Cancer最新文献

{"title":"Oral vitamin C supplementation in patients with clonal cytopenia of undetermined significance or lower-risk myeloid malignancies: Results from EVITA, a phase 2 randomized, placebo-controlled trial","authors":"Stine Ulrik Mikkelsen MD, PhD,&nbsp;Ali Al-Mousawi MD,&nbsp;Amalie Bach Puglisi MD,&nbsp;Anders Pommer Vallentin MD,&nbsp;Astrid Østergaard Mortensen BSc,&nbsp;Zachary Madaj MSc,&nbsp;Toshinori Hinoue MSc, PhD,&nbsp;Heidi Naomi Ottesen BSc,&nbsp;Jakob Schmidt Jespersen MSc, PhD,&nbsp;Linn Gillberg MSc, PhD,&nbsp;Morten Tulstrup MD, MSc, PhD,&nbsp;Niels Richard Hansen MSc,&nbsp;Jakob Werner Hansen MD, PhD,&nbsp;Mette Klarskov Andersen MD, DMSc,&nbsp;Stacey Lyn Thomas MSc, PhD,&nbsp;Christine Isaguirre BSc,&nbsp;Ryan Sheldon MSc, PhD,&nbsp;Marie Adams MSc,&nbsp;Ryan Burgos BSc,&nbsp;Stephen Baylin MD,&nbsp;Bo Kok Mortensen MD, PhD,&nbsp;Casey Lee O’Connell MD,&nbsp;Marianne Tang Severinsen MD, PhD,&nbsp;Peter William Laird PhD,&nbsp;Jens Lykkesfeldt PhD, DMSc,&nbsp;Peter Jones PhD, DSc,&nbsp;Kirsten Grønbæk MD, DMSc","doi":"10.1002/cncr.70549","DOIUrl":"10.1002/cncr.70549","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Vitamin C (VitC) is a cofactor for TET enzymes involved in DNA demethylation and epigenetic regulation. Mutations in <i>TET2</i> are common drivers of leukemia. Preclinical studies suggest that VitC may delay leukemia progression. This study aimed to evaluate the biological activity, safety, and clinical impact of oral VitC in patients with clonal cytopenia of undetermined significance (CCUS) or lower risk myeloid malignancies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>EVITA (Epigenetics, Vitamin C, and Abnormal Hematopoiesis) was a double-blind, randomized, placebo-controlled, phase 2 trial conducted in Denmark and the United States. Adults with CCUS or lower risk myeloid malignancies not receiving anticancer therapy were randomly assigned (1:1) to receive oral VitC (1000 mg/day) or placebo for 12 months, followed by long-term follow-up. The primary end point was the median clonal growth rate from baseline to end of treatment. EVITA was registered at ClinicalTrials.gov (NCT03682029), and is now completed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Between November 1, 2017, and September 28, 2022, 109 patients were enrolled (VitC, <i>n</i> = 55; placebo, <i>n</i> = 54). Although the primary end point, median clonal growth rate, did not differ between groups (−0.016; 95% CI, −0.096 to 0.064; <i>p</i> = .70), secondary outcomes included differences in inflammatory cytokine trajectories and fewer serious adverse events in the VitC group versus placebo (18 of 55 [33%] vs. 30 of 53 [57%]). In exploratory analyses, overall survival was significantly longer with VitC (hazard ratio, 0.35; 95% CI, 0.17 to 0.71; <i>p</i> = .0025).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest oral VitC as a safe, biologically active intervention in patients with early-stage myeloid malignancies and precursor conditions. A phase 3 trial is warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 19","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011700","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":"Outcomes of adult patients with Li-Fraumeni syndrome and myeloid neoplasms","authors":"Jayastu Senapati MD, DM,&nbsp;Hiam M. Abdel-Salam MS,&nbsp;Vladislav D. Jdanov MD,&nbsp;Sanam Loghavi MD,&nbsp;Ashley Woodson MS,&nbsp;Jessica Corredor MS,&nbsp;Gautam Borthakur MD,&nbsp;Naval G. Daver MD,&nbsp;Tapan M. Kadia MD,&nbsp;Koichi Takahashi MD, PHD,&nbsp;Yesid Alvarado MD,&nbsp;Naveen Pemmaraju MD,&nbsp;Uday R. Popat MD,&nbsp;Elizabeth J. Shpall MD,&nbsp;Farhad Ravandi MD,&nbsp;Florencia McAllister MD,&nbsp;Najat C. Daw MD,&nbsp;Guillermo Garcia-Manero MD,&nbsp;Banu K. Arun MD,&nbsp;Courtney D. DiNardo MD, MSCE","doi":"10.1002/cncr.70613","DOIUrl":"10.1002/cncr.70613","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Li-Fraumeni syndrome (LFS) is an inherited cancer predisposition syndrome. Hematologic malignancies are not considered LFS defining tumors, however, both acute lymphoblastic leukemia and therapy-related myeloid neoplasms (MNs) in LFS are described. Treatment approaches and outcomes of MN in LFS need further