Annals of Oncology最新文献

{"title":"Artificial intelligence-assisted personalized adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma","authors":"Y. Shimazu","doi":"10.1016/j.annonc.2024.09.015","DOIUrl":"10.1016/j.annonc.2024.09.015","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 1","pages":"Page 118"},"PeriodicalIF":56.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339689","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":"Pembrolizumab plus chemotherapy for advanced and recurrent cervical cancer: final analysis according to bevacizumab use in the randomized KEYNOTE-826 study☆","authors":"D. Lorusso ,&nbsp;N. Colombo ,&nbsp;C. Dubot ,&nbsp;M.V. Cáceres ,&nbsp;K. Hasegawa ,&nbsp;R. Shapira-Frommer ,&nbsp;P. Salman ,&nbsp;E. Yañez ,&nbsp;M. Gümüş ,&nbsp;M. Olivera ,&nbsp;V. Samouëlian ,&nbsp;V. Castonguay ,&nbsp;A. Arkhipov ,&nbsp;K. Li ,&nbsp;S. Toker ,&nbsp;C. Tekin ,&nbsp;K.S. Tewari ,&nbsp;B.J. Monk","doi":"10.1016/j.annonc.2024.10.002","DOIUrl":"10.1016/j.annonc.2024.10.002","url":null,"abstract":"<div><h3>Background</h3><div>In KEYNOTE-826 (NCT03635567), pembrolizumab plus chemotherapy (±bevacizumab) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent, or metastatic cervical cancer. This exploratory analysis examined outcomes in patient subgroups defined by bevacizumab use.</div></div><div><h3>Patients and methods</h3><div>Eligible adult patients had persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not previously treated with chemotherapy and not amenable to curative treatment; measurable disease per RECIST v1.1; and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomly allocated 1 : 1 to pembrolizumab 200 mg every 3 weeks or placebo for up to 35 cycles plus chemotherapy (±bevacizumab 15 mg/kg). Dual primary endpoints were OS and PFS per RECIST v1.1 by investigator assessment. Outcomes were assessed in subgroups defined by bevacizumab use. Hazard ratios (HRs) and 95% confidence intervals (CIs) were based on a stratified Cox regression model.</div></div><div><h3>Results</h3><div>A total of 617 patients were randomly assigned [pembrolizumab arm, <em>n</em> = 308 (63.6% with bevacizumab); placebo arm, <em>n</em> = 309 (62.5% with bevacizumab)]. The most common reason for bevacizumab exclusion was medical contraindication (75.9%). Among patients who received bevacizumab, HRs (95% CIs) for PFS favored the pembrolizumab arm in the programmed cell death-ligand 1 combined positive score ≥1 [0.56 (0.43-0.73)] and all-comer [0.57 (0.45-0.73)] populations; OS results were 0.60 (0.45-0.79) and 0.61 (0.47-0.80), respectively. Among patients who did not receive bevacizumab, HRs (95% CIs) for PFS also favored the pembrolizumab arm in the programmed cell death-ligand 1 combined positive score ≥1 [0.61 (0.44-0.85)] and all-comer [0.69 (0.50-0.94)] populations; OS results were 0.61 (0.44-0.85) and 0.67 (0.49-0.91), respectively. Among patients who received bevacizumab, grade ≥3 treatment-related adverse events occurred in 74.0% of patients in the pembrolizumab arm and 66.8% in the placebo arm.</div></div><div><h3>Conclusion</h3><div>Pembrolizumab plus chemotherapy prolonged PFS and OS and had manageable safety compared with placebo plus chemotherapy in patient subgroups defined by bevacizumab use.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 1","pages":"Pages 65-75"},"PeriodicalIF":56.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405946","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":"Basal/squamous and mixed subtype bladder cancers present poor outcomes after neoadjuvant chemotherapy in the VESPER trial","authors":"C.S. Groeneveld ,&nbsp;C. Pfister ,&nbsp;S. Culine ,&nbsp;V. Harter ,&nbsp;C. Krucker ,&nbsp;J. Fontugne ,&nbsp;V. Dixon ,&nbsp;N. Sirab ,&nbsp;I. Bernard-Pierrot ,&nbsp;A. de Reyniès ,&nbsp;F. Radvanyi ,&nbsp;Y. Allory","doi":"10.1016/j.annonc.2024.09.008","DOIUrl":"10.1016/j.annonc.2024.09.008","url":null,"abstract":"<div><h3>Background</h3><div>Neoadjuvant chemotherapy (NAC) is the standard treatment for muscle-invasive bladder cancer (MIBC), yet 40% of patients progress, emphasizing the need for biomarkers predictive for response or chemoresistance. Gene expression-based subtypes may serve as biomarkers, though which subtypes will respond, notably when it comes to the basal subtype, remains contentious.