ESMO Open最新文献

{"title":"Survival analysis of the non-metastatic cohort of the Italian Association for Medical Oncology (AIOM) Guideline Application in Real world: multi-Institutional Based survey of Adjuvant and first-Line pancreatic Ductal adenocarcinoma treatment in Italy (GARIBALDI)","authors":"M. Reni ,&nbsp;M. Milella ,&nbsp;F. Bergamo ,&nbsp;M. Di Marco ,&nbsp;E. Giommoni ,&nbsp;G.G. Cardellino ,&nbsp;L. Cavanna ,&nbsp;M. Bonomi ,&nbsp;F. Zustovich ,&nbsp;S. Bozzarelli ,&nbsp;F. Salmaso ,&nbsp;M. Spada ,&nbsp;G. Orsi ,&nbsp;M. Macchini ,&nbsp;J. Insolda ,&nbsp;L. Procaccio ,&nbsp;A. Santoni ,&nbsp;I. De Simone ,&nbsp;L. Caldirola ,&nbsp;F. Galli ,&nbsp;C. Pinto","doi":"10.1016/j.esmoop.2024.104001","DOIUrl":"10.1016/j.esmoop.2024.104001","url":null,"abstract":"<div><h3>Background</h3><div>Non-metastatic pancreatic ductal adenocarcinoma (PDAC) presents a challenging scenario: the rarity of the disease, the limited number of completed prospective trials, and the shortcomings of comparability across series produce several controversial topics and unanswered questions. Guideline recommendations usually include all the different therapeutic options, <em>de facto</em> transferring to the multidisciplinary team the responsibility on the final decision. This secondary analysis of the GARIBALDI study was aimed to explore the correlation of center type, self-declared volume, and commitment with the overall survival (OS) in patients with non-metastatic PDAC.</div></div><div><h3>Patients and methods</h3><div>Treatment-naïve patients aged ≥18 years with a pathological diagnosis of non-metastatic PDAC, enrolled between July 2017 and October 2019, were analyzed. OS was defined as the time from treatment start to death. The impact of centers and clinical–demographic characteristics on OS was evaluated using Cox models.</div></div><div><h3>Results</h3><div>Overall, 402 patients enrolled in 41 centers were eligible for this analysis. The median age was 68.4 years (range 35.6-88.8 years), 49.5% were females, 93.5% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, 16.7% had prior cancer history, and the median CA 19-9 level was 171.5 IU/ml (first-third quartile 24.5-937.5 IU/ml). For 79.8% of patients treatment started within 1 month from diagnosis. Thirty six point six percent of patients underwent upfront surgery and 91.8% of these received a subsequent adjuvant chemotherapy; 14.2% received chemotherapy followed by surgery and 49.3% chemotherapy without surgery. The preferred chemotherapy schemes were gemcitabine (54.8%) for adjuvant chemotherapy and nab-paclitaxel + gemcitabine (55.3%) for upfront chemotherapy. The median follow-up was 57.6 months and 300 patients died. A statistically significant shorter OS was observed in both low- [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.12-2.32, <em>P</em> = 0.0099] and medium-commitment (HR 1.57, 95% CI 1.10-2.23, <em>P</em> = 0.0120) compared to high-commitment institutions, when adjusting for clinically relevant covariates.</div></div><div><h3>Conclusion</h3><div>The GARIBALDI study suggests that the volume and the academic brand are not associated with OS in patients with non-metastatic PDAC, while center commitment warrants further exploration.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"Article 104001"},"PeriodicalIF":7.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926923","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":"Comparative overall survival of CDK4/6 inhibitors plus an aromatase inhibitor in HR+/HER2− metastatic breast cancer in the US real-world setting☆","authors":"H.S. Rugo ,&nbsp;R.M. Layman ,&nbsp;F. Lynce ,&nbsp;X. Liu ,&nbsp;B. Li ,&nbsp;L. McRoy ,&nbsp;A.B. Cohen ,&nbsp;M. Estevez ,&nbsp;G. Curigliano ,&nbsp;A. Brufsky","doi":"10.1016/j.esmoop.2024.104103","DOIUrl":"10.1016/j.esmoop.2024.104103","url":null,"abstract":"<div><h3>Background</h3><div>Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line (1L) treatment of patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (mBC). Several real-world studies compared CDK4/6i effectiveness, with inconsistent findings. This study compared overall survival (OS) of patients with HR+/HER2− mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination with an aromatase inhibitor (AI), in US clinical practice.