evaluation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors performed a retrospective analysis to understand treatment approaches and outcomes in patients with LFS who developed an MN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 190 patients with LFS between February 2001 and February 2026 with a history of at least one neoplasm, 14 (7%) had an MN. Median age at MN diagnosis was 43 years (range, 25–73) and 11 (79%) patients were female. Overall, eight (57%) patients had myelodysplastic syndrome (MDS), five (36%) had acute myeloid leukemia (AML), and one (7%) had T-myeloid mixed phenotype acute leukemia (MPAL). With frontline therapy, six (75%) patients with MDS and one (17%) patient with AML achieved an overall response. Considering all lines of therapy received, cumulatively six (75%) patients with MDS and five (83%) patients with AML/MPAL achieved an overall response. At a median follow-up of 28.8 months, the median overall survival (OS) was 18.2 months, and 1-year and 2-year OS rates were 77% and 17%, respectively. Five patients (two MDS, two AML, and one MPAL) underwent hematopoietic stem cell transplantation during their MN therapy with a median OS of 19.3 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although short-lived responses to leukemia-directed therapy are common, long-term survival in most patients with LFS developing MN are poor. Additional research and understanding of the mechanisms to prevent MN and to improve MN treatment in LFS are needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 19","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70613","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987434","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":"Impact of post-chemotherapy classification on outcomes in stage III and IV unilateral favorable histology Wilms tumor: Pooled data from Children’s Oncology Group AREN0532, AREN0533, and AREN03B2 studies","authors":"Nicholas F. Evageliou MD,&nbsp;Lindsay A. Renfro PhD,&nbsp;Kelly L. Vallance MD,&nbsp;Carly R. Varela MD,&nbsp;Daniel J. Benedetti MD, MA,&nbsp;Nicholas G. Cost MD,&nbsp;Peter F. Ehrlich MD,&nbsp;John A. Kalapurakal MD,&nbsp;Geetika Khanna MD,&nbsp;Jennifer H. Aldrink MD,&nbsp;Richard D. Glick MD,&nbsp;Michael V. Ortiz MD,&nbsp;Lauren N. Parsons MD,&nbsp;Arnold C. Paulino MD,&nbsp;Maddy Artunduaga MD,&nbsp;Ethan A. Smith MD,&nbsp;David B. Dix MBChB,&nbsp;Conrad V. Fernandez MD,&nbsp;Jeffrey S. Dome MD, PhD,&nbsp;James I. Geller MD,&nbsp;Elizabeth A. Mullen MD","doi":"10.1002/cncr.70610","DOIUrl":"https://doi.org/10.1002/cncr.70610","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Improvements in therapy for patients with favorable histology Wilms tumor (FHWT) have relied on refinement of risk stratification for therapeutic assignment through identification of favorable and unfavorable prognostic factors. Although well established in International Society of Pediatric Oncology-Renal Tumor Study Group protocols, the Children’s Oncology Group (COG) has not historically used post-chemotherapy histology (PCH) to guide therapy. This study examines whether outcomes are associated with PCH classification in the COG treatment context.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors identified 2386 patients with stage III or IV FHWT enrolled on AREN0532, AREN0533, or AREN03B2-only from 2006 to 2019. Inclusion criteria included delayed nephrectomy more than 5 and fewer than 16 weeks after initial biopsy, treatment on or as per protocol with DD4A or Regimen M, and known PCH classification and outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 352 included patients, 45 (12.7%) were classified as low risk (LR), 287 (81.5%) as intermediate risk (IR), and 20 (5.6%) as high risk (HR). PCH classification was significantly prognostic for event-free survival (EFS) (<i>p</i> &lt; .0001) and overall survival (OS) (<i>p</i> &lt; .0001). Four-year EFS for LR, IR, and HR groups was 93% (95% CI, 86%–100%), 85% (95% CI, 81%–89%), and 53% (95% CI, 35%–81%); 4-year OS was 96% (95% CI, 90%–100%), 93% (95% CI, 89%–96%), and 62% (95% CI, 44%–89%). Compared with LR or IR, EFS and OS were significantly lower for HR, regardless of stage or treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PCH is a significant prognostic factor in