</div></div><div><h3>Patients and methods</h3><div>This <em>post hoc</em> study analyzed 300 NAC-treated patients enrolled in the GETUG/AFU VESPER trial, with transurethral diagnostic formalin-fixed paraffin-embedded tissue which underwent pathological review before being sequenced. ‘Mixed’ subtype was defined for tumors displaying at least two different Consensus molecular subtypes in separate regions. We evaluated the association between molecular subtypes and outcome after NAC. Tumors with remaining tissue at cystectomy (<em>n</em> = 83) were compared with pre-treatment tumors.</div></div><div><h3>Results</h3><div>Cases were classified basal/squamous (Ba/Sq) (<em>n</em> = 84), luminal unstable (<em>n</em> = 57), stroma-rich (<em>n</em> = 53), mixed (<em>n</em> = 48), luminal papillary (<em>n</em> = 39), luminal non-specific (<em>n</em> = 18), and neuroendocrine-like (<em>n</em> = 1), with 30/48 mixed cases including a Ba/Sq component. Compared with other molecular subtypes in a multivariate Cox model, Ba/Sq (pure or mixed) patients had an increased hazard ratio (HR) of progression-free survival [HR 2.0, 95% confidence interval (CI) 1.36-3.0]. Mixed tumors were associated with decreased metabolic activity that could account for chemoresistance. Ba/Sq and mixed non-responders mostly maintained their subtype at cystectomy and have fewer myeloid dendritic cells after NAC. Tumors classified luminal papillary at transurethral resection of the urinary bladder tumor exhibited an increase in T CD4+ and macrophage signatures after NAC. Other subtypes did not show significant immune changes after NAC. Our study design relied on detailed pathological review, which precluded evaluating the mixed subtype in published datasets. Furthermore, the sample size for post-NAC analyses constrained the statistical power of these findings.</div></div><div><h3>Conclusions</h3><div>Our findings underscore the importance of recognizing intra-tumor heterogeneity in MIBC and its role in chemoresistance associated with Ba/Sq subtype, and provide valuable insights that could help future treatment development and improve patient outcomes.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 1","pages":"Pages 89-98"},"PeriodicalIF":56.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279653","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":"Avelumab + axitinib versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma: final analysis of the phase III JAVELIN Renal 101 trial","authors":"T.K. Choueiri ,&nbsp;K. Penkov ,&nbsp;H. Uemura ,&nbsp;M.T. Campbell ,&nbsp;S. Pal ,&nbsp;C. Kollmannsberger ,&nbsp;J.L. Lee ,&nbsp;B. Venugopal ,&nbsp;A.J.M. van den Eertwegh ,&nbsp;S. Negrier ,&nbsp;H. Gurney ,&nbsp;L. Albiges ,&nbsp;R. Berger ,&nbsp;J.B.A.G. Haanen ,&nbsp;V. Oyervides Juárez ,&nbsp;B.I. Rini ,&nbsp;J. Larkin ,&nbsp;F. Nolè ,&nbsp;M. Schmidinger ,&nbsp;M.B. Atkins ,&nbsp;R.J. Motzer","doi":"10.1016/j.annonc.2024.12.008","DOIUrl":"10.1016/j.annonc.2024.12.008","url":null,"abstract":"<div><h3>Background</h3><div>In the phase III JAVELIN Renal 101 trial (NCT02684006), first-line treatment with avelumab + axitinib resulted in significantly longer progression-free survival (PFS) and a higher objective response rate (ORR) versus sunitinib in patients with advanced renal cell carcinoma (aRCC). We report the final analysis, including the primary analysis of overall survival (OS).</div></div><div><h3>Patients and methods</h3><div>Patients with untreated aRCC (any prognostic risk score) were enrolled. The primary endpoints were OS and PFS in the programmed death-ligand 1-positive (PD-L1+) population. ORR, duration of response, safety, and patient-reported outcomes (PROs) were also assessed.</div></div><div><h3>Results</h3><div>The minimum follow-up was 68 months in all patients. The median OS with avelumab + axitinib versus sunitinib, respectively, was 43.2 months [95% confidence interval (CI) 36.5-51.7 months] versus 36.2 months (95% CI 29.8-44.2 months) in the PD-L1+ population [hazard ratio (HR) 0.86 (95% CI 0.701-1.057); <em>P</em> = 0.0755] and 44.8 months (95% CI 39.7-51.1 months) versus 38.9 months (95% CI 31.4-45.2 months) in the overall population [HR 0.88 (95% CI 0.749-1.039); <em>P</em> = 0.0669]. Investigator-assessed PFS remained prolonged with avelumab + axitinib versus sunitinib [5-year event-free rate in the overall population, 12.0% (95% CI 8.9% to 15.6%) versus 4.4% (95% CI 2.5% to 7.3%)]. ORR in the overall population was 59.7% (95% CI 55.0% to 64.3%) with avelumab + axitinib versus 32.0% (95% CI 27.7% to 36.5%) with sunitinib; duration of response was ≥5 years in 16.4% (95% CI 12.0% to 21.4%) versus 9.2% (95% CI 4.6% to 15.7%), respectively. Rates of grade ≥3 treatment-related adverse events were 66.8% versus 61.5%, respectively. PROs were similar between arms.