Annals of Oncology最新文献

{"title":"Reply to Letters to the Editor by Mimura et al. and Hu and Yang regarding the NATALEE final invasive disease-free survival analysis.","authors":"G N Hortobagyi, M Ruiz Borrego","doi":"10.1016/j.annonc.2025.06.013","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.06.013","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758992","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":"Mechanisms of genomic resistance across emerging classes of KRAS inhibitors.","authors":"J M Riedl, R B Corcoran","doi":"10.1016/j.annonc.2025.06.019","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.06.019","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758991","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":"Cancer of unknown primary site and TNM staging: a new paradigm for patient management.","authors":"F Anthony Greco","doi":"10.1016/j.annonc.2025.07.007","DOIUrl":"10.1016/j.annonc.2025.07.007","url":null,"abstract":"<p><p>Cancer of unknown primary site (CUP) is a syndrome of many different metastatic cancers arising from clinically occult primary tumors. There has been no established staging system applicable since it has not been possible to identify an anatomical primary tumor. In recent years, the globally accepted American Joint Committee on Cancer TNM (tumor-node-metastasis) staging manuals briefly addressed a few rare CUP subsets with highly suspected primary tumors (breast, oropharynx, nasopharynx, melanoma) that could be designated as primary category T0 (no evidence of primary tumor). Similar logic may now be applied to many other patients and TNM staging is an evolving narrative. Diagnostic pathology, particularly immunohistochemical staining and molecular testing, interpreted in the context of clinical features are now capable of diagnosing presumptive occult primaries with reasonable certainty in many other patients creating an avenue for a T0 category as a specific cancer type. This new diagnostic paradigm of lifting the veil of the unknown for some patients and separating them from the historical nondescript CUP diagnosis allows for TNM staging, precision site-specific therapy (SST), prognostication, evaluating treatment results and continuing investigation. Once the tumor type is unmasked and staged, additional molecular characterization and SST are indicated. Many CUP subsets now meet these criteria and considerable clinical trial data have revealed that their outcomes from SST appear superior to empiric chemotherapy and similar to their counterparts with overt primary tumors, although additional prospective comparative studies are warranted. Eventually most of the cancers responsible for the enigmatic CUP syndrome will be identified, making CUP an irrelevant clinical entity.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697445","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":"Tumour-infiltrating lymphocytes in refractory melanoma—not as hard as we thought?","authors":"A. Javaid ,&nbsp;S.P. Patel ,&nbsp;J. Larkin","doi":"10.1016/j.annonc.2025.07.010","DOIUrl":"10.1016/j.annonc.2025.07.010","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 10","pages":"Pages 1116-1118"},"PeriodicalIF":65.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697447","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 challenges and proposed solutions for patients with invasive lobular breast cancer.","authors":"K Van Baelen, E Sawyer, J Van Cauwenberge, P Aftimos, M F Covington, M Maetens, G Zels, C Brisken, L Djerroudi, R Dresen, A Fitzpatrick, R L Flaherty, G Floris, S Freeney, A B Hanker, D Honey, C M Isacke, R C Jankowitz, R Jeselsohn, T Koorman, C Kuhl, S Linn, C J Lord, C Malhaire, J Mouabbi, R Mukhtar, G Nader-Marta, R Natrajan, P Neven, S Oesterreich, J L Sandoval, S J Schnitt, E Senkus, C Turner, V Vandecaveye, H Wildiers, A Vincent-Salomon, P W B Derksen, C Desmedt","doi":"10.1016/j.annonc.2025.07.008","DOIUrl":"10.1016/j.annonc.2025.07.008","url":null,"abstract":"<p><strong>Background: </strong>Invasive lobular carcinoma (ILC) is the second most common type of breast cancer and is increasingly recognized as a separate entity from invasive breast cancer of no-special type. Here, we present the current standings and challenges of clinical ILC research and discuss possible solutions to address these challenges.</p><p><strong>Design: </strong>European and United States experts on ILC have summarized the recent developments, ongoing endeavors and remaining challenges concerning the histopathological diagnosis, imaging and treatment of ILC.</p><p><strong>Results: </strong>Recent endeavors have led to guidelines for a more uniform and standardized pathological diagnosis of ILC. Future efforts are needed to refine the histological and biological subclassification and determine the indications for use of artificial intelligence for pathological diagnosis. Since standard-of-care imaging tools are suboptimal for ILC screening and local and systemic staging, new modalities such as contrast-enhanced mammography, novel positron emission tomography tracers and diffusion-weighted magnetic resonance imaging are under investigation. An alternative to the currently used RECIST v1.1 criteria is needed for clinical trial response assessment, as it is not uniformly applicable for patients with metastatic ILC. The use of liquid biopsies for detecting disease progression needs dedicated research. Regarding treatment, the efficacy of novel breast cancer therapies needs to be examined specifically for ILC, and evaluation of drugs targeting ILC-specific or enriched targets is warranted.