unilateral FHWT treated on COG regimens, strongly supporting its incorporation into therapeutic stratification in prospective COG trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 19","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148974989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing matters: Impact of covalent BTK inhibitor dose modifications on outcomes in chronic lymphocytic leukemia/small lymphocytic leukemia—A 7-year real-world study","authors":"Jiaojiao Zhang MS,&nbsp;Jing Luo MD,&nbsp;Xiaozhong Shen BS,&nbsp;Jiayi Ren MD,&nbsp;Weiyang Liu MD,&nbsp;Li Chen MD,&nbsp;Lu Jiang MD,&nbsp;Xiangqin Weng MD,&nbsp;Jin Wang MD,&nbsp;Jian-Qing Mi MD","doi":"10.1002/cncr.70578","DOIUrl":"10.1002/cncr.70578","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Covalent BTK inhibitors (cBTKis) are the cornerstone of chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) therapy, yet real-world data on dose modifications and their differential impact on long-term outcomes remain incompletely defined. This study investigated the incidence, timing, and the effectiveness of drug switching in a real-world CLL cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this 7-year retrospective real-world study, 324 CLL/SLL patients treated at a specialized Shanghai outpatient clinic (April 2018–April 2025; median follow-up, 42 months) were analyzed. Dose modifications were classified as dose interruption (DI) or dose reduction (DR). Their prognostic impact on progression-free (PFS) and overall survival (OS) was assessed by Kaplan–Meier analysis and multivariate Cox regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 42-month PFS rate was 70.2%. Of 324 patients, 229 (70.7%) experienced dose reductions or interruptions; infections were the predominant cause (61.9%). The full-dose (FD) group (<i>n</i> = 90) demonstrated superior 4-year PFS (93% vs. 58%, <i>p</i> &lt; .001) and OS (98% vs. 76%, <i>p</i> = .007). Early modifications (0–3 months) were independent predictors of inferior PFS (hazard ratio [HR], 3.93, <i>p</i> = .008) and OS (HR, 3.29, <i>p</i> = .014). Prolonged DI (&gt;14 days) was associated with inferior PFS (HR, 2.64) and OS (HR, 2.15), whereas DR and short DI (≤14 days) had negligible impact. Early (0–3 months) prolonged DI was devastating (3-year PFS, 41.2%; HR, 3.84, <i>p</i> &lt; .001). cBTKi switching (<i>n</i> = 82; 100% nonprogression-driven) shortened DI (median, 6 vs. 14 days) and was independently associated with superior OS (HR, 0.34, <i>p</i> = .018) and PFS (HR, 0.36, <i>p</i> = .022).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Early prolonged DI is the dominant adverse prognostic factor in cBTKi-treated CLL/SLL. Proactive switching minimizes treatment gaps and improves survival, supporting a timing-aware, DI- versus DR-informed approach to dose management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 18","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term patient-reported outcomes and toxicity following salvage radiotherapy for biochemical recurrence after radical prostatectomy","authors":"Connor Lynch MD,&nbsp;Muzamil Arshad MD,&nbsp;Greeshma Rajeev-Kumar MD,&nbsp;Yan Che MS,&nbsp;Ted A. Skolarus MD,&nbsp;Parth K. Modi MD,&nbsp;Stanley L. Liauw MD","doi":"10.1002/cncr.70609","DOIUrl":"10.1002/cncr.70609","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Salvage radiotherapy (RT) after prostatectomy is common, but studies reporting long-term follow-up on patient-reported outcomes (PROs) and toxicity are limited. The authors report the largest cohort of patients treated with intensity modulated radiotherapy (IMRT) to date assessing patient-reported quality of life (QOL) and physician-rated toxicity with long-term follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PROs were prospectively collected for men undergoing post-prostatectomy salvage IMRT. Declines in quality of life were defined using established minimum clinically important difference (MCID) thresholds for bowel function (BF), sexual function (SF), urinary incontinence (UI), and urinary obstruction/irritation (UO) domains. Physician-reported genitourinary (GU) and gastrointestinal (GI) toxicities were recorded with Common Terminology Criteria for Adverse Events v3.0.