Annals of Oncology最新文献

{"title":"Corrigendum to 'Subcutaneous versus intravenous nivolumab for renal cell carcinoma': [Annals of Oncology volume 36 (2025) 99-107].","authors":"L Albiges, M T Bourlon, M Chacón, H J Cutuli, Y A L Chuken, B Zurawski, J M Mota, I Magri, M Burotto, M Luz, J de Menezes, E P Y Ruiz, S Fu, M Richardet, B P Valderrama, M Maruzzo, S Bracarda, M Breckenridge, H E Vezina, D Rathod, Z Yu, Y Zhao, M Dixon, D Perumal, S George","doi":"10.1016/j.annonc.2026.03.007","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.03.007","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A chemotherapy-free, pathological response-adapted strategy using trastuzumab-pertuzumab and T-DM1 in HER2-positive early breast cancer: the PHERGain-2 study.","authors":"L Garrigós, M Ruiz-Borrego, J M Pérez-García, A Guerrero-Zotano, A Cortés-Salgado, S Kuemmel, M Colleoni, C Reboredo-Rendo, B Bermejo, I Blancas, J Gavila, A Fabi, C Morales, A Stradella, V Carañana, E Martínez-de Dueñas, C Albacar, O Ballesteros-Cidras, G Martrat, S Iacobucci, O Boix, P Berenguer-Molins, D Alcalá-López, J Cortés, A Llombart-Cussac","doi":"10.1016/j.annonc.2026.01.013","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.01.013","url":null,"abstract":"<p><strong>Background: </strong>PHERGain-2 is a multicenter, single-arm, phase II study evaluating a pathologic complete response (pCR)-guided de-escalation strategy to omit chemotherapy in selected patients with HER2-positive early breast cancer (EBC).</p><p><strong>Patients and methods: </strong>Eligible patients were adults, treatment-naive, centrally confirmed HER2-positive (immunohistochemistry 3+), node-negative EBC, with tumors 5-30 mm by magnetic resonance imaging. Patients received eight cycles of neoadjuvant trastuzumab-pertuzumab (HP) (600 mg H + 1200 mg P loading dose, followed by 600 mg H + 600 mg P maintenance dose) every 3 weeks. Patients with hormone receptor (HR)-positive tumors also received endocrine therapy. After surgery, patients received 10 cycles of adjuvant therapy guided by the pathological response: HP for patients with pCR (ypT0/is ypN0) (cohort A), trastuzumab emtansine (T-DM1; 3.6 mg/kg) for patients with residual invasive breast tumors and/or ypN0(i+/mol+), ypN1mi (cohort B), and optional chemotherapy followed by T-DM1 for patients with ypN1-3 (cohort C). Co-primary endpoints were 1-year health-related quality of life (HRQoL) decline (based on the European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire) and 3-year recurrence-free interval (based on the Standardized Definitions for Efficacy End Points). Key secondary endpoints included overall and HR-specific pCR rates and safety.</p><p><strong>Results: </strong>From August 2021 to March 2024, 396 patients initiated neoadjuvant treatment, 391 (98.7%) underwent surgery. A total of 236 patients (59.6%) achieved pCR (cohort A). Among those with residual disease, 148 (37.8%) entered cohort B and 7 (1.8%) cohort C. One year after initiation of neoadjuvant treatment, ≥10% decline rate in global HRQoL was 42.8% [95% confidence interval (CI) 36.9% to 48.8%]; 37.3% (95% CI 30.1% to 44.9%) in patients with pCR and 51.9% (95% CI 41.9% to 61.7%) in those with residual disease. Treatment-related adverse events occurred in 86.6% of patients (5.6% grade ≥3). Serious adverse events occurred in 6.1% of patients. One death (0.3%) due to pneumonitis was attributed to T-DM1.</p><p><strong>Conclusions: </strong>PHERGain-2 shows meaningful HRQoL preservation, expected HP/T-DM1 toxicity, and an outstanding pCR rate comparable with standard chemotherapy plus HP regimens in this patient population.