Alger E, Regnault A, Dueck AC
… +16 more, Pe M, Grayling MJ, Calvert MJ, Hansen AR, Kholmanskikh O, Lai-Kwon J, Lee JJ, Minchom A, Qiao Y, Rantell KR, Roydhouse J, Snyder C, Symeonides SN, Wages NA, Wilson R, Yap C
Patient-reported outcomes (PROs) are increasingly recognised for their role in assessing tolerability in dose-finding oncology trials (DFOTs). However, analysis and reporting of PRO data within DFOTs are often unclear an...Patient-reported outcomes (PROs) are increasingly recognised for their role in assessing tolerability in dose-finding oncology trials (DFOTs). However, analysis and reporting of PRO data within DFOTs are often unclear and inconsistent. OPTIMISE-AR (Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Analysis Recommendations) establishes a practical toolkit supporting the statistical analysis, visualisation, and reporting of PRO data within DFOT publications. International, multidisciplinary, cross-sector statistical analysis and data visualisation working groups identified analytical and visualisation approaches for PROs data, addressing key DFOT PRO research objectives. Informed by existing literature, case studies and recommendations are provided in this Policy Review for analysing binary, ordinal, and continuous PRO data to assess tolerability across doses and timepoints, and to integrate PROs into interim and final dose-decision processes. The OPTIMISE-AR toolkit is structured around four methodological domains aligned with key DFOT PRO research objectives, providing statistical analysis and data visualisation recommendations for (1) PRO endpoints across timepoints, (2) PRO endpoints between timepoints, (3) time-to-event PRO endpoints, and (4) PRO endpoints for formal dose-decision making in model-based dose-finding designs. As PROs have an increasing role in tolerability assessment, this Policy Review promotes analysis and data visualisation of PRO data, facilitating robust, patient-centred tolerability conclusions and supporting the broader development of tolerable and effective treatments.
Shamai G, Cohen S, Binenbaum Y
… +13 more, Sabo E, Cretu A, Mayer C, Barshack I, Goldman T, Bar-Sela G, Polónia A, Huo D, Pearson AT, Howard FM, Sparano JA, Kimmel R, Aran D
Lancet Oncol
· 2026 Apr · PMID 41831466
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BACKGROUND: Genomic assays such as Oncotype DX have transformed adjuvant treatment selection for hormone receptor-positive, HER2-negative, early breast cancer but remain inaccessible to many patients because of high cost...BACKGROUND: Genomic assays such as Oncotype DX have transformed adjuvant treatment selection for hormone receptor-positive, HER2-negative, early breast cancer but remain inaccessible to many patients because of high cost and logistical barriers. We aimed to develop and validate an artificial intelligence (AI) model that estimates Oncotype DX 21-gene recurrence scores directly from routine histopathology slides and clinicopathological variables. METHODS: In this multicentre, model development and validation study, a multimodal deep-learning model was trained on digital whole-slide images and clinical features using a foundation model pre-trained on 171 189 histopathology slides for predicting Oncotype DX recurrence score. We included slides from patients with hormone receptor-positive, HER2-negative, invasive breast cancers and without scanning artifacts and with at least 100 tissue tiles (1·6 mm). The model was fine-tuned and validated on the TAILORx randomised trial (8284 patients after quality control). Prognostic and predictive performance was assessed in the TAILORx-test set and externally validated in six independent cohorts (Carmel, Haemek, and Sheba medical centres [Israel], the University of Chicago Medical Center [USA], the Australian Breast Cancer Tissue Bank [Australia], and the Cancer Genome Atlas Breast Invasive Carcinoma project [USA]). FINDINGS: In the TAILORx-test set (n=2407), the AI model classified 1097 (45·6%) patients as low risk, 1021 (42·4%) as intermediate risk, and 289 (12·0%) as high risk. For identifying high genomic-risk disease (recurrence score ≥26), the area under the curve (AUC) was 0·898 (95% CI 0·879-0·913). AI-based risk stratification was prognostic for recurrence-free interval (hazard ratio 2·61 [95% CI 1·68-4·04]), distant recurrence-free interval (2·88 [1·73-4·79]), and disease-free survival (1·32 [0·92-1·89]). Chemotherapy benefit was evident in premenopausal patients classified by AI as being at high risk (0·63 [0·46-0·86]) but absent in postmenopausal patients classified by AI as being at low risk (0·94 [0·78-1·12]). 151 (31·3%) clinically high-risk postmenopausal women (by MINDACT criteria) were reclassified as low AI risk with no chemotherapy benefit. Analysis on external cohorts (5497 patients) showed that the model is transferable to new data with high generalisability (recurrence score ≥26 AUC ranging from 0·858 to 0·903). INTERPRETATION: These findings show that AI applied to routine histopathology can serve as a practical and scalable tool for guiding chemotherapy decisions in hormone receptor-positive, HER2-negative, early breast cancer. This approach has the potential to reduce unnecessary chemotherapy and broaden access to precision oncology, particularly in resource-limited settings where genomic testing remains unavailable or unaffordable. FUNDING: Israel Innovation Authority (Kamin), Zimin Institute for Artificial Intelligence Solutions in Healthcare, Israel Precision Medicine Partnership program, and Israel Cancer Research Fund.
