Oncologist最新文献

{"title":"Site-Specific Outcomes and Genomics in Metastatic Pancreatic Ductal Adenocarcinoma.","authors":"Mahmoud Yousef, Saikat Chowdhury, Sali Albarouki, Ahmed Elhariri, Guglielmo Vetere, Sacha El Khoury, Mohammad Fanaeian, Abdelrahman Yousef, Ashwathy Balachandran Pillai, Kristin Alfaro-Munoz, Mark Knafl, Paul Roy, Mark W Hurd, Brandon G Smaglo, Robert A Wolff, Shubham Pant, Jason Willis, Ryan Huey, Michael J Overman, Camila Lopez, Anthony Chen, Ethan B Ludmir, Eugene J Koay, Rebecca A Snyder, Ching-Wei Tzeng, Michael P Kim, Naruhiko Ikoma, Jessica E Maxwell, Huamin Wang, Anirban Maitra, Matthew H G Katz, Yang Chen, Haoqiang Ying, John Paul Shen, Dan Zhao","doi":"10.1093/oncolo/oyag423","DOIUrl":"https://doi.org/10.1093/oncolo/oyag423","url":null,"abstract":"<p><strong>Background: </strong>Clinical and molecular features of pancreatic adenocarcinoma (PDAC) according to involved metastatic sites have not been well characterized.</p><p><strong>Materials and methods: </strong>We used the Foundry platform to query information for patients with metastatic PDAC at MD Anderson Cancer Center. Involved metastatic sites were extracted using natural language processing from imaging reports and verified by chart reviews. Overall survival (OS) and next generation sequencing (NGS) data were analyzed.</p><p><strong>Results: </strong>In a cohort of 1,095 patients (median overall survival [OS]: 22.8 months), lung-only metastasis was associated with longer median OS (57.6 months, p<0.0001). Patients with metastases not involving the liver had OS of 41.3 months, while liver-only (19.5 months) and multiple sites including liver (19.3 months) had the poorest survival. TP53 mutation rates were higher in liver-involved groups (84-85%) versus lung-only (73%) and non-liver metastases (67%, p<0.0001). Lower rates of GNAS mutations were detected in liver-only (5%) and liver-involved (2%) cases, higher in lung-only (8%) and non-liver (10%, p<0.01). The frequency of KRAS mutation and mutant allele distribution were not significantly different in tissue based NGS. However, in liquid biopsy analysis (n = 240), lung-only metastasis showed the lowest mutation detection (50%), TP53 (23%) and KRAS (10%), compared to liver-only detection rates of 65%, 46%, and 52% respectively (p values: 0.009, 0.02, <0.001).</p><p><strong>Conclusions: </strong>Patients with PDAC without liver metastasis have significantly improved OS and lower rates of TP53 mutation. Patients with lung-only metastasis had longer OS, a lower liquid-biopsy positivity rate, and a lower rate of KRAS detection by liquid biopsy; because liquid biopsy may under-detect KRAS in lung-only disease, tumor-tissue sequencing should be prioritized in these patients as KRAS-directed therapies emerge.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229446","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":"From Efficacy to Effectiveness in Gynecologic Oncology: Social Determinants, Therapeutic Transportability, and Biological Weathering.","authors":"Ziwen Zheng, Yamei Chen, Xinyu Yao, Chao Wang, Ling Li","doi":"10.1093/oncolo/oyag415","DOIUrl":"https://doi.org/10.1093/oncolo/oyag415","url":null,"abstract":"<p><p>Precision therapeutics have improved outcomes in gynecologic oncology, but their population-level impact depends on both biological efficacy and reliable treatment delivery. Randomized controlled trials establish causal effects under defined conditions; real-world evidence characterizes implementation and transportability while introducing distinct confounding and measurement challenges. This contextual narrative review integrates pivotal and updated therapeutic studies with clinical, social and translational evidence available through September 2026. Progression-free survival and overall survival are distinct endpoints, whereas effectiveness concerns benefit in routine care; cross-study interpretation requires aligned populations, treatment strategies, follow-up and estimands. The benefits of poly(ADP-ribose) polymerase inhibitors and immunotherapy are examined separately by molecular subgroup and treatment setting. Financial hardship, geographic access, caregiving and health-system constraints can affect initiation, tolerable exposure and continuity. We use the proposed term \"social discontinuation\" for