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Between 2007 and 2019, 317 men were treated to a median dose of 68.4 Gy to the prostate bed with 72% receiving pelvic nodal treatment and 72% receiving androgen deprivation therapy. Median follow-up was 63 months. The median scores for UI, UO, BF, and SF did not decline more than the MCID at any time point except for the 6-week bowel score. At 5 years, the percentage of men with QOL decline exceeding MCID for BF, SF, UI, and UO domains were 23%, 25%, 29%, and 31%, respectively. The cumulative incidences of grade 3+ GU and GI toxicity at 5 years were 5.1% and 1.6%, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Median patient-reported QOL scores remained largely stable following salvage RT after radical prostatectomy, although clinically meaningful declines occurred in a subset of patients. QOL decline and physician-rated toxicity were transient in approximately one-third of affected patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 18","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975069","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":"Prognostic stratification of patients with biliary tract cancer treated with chemoimmunotherapy: A retrospective multicenter real-world study","authors":"Mara Persano MD,&nbsp;Andrea Casadei-Gardini MD,&nbsp;Lorenzo Fornaro MD,&nbsp;Tomoyuki Satake MD, PhD,&nbsp;Oluseyi Abidoye MD,&nbsp;Federica Lo Prinzi MD,&nbsp;Lorenzo Antonuzzo MD,&nbsp;Jin Won Kim MD, PhD,&nbsp;Francesca Bergamo MD,&nbsp;Melanie Bathon MD,&nbsp;Anna Saborowski MD,&nbsp;Tiziana Pressiani MD,&nbsp;Caterina Vivaldi MD,&nbsp;Ilario Giovanni Rapposelli MD,&nbsp;Frederik Peeters MD,&nbsp;Chiara Braconi MD, PhD,&nbsp;David J. Pinato MD, PhD,&nbsp;Emiliano Tamburini MD,&nbsp;Monica Niger MD,&nbsp;Stefano Tamberi MD,&nbsp;Florian Castet MD,&nbsp;Monica Verrico MD,&nbsp;Alessandro Parisi MD,&nbsp;Nuno Couto MD,&nbsp;Hong Jae Chon MD, PhD,&nbsp;Angela Lamarca MD, PhD,&nbsp;Guido Giordano MD,&nbsp;Fabian Finkelmeier MD,&nbsp;Ester Oneda MD,&nbsp;Antonio Avallone MD,&nbsp;Lukas Perkhofer MD,&nbsp;Il Hwan Kim MD, PhD,&nbsp;Ingrid Garajova MD,&nbsp;Salvatore Corallo MD,&nbsp;Elisabetta Fenocchio MD,&nbsp;Emanuela Dell’Aquila MD,&nbsp;Chiara Pirrone MD,&nbsp;Lorenzo Lucidi MD,&nbsp;Giulia Tesini MD,&nbsp;Elena Valenzi MD,&nbsp;Anna Diana MD,&nbsp;Changhoon Yoo MD, PhD,&nbsp;Marta Schirripa MD,&nbsp;Vincenzo Formica MD,&nbsp;Maria Grazia Rodriquenz MD,&nbsp;Mario Scartozzi MD,&nbsp;Jorge Adeva MD,&nbsp;Michele Ghidini MD,&nbsp;Gerald W. Prager MD,&nbsp;Giuseppe Aprile MD,&nbsp;Gian Paolo Spinelli MD,&nbsp;Su Yung-Yeh MD, PhD,&nbsp;Stephen L. Chan MD,&nbsp;Masafumi Ikeda MD,&nbsp;Tanios Bekaii-Saab MD,&nbsp;Jessica Lucchetti MD,&nbsp;Daniele Lavacchi MD,&nbsp;Minsu Kang MD,&nbsp;Rita Balsano MD,&nbsp;Francesca Salani MD,&nbsp;Silvia Camera MD,&nbsp;Gianluca Masi MD,&nbsp;Sara Lonardi MD,&nbsp;Arndt Vogel MD, PhD,&nbsp;Lorenza Rimassa MD,&nbsp;Margherita Rimini MD","doi":"10.1002/cncr.70601","DOIUrl":"10.1002/cncr.70601","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The objective of this study is to explore and validate a novel prognostic index for patients with locally advanced or metastatic biliary tract cancer (BTC) treated with first-line therapy with cisplatin, gemcitabine, and durvalumab.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a retrospective, multicenter, real-world study including 712 patients in the training cohort and 646 patients in the validation cohort. Using multivariate analysis for overall survival (OS) and applying the adjustment methods of Holm-Bonferroni, Benjamini-Hochberg, and Hommel, the authors identified five baseline statistically significant variables: disease stage, neutrophils, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA 19-9) levels, and Eastern Cooperative Oncology Group performance status (ECOG PS). According to the HR of each variable, β coefficients were calculated and the following formula was applied: (0.1757 * neutrophils value) + (0.5055 * ECOG PS) + (1.4037 * disease stage) + (0.1108 * CA 19-9) + (0.2126 * CEA). According to tertiles, the authors developed a prognostic model called the SENECA index, dividing the population into three risk groups: low-risk (≤2.14), intermediate-risk (2.15–2.89), and high-risk (&gt;2.89).