Zhong H, Wang J, Yang R
… +24 more, Luo Y, Zuo W, Zhang W, Xie C, Li Q, Liu Q, Xu X, Wang Q, Yu Y, Chen Y, Yi T, Min X, Shi J, Yang J, Sun H, Chen H, Shi H, Gao J, Shi J, Zhang B, Chu T, Li K, Han B, CAMPASS Investigators
BACKGROUND: PD-1 and PD-L1 inhibitors have been shown to synergise with anti-angiogenic agents in non-small-cell lung cancer (NSCLC). We aimed to compare benmelstobart plus anlotinib with pembrolizumab in patients with p...BACKGROUND: PD-1 and PD-L1 inhibitors have been shown to synergise with anti-angiogenic agents in non-small-cell lung cancer (NSCLC). We aimed to compare benmelstobart plus anlotinib with pembrolizumab in patients with previously untreated, driver gene-negative, PD-L1-positive, advanced NSCLC. METHODS: The blinded, randomised, controlled, phase 3 CAMPASS trial was conducted in 79 centres across China. Patients aged 18-75 years with stage IIIB-IV squamous or non-squamous NSCLC, no previous systemic treatment for advanced, recurrent or metastatic diseases, a PD-L1 tumour proportion score of 1% or greater, a life expectancy of 3 months or longer, at least one measurable lesion, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (2:1) to receive intravenous benmelstobart (1200 mg once on day 1) plus oral anlotinib (12 mg daily on days 1-14) or intravenous pembrolizumab (200 mg once on day 1) plus placebo every 3 weeks. Randomisation was done centrally and stratified by tumour histology, PD-L1 tumour proportion score, and brain metastases. Treatment allocation was open label for investigators and masked to patients and statisticians. The primary endpoint was progression-free survival as assessed by a blinded independent review committee per Response Evalutation Criteria in Solid Tumours version 1.1 in the intention-to-treat population (all randomly assigned patients). Safety was assessed in all randomly assigned patients who received at least dose of study drug. Results reported here are from a preplanned final analysis for progression-free survival. This ongoing study is closed to recruitment and is registered with ClinicalTrials.gov, NCT04964479. FINDINGS: Between Aug 6, 2021, and Dec 14, 2022, 531 patients were randomly assigned (354 to the benmelstobart plus anlotinib group and 177 to the pembrolizumab plus placebo group). 449 (85%) patients were male, 82 (15%) were female, and 493 (93%) were of Han ethnicity. Two patients in the benmelstobart plus anlotinib group and one patients in the pembrolizumab plus placebo group were untreated and therefore excluded from the safety population. After a median follow-up of 11·4 months (95% CI 9·4-13·1) for the benmelstobart plus anlotinib group and 10·6 months (9·0-13·0) for the pembrolizumab plus placebo group, median progression-free survival was 11·0 months (9·2-12·6) and 7·1 months (5·8-9·5), respectively (hazard ratio [HR] 0·70 [95% CI 0·54-0·90]; log-rank p=0·0057). Grade 3 or worse treatment-related adverse events occurred in 206 (59%) of 352 patients in the benmelstobart plus anlotinib group and 51 (29%) of 176 patients in the pembrolizumab plus placebo group, and the most frequent one was hypertension (90 [26%] vs five [3%]). Serious treatment-related adverse events occurred in 89 (25%) patients in the benmelstobart plus anlotinib group and 37 (21%) patients in the pembrolizumab plus placebo group, the most common of which were haemoptysis (nine [3%] vs none) and immune-mediated pulmonary diseases (eight [2%] vs five [3%]). Five (1%) treatment-related deaths occurred in the benmelstobart plus anlotinib group (two due to haemoptysis and one each due to immune-mediated pulmonary disease, disease progression, and infection pneumonia) and four (2%) occurred in the pembrolizumab plus placebo group (one each due to respiratory failure, pulmonary inflammation, disease progression, and myocardial injury). INTERPRETATION: Benmelstobart plus anlotinib showed longer progression-free survival than pembrolizumab plus placebo and no unexpected safety signals were reported, suggesting benmelstobart plus anlotinib as a potential first-line option in driver gene-negative, PD-L1-positive, advanced NSCLC. Longer term follow-up is needed to establish effects on overall survival. FUNDING: Chia Tai Tianqing Pharmaceutical Group.