</p><p><strong>Conclusions: </strong>While great progress has been made in ILC research, many challenges remain and require further investigation in the clinic to optimize treatment and outcomes for those diagnosed with this common tumor type.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697446","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":"From epigenetic alterations to clinical impact: the role of DNMT3A in modulating immunotherapy response","authors":"M. Khalil ,&nbsp;M.S. Tsao","doi":"10.1016/j.annonc.2025.07.009","DOIUrl":"10.1016/j.annonc.2025.07.009","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 10","pages":"Pages 1113-1115"},"PeriodicalIF":65.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681854","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":"The OpeRa trial: the active role of the patient in the clinical decision-making process and surgical planning.","authors":"A Larcher, F Cei, A Mottrie, A Salonia, U Capitanio, F Montorsi","doi":"10.1016/j.annonc.2025.07.006","DOIUrl":"10.1016/j.annonc.2025.07.006","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681855","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":"Final overall survival and safety analyses of the phase III PSMAfore trial of [¹⁷⁷Lu]Lu-PSMA-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer.","authors":"K Fizazi, K N Chi, N D Shore, K Herrmann, J S de Bono, D Castellano, J M Piulats, A Fléchon, X X Wei, H Mahammedi, G Roubaud, M Fleming, T Haas, S Ghebremariam, T N Kreisl, S Rajagopalan, O Sartor, M J Morris","doi":"10.1016/j.annonc.2025.07.003","DOIUrl":"10.1016/j.annonc.2025.07.003","url":null,"abstract":"<p><strong>Background: </strong>In PSMAfore, [¹⁷⁷Lu]Lu-PSMA-617 (¹⁷⁷Lu-PSMA-617) prolonged radiographic progression-free survival (rPFS) in taxane-naive patients with metastatic castration-resistant prostate cancer (mCRPC), with a favourable safety profile, versus a change in androgen receptor pathway inhibitor (ARPI). We report the final overall survival (OS) analysis and updated safety data.</p><p><strong>Patients and methods: </strong>PSMAfore (NCT04689828) was an open-label, international, phase III trial. Patients with prostate-specific membrane antigen (PSMA)-positive mCRPC who had experienced disease progression once on a previous ARPI and were candidates for ARPI change were randomized 1 : 1 to ¹⁷⁷Lu-PSMA-617 or ARPI change to abiraterone or enzalutamide. Crossover from ARPI change to ¹⁷⁷Lu-PSMA-617 was allowed after centrally confirmed radiographic progression. Endpoints included rPFS (primary), OS (key secondary), and safety (secondary).</p><p><strong>Results: </strong>Patients were randomized to ¹⁷⁷Lu-PSMA-617 or ARPI change (n = 234 each): 141/234 participants (60.3%) randomized to ARPI change crossed over (75.4% of those with centrally confirmed radiographic progression). The median OS was 24.48 months [95% confidence interval (CI) 19.55-28.94 months] with ¹⁷⁷Lu-PSMA-617 versus 23.13 months (95% CI 19.61-25.53 months) with ARPI change [hazard ratio (HR) 0.91, 95% CI 0.72-1.14, P = 0.20] based on the intention-to-treat (ITT) principle; the crossover-adjusted OS HR by inverse probability of censoring weighting modelling was 0.59 (95% CI 0.38-0.91). For ¹⁷⁷Lu-PSMA-617 versus ARPI change, exposure-adjusted incidences of grade ≥3 and serious treatment-emergent adverse events were 60.8 versus 85.1 and 32.5 versus 49.9 per 100 patient-treatment years, respectively. Dry mouth occurred in 135/227 participants (59.5%; 2/227 grade ≥3) and anaemia in 62/227 (27.3%; 14/227 grade ≥3) in the ¹⁷⁷Lu-PSMA-617 arm.</p><p><strong>Conclusions: </strong>OS analyses did not show a statistically significant difference between the ¹⁷⁷Lu-PSMA-617 and ARPI arms based on the ITT principle; results were likely confounded by the high rate of crossover. The safety profile of ¹⁷⁷Lu-PSMA-617 was favourable with no new safety signals identified.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fracture-related hospitalisations in newly diagnosed high-risk localised or metastatic hormone-sensitive prostate cancer: secondary analysis of the STAMPEDE phase III trials of docetaxel and zoledronic acid using healthcare systems data.","authors":"C Jones, P Dutey-Magni, L R Murphy, M L Murray, J E Brown, E McCloskey, M Brown, C L Amos, D C Gilbert, R J Jones, W Cross, D Matheson, R Millman, M K B Parmar, G Attard, M R Sydes, L C Brown, N D James, N W Clarke, A Sachdeva","doi":"10.1016/j.annonc.2025.07.005","DOIUrl":"10.1016/j.annonc.2025.07.005","url":null,"abstract":"<p><strong>Background: </strong>Androgen deprivation therapy (ADT), the mainstay systemic treatment for high risk non-metastatic (M0) and metastatic (M1) prostate cancer is associated with bone loss and increased fracture risk. The STAMPEDE trial tested the addition of zoledronic acid (ZA) ± docetaxel (with prednisolone) to ADT. Both regimens may impact bone health. However, long-term fracture incidence remains uncertain.