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Median OS was 23.4 months in low-risk group,16.1 months in intermediate-risk group, and 8.3 months in high-risk group (low-risk hazard ratio [HR], 0.20; intermediate-risk HR, 0.36; high-risk HR, 1; <i>p</i> &lt; .0001). Median progression-free survival was 11.0 months in low-risk group (33.1%), 8.8 months in intermediate-risk group (33.3%), and 5.5 months in high-risk group (33.5%) (low-risk HR, 0.35; intermediate-risk HR, 0.55; and high-risk HR, 1; <i>p</i> &lt; .0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The SENECA index is a practical instrument for prognostic stratification of patients with BTC receiving chemoimmunotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 18","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IMMU-NO versus yes: Applicability of immune checkpoint inhibitors in gynecologic cancers","authors":"William B. Manning MD,&nbsp;Alicia M. Youssef MD,&nbsp;Oladapo O. Yeku MD, PhD","doi":"10.1002/cncr.70611","DOIUrl":"10.1002/cncr.70611","url":null,"abstract":"<p>Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for patients with gynecologic malignancies. ICIs have led to improved survival outcomes in uterine and cervical cancer, although with only modest success in ovarian cancer. In endometrial cancer, The Cancer Genome Atlas provided the framework for the molecular classification of endometrial cancer, enabling identification of the predominant predictive biomarker: mismatch repair (MMR) status. US Food and Drug Administration approvals for ICI monotherapy and in combination with targeted therapy based on MMR status quickly followed. Further research demonstrated a role for ICIs in combination with chemotherapy regardless of MMR status in the initial treatment of advanced or metastatic disease. In cervical cancer, ICIs are approved for use in combination with chemotherapy-sensitized radiation and in combination with systemic chemotherapy in patients who have recurrent or metastatic disease. In ovarian cancer, the tumor microenvironment, low tumor mutational burden, and the absence of a reliable predictive biomarker have limited the efficacy of ICIs, with most combination approaches failing to demonstrate meaningful benefit. A notable exception is KEYNOTE-B96, a randomized trial of pembrolizumab versus placebo with weekly paclitaxel, with or without bevacizumab, in patients with platinum-resistant ovarian cancer. Continued investigation into predictive biomarkers, resistance mechanisms, and alternative therapeutic targets is critically needed to extend the benefits of immunotherapy to patients with ovarian cancer. In this review, the authors describe the current immunotherapy landscape across gynecologic cancers, highlighting when ICI use is, and is not, supported by the evidence.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 18","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent studies explore the evolving use of radiation in patients with solid tumors","authors":"Leah Lawrence","doi":"10.1002/cncr.70551","DOIUrl":"10.1002/cncr.70551","url":null,"abstract":"&lt;p&gt;Two recently published studies explored the possibility of increasing the role of radiotherapy in the treatment of certain solid tumors, and although both studies add relevant data to shared decision-making conversations, more trials are needed to compare these radiation techniques to other existing standards of care.&lt;/p&gt;&lt;p&gt;The phase 2 FASTRACK II study was designed to evaluate the use of stereotactic ablative body radiotherapy (SABR) as a noninvasive treatment for patients with primary kidney cancer who are not candidates for surgery. The study, led by Shankar Siva, MBBS, PhD, a radiation oncologist at the Peter MacCallum Cancer Centre in Melbourne, Australia, enrolled 71 patients with tumors 10 cm or smaller and treated them with a single fraction of SABR of 26 Gy (tumors ≤4 cm) or with 42 Gy in three fractions (tumors &gt;4 cm).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;For the final long-term outcomes of the trial, patients had a median follow-up of 62 months. Treatment with SABR resulted in 100% disease control at 36, 60, and 84 months. Additionally, cancer-specific survival was 100%.