treatment disruption with a material social contribution, while distinguishing clinical reasons and patient preference. Biological weathering provides plausible links between cumulative adversity and inflammatory, neuroendocrine, epigenetic and immune phenotypes. Human epidemiological associations, translational findings and experimental mechanisms support different inferences; mediation through treatment delivery remains distinct from biological modification of treatment effect. Priorities include justified broader eligibility, prospective social-needs and exposure measurement, responsive symptom management, navigation and hybrid care. Automated extraction and prediction tools require external validation, fairness assessment and prospective clinical-impact evaluation. Integrating randomized and real-world evidence can identify remediable barriers without diminishing the clinical value of effective therapies.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149231275","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":"Pancreatic Enzyme Replacement Therapy (PERT) in Pancreatic Cancer: First U.S. Consensus Highlights on Dosing, Management, and Provider Inertia.","authors":"Dallas Gallagher, Shelby Yaceczko, Megan Kitagawa, Ashley Cox, Shelli Hardy, Bailey Irvin, Kaitland Lauterbach, Amy Hacker-Prietz, Mary-Eve Brown, Maria Q B Petzel, Jeannine B Mills, Cassadie Moravek, Allison Rosenzweig, Rebecca Muñoz","doi":"10.1093/oncolo/oyag389","DOIUrl":"https://doi.org/10.1093/oncolo/oyag389","url":null,"abstract":"<p><strong>Purpose: </strong>Exocrine pancreatic insufficiency (EPI) is a highly prevalent, yet modifiable determinant of treatment tolerance in pancreatic cancer (PC). Despite its clinical significance, management remains inconsistent due to a lack of oncology-specific guidelines. This project aimed to establish the first U.S. multidisciplinary consensus to standardize pancreatic enzyme replacement therapy (PERT) dosing, education, and longitudinal management in pancreatic oncology.</p><p><strong>Methods: </strong>A mixed-methods design was employed, integrating a parallel literature review, six virtual focus groups with patients and clinicians (n = 28), and a formal modified Delphi process. A multidisciplinary panel of 17 experts, including medical, surgical, and radiation oncologists, advanced practice providers, and oncology dietitians, independently rated and refined draft statements over two iterative rounds. Consensus was defined a priori as ≥ 70% agreement.</p><p><strong>Results: </strong>The process yielded 15 final Consensus Statements, all achieving ≥ 81% agreement. This manuscript highlights a critical subset of six statements focusing on clinical application (CS 10-15), which achieved 94%-100% consensus. Recommendations define standardized starting doses (48,000-72,000 lipase units per meal), evidence-based titration protocols, multi-level patient education requirements, and strategies to mitigate financial toxicity and pill burden.</p><p><strong>Conclusion: </strong>These consensus statements provide a practical, evidence-based framework to reduce provider inertia and practice variability. Broad implementation of these standards offers a vital opportunity to stabilize nutritional status, improve quality of life, and optimize treatment continuity for patients with PC.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229407","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 efficacy, clinical outcomes, and safety of vimseltinib in patients with tenosynovial giant cell tumor: results from the MOTION phase 3 trial.","authors":"Vivek Bhadri, Hans Gelderblom, Silvia Stacchiotti, Sebastian Bauer, Andrew J Wagner, Michiel van de Sande, Nicholas M Bernthal, Antonio López Pousa, Albiruni Abdul Razak, Antoine Italiano, Mahbubl Ahmed, Axel Le Cesne, Gabriel Tinoco, Kjetil Boye, Javier Martín-Broto, Emanuela Palmerini, Salvatore Tafuto, Sarah Pratap, Benjamin C Powers, Peter Reichardt, Antonio Casado Herráez, Piotr Rutkowski, Christopher Tait, Giulia Agnello, Brooke Harrow, Amanda Saunders, Maitreyi G Sharma, Matthew L Sherman, Jean-Yves Blay, William D Tap","doi":"10.1093/oncolo/oyag421","DOIUrl":"https://doi.org/10.1093/oncolo/oyag421","url":null,"abstract":"<p><strong>Background: </strong>Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by colony-stimulating factor 1 (CSF1) gene dysregulation. Vimseltinib is an oral, switch-control tyrosine kinase inhibitor of the CSF1 receptor. In part 1 of the MOTION phase 3 trial, vimseltinib demonstrated statistically significant and clinically meaningful improvements in antitumor activity and clinical outcome assessments (COAs). Here, we report long-term results from MOTION in patients with >2 years of follow-up on study.