Karpinski MJ, Civan C, Rauscher I
… +54 more, Güven O, Eiber M, Hoberück S, Miederer M, Bundschuh RA, Hölscher T, Calais J, Theus L, Nguyen AT, Scholtissek H, Lapa C, Di Giorgio A, Farolfi A, Ufton D, Drzezga A, Kunikowska J, Pełka K, Evangelista L, Bauman G, Alçın G, Beintner-Skawran S, Rohani MFM, Miksch J, Hüsing A, Kesch C, Herrmann K, Stuschke M, Umutlu L, Gafita A, Hofman MS, Hope TA, Goffin K, Kind F, Pizzuto DA, Soeterik TFW, Kömek H, Emmett L, Vondrak A, Pinter T, Lanfranchi F, Bauckneht M, Unterrainer LM, Holzgreve A, Bjartell A, Trägårdh E, Rasul S, Miszczyk M, Bögemann M, Rodriguez SantAnna Jauregui N, Schäfers M, Rahbar K, Hadaschik BA, Fendler WP, PROMISE Registry Group
BACKGROUND: Prostate-specific membrane antigen (PSMA)-PET usage in patients with prostate cancer is growing rapidly. Thus, novel risk-group definitions based on PSMA-PET are urgently needed for guidelines, clinical use,...BACKGROUND: Prostate-specific membrane antigen (PSMA)-PET usage in patients with prostate cancer is growing rapidly. Thus, novel risk-group definitions based on PSMA-PET are urgently needed for guidelines, clinical use, and trial study design. We report improved risk classification based on PSMA-PET Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE; PPP) nomograms (PPP3) to prognosticate 3-year, 5-year, and 7-year overall survival. METHODS: In this international, retrospective, registry-based cohort study, we collected data from the PROMISE PET registry with ongoing overall survival follow-up. Male patients (aged ≥18 years) with histological proven prostate cancer at any disease stage and any performance status, who underwent any PSMA-PET between Dec 6, 2012, and June 26, 2024, were included in the registry. Patients with neuroendocrine pattern or metastasised or disseminated malignancy other than prostate cancer were excluded. 35 investigator sites in Europe, Asia, Australia, North America, and South America were split pairwise (2:1) into development and validation cohorts. Entire investigator sites were split pairwise according to their site characteristics (ie, number of patients per disease group, country, follow-up). The primary study objective was overall survival. PPP3 nomograms were created based on Cox regression models with least absolute shrinkage and selection operator penalty to prognosticate 3-year, 5-year, and 7-year overall survival. Calibration curves and Harrell's c indices were applied and head-to-head comparison with clinical risk scores separated for each disease subgroup was conducted. Based on the visual PPP3 nomogram, a simplified risk-stratification table was created. FINDINGS: We analysed 11 154 patients and 7253 were included in the development cohort and 3901 in the validation cohort. Median follow-up to censoring or death was 4·9 years (IQR 3·5-6·6). Clinical disease group and PROMISE metrics were combined into visual and quantitative PPP3 nomograms, respectively. C indices were 0·83 (95% CI 0·82-0·84) for the visual nomogram and 0·84 (0·82-0·85) for the quantitative nomogram. Both nomograms and the simplified risk stratification table were accurate and equal or superior compared with established clinical risk scores (International Staging Collaboration for Cancer of the Prostate, European Association of Urology, a nomogram defined by Gafita and colleagues, and National Comprehensive Cancer Network). INTERPRETATION: We present new risk nomograms by PROMISE along with a simple table to prognosticate 3-year, 5-year, and 7-year overall survival in prostate cancer. PROMISE and PPP3 assessments are freely available online for global implementation. FUNDING: German Research Foundation, Prostate Cancer Foundation, Innovative Health Initiative Joint Undertaking, Novartis, AstraZeneca, and Amgen.