</div></div><div><h3>Conclusions</h3><div>JAVELIN Renal 101 provides the longest follow-up to date for immune checkpoint inhibitor + tyrosine kinase inhibitor combination treatment from a phase III trial in aRCC. OS analyses favored avelumab + axitinib versus sunitinib but did not reach statistical significance; subsequent treatment may have impacted results. Avelumab + axitinib provided long-term efficacy benefits versus sunitinib, including prolonged PFS, a nearly doubled ORR, and more durable responses, with a manageable long-term safety profile.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 4","pages":"Pages 387-392"},"PeriodicalIF":56.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870677","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":"A model for decoding resistance in precision oncology: acquired resistance to FGFR inhibitors in cholangiocarcinoma","authors":"L. Goyal ,&nbsp;D. DiToro ,&nbsp;F. Facchinetti ,&nbsp;E.E. Martin ,&nbsp;P. Peng ,&nbsp;I. Baiev ,&nbsp;R. Iyer ,&nbsp;J. Maurer ,&nbsp;S. Reyes ,&nbsp;K. Zhang ,&nbsp;U. Majeed ,&nbsp;J.E. Berchuck ,&nbsp;C.T. Chen ,&nbsp;C. Walmsley ,&nbsp;C. Pinto ,&nbsp;D. Vasseur ,&nbsp;J.D. Gordan ,&nbsp;K. Mody ,&nbsp;M. Borad ,&nbsp;T. Karasic ,&nbsp;D. Juric","doi":"10.1016/j.annonc.2024.12.011","DOIUrl":"10.1016/j.annonc.2024.12.011","url":null,"abstract":"<div><h3>Background</h3><div>Fibroblast growth factor receptor (FGFR) inhibitors have significantly improved outcomes for patients with FGFR-altered cholangiocarcinoma, leading to their regulatory approval in multiple countries. As with many targeted therapies, however, acquired resistance limits their efficacy. A comprehensive, multimodal approach is crucial to characterizing resistance patterns to FGFR inhibitors.</div></div><div><h3>Patients and methods</h3><div>This study integrated data from six investigative strategies: cell-free DNA, tissue biopsy, rapid autopsy, statistical genomics, <em>in vitro</em> and <em>in vivo</em> studies, and pharmacology. We characterized the diversity, clonality, frequency, and mechanisms of acquired resistance to FGFR inhibitors in patients with FGFR-altered cholangiocarcinoma. Clinical samples were analyzed longitudinally as part of routine care across 10 institutions.</div></div><div><h3>Results</h3><div>Among 138 patients evaluated, 77 met eligibility, yielding a total of 486 clinical samples. Patients with clinical benefit exhibited a significantly higher rate of <em>FGFR2</em> kinase domain mutations compared with those without clinical benefit (65% versus 10%, <em>P</em> &lt; 0.0001). We identified 26 distinct <em>FGFR2</em> kinase domain mutations, with 63% of patients harboring multiple. While IC50 assessments indicated strong potency of pan-FGFR inhibitors against common resistance mutations, pharmacokinetic studies revealed that low clinically achievable drug concentrations may underly polyclonal resistance. Molecular brake and gatekeeper mutations predominated, with 94% of patients with <em>FGFR2</em> mutations exhibiting one or both, whereas mutations at the cysteine residue targeted by covalent inhibitors were rare. Statistical genomics and functional studies demonstrated that mutation frequencies were driven by their combined effects on drug binding and kinase activity rather than intrinsic mutational processes.</div></div><div><h3>Conclusion</h3><div>Our multimodal analysis led to a model characterizing the biology of acquired resistance, informing the rational design of next-generation FGFR inhibitors. FGFR inhibitors should be small, high-affinity, and selective for specific FGFR family members. Tinengotinib, a novel small molecule inhibitor with these characteristics, exhibited preclinical and clinical activity against key resistance mutations. This integrated approach offers a blueprint for advancing drug resistance research across cancer types.