</p><p><strong>Patients and methods: </strong>MOTION is a randomized, double-blind, placebo-controlled, phase 3 trial with double-blind (part 1; to week 25), open-label (part 2; weeks 25-49), and extension periods (NCT05059262). Eligible adult patients with histologically confirmed TGCT not amenable to surgery received vimseltinib 30 mg twice weekly. Efficacy was assessed by objective response rate (ORR) on study evaluated by independent radiological review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and Tumor Volume Score. COAs and safety were assessed.</p><p><strong>Results: </strong>In total, 118 patients received vimseltinib during MOTION (randomized to vimseltinib, n = 83; crossover, n = 35), with 51% (60/118) remaining on treatment. ORR on study per RECIST v1.1 was 48% (40/83) for patients randomized to vimseltinib and 54% (19/35) for crossover. Patients in both groups experienced long-term improvements in COAs. The safety profile was consistent with prior reports, with no evidence of cholestatic hepatotoxicity or drug-induced liver injury.</p><p><strong>Conclusion: </strong>Vimseltinib continued to provide robust and durable antitumor activity and demonstrated long-term improvements in COAs, with manageable safety for the treatment of patients with TGCT not amenable to surgery.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225252","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":"Hormone Receptor-Positive HER2-Negative Oligometastatic Breast Cancer: prognostic stratification and pattern of progression.","authors":"Jean-Louis Lacaze, Bastien Cabarrou, Thibaut Cassou-Mounat, Ciprian Chira, Celine Dalmasso, Eleonora De Maio, Eva Jouve, Clément Korenbaum, Carole Massabeau, Vincent Nicolai, François Poumeaud, Gabrielle Selmes, Mony Ung","doi":"10.1093/oncolo/oyag413","DOIUrl":"https://doi.org/10.1093/oncolo/oyag413","url":null,"abstract":"<p><strong>Background: </strong>The management of oligometastatic breast cancer (OMBC) remains controversial, particularly regarding selection for local ablative treatment (LAT). In HR+/HER2- OMBC, where prolonged survival is often the case, improved stratification and characterization of progression may guide treatment. We aimed to define prognostic subsets, assess the contribution of Modern-Imaging-Methods (MIMs; 18F-FDG-PET/CT or WB-MRI) to LAT selection, and describe progression after first-line therapy in these subgroups of patients.</p><p><strong>Materials and methods: </strong>All consecutive patients with HR+/HER2- OMBC treated at our institution between 2012 and 2020 were included. OMBC was defined as ≤ 5 metastases. Prognostic factors including biological subtype, anatomical distribution, imaging modality, and LAT were evaluated for overall and progression-free survival (OS, PFS).</p><p><strong>Results: </strong>Among 145 patients (median follow-up 82.8 months), median OS and PFS were, respectively, 81.1 and 26.5 months. Luminal-A-like subtypes, absence of liver metastases, and use of MIMs independently predicted better survival. LAT improved PFS (hazard ratio [HR]=0.52; 95%CI[0.29-0.91], p=0.0233) and showed a trend toward longer OS. In patients staged with MIMs, LAT significantly improved both OS (HR = 0.29; 95%CI[0.12-0.73], p=0.008) and PFS (HR = 0.40; 95%CI[0.21-0.77], p=0.0064). After first-line systemic therapy, only 18% developed polymetastatic progression.</p><p><strong>Conclusion: </strong>In HR+/HER2- OMBC, three actionable considerations emerge: staging must incorporate modern imaging to accurately define metastatic burden; LAT may be considered in selected patients with low-grade disease, absence of liver metastases, and long disease-free interval; in oligoprogression after first-line therapy, LAT should be re-evaluated within a multidisciplinary setting. These data offer pragmatic benchmarks to individualize treatment while awaiting definitive randomized evidence.