BACKGROUND: It is unproven whether sentinel node biopsy (SNB) for people with cutaneous melanoma improves survival. This study aimed to establish whether there is a reduction in the risk of death from melanoma after SNB....BACKGROUND: It is unproven whether sentinel node biopsy (SNB) for people with cutaneous melanoma improves survival. This study aimed to establish whether there is a reduction in the risk of death from melanoma after SNB. METHODS: This systematic review and meta-analysis involved searches of Medline, Embase, Cochrane CENTRAL, and ClinicalTrials.gov (up to Jan 8, 2025) using terms for melanoma, SNB, and survival. Studies were included if they reported survival in adults (ie, aged ≥18 years) with melanoma who underwent SNB relative to those who did not, and excluded studies without these data, because survival risk in people with melanoma could not be calculated. Duplicate title review (by GJW and CAG) and data extraction (by GJW and MBW) were performed. The primary outcome was death from melanoma. Risk of bias was assessed using the Newcastle-Ottawa and Cochrane Collaboration tools. This study was registered with PROSPERO (number CRD4203494674). FINDINGS: From 1560 screened records, 60 studies were eligible for analysis. After the exclusion of one study with high selection bias meta-analysis, 13 studies (40 287 participants) reporting an adjusted risk were analysed and showed a significantly reduced risk of death from melanoma for people who underwent SNB: hazard ratio (HR) 0·86 (95% CI 0·81-0·92, p<0·0001), with low heterogeneity (I 16%). Sensitivity analyses confirmed that this result was not dependent on any single study or on the use of systemic therapy. A similar result was obtained from the analysis of the five studies (27 540 participants) that reported 5-year risk of death from melanoma: HR 0·84 (95% CI 0·78-0·90, p<0·0001) with low heterogeneity (I 15%). A 10-year risk of death from melanoma was reported in two studies with three estimates: 0·87 (0·71-1·06; p=0·17) and with greater heterogeneity (I 41%). From nine studies (11 625 participants) reporting an adjusted risk of recurrence, the HR was 0·71 (95% CI 0·66-0·76, p<0·0001) with low heterogeneity (I 23%). INTERPRETATION: This meta-analysis showed that people with melanoma who underwent SNB had a significantly reduced risk of death from melanoma and recurrence compared with those who did not. These findings are consistent with the only published randomised controlled trial and were robust on sensitivity analyses, indicating that SNB confers true survival and recurrence benefits. FUNDING: None.
This international Delphi study, led by the European Society of Radiation Oncology as part of their Value-Based Radiation Oncology programme, brought together key experts from the radiation oncology community to build co...This international Delphi study, led by the European Society of Radiation Oncology as part of their Value-Based Radiation Oncology programme, brought together key experts from the radiation oncology community to build consensus on both the level of evidence and the endpoints that are essential to support clinical implementation or policy decisions (eg, reimbursement) for different types of radiotherapy innovations. Although randomised trial evidence remained a high priority across most innovation types, other evidence, such as high-quality prospective observational studies or alternative designs such as pragmatic trials, was found to be a suitable alternative in specific scenarios. In addition, the importance of a broader set of clinical endpoints beyond overall survival was acknowledged, including quality of life, local control, and functional endpoints. These consensus criteria aim to inform the development of a structured appraisal framework for radiotherapy innovation, guiding health-care providers and policy makers in identifying and promoting high-value radiotherapy that offers meaningful benefit to patients and supports implementation.
Radiotherapy and systemic therapies have revolutionised cancer treatments and improved survival, with generally acceptable toxicity. Modern radiotherapy techniques offer precision in targeting tumours, while minimising h...Radiotherapy and systemic therapies have revolutionised cancer treatments and improved survival, with generally acceptable toxicity. Modern radiotherapy techniques offer precision in targeting tumours, while minimising harm to the surrounding tissues. Novel systemic therapies represent opportunities for combining innovative treatments with radiotherapy. New agents are increasingly more tumour-specific than chemotherapy, and new rational combinations with radiotherapy are emerging, allowing for a more personalised approach. The European Society for Radiotherapy and Oncology (ESTRO) has formed a focus group to explore the integration of innovative agents with radiotherapy. This Policy Review highlights the potential of combining radiotherapy with novel drugs, while addressing current evidence gaps and unmet needs in cancer care. The group emphasises a collaborative approach involving multiple stakeholders to drive sustainable improvements in oncological therapies, suggesting careful selection of combinations based on robust preclinical data. Key insights and proactive strategies can shape future clinical practices, particularly with the early introduction of radiotherapy in the development of novel agents.