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival outcomes in POD1UM-303/InterAACT-2: a phase 3 study of retifanlimab plus carboplatin-paclitaxel in first-line advanced squamous anal cancer.","authors":"S Rao, E Samalin-Scalzi, L Evesque, M Ben Abdelghani, F Morano, A Roy, L Dahan, S Tamberi, A S Dhadda, M G Zampino, N Casanova, R Guimbaud, A Lievre, J Maurel, P Zhang, M C Munteanu, M Jones, C de la Fouchardiere, A Takashima, M Fakih, J Spano","doi":"10.1016/j.annonc.2026.04.016","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.04.016","url":null,"abstract":"<p><strong>Background: </strong>In the primary analysis of the POD1UM-303/InterAACT 2 trial, median progression-free survival (PFS) was significantly longer with retifanlimab plus carboplatin-paclitaxel than with placebo plus carboplatin-paclitaxel in adult, systemic treatment-naïve patients with advanced/metastatic squamous cell carcinoma of the anal canal (SCAC). Here, the final overall survival (OS) data from PODIUM-303/InterAACT 2, along with subgroup and exploratory analyses, are presented.</p><p><strong>Patients and methods: </strong>POD1UM-303/InterAACT-2 was a phase 3, randomized, double-blind, controlled, multicenter trial with an optional crossover period undertaken in Europe, Australia, Japan, the UK, and the US. The primary endpoint was PFS, and OS was the key secondary endpoint. Other endpoints included response, safety, and exploratory subgroup analyses.</p><p><strong>Results: </strong>A total of 308 patients were randomized (n = 154 for each of the retifanlimab + carboplatin-paclitaxel and placebo + carboplatin-paclitaxel groups), and 77 patients in the placebo plus carboplatin-paclitaxel group crossed over to receive retifanlimab monotherapy. When retifanlimab plus carboplatin-paclitaxel was compared with placebo plus carboplatin-paclitaxel in the updated efficacy analysis, there was a continued PFS benefit (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.47-0.81; nominal P = 0.0002) and a consistent and clinically meaningful improvement in OS (HR 0.75, 95% CI 0.55-1.01; P = 0.0305); median OS was 32.8 versus 22.2 months. Overall response rate was 56.5% versus 44.8%, and disease control rates were 87.7% versus 80.5%. The results of the crossover-adjusted analysis were consistent with the main analysis, and there was a consistent OS benefit in favor of retifanlimab plus carboplatin-paclitaxel in all subgroups analyzed. No new safety signals or trends were reported.</p><p><strong>Conclusion: </strong>This final analysis confirms the benefits of retifanlimab plus chemotherapy in SCAC. The results suggest that retifanlimab represents a new reference treatment and standard of care for patients with inoperable, locally recurrent or metastatic SCAC.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Regulatory T Cells for Cancer Immunotherapy: Promises and Pitfalls.","authors":"O Mirallas, G Pretelli, M Balsa, P Jiménez-Labaig, A Hernando-Calvo, H Nathan Tan, P Selvadurai, P Tallón de Lara, M Vieito, J Martin-Liberal, K J Harrington, S Champiat, E Garralda","doi":"10.1016/j.annonc.2026.04.015","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.04.015","url":null,"abstract":"<p><strong>Background: </strong>Regulatory T cells (Tregs) form a distinct subset of CD4⁺ T cells essential for maintaining immune balance and preventing autoimmunity by expressing CD25 and CTLA-4. Tregs, which are defined by the expression of the transcription factor FOXP3 in mice, restrain excessive immune activation through mechanisms such as IL-10 expression, TGF-β expression, metabolic regulation, acting as an IL-2 cytokine sink, and cell-to-cell interaction through co-inhibitory receptors. Although they are indispensable for immune tolerance, Tregs can be co-opted by tumors, where their suppressive activity promotes immune escape. High Treg infiltration within the tumor microenvironment has been linked to variable prognosis depending on the tumor type, highlighting Tregs' contradictory roles as both guardians of tolerance and enablers of tumor progression.</p><p><strong>Design: </strong>In this review, we summarize Treg biology, Tregs' contribution to cancer immunity, and emerging therapeutic strategies designed to modulate or deplete Tregs. We conducted a targeted literature review using PubMed/MEDLINE, Web of Science, ClinicalTrials.gov, and ASCO/ESMO meeting libraries, complemented by manual reference screening. We also discuss the limitations of existing therapeutic approaches and outline future directions.