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225321","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":"Clinical Endpoints in Trials of Metastasis-Directed Therapy in Oligometastatic Cancer: A Systematic Review and Surrogacy Analysis.","authors":"David Chen, Ealia Khoshkish, Seungmin Lee, Joshua Yi, Kristen Arnold, Ryan S Huang, Jane Jomy, Nina Sanford, David Palma, Xiang Y Ye, Zhihui Amy Liu, Gabriel Boldt, Philip Wong, Srinivas Raman","doi":"10.1093/oncolo/oyag315","DOIUrl":"https://doi.org/10.1093/oncolo/oyag315","url":null,"abstract":"<p><strong>Background: </strong>The oligometastatic state is characterized by limited metastatic burden for which metastasis-directed therapy (MDT) may provide durable control. Endpoint selection in MDT trials is poorly standardized and may not reflect long-term benefit or patient priorities. We systematically reviewed clinical endpoints in prospective MDT trials and registrations and evaluated progression-free survival (PFS) as a surrogate for overall survival (OS).</p><p><strong>Methods: </strong>We searched Ovid MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov from inception to June 2025 for prospective studies that exclusively enrolled oligometastatic patients and evaluated MDT. Two reviewers screened and extracted data, and endpoints were summarized descriptively and stratified by trial phase. We conducted a trial-level surrogacy meta-analysis of randomized trials reporting both PFS and OS hazard ratios.</p><p><strong>Findings: </strong>We included 235 trials: 29 randomized (25 [86%] phase II), 35 non-randomized, and 171 registrations. In randomized trials, PFS was the most frequent primary endpoint (n = 20, 67%), followed by OS (n = 4, 13%). Among 18 randomized trials reporting both endpoints, PFS and OS were moderately correlated (r = 0.80, 95% CI 0.64-0.91), with a surrogate threshold effect HR of 0.79 (95% CI 0.71-0.87).</p><p><strong>Interpretation: </strong>Because most trials were phase II, for which OS is neither expected nor appropriate as a sole endpoint, MDT trials predominantly use progression-based endpoints. We recommend phase-appropriate, patient-centered strategies that pair standardized PFS and local control with quality of life or systemic-therapy-free survival, reserving OS or validated surrogates for later-phase trials.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197814","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":"Whole Genome Sequencing-based tumor-informed circulating tumor DNA monitoring for early detection of recurrence in patients with solid tumors.","authors":"Mridula George, Gary S Schwartz, Wassim McHayleh, Vitaly Margulis, Hideaki Bando, Takayuki Yoshino, George Ansstas, Carly Bess Scalise, Sumedha Sudhaman, Arkarachai Fungtammasan, Bharat Sridhar, Jordan Feeney, Himanshu Sethi, Morgan M Quail, Sharlene Velichko, Wilson Tan, Alexander Hsieh, Anastasia Butskova, Ryan Ptashkin, Carcia Carson, Ashley Wray, Charuta C Palsuledesai, Meenakshi Malhotra, Ahmet Zehir, Eser Kirkizlar, Matthew Rabinowitz, Ryan K Swenerton, Gabrielle Heilek, Adham Jurdi, Adam C ElNaggar, Michael Krainock, Caitlin A Schonewolf, Angel A Rodriguez, Shruti Sharma, Ekaterina Kalashnikova, Minetta C Liu, Alexey Aleshin, Matthew D Galsky","doi":"10.1093/oncolo/oyag404","DOIUrl":"https://doi.org/10.1093/oncolo/oyag404","url":null,"abstract":"<p><strong>Background: </strong>Circulating tumor DNA (ctDNA) assays can transform patient management by enabling molecular residual disease (MRD) detection, prognosis prediction, and treatment monitoring. Here, we report clinical performance of Signatera™ Genome, a whole genome sequencing (WGS)-based ctDNA assay, in a diverse pan-cancer cohort at landmark and longitudinal settings post-definitive treatment.</p><p><strong>Methods: </strong>We performed a retrospective analysis of 386 patients with one of the following cancers: breast, colorectal, non-small cell lung, melanoma, or renal cell carcinoma. Signatera™ Genome assays, designed with high-quality variants selected from the matched tumor and normal WGS data, were used to detect ctDNA in the associated patients' longitudinal plasma samples collected post-operatively. The correlation between ctDNA-based MRD status and systemic, distant recurrence-free survival (systemic DRFS) was assessed using Cox regression analysis.