Leonhardt CS, Adham M, Bazarbashi S
… +64 more, Ben-Aharon I, Beets-Tan RGH, Boggi U, Brunner TB, Cellini F, Chiti A, Daamen L, De Bari B, De Dosso S, Ducreux M, Eng C, Falconi M, Ferrone CR, Frigerio I, Garajova I, Gerum S, Ghadimi M, Gruenberger T, Hammel P, Haustermans K, Hawkins M, He J, Heerkens HD, Huguet F, Intven MPW, Klaiber U, Kroese TE, Laurent-Puig P, Lordick F, Ludmir EB, Macarulla T, Matzinger O, Morganti AG, Mukherjee S, O'Reilly EM, Park JO, Papamichael D, Pfeiffer P, Ramia JM, Roeder F, Ruiz-García E, Satoi S, Scorsetti M, Schneider M, Seufferlein T, Serrablo A, Shrikhande SV, Smyth EC, Svrcek M, Takaori K, Tempero MA, Tissera NS, Tie J, Torres OJM, Turpin A, Van Cutsem E, Versteijne E, Vivaldi C, Wainberg ZA, Weichselbaum RR, Weitz J, Wolfgang CL, Prager GW, Strobel O
Currently, no consensus exists regarding the definition of oligometastatic pancreatic ductal adenocarcinoma, its necessary diagnostic measures, and potential treatment approaches. To address these knowledge gaps, the Oli...Currently, no consensus exists regarding the definition of oligometastatic pancreatic ductal adenocarcinoma, its necessary diagnostic measures, and potential treatment approaches. To address these knowledge gaps, the OligoPanc project brought together an interdisciplinary group of experts to establish consensus using a modified Delphi process and clinical vignettes. Participants agreed that the number of metastatic lesions and the number of affected organs are key elements in defining oligometastatic pancreatic ductal adenocarcinoma. Specifically, up to three lesions in a single organ, either the liver or the lung, define oligometastatic pancreatic ductal adenocarcinoma and could be either synchronous or metachronous. Necessary diagnostics include a triple-phase contrast-enhanced CT scan of the chest and abdomen and MRI of the liver with a hepatocyte-specific contrast agent. In unclear cases, [F]fluorodeoxyglucose-PET CT or MRI can be considered. A multidisciplinary tumour board is essential. Patient-intrinsic factors, including age, do not define oligometastatic disease but should be considered for any treatment decision. Systemic treatment before any local consolidative treatment, including surgery, stereotactic ablative radiotherapy, or other locally ablative techniques, is mandatory. The proposed definition should be incorporated into future trials to improve comparability and enable validation.
Concurrent chemoradiotherapy followed by immune checkpoint inhibitor (ICI) consolidation is now the standard of care for unresectable stage III non-small-cell lung cancer (NSCLC) and is increasingly applied to other thor...Concurrent chemoradiotherapy followed by immune checkpoint inhibitor (ICI) consolidation is now the standard of care for unresectable stage III non-small-cell lung cancer (NSCLC) and is increasingly applied to other thoracic malignancies. Although survival outcomes have improved, concerns about cardiac toxicity have emerged, as both chemoradiotherapy and ICIs are independently cardiotoxic and their combined effects remain unclear. This scoping review first examines chemoradiotherapy-associated and ICI-associated cardiac toxicity separately, and then evaluates their convergence in combined chemoradiotherapy and ICI therapy. For this examination and evaluation, we draw on ten clinical studies, two reviews, and five preclinical reports that together address six key questions: (1) does ICI add cardiac risks to chemoradiotherapy, (2) does previous radiotherapy increase cardiac risks with ICI, (3) does ICI alter the radiosensitivity of cardiac subregions, (4) how should cardiac endpoints be defined, (5) can molecular or pharmacological interventions mitigate toxicity, and (6) what are the major risk factors and management strategies? We also highlight four major gaps: extension beyond NSCLC, long-term survivorship, the potential of advanced radiotherapy techniques, and the interplay between lymphopenia and cardiotoxicity. The convergence of chemoradiotherapy and ICIs represents a new cardiac risk profile. Addressing these questions through larger, long-term studies is essential to balance oncological efficacy with cardiovascular safety.