Journal of Clinical Oncology最新文献

{"title":"Hypofractionated, Dose-Escalated Radiation Versus Conventionally Fractionated Radiation for Localized Prostate Cancer: Long-Term Update of a Phase III, Prospective, Randomized Controlled Trial.","authors":"Comron Hassanzadeh, Deborah Kuban, Sarah Pasyar, Roland Bassett, Patricia Troncoso, Maheen Ansari, Pamela Schlembach, Sean McGuire, Quynh Nguyen, Steven Frank, Henry Mok, Osama Mohamad, Ryan Park, Chad Tang, Weiliang Du, Rajat Kudchadker, Seungtaek Choi, Karen Hoffman","doi":"10.1200/JCO-24-02057","DOIUrl":"https://doi.org/10.1200/JCO-24-02057","url":null,"abstract":"<p><p>The MD Anderson dose-escalated, hypofractionated prostate radiation study was a phase III randomized trial comparing conventionally fractionated intensity-modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) with dose-escalated, hypofractionated intensity-modulated radiation (HIMRT, 72 Gy in 2.4-Gy fractions) in patients with localized prostate cancer, predominantly low-risk and intermediate-risk disease. The initial publication highlighted statistically fewer treatment failures in the HIMRT arm. We present long-term updated 13-year outcomes to determine whether cancer control benefit was maintained and to evaluate distant metastases post hoc. With a median follow-up of 13.2 years (IQR, 8.8-15.9 years), treatment failure occurred less frequently in men undergoing HIMRT (n = 13) compared with those undergoing CIMRT (n = 22), although the difference no longer meets statistical significance (<i>P =</i> .08). Distant metastases were rare, and no statistically significant difference was noted (<i>P</i> = .2). There remained no statistically significant difference in late GI 2+ (10-year 10% HIMRT <i>v</i> 4% CIMRT, <i>P</i> = .09) or genitourinary grade 2+ toxicity (10-year 26% <i>v</i> 23%, <i>P</i> = .5).</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402057"},"PeriodicalIF":42.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078254","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":"Transcription: Phone Call, 2018.","authors":"Elane Kim","doi":"10.1200/JCO-25-00011","DOIUrl":"https://doi.org/10.1200/JCO-25-00011","url":null,"abstract":"<p><p>A mother and daughter navigate illness, memory: a poem that lingers in the spaces between words.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500011"},"PeriodicalIF":42.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968315","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":"Practical Guidelines for the Treatment of Gestational Trophoblastic Disease: Collaboration of the European Organisation for the Treatment of Trophoblastic Disease (EOTTD)-European Society of Gynaecologic Oncology (ESGO)-Gynecologic Cancer InterGroup (GCIG)-International Society for the Study of Trophoblastic Diseases (ISSTD).","authors":"Christianne Lok,Nienke van Trommel,Elena Ioana Braicu,Francois Planchamp,Ross Berkowitz,Michael Seckl,","doi":"10.1200/jco-24-02326","DOIUrl":"https://doi.org/10.1200/jco-24-02326","url":null,"abstract":"Gestational trophoblastic diseases (GTDs) are a group of pregnancy-related premalignant and malignant diseases with generally a favorable prognosis when treated adequately. Many different treatment protocols exist worldwide. To our knowledge, this is the first set of global consensus-based guidelines for GTD. Four international organizations (European Organisation for the Treatment of Trophoblastic Diseases, European Society of Gynecologic Oncology, Gynecologic Cancer Intergroup, and International Society for the Study of Trophoblastic Diseases) delegated 53 expert GTD clinicians from 31 countries who formulated nine consensus-based definitions and the minimum criteria required to be a GTD center. Furthermore, 18 flow diagrams were developed to diagnose, treat, and follow up all forms of primary or recurrent GTD. The definitions and flow diagrams were drafted and adapted in consecutive (online) meetings until consensus was reached followed by an external review process. Here, the final guidelines are presented together with the available supporting evidence from the literature.