&lt;/p&gt;&lt;p&gt;At 36 months, the cumulative incidence of distant progression was 3%; this increased to 16% at 84 months. Estimated overall survival (OS) was 82% at 36 months, 70% at 60 months, and 64% at 84 months.&lt;/p&gt;&lt;p&gt;“There have been a few single-arm studies demonstrating that radiation to primary kidney tumors has excellent local control,” says Yu-Wei Chen, MD, MS, an assistant professor of medicine and a medical oncologist at UC San Diego Health in California. “Most of these have demonstrated a near 100% disease control and almost 100% cancer-specific survival. For patients who are frail, have poor kidney function, or where a surgeon is worried about taking a patient to dialysis after surgery, radiation certainly plays a role.”&lt;/p&gt;&lt;p&gt;Dr Siva notes that “SABR as a treatment for primary kidney cancer is endorsed by the NCCN [National Comprehensive Cancer Network], NICE [National Institute for Health and Care Excellence], and EAU [European Association of Urology] guidelines,” primarily for the treatment of patients not suited for or who have declined surgery.&lt;/p&gt;&lt;p&gt;“It is particularly useful in those cases where a total nephrectomy may be required in patients with intercurrent medical conditions or pre-existing kidney dysfunction, or when there is a risk of post-surgical dialysis,” Dr Siva says.&lt;/p&gt;&lt;p&gt;However, compared with data from prior single-center studies, the data from FASTRACK II carry greater external validity and the results should be more generalizable, as it was a multicenter trial conducted at eight hospitals in Australia and the Netherlands, says Dr Siva.&lt;/p&gt;&lt;p&gt;Future research should explore additional ways to incorporate SABR into the treatment of kidney cancer.&lt;/p&gt;&lt;p&gt;“The patients in this study were not ideal surgical candidates, but the outcomes reported were extremely encouraging,” Dr Siva says. “Ideally a future trial would test SABR head-to-head against p","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 18","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70551","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975047","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":"Effect of demographic characteristics on the outcome of prostate cancer salvage radiotherapy: Analysis from a randomized controlled trial","authors":"Ismaheel O. Lawal MD, PhD,&nbsp;Ashesh B. Jani MD,&nbsp;Subir Goyal PhD,&nbsp;Olayinka Abiodun-Ojo MD,&nbsp;Vishal Dhere MD,&nbsp;Sarah Bell MS, MPH,&nbsp;Pretesh Patel MD,&nbsp;Bruce Hershatter MD,&nbsp;Krishna Chaudhary MD,&nbsp;Aliza Mushtaq MD,&nbsp;Joseph Shelton MD,&nbsp;Sheela Hanasoge MD,&nbsp;Nikhil Sebastian MD,&nbsp;Sagar A. Patel MD,&nbsp;Raghuveer Halkar MD,&nbsp;Viraj A. Master MD,&nbsp;Ruth C. Carlos MD,&nbsp;David M. Schuster MD","doi":"10.1002/cncr.70602","DOIUrl":"10.1002/cncr.70602","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study investigated the impact of advanced molecular imaging, race, socioeconomic status, and metabolic dysregulation on the outcome of salvage radiotherapy (sRT) for prostate cancer recurrence in a clinical trial setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors randomized post-prostatectomy men with detectable prostate-specific antigen to sRT guided by conventional imaging (arm A) or ¹⁸F-fluciclovine–positron emission tomography/computed tomography (arm B) and followed them up for up to 48 months to determine failure-free survival (FFS). The authors computed socioeconomic status (SES) and allostatic load (AL) scores to quantify socioeconomic status and level of metabolic dysregulation. They stratified patients by race as African American men (AAM) versus men of other races (MOR) and compared FFS between them using the <i>z</i>-test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighty-one (AAM = 29, MOR = 52) and 76 (AAM = 26, MOR = 50) men completed per-protocol sRT in arms A and B, respectively. Across study arms, AAM showed a higher FFS rate than MOR (72.8% [95% CI, 53.8%–85.0%] vs. 58.7% [95% CI, 46.6%–68.9%]; <i>p</i> = .002). In arm A, FFS rate was better for AAM than MOR, (64.0% [95% CI, 34.4%–82.9%] vs. 45.3% [95% CI, 28.8%–60.4%]; <i>p</i> = .008). In arm B, FFS improved for both groups but less