</div></div><div><h3>Patients and methods</h3><div>This retrospective study used real-world data from the Flatiron Health electronic health record-derived deidentified longitudinal database. Patients with HR+/HER2− mBC aged ≥18 years at mBC diagnosis started 1L CDK4/6i therapy (index treatment) between February 2015 and November 2023, with a potential ≥6-month follow-up. OS was defined as months from start of index treatment to death. Stabilized inverse probability of treatment weighting (sIPTW; primary analysis) was used to balance baseline patient characteristics. Multivariable Cox proportional hazards model was carried out as a sensitivity analysis.</div></div><div><h3>Results</h3><div>Of 9146 eligible patients, 6831, 1279, and 1036 received palbociclib plus AI, ribociclib plus AI, or abemaciclib plus AI, respectively. After sIPTW, baseline characteristics were balanced between treatment groups. After sIPTW, no significant OS differences were found between treatment groups [ribociclib versus palbociclib: adjusted hazard ratio (aHR) 0.98, 95% confidence interval (CI) 0.87-1.10, <em>P</em> = 0.7531; abemaciclib versus palbociclib: aHR 0.95, 95% CI 0.84-1.08, <em>P</em> = 0.4292; abemaciclib versus ribociclib: aHR 0.97, 95% CI 0.82-1.14, <em>P</em> = 0.6956]. Sensitivity analysis including a subanalysis of patients who started index treatment in 2017 or later also showed no significant OS differences between treatment groups.</div></div><div><h3>Conclusions</h3><div>This large real-world study suggested that there were no significant OS differences between 1L ribociclib, abemaciclib, and palbociclib in combination with an AI for patients with HR+/HER2− mBC. These findings together with other factors such as safety and quality of life are helpful in the selection of CDK4/6i combination therapy for patients with HR+/HER2− mBC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"Article 104103"},"PeriodicalIF":7.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926857","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":"Results of a patient-level pooled analysis of three studies of trastuzumab deruxtecan in HER2-positive breast cancer with active brain metastasis","authors":"R. Bartsch ,&nbsp;J.M. Pérez-García ,&nbsp;J. Furtner ,&nbsp;A.S. Berghoff ,&nbsp;M. Marhold ,&nbsp;A.M. Starzer ,&nbsp;M. Hughes ,&nbsp;S. Kabraji ,&nbsp;S. Sammons ,&nbsp;C. Anders ,&nbsp;R.K. Murthy ,&nbsp;A.E.D. Van Swearingen ,&nbsp;A. Pereslete ,&nbsp;M. Gion ,&nbsp;M. Vaz Batista ,&nbsp;S. Braga ,&nbsp;P.B.C. Pinto ,&nbsp;M. Sampayo-Cordero ,&nbsp;A. Llombart-Cussac ,&nbsp;M. Preusser ,&nbsp;N.U. Lin","doi":"10.1016/j.esmoop.2024.104092","DOIUrl":"10.1016/j.esmoop.2024.104092","url":null,"abstract":"<div><h3>Background</h3><div>Brain metastases (BMs) are common in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer, increasing morbidity and mortality. Systemic therapy for BMs can be effective, with the triple combination of trastuzumab, capecitabine, and tucatinib being a potential standard. More recently, intracranial activity of antibody–drug conjugates has been reported, but the size of individual studies has been small. Therefore, this patient-level pooled analysis was conducted.</div></div><div><h3>Patients and methods</h3><div>This is a patient-level pooled analysis of the prospective phase II DEBBRAH and TUXEDO-1 trials and the retrospective DFCI/Duke/MDACC cohort. Patients with evaluable active BMs (defined as newly diagnosed and untreated or progressing with measurable tumor-related size after previous local therapy) from HER2-positive breast cancer (BC) and treated with trastuzumab deruxtecan (T-DXd) included in these studies were eligible. The primary endpoint was intracranial objective response rate (ORR-IC) by Response Assessment in Neuro-Oncology (RANO)-BM criteria.</div></div><div><h3>Results</h3><div>Overall, 37 patients were assessable for intracranial response assessment. BMs progressing after prior local therapy were present in 64.9% of patients. The median patient age was 49.1 years. All patients had received prior trastuzumab and the median number of prior systemic treatment lines was 3 (0-13). The pooled ORR-IC by RANO-BM criteria was 64.9% [95% confidence interval (CI) 47.5% to 79.8%] with low heterogeneity observed between the studies included. The clinical benefit rate by RANO-BM was 81.1% (95% CI 64.8% to 92.0%). The median progression-free survival was 13.3 months (95% CI 8.4-22.6 months) and the median overall survival was 22.5 months (95% CI 14.9 months-not achieved) with high heterogeneity between studies and numerically longer in patients with few prior treatment lines. Quality of life remained stable throughout treatment, with no new safety concerns.