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 4","pages":"Pages 426-443"},"PeriodicalIF":56.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870671","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":"Prognostic value of residual disease (RD) biology and gene expression changes during the neoadjuvant treatment in patients with HER2-positive early breast cancer (EBC)☆","authors":"A. Fernandez-Martinez ,&nbsp;M. Tanioka ,&nbsp;S.G. Ahn ,&nbsp;P. Zagami ,&nbsp;T. Pascual ,&nbsp;M. Rediti ,&nbsp;G. Tang ,&nbsp;K.A. Hoadley ,&nbsp;D. Venet ,&nbsp;N.U. Rashid ,&nbsp;P.A. Spears ,&nbsp;S. Di Cosimo ,&nbsp;E. de Azambuja ,&nbsp;A. Choudhury ,&nbsp;P. Rastogi ,&nbsp;M.N. Islam ,&nbsp;J. Cortes ,&nbsp;A. Llombart-Cussac ,&nbsp;S.M. Swain ,&nbsp;C. Sotiriou ,&nbsp;L.A. Carey","doi":"10.1016/j.annonc.2024.12.010","DOIUrl":"10.1016/j.annonc.2024.12.010","url":null,"abstract":"<div><h3>Background</h3><div>In human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), we investigated tumor and immune changes during neoadjuvant treatment and their impact on residual disease (RD) biology and prognostic implications across four neoadjuvant studies of trastuzumab with or without lapatinib, and with or without chemotherapy: CALGB 40601, PAMELA, NeoALTTO, and NSABP B-41.</div></div><div><h3>Patients and methods</h3><div>We compared tumor and immune gene expression changes during neoadjuvant treatment and their association with event-free survival (EFS) by uni- and multivariable Cox regression models in different cohorts and timepoints: 452 RD samples at baseline including 169 with a paired RD, and biomarker changes during neoadjuvant therapy, evaluating model performance via the c-index.</div></div><div><h3>Results</h3><div>Analysis of 169 paired tumor samples revealed a shift in intrinsic subtype proportions from HER2-enriched at baseline (50.3%) to normal-like (49.1%) followed by luminal A (18.9%) in RD. This luminal phenotypic change was supported by decreased correlation to the HER2-enriched centroid, <em>ERBB2</em>, and HER2 amplicon genes and increased correlation to the luminal A centroid (Wilcoxon test <em>P</em> &lt; 0.001). Additionally, RD showed relative immune activation marked by significant increases in B-cell, CD8 T-cell, and natural killer cell signatures (Wilcoxon test <em>P</em> &lt; 0.05). In multivariable Cox models, intrinsic subtypes at baseline provided more prognostic information, while immune gene expression signatures provided more prognostic information in RD. Notably, the best multivariable EFS model (c-index = 0.77) integrated the immunoglobulin G signature from RD samples (adjusted hazard ratio 0.45, 95% confidence interval 0.30-0.67, adjusted <em>P</em> = 0.002).</div></div><div><h3>Conclusions</h3><div>In patients with HER2-positive EBC and RD, tumor biomarkers provide more prognostic information at baseline. In contrast, immune biomarkers perform better for EFS prognosis in RD.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 4","pages":"Pages 403-413"},"PeriodicalIF":56.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870818","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":"Correlation between progression-free and overall survival in patients with Hodgkin lymphoma: a comprehensive analysis of individual patient data from randomized German Hodgkin Study Group (GHSG) trials☆","authors":"P.J. Bröckelmann ,&nbsp;H. Müller ,&nbsp;M. Fuchs ,&nbsp;S. Gillessen ,&nbsp;D.A. Eichenauer ,&nbsp;S. Borchmann ,&nbsp;A.S. Jacob ,&nbsp;K. Behringer ,&nbsp;J. Momotow ,&nbsp;J. Ferdinandus ,&nbsp;B. Böll ,&nbsp;X. Yang ,&nbsp;C. Kobe ,&nbsp;H.-T. Eich ,&nbsp;C. Baues ,&nbsp;W. Klapper ,&nbsp;A. Engert ,&nbsp;P. Borchmann ,&nbsp;B. von Tresckow","doi":"10.1016/j.annonc.2024.12.009","DOIUrl":"10.1016/j.annonc.2024.12.009","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to evaluate the correlation between progression-free (PFS) and overall survival (OS) after first-line treatment of classical Hodgkin lymphoma (HL) and to assess the potential of PFS as a surrogate parameter for OS.