</p><p><strong>Results: </strong>Efforts to therapeutically modulate Tregs have focused on three main strategies: depletion (e.g., anti-CD25, anti-CCR4, or anti-CCR8 antibodies), functional blockade (e.g., targeting CTLA-4 or TIGIT), and disruption of metabolic pathways (e.g., adenosine or PI3K signaling) that support Tregs' biological functions. Although preclinical studies have shown that targeting Tregs have antitumor effects, clinical trials have demonstrated variable efficacy and toxic effects, reflecting the fine balance between immune activation and tolerance. Newer approaches aim to selectively impair intratumoral Tregs while preserving peripheral immune control, guided by T-cell subsets such as FOXP3⁺Helios⁺CCR8⁺ cells, which may help predict therapeutic response.</p><p><strong>Conclusion(s): </strong>A deeper understanding of Treg regulation is needed to unlock their therapeutic potential without compromising immune equilibrium.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung cancer brain metastases management at the dawn of personalized medicine: are we ready to break the barriers?","authors":"A Mavrikios, M Bortolot, C Le Péchoux, J Remon, A Botticella, M Aldea, P D Brown, C G Rusthoven, P Lavaud, M Frelaut, P Abdayem, D Lavigne, A Camps-Malea, B Besse, D Planchard, F Barlesi, J Jacob, P Gougis, S Knafo, C Chargari, F Dhermain, E Deutsch, C Faivre-Finn, A Levy","doi":"10.1016/j.annonc.2026.04.014","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.04.014","url":null,"abstract":"<p><p>Brain metastases (BM) occur in nearly half of patients with lung cancer and significantly impair survival and quality of life. Historically, limited blood-brain barrier penetration and low intracranial efficacy of systemic therapies restricted treatment options. However, advances in immune checkpoint inhibitors and next-generation CNS-penetrant targeted therapies have reshaped the therapeutic landscape, improving intracranial control and patient outcomes. In parallel, stereotactic radiotherapy has emerged as a precise and effective local treatment with a more favorable safety profile compared with whole-brain radiotherapy. The integration of systemic and local approaches, guided by personalized medicine, offers new opportunities to optimize central nervous system disease control. Nevertheless, these advances raise key challenges regarding treatment sequencing, patient selection, and risk-adapted strategies. This review summarizes the evolving management of lung cancer BM and highlights future directions for clinical trial design, emphasizing the integration of clinical, biological, and radiological tools to guide individualized treatment strategies.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IO102-IO103 immune-modulatory cancer vaccine and pembrolizumab in melanoma.","authors":"J C Hassel, A Arance, M S Carlino, L Mortier, P A Ascierto, P Rutkowski, S Sandhu, C Coetzee, I Puzanov, S B Karaca, A M Eggermont, O Hamid, S Grabbe, A Poklepovic, T Amaral, D Schadendorf, B Schilling, A Vedel Christiansen, B Wang, A Wakatsuki Pedersen, Q Ahmad, M B Zocca, F Ringeisen, C Robert, I M Svane","doi":"10.1016/j.annonc.2026.04.010","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.04.010","url":null,"abstract":"<p><strong>Background: </strong>IO102-IO103, an investigational, immune-modulatory cancer vaccine, targets both tumor cells and immune-suppressive cells within the tumor microenvironment through activation and expansion of T cells against indoleamine 2,3-dioxygenase 1(IDO1)-positive and/or programmed death ligand 1 (PD-L1)-positive cells.</p><p><strong>Patients and methods: </strong>This open-label, Phase 3 trial randomized 407 patients with untreated advanced melanoma in a 1:1 ratio to receive subcutaneous IO102-IO103 (85 μg each) plus pembrolizumab 200 mg intravenously every 3 weeks or pembrolizumab alone for up to 2 years. The primary endpoint was progression-free survival (PFS) by blinded independent central review per RECIST v1.1.