</div></div><div><h3>Conclusions</h3><div>This patient-level pooled analysis of DEBBRAH, TUXEDO-1, and the DFCI/Duke/MDACC cohort indicates clinically relevant intracranial activity of T-DXd in patients with active HER2-positive BC, BMs, and extensive systemic pretreatment. The results therefore support the use of T-DXd when clinically indicated irrespective of BMs.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"Article 104092"},"PeriodicalIF":7.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926922","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":"The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP)","authors":"K. Verkerk ,&nbsp;L.J. Zeverijn ,&nbsp;J. van de Haar ,&nbsp;P. Roepman ,&nbsp;B.S. Geurts ,&nbsp;A.C. Spiekman ,&nbsp;V. van der Noort ,&nbsp;J.M. van Berge Henegouwen ,&nbsp;L.R. Hoes ,&nbsp;H. van der Wijngaart ,&nbsp;A.M.L. Jansen ,&nbsp;W.W.J. de Leng ,&nbsp;A.J. Gelderblom ,&nbsp;H.M.W. Verheul ,&nbsp;E.E. Voest","doi":"10.1016/j.esmoop.2024.104112","DOIUrl":"10.1016/j.esmoop.2024.104112","url":null,"abstract":"<div><h3>Background</h3><div>Many patients with cancer exhibit primary or rapid secondary resistance to targeted therapy (TT). We hypothesized that a higher number of altered oncogenic signaling pathways [pathway alteration load (PAL)] would reduce the benefit of TT which only intervenes in one pathway. This hypothesis was tested in the Drug Rediscovery Protocol (DRUP).</div></div><div><h3>Patients and methods</h3><div>DRUP is a prospective, pan-cancer, non-randomized clinical trial (NCT02925234) that treats patients with therapy-refractory metastatic cancer and an actionable molecular profile using matched off-label targeted and immunotherapies. All patients treated with TT with available clinical outcomes and whole genome sequencing were included. PAL was determined based on driver gene alterations and correlated with clinical benefit rate (CBR), progression-free survival (PFS) and overall survival (OS). Outcomes were validated in the independent Hartwig Medical database of metastatic cancers.</div></div><div><h3>Results</h3><div>In 154 patients treated with TT, the median PAL was 3. Patients with a PAL below median (<em>n</em> = 60) demonstrated a higher CBR (41.7% versus 25.5%, odds ratio 0.48, <em>P</em> = 0.051), longer PFS [median 4.7 versus 2.9 months, adjusted hazard ratio (aHR) 1.70, <em>P</em> = 0.020] and OS (median 13.7 versus 5.6 months, aHR 3.80, <em>P</em> &lt; 0.001) compared with those with PAL ≥3. Two hundred and fifty-eight patients in the Hartwig database showed similar results for CBR (54.2% versus 36.7%, odds ratio 2.04, <em>P</em> = 0.009) and PFS (7.0 versus 4.2 months, aHR 1.55, <em>P</em> = 0.009).</div></div><div><h3>Conclusions</h3><div>In our population, PAL emerged as a pan-cancer determinant of outcome to TT. Our findings support refined patient selection for TT and highlight the rationale for combinatorial treatment strategies in patients with multiple affected pathways.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"Article 104112"},"PeriodicalIF":7.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946611","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":"Anti-IL-6R Ab tocilizumab to treat paraneoplastic inflammatory syndrome of solid cancers","authors":"J.-Y. Blay ,&nbsp;M. Brahmi ,&nbsp;A. Dufresne ,&nbsp;A. Swalduz ,&nbsp;V. Avrillon ,&nbsp;S. Assaad ,&nbsp;C. Decroisette ,&nbsp;B. Mastroianni ,&nbsp;M. Dupont ,&nbsp;F. Bourbotte-Salmon ,&nbsp;I. Ray-Coquard ,&nbsp;P. Meeus ,&nbsp;A. Dutour ,&nbsp;M. Castets ,&nbsp;M. Perol ,&nbsp;P. Heudel","doi":"10.1016/j.esmoop.2024.104088","DOIUrl":"10.1016/j.esmoop.2024.104088","url":null,"abstract":"<div><h3>Background</h3><div>Paraneoplastic inflammatory syndrome (PIS) with fever and biological inflammation is a rare but severe condition often caused by the systemic production of interleukin 6 (IL-6) by cancer cells. We report on the efficacy of tocilizumab, an anti-IL-6 receptor antibody, in 35 patients with severe PIS.</div></div><div><h3>Patients and methods</h3><div>All 35 patients with solid cancers (sarcomas, lung carcinoma, and breast carcinoma) diagnosed with a PIS from 2019 to 2024 treated with tocilizumab were analyzed in this single-center study (health authorities’ approval R201-004-478). Patients’ characteristics and clinical and biological effects of tocilizumab administration are presented.