr.70299","url":null,"abstract":"<p>The combination of teclistamab plus daratumumab in patients with early relapsed myeloma significantly improved progression-free survival (PFS) and led to an overall survival (OS) advantage in comparison with the standard of care (SOC) in patients with relapsed or refractory multiple myeloma (RRMM) according to results of the phase 3 MajesTEC-3 trial.</p><p>“What we are seeing in the MajesTEC-3 trial is a combination of dual targeting with a B-cell maturation antigen [BCMA] × CD3 bispecific antibody and a CD38 monoclonal antibody that has outperformed any regimen evaluated in the early relapse space in multiple myeloma,” says study researcher Ajay K. Nooka, MD, MPH, a professor at the Emory University School of Medicine in Atlanta, Georgia. Dr Nooka and his colleagues reported the results of the planned first interim analysis at the 2025 American Society of Hematology Annual Meeting and Exposition; the results were published simultaneously in <i>The New England Journal of Medicine</i>.<span><sup>1</sup></span></p><p>This trial was the first to test a combination of a bispecific antibody in the setting of first to third relapse after initial treatment for multiple myeloma. Teclistamab, which targets CD3 on T-cell surfaces and BCMA on myeloma cells, currently is approved as a single agent in patients with RRMM who have had at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and a CD38 monoclonal antibody.<span><sup>2</sup></span> Monoclonal antibody daratumumab targets CD38 and is used in combination with other therapies in patients who are newly diagnosed or who have RRMM.</p><p>In the MajesTEC-3 trial, 587 patients with RRMM who had received one to three prior lines of therapy were randomly assigned to a combination treatment with teclistamab plus daratumumab or daratumumab combined with dexamethasone and the investigator’s choice of pomalidomide (DPd) or bortezomib (DVd). The median number of prior lines of therapy in both study arms was two.</p><p>“Already at the first interim analysis, with close to three years of follow-up, we have a substantial improvement in PFS,” says study researcher Luciano J. Costa, MD, PhD, a professor of medicine at the University of Alabama at Birmingham.</p><p>Patients assigned to teclistamab plus daratumumab had an 83% reduction in the risk for progression or death in comparison with the SOC arm (hazard ratio, 0.17; 95% CI, 0.12–0.23; <i>p</i> < .001). The estimated 36-month PFS rate was 83.4% in the teclistamab–daratumumab arm but 29.7% in the DPd or DVd group.</p><p>“What was even more surprising was that there was also superiority in OS seen at the first interim analysis,” says Dr Costa. The 36-month OS rate was 83.3% with teclistamab plus daratumumab but 65.0% with the DPd or DVd regimen.</p><p>Patients assigned to teclistamab and daratumumab also experienced a greater depth of response. A complete response occurred in 81.8% of the patients assigned to teclista","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Retrospective analysis of cutaneous immune-related adverse events following checkpoint inhibitor therapy in melanoma patients reveals increased risk associated with the HLA-B*51:01 allele”","authors":"","doi":"10.1002/cncr.70350","DOIUrl":"10.1002/cncr.70350","url":null,"abstract":"<p>DiLeo M, Oglesby S, Leung CH, et al. Retrospective analysis of cutaneous immune-related adverse events following checkpoint inhibitor therapy in melanoma patients reveals increased risk associated with the HLA-B*51:01 allele. <i>Cancer</i>. 2026;e70262. doi:10.1002/cncr.70262</p><p>The y-axis of Figure 2 was misspelled in the originally published version of this article. The correct y-axis is Incidence of irAE.</p><p>Figure 2:</p><p>We apologize for this error.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Valued Living intervention to increase advance care planning and well-being in depressed and anxious adults with advanced cancer: Randomized trial in community oncology clinics","authors":"Joanna J. Arch PhD,&nbsp;Jill L. Mitchell PhD, MSW,&nbsp;Sarah J. Schmiege PhD,&nbsp;Michael E. Levin PhD,&nbsp;Madeline S. Nealis MPH,&nbsp;Sarah R. Genung BA,&nbsp;Regina M. Fink PhD, APRN,&nbsp;David J. Andorsky MD,&nbsp;Jean S. Kutner MD, MSPH","doi":"10.1002/cncr.70349","DOIUrl":"10.1002/cncr.70349","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Adults with advanced cancer often experience low engagement with advance care planning (ACP) and high levels of depression, anxiety, and fear of death/dying. Access to specialist palliative care is limited. This study tests Valued Living, a novel online acceptance-based group intervention