</p><p><strong>Results: </strong>In the pan-cancer cohort, landmark analysis at 3 months post-surgery revealed that patients with MRD-positivity had significantly inferior systemic DRFS compared to ctDNA-negative patients (HR: 23.7, p < 0.0001). Additionally, ∼30% improvement in 24-month systemic DRFS was observed among adjuvant-treated MRD-positive patients, whereas MRD-negative patients derived no clear benefit from adjuvant therapy. In the longitudinal setting, MRD positivity anytime post-definitive treatment surveillance significantly correlated with shorter systemic DRFS compared to serial MRD negativity (HR: 104.7, p < 0.0001). Tumor-specific analyses yielded similar findings. Notably, 62% (72/116) of patients had ctDNA detected in the ultra-sensitive range of < 100 ppm.</p><p><strong>Conclusions: </strong>Our findings underscore the robust clinical performance of the Signatera Genome assay for MRD detection across solid tumors. Its broad applicability and high specificity support its integration into clinical practice and prospective trials.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208332","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":"Association of Irreversible Electroporation Treatment with Overall Survival in Stage III Pancreatic Ductal Adenocarcinoma: DIRECT Registry Results.","authors":"Robert C G Martin, Rebekah Ruth White, Malcolm M Bilimoria, Govindarajan Narayanan, Michael D Kluger, David A Iannitti, Patricio M Polanco, Chet W Hammill, Sean P Cleary, Robert Evans Heithaus, Theodore Welling, Carlos H F Chan","doi":"10.1093/oncolo/oyag416","DOIUrl":"https://doi.org/10.1093/oncolo/oyag416","url":null,"abstract":"<p><strong>Background: </strong>Irreversible electroporation (IRE) is used in selected patients with Stage III pancreatic ductal adenocarcinoma (PDAC), but its association with survival relative to standard-of-care (SOC) therapy remains uncertain.</p><p><strong>Methods: </strong>This multicenter observational study included 137 patients from the DIRECT registry: 99 treated within an IRE-based strategy and 38 receiving SOC without IRE. Overall survival (OS) from diagnosis was evaluated using propensity-score overlap weighting as the principal adjusted analysis. Conventional inverse probability of treatment weighting (IPTW), propensity-score matching, 3- and 6-month landmark analyses, and a time-dependent Cox model treating IRE as a time-varying exposure were sensitivity analyses. Restricted mean survival time (RMST) at 24 months was estimated.</p><p><strong>Results: </strong>Median time from diagnosis to enrollment was 8 months (IQR, 6-10) with IRE and 4 months (IQR, 3-6) with SOC (P < 0.0001). Unadjusted median OS was 28 months (95% CI, 23-33) and 15 months (95% CI, 12-21), respectively. Overlap weighting was associated with lower mortality with IRE (HR, 0.28; 95% bootstrap CI, 0.12-0.48). Twenty-four-month RMST was 21.22 versus 16.24 months, an absolute difference of 4.99 months (95% bootstrap CI, 1.15-8.12). The time-dependent analysis attenuated but retained the association (HR, 0.59; 95% bootstrap CI, 0.37-0.94). Other sensitivity analyses were directionally consistent.</p><p><strong>Conclusions: </strong>An IRE-based treatment strategy was associated with longer OS than SOC without IRE. Attenuation in the time-dependent analysis indicates that treatment timing and selection contributed to the observed difference. Given the nonrandomized design and potential residual confounding, these findings demonstrate association rather than an independent causal effect of IRE.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186158","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":"A randomized phase II study of fulvestrant with or without ganetespib in patients with endocrine resistant metastatic breast cancer.","authors":"Albert Grinshpun, Adrienne G Waks, Jingxin Fu, Patrick Kurnia, Hao Guo, Tianyu Li, McKenna Moore, Molly DiLullo, Ashka Patel, Luke Whitesell, Stefan Atanasov, Ann H Partridge, Erica L Mayer, Ian E Krop, Sandro Santagata, Myles Brown, Eric P Winer, Katherine Reeder-Hayes, Carey Anders, Rinath Jeselsohn, Nancy U Lin","doi":"10.1093/oncolo/oyag414","DOIUrl":"https://doi.org/10.1093/oncolo/oyag414","url":null,"abstract":"<p><strong>Background: </strong>Patients with endocrine-resistant hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC) have limited effective treatment options. Heat shock protein 90 (HSP90) regulates estrogen receptor stability and function; its inhibition has been proposed as a strategy to overcome endocrine resistance. Ganetespib is a second-generation HSP90 inhibitor with demonstrated anti-tumor activity in preclinical breast cancer models.