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"113 1","pages":"JCO2402326"},"PeriodicalIF":45.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945385","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":"Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia.","authors":"Inna M Chen, Julia S Johansen, Susann Theile, Libbie M Silverman, Katherine R Pelz, Kasper Madsen, Olav Dajani, Kevin Z M Lim, Torben Lorentzen, Omnia Gaafer, Leonidas G Koniaris, Anna C Ferreira, Brian Neelon, Denis C Guttridge, Michael C Ostrowski, Teresa A Zimmers, Dorte Nielsen","doi":"10.1200/JCO.23.01965","DOIUrl":"https://doi.org/10.1200/JCO.23.01965","url":null,"abstract":"<p><strong>Purpose: </strong>This randomized phase-II trial (ClinicalTrials.gov identifier: NCT02767557) compared efficacy of gemcitabine/nab-paclitaxel (Gem/Nab) with or without the anti-interleukin-6 (IL-6) receptor antibody tocilizumab (Toc) for advanced pancreatic cancer (PC).</p><p><strong>Methods: </strong>A safety cohort received Gem 1,000 mg/m² and Nab 125 mg/m² on days 1, 8, and 15, and Toc 8 mg/kg on day 1 for each 28-day cycle. Participants with modified Glasgow prognostic scores of 1 or 2 were randomly assigned 1:1 to receive Gem/Nab/Toc or Gem/Nab. The primary end point was the overall survival (OS) rate at 6 months (OS6). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Exploratory end points were cachexia, quality of life, and biomarkers, including the cachexia-promoting protein, growth differentiation factor 15 (GDF15).</p><p><strong>Results: </strong>Overall, 147 patients were treated, including six safety cohort participants. The median follow-up period was 8.1 months (IQR, 4.2-13.9). OS6 was 68.6% (95% CI, 56.3 to 78.1) for the Gem/Nab/Toc group and 62.0% (49.6-72.1) for the Gem/Nab group (<i>P</i> = .409). OS for Gem/Nab/Toc versus Gem/Nab improved at 18 months (27.1% <i>v</i> 7.0%, <i>P</i> = .001). No differences in median OS, PFS, or ORR were observed. Incidence of grade-3+ treatment-related adverse events (TrAEs) was 88.1% for Gem/Nab/Toc and 63.4% for Gem/Nab (<i>P</i> < .001). Gem/Nab/Toc decreased muscle loss versus Gem/Nab, with median change +0.1013% versus -3.430% (<i>P</i> = .0012) at 2 months and +0.7044 versus -3.353% (<i>P</i> = .036) at 4 months. Incidence of muscle loss was 43.48% on Gem/Nab/Toc versus 73.52% on Gem/Nab at 2 months (<i>P</i> = .0045) and 41.82% versus 68.75% (<i>P</i> = .0062) at 4 months. GDF15 was not changed by Gem/Nab or Gem/Nab/Toc.</p><p><strong>Conclusion: </strong>Although the primary end point was not met and TrAEs were increased by Toc, increased survival at 18 months and reduced muscle wasting support an anticachexia effect of IL-6 blockade independent of GDF15. Further studies could leverage these findings for precision anticachexia therapy.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2301965"},"PeriodicalIF":42.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002191","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":"Financial Toxicity in Cancer Clinical Trials: An Issue in Need of Clarity and Solutions.","authors":"Elizabeth K S Barksdale, Wendy Selig, Willyanne DeCormier Plosky, Erin Miller, Keri McDonough, Chelsea Backler, Elizabeth George, Mark E Fleury, Marc J Taylor, Diana E Pankevich, Jim Murphy, Kristin Hermann, Leigh Ann Davis, Gissoo DeCotiis, Cecile Gonzalez-Cerimele, Colleen Cook, Sandra Shaw, Luke Gelinas, Dana L Dornsife, Barbara E Bierer, David E Gerber","doi":"10.1200/JCO-24-01577","DOIUrl":"https://doi.org/10.1200/JCO-24-01577","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401577"},"PeriodicalIF":42.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970873","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":"Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases.","authors":"Sarah A Weiss, Dijana Djureinovic, Wei Wei, Thuy Tran, Matthew Austin, Joseph Markowitz, Zeynep Eroglu, Nikhil I Khushalani, Upendra Hegde, Justine Cohen, Mario Sznol, Gail Anderson, Barbara Johnson, Cecily Piteo, Amit Mahajan, Adebowale Adeniran, Lucia Jilaveanu, Sarah Goldberg, Veronica Chiang, Peter Forsyth, Harriet M Kluger","doi":"10.1200/JCO-24-02219","DOIUrl":"10.1200/JCO-24-02219","url":null,"abstract":"<p><strong>Purpose: </strong>Anti-vascular endothelial growth factor therapy enhances PD-1 inhibitor activity in preclinical models and has been used to treat perilesional cerebral edema and radiation necrosis.