</p><p><strong>Patients and methods: </strong>Health systems data were obtained for patients recruited from England and randomised to standard-of-care (SOC) ADT compared with SOC plus ZA or docetaxel or both docetaxel and ZA. ICD10 diagnosis and OPCS procedure codes from inpatient hospital admissions were used to identify fracture-related hospitalisations. Flexible parametric competing risks models were used to estimate 5- and 10-year cumulative incidence and sub-distribution hazard ratios (SDHR).</p><p><strong>Results: </strong>2140 of 2705 (79%) patients recruited from trial sites in England were eligible for this secondary analysis. Linked data were available for 2042/2140 (96%) pts (734 M0, 1308 M1). 5-year cumulative incidence of fracture for M0 and M1 patients treated with SOC only was 11% [95% confidence interval (CI), 8% to 15%] and 23% (95% CI, 19% to 28%), respectively. 10-year cumulative incidence in M0 patients was 26% (95% CI, 20% to 33%). Allocation to ZA significantly reduced the risk of fracture in M1 patients (SDHR 0.73, 95% CI 0.55-0.97; P = 0.015) but not M0 patients (SDHR 0.88, 95% CI 0.59-1.32; P = 0.549). Docetaxel had no clear effect on the risk of fracture in M0 (P = 0.570) or M1 (P = 0.264) patients.</p><p><strong>Conclusions: </strong>High cumulative incidence of fracture was observed in both M0 and M1 prostate cancer patients receiving ADT. The addition of ZA to ADT ± docetaxel significantly reduced long-term fracture risk in M1 participants but had no clear effect in M0 disease. These data support the use of bone protective agents to reduce fracture risk in men with M1 prostate cancer undergoing ADT.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666842","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-examining post-operative chemoradiotherapy in head and neck cancer: an updated long-term combined analysis of RTOG 9501/EORTC 22931.","authors":"Z S Zumsteg, M Luu, C Fortpied, J K Jang, M M Chen, J Mallen-St Clair, E Walgama, Q T Le, M Machtay, S Tribius, A Forastiere, S Wong, E M Ozsahin, V Gregoire, J B Vermorken, A S Ho, S S Yom","doi":"10.1016/j.annonc.2025.07.004","DOIUrl":"10.1016/j.annonc.2025.07.004","url":null,"abstract":"<p><strong>Background: </strong>Post-operative chemoradiation (CRT) is generally recommended for head and neck cancer patients with extranodal extension (ENE) and/or positive margins, but not for patients without these features, based on a post hoc analysis of Radiation Therapy Oncology Group (RTOG) 9501 and European Organisation for Research and Treatment of Cancer (EORTC) 22931. However, this analysis lacked tests of interaction necessary to identify a predictive biomarker. In addition, updated data are now available.</p><p><strong>Patients and methods: </strong>This study assessed 744 patients enrolled on RTOG 9501 and EORTC 22931, randomized trials that compared CRT with radiation (RT) following surgery. Overall survival (OS) was analyzed with Cox regression. Cancer-specific mortality (CSM), other-cause mortality (OCM), and recurrence outcomes were analyzed with competing risks methodology. Tests of interaction assessed for differential benefits of CRT in various subgroups.</p><p><strong>Results: </strong>Median follow-up was 6.9 years. Among all patients, CRT improved OS [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.68-0.97, P = 0.026]. Although CRT improved OS in the subgroup with ENE and/or positive margins (HR 0.71, 95% CI 0.57-0.89, P = 0.003) and not in those without these features (HR 0.94, 95% CI 0.68-1.30, P = 0.7), tests of interaction showed no evidence of a differential effect of CRT in these subgroups (P-interaction = 0.17). There was also no evidence of interaction when analyzing other outcomes, or when assessing ENE and margin status individually. While CRT significantly reduced CSM (HR 0.68, 95% CI 0.55-0.83, P < 0.001), it also significantly increased OCM (HR 1.51, 95% CI 1.07-2.12, P = 0.018). Post-operative CRT improved locoregional recurrence (HR 0.64, 95% CI 0.48-0.85, P = 0.002), but not distant metastasis (HR 0.83, 95% CI 0.64-1.08, P = 0.17).</p><p><strong>Conclusions: </strong>Concurrent chemotherapy improved OS in head and neck cancer patients undergoing post-operative radiotherapy in the combined populations of EORTC 22931 and RTOG 9501. ENE and/or positive margins are not predictive biomarkers, and patients without these features may still benefit from CRT. CRT improved CSM, but this was partly offset by higher OCM. Refining the population most likely to benefit from post-operative CRT, taking into consideration both oncologic and patient-related factors, needs further exploration.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":65.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}