</div></div><div><h3>Patients and methods</h3><div>We analyzed individual patient data collected during and after treatment with polychemotherapy in nine randomized phase III trials [German Hodgkin Study Group (GHSG) HD7-HD15] between January 1993 and August 2018. The effects of 16 experimental treatments on PFS and OS at the trial level were evaluated using Cox proportional hazards (PH) regression and linear weighted least squares regression. At the patient level, marginal Cox PH models for multiple endpoints were applied using the Wei–Lin–Weissfeld method.</div></div><div><h3>Results</h3><div>At least one PFS and OS event was recorded in 1682 and 1064 of 10 605 patients, respectively. At the trial level, there was a strong correlation between treatment effects on PFS and OS (weighted Pearson <em>r</em> = 0.72, <em>R</em>² = 0.54, <em>P</em> &lt; 0.001). At the patient level, a moderate to strong correlation between treatment effects on PFS and OS was observed, with Pearson <em>r</em> values ranging between 0.61 and 0.85 (each <em>P</em> &lt; 0.001) and an overall <em>r</em> = 0.74. A regression model that accounted for different types of experimental treatments and historical progress across trial generations achieved a very strong correlation (<em>R</em>² = 0.93). When applied to data from the contemporary first-line ECHELON-1 trial, this model successfully predicted OS from PFS {prognosticated ln[HR(OS)] = −0.68 as compared with observed ln[HR(0.59)] = −0.53}.</div></div><div><h3>Conclusion</h3><div>In first-line trials of HL, PFS and OS, as well as treatment effects and prognostic effects on these endpoints, are strongly correlated. PFS serves as a strong predictor of treatment effects on OS, providing valuable insights many years before OS can be reliably assessed.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 4","pages":"Pages 393-402"},"PeriodicalIF":56.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870734","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":"Tocilizumab and immune signatures for targeted management of cytokine release syndrome in immune checkpoint therapy","authors":"D. Daoudlarian ,&nbsp;A. Segot ,&nbsp;S. Latifyan ,&nbsp;R. Bartolini ,&nbsp;V. Joo ,&nbsp;N. Mederos ,&nbsp;H. Bouchaab ,&nbsp;R. Demicheli ,&nbsp;K. Abdelhamid ,&nbsp;N. Ferahta ,&nbsp;J. Doms ,&nbsp;G. Stalder ,&nbsp;A. Noto ,&nbsp;L. Mencarelli ,&nbsp;V. Mosimann ,&nbsp;D. Berthold ,&nbsp;A. Stravodimou ,&nbsp;C. Sartori ,&nbsp;K. Shabafrouz ,&nbsp;J.A. Thompson ,&nbsp;M. Obeid","doi":"10.1016/j.annonc.2024.12.004","DOIUrl":"10.1016/j.annonc.2024.12.004","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to identify specific biomarkers in oncology patients experiencing immune-related cytokine release syndrome (irCRS)-like symptoms during immune checkpoint inhibitor (ICI) therapy, including severe cases like hemophagocytic lymphohistiocytosis (irHLH), and to distinguish these from sepsis. A secondary objective was to retrospectively analyze the efficacy of tocilizumab (TCZ) in treating corticosteroid (CS)-refractory high-grade irCRS.</div></div><div><h3>Patients and methods</h3><div>A cohort of 35 patients presenting with irCRS-like symptoms was studied, including 9 with irHLH-like manifestations and 8 with sepsis. Immune profiling was carried out using 48 mass cytometry markers, along with an analysis of 45 serum biomarkers, including 27 cytokines and 18 additional markers from the HScore. Twelve patients with high-grade irCRS refractory to CS were treated with TCZ.</div></div><div><h3>Results</h3><div>Twenty-four biomarkers significantly distinguished between irHLH and grade 3 irCRS (<em>P</em> = 0.0027-0.0455). Hepatocyte growth factor (HGF) and ferritin had superior predictive values compared with the traditional HScore, both with a positive predictive value (PPV) and negative predictive value (NPV) of 100%. CXCL9 differentiated irHLH from grade 3 irCRS and predicted the need for TCZ treatment intensification (PPV = 90%, NPV = 100%). Additional biomarkers, including leukocyte count, neutrophils, ferritin, interleukin (IL)-6, IL-7, epidermal growth factor, fibrinogen, and granulocyte–macrophage colony-stimulating factor (GM-CSF), discriminated sepsis from high-grade irCRS (PPV = 75%-80%, NPV = 100%). Elevated frequencies of CXCR5+ or CCR4+ CD8 memory cells, CD38+ intermediate monocytes, and CD62L+ neutrophils were observed in high-grade irCRS compared with sepsis. All 12 patients with high-grade irCRS refractory to CS treated with TCZ experienced complete resolution.