designed to increase ACP and improve psychological/spiritual well-being among adults with advanced cancer screening positive for depression or anxiety. Valued Living was delivered online by social workers in community oncology settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adults with advanced solid tumor cancer (<i>N</i> = 240) and significant depression or anxiety symptoms were randomized 1:1 within cohorts to Valued Living or usual care (UC). Valued Living provided five weekly group sessions by videoconference plus self-paced online modules. Primary outcome was the total number of ACP behavioral steps completed of 12 potential steps (e.g., selecting health care proxy, advanced directives) by 3.5-month follow-up. Secondary outcomes included fear of death, rigid cognitive avoidance of death, depression, anxiety, and spiritual well-being.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Valued Living participants completed 1.27 more ACP steps (95% CI, 0.36–2.18; <i>d</i> = 0.36; <i>p</i> = .006) than UC. Largest condition differences were identifying (97.4% vs. 84.2%) and documenting a health care proxy (83.3% vs. 64.9%). Valued Living participants improved more in cognitive avoidance of death (<i>d</i> = 0.36; <i>p</i> = .005), and spiritual well-being (<i>d</i> = 0.42; <i>p</i> &lt; .001) but not fear of death or anxiety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The online Valued Living intervention, implemented by social workers in community oncology clinics, increased ACP and well-being among depressed and anxious adults with advanced cancer. Findings support this supportive care approach for the growing population living with advanced cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The trial registration is ClinicalTrials.gov NCT04773639.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12997518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant systemic immunotherapy for skin cancers","authors":"Clio Dessinioti MD, PhD,&nbsp;Alexander Stratigos MD, PhD","doi":"10.1002/cncr.70354","DOIUrl":"10.1002/cncr.70354","url":null,"abstract":"<p>Neoadjuvant treatment for skin cancer refers to treatment given to resectable tumors before surgery with the primary aim of improving prognostic outcomes. In addition, it may downstage the tumor to decrease surgical morbidity, and may de-escalate adjuvant therapies in cases of complete response. This in-depth review discusses the principles of neoadjuvant immunotherapy for cutaneous melanoma and invasive cutaneous squamous cell carcinoma (CSCC). Lessons learned from prospective neoadjuvant systemic immunotherapy clinical trials in melanoma are explored, available evidence from research studies for resectable CSCC is detailed, and key studies are illustrated in schematic figures. Outcomes and limitations of current evidence are presented and practical considerations are highlighted, including the risks of immune-related adverse events and the need for biomarkers to identify patients most likely to benefit. Implications are illustrated for response-adapted treatment de-escalation protocols, and trials are indicated that could inform future standards of care. While clinical trials on neoadjuvant immunotherapy and dual checkpoint blockade strategies for melanoma is a rapidly growing field, the small number of clinical trials in CSCC highlights the need to design and perform clinical trials for patients with CSCC in order to be able to provide for them treatments based on high standards of research.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eligibility criteria in phase 3 randomized controlled trials in metastatic non–small cell lung cancer","authors":"Jan Borysowski MD, PhD,&nbsp;Danuta Kłosowska MSc,&nbsp;Marek Harhala PhD,&nbsp;Magdalena Knetki-Wróblewska MD, PhD,&nbsp;Maciej Krzakowski MD, PhD","doi":"10.1002/cncr.70361","DOIUrl":"10.1002/cncr.70361","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The purpose of this study was to assess the eligibility criteria in randomized controlled trials (RCTs) in metastatic non–small cell lung cancer (NSCLC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eligible trials were phase 3 RCTs of systemic treatments for metastatic NSCLC, registered with the World Health Organization International Clinical Trials Registry Platform and started between 2009 and 2023. The odds of selected eligibility criteria were determined with multivariable logistic regression. Trends in the use of the eligibility criteria over time were assessed with the Fisher's exact test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 274 of 386 trials (71%) excluded patients with an Eastern