</div></div><div><h3>Results</h3><div>Thirty-five (97%) patients had paraneoplastic fever. The median performance status (PS) was 2 (range 1-4). Forty percent of patients had lost 10% of body weight. All had increased serum C-reactive protein (CRP) levels (median 212 mg/l), and 74% and 48% had increased polymorphonuclear leukocyte (PMN) and platelet counts, respectively. Ninety-four percent had inflammatory anemia. Tocilizumab was given once in 23 (66%) patients and more than once in 12 patients. All patients experienced resolution of paraneoplastic fever, and 11 (31%) had improved PS. CRP, PMN, and platelet count decreases were observed in 100%, 85%, and 94% of patients, respectively. Seventy-seven percent of patients had increased hemoglobin levels. CRP and inflammatory symptoms often relapsed 4-6 weeks after tocilizumab in patients receiving only one injection.</div></div><div><h3>Conclusions</h3><div>Tocilizumab is an efficient treatment for severe PIS providing significant improvement in clinical symptoms and biological abnormalities.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"Article 104088"},"PeriodicalIF":7.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926850","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":"Ethnic origin in cancer clinical trials: overrated or understated? A comprehensive analysis of cancer clinical trials leading to FDA and EMA approvals between 2020 and 2022","authors":"H.C. Puhr ,&nbsp;E.C. Winkler ,&nbsp;M. Preusser","doi":"10.1016/j.esmoop.2024.104093","DOIUrl":"10.1016/j.esmoop.2024.104093","url":null,"abstract":"<div><h3>Background</h3><div>Ethnic diversity in cancer clinical trials is essential to ensure that therapeutic advances are equitable and broadly applicable in multicultural societies. Yet, missing consensus on the documentation of ethnic origin, partially based on the complexity of the terminology and fear of discrimination, leads to suboptimal patient management of minority populations. Additionally, eligibility criteria, such as stringent laboratory cut-offs, often fail to account for variations across ethnic groups, potentially excluding patients without evidence-based justification.</div></div><div><h3>Patients and methods</h3><div>This analysis addresses this issue by investigating ethnic diversity in clinical trials that led to European Medicines Agency (EMA) and Food and Drug Administration (FDA) approvals between 2020 and 2022. Trials were identified from FDA and EMA databases, and available protocols and full-text publications were reviewed for documentation of ethnic background and eligibility criteria for organ function (bone marrow, liver, and renal). Descriptive statistics were applied to summarize the findings.</div></div><div><h3>Results</h3><div>Of the 56 trials analyzed, only two-thirds of primary result publications included information on ethnic origin. Caucasian and Asian groups were documented in most of those trials and also had the highest percentages of participants across trials, while other ethnic subgroups were less frequently documented and only made up a small proportion of trial participants. Eligibility criteria often set strict organ function cut-offs that did not consider variations among ethnic groups, potentially excluding minorities. The Cockcroft–Gault formula was frequently used to assess kidney function, despite its known limitations for multiethnic cohorts.</div></div><div><h3>Conclusions</h3><div>Ethnic homogenous participants and eligibility criteria that favor majority groups limit the applicability of findings in diverse populations, leading to inadequate patient management. While United States guidelines encourage inclusivity, similar recommendations are lacking in Europe. Thus European regulatory authorities, research organizations, and patient advocates should establish guidelines to improve ethnic diversity in cancer clinical trials, aligning research practices with the increasingly multicultural composition of European societies.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"Article 104093"},"PeriodicalIF":7.