</p><p><strong>Results: </strong>The median PFS was 19.4 months (95% confidence interval [CI], 9.7 to not reached) for IO102-IO103 plus pembrolizumab versus 11.0 months (95% CI, 6.0 to 14.8) for pembrolizumab (hazard ratio [HR] [95% CI], 0.77 [0.58 to 1.00]; P = 0.0558); the statistical significance threshold (P ≤ 0.045) was missed. A longer PFS was observed in the combination arm across most subgroups, notably in patients with PD-L1-negative tumors (median PFS 16.6 versus 3.0 months [HR, 0.54; 95% CI, 0.35 to 0.85]), anti-PD-1 naïve patients (24.8 versus 11.0 months [HR, 0.74; 95% CI, 0.56 to 0.98]), proto-oncogene B-Raf (BRAF) mutated tumors, or elevated lactate dehydrogenase. There was no increase in the frequency of treatment-related adverse events grade ≥3 (14.5% versus 15.6%) or of serious adverse events (32.0% versus 32.3%) in the vaccine arm. Local vaccine-related injection site reactions were reported in 56.0% of patients and were mostly grade 1/2.</p><p><strong>Conclusions: </strong>IO102-IO103 plus pembrolizumab prolonged progression-free survival compared with pembrolizumab alone in patients with advanced melanoma in the first-line setting; however, statistical significance was missed for the primary endpoint. The combination was well tolerated with no added significant systemic toxicity. These data show the potential benefit of this combination in untreated advanced melanoma.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-Evaluating Antibody-Drug Conjugate Linker Stability: Assessment, Interpretation, and Clinical Translation.","authors":"R Colombo, S Seredick, S D Barnscher, J R Rich","doi":"10.1016/j.annonc.2026.04.008","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.04.008","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) have emerged as an important class of anticancer therapeutics. Their highly modular design offers multiple opportunities to refine their properties and improve clinical performance by tuning individual components, including the antibody, linker, and payload. Recent ADC optimization efforts have focused on more stable linker designs, apparently based on the assumption that premature payload release, rather than ADC uptake and intracellular catabolism, is the primary driver of off-target toxicity and limited antitumor activity. However, clinical data highlight a more complex picture. Several clinically successful ADCs employ relatively unstable linkers, including some with short systemic half-lives. In contrast, ADCs with increased linker stability have not consistently demonstrated improved clinical outcomes and, in many cases, have been associated with unexpected toxicities. In this article, we examine common assumptions regarding ADC linker stability, highlight limitations of preclinical models in predicting human payload exposure, address appropriate methods to assess ADC stability, and discuss the clinical implications of altering ADC linker stability. By re-evaluating the role of linker stability in ADC design, this work aims to inform more rational strategies for the development of next-generation ADCs.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Including tumor-infiltrating lymphocytes into the PREDICT prognostic model for triple-negative breast cancer survival.","authors":"Y Wang, D Drubay, S F Jonas, J Dixon-Douglas, B Acs, S Adams, F André, S Badve, G Bataillon, J M Carter, S Chia, V Cockenpot, M A Colleoni, C Criscitiello, G Curigliano, G M H E Dackus, S Demaria, C Denkert, C H M van Deurzen, M V Dieci, D Giardiello, M P Goetz, R J Gray, M Hauptmann, N D Ter Hoeve, K Jóźwiak, E A Koop, V M T de Jong, H Joensuu, G Jules-Clément, R Kammler, P L Kellokumpu-Lehtinen, S B Kim, M Kok, M Lacroix-Triki, M Lambertini, H J Lee, J Lemonnier, R A Leon-Ferre, S Leung, B Linderholm, S Loibl, J W M Martens, T O Nielsen, M Opdam, P Pharoah, F Penault-Llorca, M Piccart, L Pustzai, N Riaz, A Vincent-Salomon, J Sparano, T Shimoi, C Sotiriou, V J Suman, A M Timmermans, P J van Diest, A C Voogd, G Viale, A C Wolff, S Yazaki, M Yoshida, R Salgado, S C Linn, M K Schmidt, S Loi, S Michiels","doi":"10.1016/j.annonc.2026.04.011","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.04.011","url":null,"abstract":"<p><strong>Background: </strong>Stromal tumor infiltrating lymphocytes (sTILs) are a strong prognostic marker in triple-negative breast cancer (TNBC) patients. We aimed to incorporate sTILs into the PREDICT model for women with early-stage TNBC to guide chemotherapy decisions.