Cooperative Oncology Group (ECOG) score of &gt;1; the odds of excluding these patients were higher in RCTs of chemotherapy (adjusted odds ratio [aOR], 3.46; 95% CI [confidence interval], 1.91–6.50; <i>p</i> &lt; .001) and immunotherapy (aOR, 3.31; 95% CI, 1.58–7.21; <i>p</i> = .001) and in recent trials (aOR, 1.83; 95% CI, 1.09–3.10; <i>p</i> = .02). A total of 95 of 386 trials (24.6%) had an upper age limit of 85 years or younger; this was more likely in trials performed in Asia (aOR, 8.83; 95% CI, 3.27–28.24; <i>p</i> &lt; .001). The proportion of trials with eligibility criteria concerning comorbidities did not significantly decrease over time (<i>p</i> &gt; .05). None of the trials had any eligibility criteria concerning frailty.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The eligibility criteria in phase 3 RCTs in metastatic NSCLC continue to be strict. In some trials, judicious modifications of these criteria should be considered to improve the enrollment of clinically relevant populations of patients, especially older adults, individuals with an ECOG score of 2, and those with selected comorbidities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteosarcoma is not a single disease: Considerations for multidisciplinary management of jaw (gnathic) osteosarcoma","authors":"Damon R. Reed MD,&nbsp;Emily K. Slotkin MD","doi":"10.1002/cncr.70362","DOIUrl":"10.1002/cncr.70362","url":null,"abstract":"","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High dietary fiber is associated with improved outcomes in patients with melanoma and sarcoma treated with immunotherapy regardless of gut microbiome dysbiosis and social vulnerability","authors":"Brittany C. Fields MD, MPH,&nbsp;Raymond S. Traweek MD,&nbsp;Kai Jiang MS,&nbsp;Russell G. Witt MD,&nbsp;Ashish Damania MS,&nbsp;Yi-Ju Chiang MSPH,&nbsp;Nadim Ajami PhD,&nbsp;Elise Nassif-Haddad MD, PhD,&nbsp;Emily Z. Keung MD,&nbsp;Manoj Chelvanambi PhD,&nbsp;Xiaotao Zhang MD, PhD,&nbsp;Christine B. Peterson PhD,&nbsp;Jennifer A. Wargo MD, MS,&nbsp;Carrie R. Daniel PhD, MPH,&nbsp;Christina L. Roland MD, MS,&nbsp;Ashley M. Holder MD","doi":"10.1002/cncr.70335","DOIUrl":"10.1002/cncr.70335","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Social vulnerability, dietary fiber, and the gut microbiome have been individually implicated in clinical outcomes for melanoma and sarcoma patients. This study hypothesized that increasing social vulnerability is associated with insufficient dietary fiber intake and negatively associated with microbiome composition and clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Clinicopathologic data, baseline fiber intake, and gut microbiome profiles were assessed in 153 patients with melanoma or sarcoma treated with immune checkpoint blockade (ICB) and prospectively followed. Patients’ social vulnerability index (SVI) and fiber intake were evaluated for associations with microbiome composition, treatment response, and overall survival (OS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SVI percentile was 0.4 (interquartile ratio [IQR], 0.2–0.7), and median dietary fiber intake was 17 (IQR, 15–20) g/day. SVI was inversely correlated with dietary fiber intake (<i>r</i>, −0.18, <i>p</i> = .0398). Gut microbiome analyses revealed community and compositional differences by SVI, including inverse associations with α-diversity and the relative abundance of favorable bacteria such as <i>Bifidobacterium longum</i> (<i>p</i> &lt; .001), contrasting the positive associations observed between fiber and these microbial markers. Increased dietary fiber intake was associated with measurable response to ICB. A difference in OS was not observed in more socially vulnerable patients (SVI, not reached vs. 81.7 months), however, a survival advantage was evident with higher dietary fiber intake (not reached, 58.9 months).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Increased social vulnerability was associated with a less favorable gut microbiome composition but not worse OS among melanoma and sarcoma patients treated with ICB. Consistent with prior findings, high dietary fiber intake emerged as a potentially modifiable pathway to improve outcomes in patients initiating ICB, particularly those with increased SVI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12989120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durvalumab combined with concurrent chemoradiotherapy in patients with limited-stage small cell lung cancer: A prospective, single-arm, phase 2 clinical trial","authors":"Chunyang Song MMed,&nbsp;Xiaohan Zhao MMed,&nbsp;Shuguang Li MD,&nbsp;Xuehan Guo MMed,&nbsp;Xueyuan Zhang MD,&nbsp;Xiaobin