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926870","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":"Unraveling the complexity of HRD assessment in ovarian cancer by combining genomic and functional approaches: translational analyses of MITO16-MaNGO-OV-2 trial","authors":"B. Pellegrino ,&nbsp;E.D. Capoluongo ,&nbsp;M. Bagnoli ,&nbsp;L. Arenare ,&nbsp;D. Califano ,&nbsp;G. Scambia ,&nbsp;S.C. Cecere ,&nbsp;E.M. Silini ,&nbsp;G.L. Scaglione ,&nbsp;A. Spina ,&nbsp;G. Tognon ,&nbsp;N. Campanini ,&nbsp;C. Pisano ,&nbsp;D. Russo ,&nbsp;A. Pettinato ,&nbsp;P. Scollo ,&nbsp;R. Iemmolo ,&nbsp;L. De Cecco ,&nbsp;A. Musolino ,&nbsp;S. Marchini ,&nbsp;S. Pignata","doi":"10.1016/j.esmoop.2024.104091","DOIUrl":"10.1016/j.esmoop.2024.104091","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer (OvC) constitutes significant management challenges primarily due to its late-stage diagnosis and the development of resistance to chemotherapy. The standard treatment regimen typically includes carboplatin and paclitaxel, with the addition of poly (ADP-ribose) polymerase inhibitors for patients with high-grade serous ovarian cancer (HGSOC) harboring <em>BRCA1</em><em>/2</em> mutations. However, the variability in treatment responses suggests the need to investigate factors beyond <em>BRCA1/2</em> mutations, such as DNA repair mechanisms and epigenetic alterations. Notably, homologous recombination repair deficiency (HRD) is observed in an additional 20% of HGSOC cases, indicating a broader spectrum of DNA repair defects. Existing commercial HRD assays have certain limitations, prompting a global effort to develop new genomic and functional tests through academic research.</div></div><div><h3>Materials and methods</h3><div>This study investigates, in the 187 high-grade serous and endometrioid tumors from the MITO16/MaNGO-OV-2 trial, academic HRD genomic tests in conjunction with a RAD51 immunofluorescence assay to assess functional activation of HRD. Additionally, the study incorporates analysis of microRNA-506 (miR-506) expression as a putative epigenetic effector.</div></div><div><h3>Results</h3><div>The RAD51 test identified HRD in 73% of the samples and genomic HRD testing in 57%, with HRD identified in 45% of samples by both tests. The significant discrepancy between the two assays emphasizes the need to refine tumor classification for HRD. A three-group genomic classification unveiled superior progression-free survival (PFS) in high- and mild-HRD tumors compared with negative-HRD tumors. High concordance between RAD51 and genomic testing in high-HRD tumors suggests a subset of ‘super-HRD’ tumors exhibiting superior PFS. High expression of miR-506 may be used to further refine HRD status.</div></div><div><h3>Conclusions</h3><div>The study underscores the complexities of HRD assessment and advocates for a combined genomic and functional approach to enhance predictive accuracy in OvC treatment responses.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"Article 104091"},"PeriodicalIF":7.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926925","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":"Actionable mutations in early-stage ovarian cancer according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT): a descriptive analysis on a large prospective cohort","authors":"F. Camarda ,&nbsp;L. Mastrantoni ,&nbsp;C. Parrillo ,&nbsp;A. Minucci ,&nbsp;F. Persiani ,&nbsp;D. Giannarelli ,&nbsp;T. Pasciuto ,&nbsp;F. Giacomini ,&nbsp;E. De Paolis ,&nbsp;M. Manfredelli ,&nbsp;C. Marchetti ,&nbsp;G.F. Zannoni ,&nbsp;A. Fagotti ,&nbsp;G. Scambia ,&nbsp;C. Nero","doi":"10.1016/j.esmoop.2024.104090","DOIUrl":"10.1016/j.esmoop.2024.104090","url":null,"abstract":"<div><h3>Background</h3><div>According to the European Society for Clinical Oncology (ESMO) guidelines, the therapeutic algorithm for early-stage epithelial ovarian carcinoma (EOC) is primarily based on grading and histotype. Adjuvant chemotherapy is usually recommended for high-grade tumors and for the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IC; however, overtreatment remains a concern. Conversely, patients truly at higher risk of recurrence currently lack access to additional therapeutic strategies.</div></div><div><h3>Patients and methods</h3><div>This study presents a descriptive analysis of early-stage EOC patients who were prospectively sequenced and stratified into high-, intermediate-, and low-risk groups based on clinicopathological features. Oncogenic alterations were identified using OncoKB and classified according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) Tier I-III. The prevalence of molecular findings was first reported for each risk subgroup, followed by an analysis on the cohort of patients who experienced relapse.