</p><p><strong>Patients and methods: </strong>We included 3698 women with early-stage TNBC, diagnosed between 1979 and 2017, from two pooled cohorts with sTILs scored according to international guidelines to update PREDICT version 2.3. The updated model, PREDICT_sTILs, is a Cox regression model with sTILs and the PREDICT prognostic index as predictors, and breast cancer-specific survival as the outcome. Internal-external validation was conducted using leave-one-region-out cross-validation, with calibration assessed by the observed-to-expected (O/E) ratio and discrimination by area under the curve (AUC). We compared the clinical values of PREDICT_sTILs and PREDICT through decision curve analysis, examining net true high-risk and low-risk classifications across risk thresholds of 10-year breast cancer mortality above 8-15%.</p><p><strong>Results: </strong>Among the 3698 patients, 1806 received chemotherapy while 1892 were chemotherapy-naïve. Chemotherapy-treated patients had a median age of 50 years, tumor size of 25mm, and 1 positive lymph node (pN). The chemotherapy-naïve patients had a median age of 55 years, tumor size of 20mm, and 0 pN. Within 5 and 10 years, 741 and 860 deaths were attributed to breast cancer, respectively. PREDICT_sTILs showed strong internal-external validity, with comparable calibration and discrimination at both time points: pooled O/E ratios of 0.98 (95% CI: 0.69-1.41) at 5 years and 0.99 (95%CI: 0.72-1.35) at 10 years, and AUCs of 0.74 (95%CI: 0.72-0.77) and 0.74 (95%CI: 0.70-0.78), respectively. Compared to PREDICT, PREDICT_sTILs identified 19-60 additional net true low-risk patients, and 3-10 additional net true high-risk patients per 1000 chemotherapy-naïve patients at the risk thresholds of 8-15% at 10 years.</p><p><strong>Conclusion: </strong>Adding sTILs to PREDICT improves its ability to inform chemotherapy decisions for early-stage TNBC patients, especially in identifying low-risk individuals who may safely forgo chemotherapy.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colorectal cancer detection using non-contrast CT and deep learning: a multicenter and international cohort study.","authors":"X Chen, M Y Qiu, J P Zhang, Y D Xia, K Cao, W W Cao, L S Yao, L Lambert, S Y Li, Y T Liang, H Lin, Y F Yu, J W Yao, W C Guo, J Xu, Z L Zheng, Y Mao, Z W Chen, Y Shi, T Kovarnik, M Vocka, X H Ye, J Zhou, C M Xie, Q F Wang, Y M Guo, D Liang, Z L Ma, L S Lai, X Huang, Y L Jia, L Zhang, Z Y Liu","doi":"10.1016/j.annonc.2026.04.009","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.04.009","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a leading cause of cancer deaths, with early screening vital to reduce mortality. While methods like colonoscopy and CT colonography are available, they face challenges such as bowel prep, invasiveness, and low adherence. We aimed to develop COCA, a novel, non-invasive, cost-effective, and scalable method for CRC screening using non-contrast CT scans.</p><p><strong>Patients and methods: </strong>This retrospective, multicenter, and international study included 1,321 CRC patients and 1,357 normal controls from two centers to develop COCA. We enhance the CRC detection capabilities of COCA by employing a joint lesion segmentation and classification architecture, optimized with mixed-supervised learning. For validation, we gathered abdominal and pelvic CT data from four external centers and chest CT data from four centers. A reader study involving 10 radiologists with varying levels of experience evaluated diagnostic performance on non-contrast CT first without COCA assistance and then with it. Additionally, we evaluated both the initial and iteratively improved versions of COCA in two real-world, multi-scenario cohorts comprising 27,433 consecutive patients.