Wang MMed,&nbsp;Youmei Li MD,&nbsp;Ke Yan MMed,&nbsp;Jingwei Su MD,&nbsp;Jinrui Xu MMed,&nbsp;Shuchai Zhu MD,&nbsp;Wenbin Shen MD","doi":"10.1002/cncr.70351","DOIUrl":"10.1002/cncr.70351","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The current standard treatment for limited-stage small cell lung cancer (LS-SCLC) is concurrent chemoradiotherapy (cCRT) plus consolidation immunotherapy, with or without prophylactic cranial irradiation (PCI). However, it remains unknown whether administering immunotherapy concurrently with chemoradiotherapy confers additional benefit. This clinical trial is designed to investigate the efficacy and safety using durvalumab with chemoradiotherapy for LS-SCLC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this single-arm phase 2 study, patients with LS-SCLC received three (1–4) cycles of etoposide, cisplatin, or carboplatin, and durvalumab every 3 weeks, following by thoracic radiotherapy of 60.0 Gy to the gross tumor volume and 54.0 Gy to the planning target volume in 30 once-daily fractions and chemoimmunotherapy. After cCRT plus durvalumab, patients received durvalumab consolidation therapy every 3 weeks for a minimum of 1 year. PCI was recommended to patients with partial or complete response when chemoradiotherapy completed. Efficacy and adverse events were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 51 patients were enrolled from March 1, 2021, to April 30, 2024, with a median follow-up of 32.0 months. The 1-, 2-, and 3-year progression-free survival (PFS) rates were 56.9%, 35.9%, and 28.2%, respectively, and the median PFS was 17.0 months. The 1-, 2-, and 3-year overall survival (OS) rates were 88.1%, 68.6%, and 49.6%, respectively, and the median OS was 32.0 months. There were 17 (33.4%) patients with grade 3 or 4 adverse events, 7 of which were immune‑related.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results suggest that the addition of durvalumab to chemoradiotherapy was well tolerated and showed encouraging efficacy, supporting further investigation in patients with LS-SCLC eligible for radical chemoradiotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12989067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poor clinical outcomes and immunoevasive contexture in gastric cancer patients bearing p16 high phenotype","authors":"Jieti Wang MD,&nbsp;Yun Gu MD,&nbsp;Ziqiu Zhang PhD,&nbsp;Zhen Ling PhD,&nbsp;Chao Lin MD,&nbsp;Hao Liu MD,&nbsp;Ruochen Li MD,&nbsp;Hongyong He MD,&nbsp;Fei Shao MD,&nbsp;Jiejie Xu PhD","doi":"10.1002/cncr.70363","DOIUrl":"10.1002/cncr.70363","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The aberrant p16^INK4a expression has been identified in gastric cancer (GC). However, the staining pattern of p16^INK4a and its associations with clinical outcomes and immune contexture remains obscure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study involved two patient cohorts, the Zhongshan Hospital (ZSHS, <i>n</i> = 443) and Samsung Medical Center (SMC, <i>n</i> = 43) cohort. Patients were divided into p16^INK4a loss, wild-type (WT), and overexpression (OE) subgroups. The patient characteristics, overall survival (OS), response to adjuvant chemotherapy (ACT) and immune checkpoint inhibitor (ICI) treatment, as well as tumor immune contexture were investigated in each subgroup.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In ZSHS cohort, 90 of 443 (20.3%) patients with p16^INK4a OE gastric cancer, who were characterized by advanced pT stage (<i>p</i> = .011), higher Ki-67 (<i>p</i> &lt; .001), Rb loss (<i>p</i> &lt; .001), and CCNE1 OE incidence (<i>p</i> &lt; .001). Patients with p16^INK4a OE tumors presented with poor OS (ZSHS: OE vs. WT, <i>p</i> = .004; specific in MSI tumors, <i>p</i> = .019), inferior responsiveness to ACT (OE vs. WT, <i>p</i> = .011; specific in MSI tumors, <i>p</i> = .024) and ICI (OE vs. WT, <i>p</i> = .045; specific in programmed death-ligand 1 CPS ≥1 and CIN tumors, <i>p</i> = .027 and <i>p</i> = .032, respectively), whereas patients with p16^INK4a loss and WT gastric cancer exhibited comparable clinical outcomes (loss vs. WT: OS, <i>p</i> = .424; ACT, <i>p</i> = .834; ICI, <i>p</i> = .223). Moreover, p16^INK4a OE gastric cancer was associated with lower antitumor M1, neutrophils, and CD8⁺T cells infiltration and higher pro-tumor TGF-β, CD73, and IDO expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identified a specific triple classification staining pattern of p16^INK4a expression in GC, and demonstrated that p16^INK4a OE was associated with poor clinical outcomes and evasive immune contexture.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}