</div></div><div><h3>Results</h3><div>A total of 180 patients with FIGO stage I-II EOC were enrolled between January 2022 and December 2023; 126 patients (70%) had at least one ESCAT Tier I-III alteration (including 51% high risk, 35% intermediate risk, and 14% low risk); among them, approximately one-quarter (26%, 95% confidence interval 19% to 35%) had an ESCAT Tier I alteration. <em>BRCA1</em> and <em>BRCA2</em> alterations were observed in about one-quarter of patients, with <em>BRCA2</em> often co-altered with <em>POLE</em> mutations (55%, <em>P</em> = 2.1 × 10⁻⁴). Notably, almost all <em>BRCA1</em> variants were found in high-risk patients. <em>BRAF V600E</em> mutation (ESCAT IC) was found in 2.4% of patients. <em>PIK3CA</em> variants were the most common Tier IIIA alterations found in 59% of patients. Among those who experienced recurrence, 60% had at least one ESCAT Tier I-III alteration, with <em>PIK3CA</em> mutations being the most frequent.</div></div><div><h3>Conclusions</h3><div>These findings highlight the potential for actionable alterations in most early-stage EOC patients and support the exploration of chemotherapy-free regimens for low- to intermediate-risk groups, as well as targeted maintenance therapy for high-risk individuals.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"Article 104090"},"PeriodicalIF":7.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871691","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":"Development of two machine learning models to predict conversion from primary HER2-0 breast cancer to HER2-low metastases: a proof-of-concept study","authors":"F. Miglietta ,&nbsp;A. Collesei ,&nbsp;C. Vernieri ,&nbsp;T. Giarratano ,&nbsp;C.A. Giorgi ,&nbsp;F. Girardi ,&nbsp;G. Griguolo ,&nbsp;M. Cacciatore ,&nbsp;A. Botticelli ,&nbsp;A. Vingiani ,&nbsp;G. Fotia ,&nbsp;F. Piacentini ,&nbsp;D. Massa ,&nbsp;F. Zanghì ,&nbsp;M. Marino ,&nbsp;G. Pruneri ,&nbsp;M. Fassan ,&nbsp;A.P. Dei Tos ,&nbsp;M.V. Dieci ,&nbsp;V. Guarneri","doi":"10.1016/j.esmoop.2024.104087","DOIUrl":"10.1016/j.esmoop.2024.104087","url":null,"abstract":"<div><h3>Background</h3><div>HER2-low expression has gained clinical relevance in breast cancer (BC) due to the availability of anti-HER2 antibody–drug conjugates for patients with HER2-low metastatic BC. The well-reported instability of HER2-low status during disease evolution highlights the need to identify patients with HER2-0 primary BC who may develop a HER2-low phenotype at relapse. In response to the urgency of maximizing treatment access, we utilized artificial intelligence to predict this occurrence.</div></div><div><h3>Patients and methods</h3><div>We included a large multicentric retrospective cohort of patients with BC who underwent tissue resampling at relapse. The dataset was preprocessed to address relevant issues such as missing data, feature abundance, and target class imbalance. We then trained two models: one focused on explainability [Extreme Gradient Boosting (XGBoost)] and another aimed at performance (an ensemble of XGBoost and support vector machine).</div></div><div><h3>Results</h3><div>A total of 1200 patients were included in this study. Among 386 patients with HER2-0 primary BC and matched HER2 status at relapse, 42.5% (<em>n</em> = 157) converted to a HER2-low phenotype. The explainable model achieved a balanced accuracy of 58%, with a sensitivity of 53% and a specificity of 64%. The most important variables for this model were primary BC phenotype [mean Shapley value (SHAP) 0.540], primary BC histological type (SHAP 0.101), grade (SHAP 0.182), and sites of relapse (SHAP 0.008-0.213). The ensemble model had a balanced accuracy of 64%, with a sensitivity of 75% and a specificity of 53%.</div></div><div><h3>Conclusions</h3><div>This work represents one of the first proof-of-concept applications of machine learning models to predict a highly relevant phenomenon for drug access in modern BC oncology. Starting with an explainable model and subsequently integrating it with an ensemble approach enabled us to enhance performance while maintaining transparency, explainability, and intelligibility.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"Article 104087"},"PeriodicalIF":7.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871692","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":"Avoiding spurious comparison of cancer stage in organized and opportunistic breast screening in Switzerland","authors":"J.-L. Bulliard,&nbsp;K. Brändle","doi":"10.1016/j.esmoop.2024.104104","DOIUrl":"10.1016/j.esmoop.2024.104104","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"Article 104104"},"PeriodicalIF":7.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926853","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}