so for AAM, (81.5% [95% CI, 57.2%–92.7%] vs. 73.0% [95% CI, 56.3%–84.1%]; <i>p</i> = .131). The authors found lower SES scores and higher AL scores for AAM in both study arms than MOR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Despite lower socioeconomic status and higher burden of metabolic dysregulation, in a clinical trial setting that controls for disparities in health care access, AAM have a more favorable sRT outcome than MOR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 18","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FDA adds vepdegestrant to options for ER-positive, HER2-negative, ESR1-mutated advanced breast cancer","authors":"Leah Lawrence","doi":"10.1002/cncr.70554","DOIUrl":"10.1002/cncr.70554","url":null,"abstract":"&lt;p&gt;The US Food and Drug Administration (FDA) has granted full approval to the heterobifunctional protein degrader vepdegestrant for adults with estrogen receptor (ER)–positive, HER2-negative, &lt;i&gt;ESR1&lt;/i&gt;-mutated advanced or metastatic breast cancer whose disease has progressed after one or two lines of endocrine therapy.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The approval was based on the results of the phase 3 VERITAC-2 trial, which enrolled 624 patients with ER-positive, HER2-negative advanced breast cancer who had received one line of CDK4/6 inhibitor therapy and one line of endocrine therapy.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Patients were randomly assigned to oral vepdegestrant or intramuscular fulvestrant.&lt;/p&gt;&lt;p&gt;Among the patients with &lt;i&gt;ESR1&lt;/i&gt; mutations, those assigned vepdegestrant had significantly longer progression-free survival (PFS) than patients who were assigned fulvestrant (hazard ratio [HR], 0.58; 95% CI, 0.43–0.78; &lt;i&gt;p&lt;/i&gt; &lt; .001). Median PFS more than doubled at 5.0 months with vepdegestrant versus 2.1 months with fulvestrant.&lt;/p&gt;&lt;p&gt;No significant difference was observed in median PFS among all patients.&lt;/p&gt;&lt;p&gt;Vepdegestrant will join a crowded field of agents for this patient population according to Ruth O’Regan, MD, chair of the Department of Medicine at the University of Rochester in New York. The FDA has previously approved both elacestrant and imlunestrant for ER-positive, HER2-negative, &lt;i&gt;ESR1&lt;/i&gt;-mutated advanced breast cancer after progression on at least one line of endocrine therapy.&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;“[Vepdegestrant] is a PROTAC [proteolysis-targeting chimera], but it degrades the estrogen receptor in a different way than other oral SERDs [selective estrogen receptor degraders],” Dr O’Regan says. “Overall, [VERITAC-2] had very similar results to the EMERALD study.”&lt;/p&gt;&lt;p&gt;The phase 3 EMERALD trial demonstrated a significant improvement in PFS for patients with &lt;i&gt;ESR1&lt;/i&gt;-mutated disease who were assigned elacestrant compared with those assigned standard-of-care endocrine therapy (HR, 0.55; 95% CI, 0.39–0.77), with a median PFS of 3.8 months versus 1.9 months.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Initial results from the EMBER-3 clinical trial showed that patients with &lt;i&gt;ESR1&lt;/i&gt; mutations assigned imlunestrant had a median PFS of 5.5 months versus 3.8 months for those with standard therapy.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Updated results also showed an 11.4-month improvement in overall survival (OS) with imlunestrant compared with endocrine therapy.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;“These agents have fairly modest efficacy overall,” Dr O’Regan says. “I think we are going to find out that—just like in the EMERALD study—the patients that have cancer that is still sensitive to endocrine therapy will probably do better with these drugs, but patients that have a shorter benefit from prior lines of endocrine therapy are probably not going to benefit very much.”&lt;/p&gt;&lt;p&gt;In addition, the EMBER-3 trial also included an arm combining imlunest","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 18","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70554","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975085","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}