</p><p><strong>Methods: </strong>We conducted a two-institution phase II trial of bevacizumab and pembrolizumab in patients with untreated melanoma brain metastasis (MBM) (ClinicalTrials.gov identifier: NCT02681549). Patients were anti-PD-(L)-1-naïve, and had ≥one asymptomatic, nonhemorrhagic 5-20 mm MBM, not requiring immediate local therapy or steroids.</p><p><strong>Results: </strong>Thirty-seven patients received four doses of bevacizumab and pembrolizumab every 3 weeks followed by up to 2 years of pembrolizumab. The brain metastasis response rate (primary end point) was 54.1% (95% CI, 36.9 to 70.5). The extracranial response rate was 56.3% (95% CI, 37.7 to 73.6). Median intracranial progression-free survival was 2.2 years (95% CI, 0.41 to not reached [NR]). Median overall survival (OS) was 4.3 years (95% CI, 1.6 to NR). Four-year OS rate was 51.6%. Grade 3 treatment-related adverse event rates from bevacizumab and pembrolizumab were 10.8% and 18.9%, respectively. Higher pretreatment vessel density in metastatic tumors and smaller on-therapy increases in circulating angiopoietin-2 were associated with response.</p><p><strong>Conclusion: </strong>Pembrolizumab with bevacizumab was well tolerated and demonstrated substantial activity in patients with untreated MBM with promising OS, justifying further evaluation of this regimen.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1685-1694"},"PeriodicalIF":42.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573173","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":"Organ Preservation in Rectal Cancer: Fear of Risks Versus the Risks of Fear.","authors":"Julio Garcia-Aguilar, Hannah Williams, Martin R Weiser, J Joshua Smith, Paul B Romesser, Christopher Crane, Li-Xuan Qin, Mithat Gonen, Andrea Cercek, Leonard B Saltz","doi":"10.1200/JCO-24-02723","DOIUrl":"10.1200/JCO-24-02723","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1745-1746"},"PeriodicalIF":42.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624852","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 Docetaxel Versus Docetaxel for Previously Treated Metastatic Castration-Resistant Prostate Cancer: The Randomized, Double-Blind, Phase III KEYNOTE-921 Trial.","authors":"Daniel P Petrylak, Raffaele Ratta, Nobuaki Matsubara, Ernesto Korbenfeld, Rustem Gafanov, Loic Mourey, Tilman Todenhöfer, Howard Gurney, Gero Kramer, Andries M Bergman, Pawel Zalewski, Maria De Santis, Andrew J Armstrong, Winald Gerritsen, Russell Pachynski, Seok Soo Byun, Margitta Retz, Eric Levesque, Ray McDermott, Sergio Bracarda, Ray Manneh, Meital Levartovsky, Xin Tong Li, Charles Schloss, Christian H Poehlein, Karim Fizazi","doi":"10.1200/JCO-24-01283","DOIUrl":"10.1200/JCO-24-01283","url":null,"abstract":"<p><strong>Purpose: </strong>The standard of care for metastatic castration-resistant prostate cancer (mCRPC) after second-generation androgen receptor pathway inhibitor (ARPI) therapy is still docetaxel. The randomized, double-blind, phase III KEYNOTE-921 trial (Clinicaltrials.gov identifier: NCT03834506) evaluated the efficacy and safety of pembrolizumab or placebo plus docetaxel for previously treated mCRPC.</p><p><strong>Methods: </strong>Adults with mCRPC who progressed after androgen-deprivation therapy and one ARPI were randomly assigned 1:1 to pembrolizumab or placebo plus docetaxel with concomitant prednisone. Dual primary end points were radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group 3-modified RECIST 1.1 and overall survival (OS). Safety was a secondary end point.