</div></div><div><h3>Conclusions</h3><div>This study highlights the importance of specific immunologic biomarkers in determining irCRS severity, predicting outcomes, and distinguishing between irHLH, irCRS, and sepsis. It also demonstrates the efficacy of TCZ in managing high-grade irCRS, underscoring the need for personalized therapeutic strategies based on these biomarkers.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 4","pages":"Pages 444-459"},"PeriodicalIF":56.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863165","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":"Reply to Letter to the Editor regarding “Clinical validation of a tissue-agnostic genome-wide methylome enrichment molecular residual disease assay for head and neck malignancies” by C. Zhang","authors":"G. Liu ,&nbsp;S.V. Bratman ,&nbsp;D.D. De Carvalho ,&nbsp;A.-R. Hartman","doi":"10.1016/j.annonc.2024.12.007","DOIUrl":"10.1016/j.annonc.2024.12.007","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 3","pages":"Pages 345-346"},"PeriodicalIF":56.7,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833765","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":"Minimal residual disease in colorectal cancer. Tumor-informed versus tumor-agnostic approaches: unraveling the optimal strategy","authors":"B. Martínez-Castedo ,&nbsp;D.G. Camblor ,&nbsp;J. Martín-Arana ,&nbsp;J.A. Carbonell-Asins ,&nbsp;B. García-Micó ,&nbsp;V. Gambardella ,&nbsp;M. Huerta ,&nbsp;S. Roselló ,&nbsp;D. Roda ,&nbsp;F. Gimeno-Valiente ,&nbsp;A. Cervantes ,&nbsp;N. Tarazona","doi":"10.1016/j.annonc.2024.12.006","DOIUrl":"10.1016/j.annonc.2024.12.006","url":null,"abstract":"<div><h3>Background</h3><div>Circulating tumor DNA (ctDNA) analysis has emerged as a minimally invasive tool for detecting minimal residual disease (MRD) in colorectal cancer (CRC) patients. This enables dynamic risk stratification, earlier recurrence detection and optimized post-surgical treatment. Two primary methodologies have been developed for ctDNA-based MRD detection: tumor-informed strategies, which identify tumor-specific mutations through initial tissue sequencing to guide ctDNA monitoring, and tumor-agnostic approaches, which utilize predefined panels to detect common cancer-associated genomic or epigenomic alterations directly from plasma without prior tissue analysis. The debate over which is superior in terms of sensitivity, specificity, cost-effectiveness and clinical feasibility remains unsolved.</div></div><div><h3>Design</h3><div>This review summarizes studies published up to November 2024, exploring the utility and performance of tumor-informed and tumor-agnostic approaches for ctDNA analysis in CRC. We evaluate the strengths and limitations of each methodology, focusing on sensitivity, specificity and clinical outcomes.</div></div><div><h3>Results</h3><div>Both strategies demonstrate clinical utility in post-operative risk stratification and guiding adjuvant chemotherapy decisions in CRC patients. Tumor-informed approaches generally exhibit superior sensitivity and specificity for recurrence prediction, attributed to their personalized tumor profile designs. However, these methods are limited by the need for prior tissue sequencing and higher associated costs. In contrast, tumor-agnostic approaches offer broader applicability due to their reliance on plasma-only analysis, although with relatively lower sensitivity. Technological advancements, including fragmentomics and multi-omic integrations, are expanding the capabilities of ctDNA-based MRD detection, enhancing the performance of both approaches.</div></div><div><h3>Conclusions</h3><div>While tumor-informed strategies currently offer higher precision in MRD detection, tumor-agnostic approaches are gaining traction due to their convenience and improving performance metrics. The integration of novel technologies in ongoing clinical trials may redefine the optimal approach for MRD detection in CRC, paving the way for more personalized and adaptive patient management strategies.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"36 3","pages":"Pages 263-276"},"PeriodicalIF":56.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827223","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}