</p><p><strong>Results: </strong>In a multicenter and international validation involving 2,053 patients across six centers, COCA demonstrated an area under the curve (AUC) ranging from 0.967 to 0.996 for CRC detection. COCA improved CRC detection sensitivity by 20.4% and specificity by 5.4% compared to radiologists. In the first real-world multi-scenario validation with 9,016 consecutive patients, COCA achieved a sensitivity of 88.2% and specificity of 99.5% for CRC detection. In the second external real-world validation involving 18,427 consecutive patients, COCA maintained a sensitivity of 86.6% and specificity of 99.8%, with a positive predictive value of 63.4%.</p><p><strong>Conclusions: </strong>COCA demonstrated robust performance across various clinical scenarios, including physical exams, emergency departments, outpatient, and inpatient settings, effectively preventing missed CRC diagnoses. These findings suggest that COCA could serve as a potential tool for large-scale opportunistic CRC screening.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and molecular biomarkers for prediction of endocrine response after short preoperative endocrine therapy in the WSG ADAPT-HR+/HER2- and ADAPTcycle trials (N=7914).","authors":"O Gluz, U Nitz, M Christgen, S Kuemmel, M Braun, M Thill, R Wuerstlein, T Link, B Aktas, K Lüdtke-Heckenkamp, M Zaiss, V Bjelic-Radisic, M Just, K Veselinovic, M Vincent, R Baehner, L Wujak, M Warm, C Schumacher, C Schem, H Forstbauer, K Krauss, O Hoffmann, M Graeser, A Hartkopf, R Kates, C Zu Eulenburg, K Jóźwiak, S Burmeister, P Schmid, H H Kreipe, N Harbeck","doi":"10.1016/j.annonc.2026.04.007","DOIUrl":"https://doi.org/10.1016/j.annonc.2026.04.007","url":null,"abstract":"<p><strong>Background: </strong>Low Ki67 after short preoperative endocrine treatment (ET) indicates a favorable prognosis in HR+/HER2- early breast cancer (eBC). We investigated predictors of ET-response in the WSG ADAPT-HR+/HER2- and ADAPTcycle trials.</p><p><strong>Patients and methods: </strong>ET-response (Ki67 ≤10%) after 2-4-week standard ET, recurrence score (RS), and nodal status were used for treatment allocation. In ADAPT-HR+/HER2-, clinical high-risk patients received ET-alone if N0-1 and RS 0-11 or RS 12-25 and ET-response. In ADAPTcycle, N0-1 patients with RS>25 and ET-response and those with RS<25 and e.g., ET-non-response, N2-3 patients with RS≤25 and ET-response, were randomized to (neo)adjuvant chemotherapy or aromatase inhibitor (AI)+ribociclib. Predictors of ET-response were identified through multivariable logistic regression models.</p><p><strong>Results: </strong>3,675 patients from ADAPT-HR+/HER2- (≤50 years and premenopausal, ≤50y: N=1,250; >50 years or postmenopausal, >50y: N=2,425) and 4,239 from the ADAPTcycle screening cohort (≤50y: N=1,336; >50y: N=2,903) were analyzed. ET-response rates were higher after AI (ADAPT-HR+/HER2-/ADAPTcycle: 81.4%/76.7%) vs. tamoxifen (ADAPT-HR+/HER2-/ADAPTcycle: 40.1%/34.7%) in both age groups, with further improvement by ovarian function suppression (OFS) in premenopausal patients. Premenopausal patients with GnRH+AI had similar ET-response rates as postmenopausal patients. ET-response predictors included AI use (+OFS in premenopausal), age >50y, lower RS and baseline Ki67 levels, and higher expression of estrogen receptor (by immunohistochemistry) and HER2 (by Oncotype DX™). In ADAPT-HR+/HER2-, 5-year dDFS in ET-responders was markedly higher vs. non-responders even in chemotherapy-treated N0-1 patients with RS>25 (87.0 vs. 80.7%) and it was only slightly lower vs. RS 12-25 group.</p><p><strong>Conclusions: </strong>We observed similar ET-response rates in two large phase III trials. Postmenopausal patients (mostly receiving AI) had higher ET-response rates compared to younger patients. However, young patients with GnRH+AI had ET-response rates comparable to postmenopausal patients, suggesting that therapy rather than biology accounts for the difference. Combining ET-response and gene expression assessment could help more luminal eBC patients avoid chemotherapy.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}