</p><p><strong>Results: </strong>Between May 30, 2019, and June 17, 2021, 515 participants were randomly assigned to pembrolizumab plus docetaxel and 515 to placebo plus docetaxel. Median time from random assignment to data cutoff date (June 20, 2022) at final analysis (FA) was 22.7 months (range, 12.1-36.7). At first interim analysis (data cutoff date: September 27, 2021), median rPFS was 8.6 months (95% CI, 8.3 to 10.2) with pembrolizumab plus docetaxel versus 8.3 months (95% CI, 8.2 to 8.5) with placebo plus docetaxel (hazard ratio [HR], 0.85 [95% CI, 0.71 to 1.01]; <i>P</i> = .03). At FA, median OS was 19.6 months (95% CI, 18.2 to 20.9) versus 19.0 months (95% CI, 17.9 to 20.9), respectively (HR, 0.92 [95% CI, 0.78 to 1.09]; <i>P</i> = .17). Grade ≥3 treatment-related adverse events occurred in 43.2% of participants who received pembrolizumab plus docetaxel and 36.6% of participants who received placebo plus docetaxel. Two and seven participants, respectively, died due to a treatment-related adverse event. Pneumonitis was the most common immune-mediated adverse event (7.0% <i>v</i> 3.1%).</p><p><strong>Conclusion: </strong>The addition of pembrolizumab to docetaxel did not significantly improve efficacy outcomes for participants with previously treated mCRPC. The current standard of care remains unchanged.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1638-1649"},"PeriodicalIF":42.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567319","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":"Allogeneic Chimeric Antigen Receptor T-Cell Products Cemacabtagene Ansegedleucel/ALLO-501 in Relapsed/Refractory Large B-Cell Lymphoma: Phase I Experience From the ALPHA2/ALPHA Clinical Studies.","authors":"Frederick L Locke, Javier L Munoz, Michael T Tees, Lazaros J Lekakis, Sven de Vos, Rajneesh Nath, Don A Stevens, Shahbaz A Malik, Geoffrey P Shouse, Mehdi Hamadani, Olalekan O Oluwole, Miguel-Angel Perales, David B Miklos, Paul W Fisher, Amy Feng, Lynn Navale, John B Le Gall, Sattva S Neelapu","doi":"10.1200/JCO-24-01933","DOIUrl":"10.1200/JCO-24-01933","url":null,"abstract":"<p><strong>Purpose: </strong>Off-the-shelf, allogeneic CD19 chimeric antigen receptor (CAR) T-cell products may improve access to treatment versus autologous ones. We report the phase I experience of the allogeneic CD19 CAR T-cell product cemacabtagene ansegedleucel (cema-cel) and its predecessor, ALLO-501, in CD19 CAR T-naïve patients with relapsed/refractory large B-cell lymphoma (R/R LBCL).</p><p><strong>Methods: </strong>In the ALPHA2/ALPHA studies, the safety and efficacy of allogeneic CD19 CAR T cells were evaluated in CD19 CAR T treatment-naïve patients with R/R LBCL. Patients received healthy donor-derived, human leukocyte antigen-unmatched cema-cel/ALLO-501 following a 3-day lymphodepletion regimen of fludarabine (30 mg/m² once daily), cyclophosphamide (300 or 500 mg/m² once daily), and escalating doses of the anti-CD52 monoclonal antibody, ALLO-647.</p><p><strong>Results: </strong>As of September 26, 2024, 33 CD19 CAR T-naïve patients with LBCL (median age, 66 years; median number of previous therapies, 3) received allogeneic CAR T cells. CAR T-cell expansion was observed following infusion, with persistence observed up to 4 months. The overall and complete response (CR) rates were 58% and 42%, respectively; the median duration of response in patients with a CR was 23.1 months. The most common treatment-emergent adverse events were hematologic toxicities. No cases of graft-versus-host disease, immune effector cell-associated neurotoxicity syndrome, or grade ≥3 cytokine release syndrome were reported.</p><p><strong>Conclusion: </strong>Allogeneic CD19 CAR T cells demonstrated promising overall and durable CR rates with a manageable safety profile in CD19 CAR T-naïve patients with R/R LBCL, supporting additional evaluation of cema-cel in patients with LBCL.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1695-1705"},"PeriodicalIF":42.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414328","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":"Where Is the Future of Adjuvant Therapy for Hepatocellular Carcinoma?","authors":"Yizhen Fu, Yaojun Zhang, Dandan Hu, Zhongguo Zhou, Li Xu, Minshan Chen","doi":"10.1200/JCO-24-02615","DOIUrl":"10.1200/JCO-24-02615","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1625-1630"},"PeriodicalIF":42.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501537","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}