</p><p><strong>Methods: </strong>In this randomized phase II study, 50 patients with HR+ MBC previously treated with endocrine therapy were randomized 1:2 to fulvestrant alone (n = 15) or fulvestrant with ganetespib (n = 35), respectively. Median age was 53 years. Fulvestrant was administered at standard dosing; ganetespib (200 mg/m2) was given intravenously on days 1, 8, and 15 of each 28-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival and safety/tolerability.</p><p><strong>Results: </strong>Median PFS was similar between arms (3.7 vs. 3.6 months; log-rank p = 0.79). Toxicity was higher with ganetespib, with substantially increased diarrhea (97% vs. 7%) and nausea (63% vs. 40%). Exploratory genomic analysis of on-treatment biopsies (n = 13) showed ESR1 mutations were enriched among patients without clinical benefit, while all patients with clinical benefit exhibited a Luminal A transcriptional subtype. Tumors lacking clinical benefit showed enrichment of proliferative and cell cycle-associated transcriptional programs.</p><p><strong>Conclusions: </strong>Adding ganetespib to fulvestrant did not improve clinical outcomes and increased toxicity in endocrine-resistant HR+ MBC. Our findings support the hypothesis that ESR1 alterations and proliferative transcriptional activity contribute to established endocrine resistance, limiting the therapeutic impact of HSP90 inhibition in this setting.</p><p><strong>Clinicaltrials.gov registration number: </strong>NCT01560416.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186148","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":"Timeliness of Pathological Diagnosis for Suspicious Breast Lesions in Northern Tanzania.","authors":"Friedemann Rabe, Angela Pallangyo, Elizabeth F Msoka, Pablo Santos, Sefonias Getachew, Adamu Addissie, Alex Mremi, Eva J Kantelhardt, Blandina Mmbaga","doi":"10.1093/oncolo/oyag400","DOIUrl":"https://doi.org/10.1093/oncolo/oyag400","url":null,"abstract":"<p><strong>Background: </strong>Most breast cancer cases in sub-Saharan Africa are diagnosed at advanced stages. The World Health Organization's Global Breast Cancer Initiative (GBCI) emphasizes early diagnosis and recommends that women with suspicious breast lesions promptly consult a health care provider (HCP) and receive a pathologic diagnosis within 60 days of their initial visit.</p><p><strong>Patients and methods: </strong>We interviewed 194 women undergoing diagnostic evaluation for suspicious breast lesions at a zonal referral hospital in northern Tanzania to assess diagnostic timeliness. Two intervals were examined: the pre-contact interval from first symptom recognition to the initial HCP visit, and the post-contact interval from the first HCP visit to the definitive pathological diagnosis. Negative binomial regression models were applied to assess factors influencing the duration of pre- and post-contact intervals.</p><p><strong>Results: </strong>The median pre-contact interval length was 1.0 month (IQR: 0.2-4.7), and the median post-contact interval was 0.9 months (IQR: 0.2-5.5). Overall, 63% of women received a pathological diagnosis within 60 days of first HCP contact, meeting the GBCI benchmark. Consulting multiple HCPs was associated with longer post-contact intervals, whereas being married and referral for pathologic evaluation at initial HCP visit were associated with shorter intervals. Breast cancer was diagnosed in 28% of participants.</p><p><strong>Conclusion: </strong>We observed comparatively short diagnostic intervals, with several modifiable factors influencing interval lengths. Targeted training of frontline HCPs and sustained breast cancer awareness efforts are particularly needed for women experiencing prolonged delays from symptom onset to diagnosis. Continued monitoring of diagnostic intervals is essential to sustain and improve diagnostic timeliness.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171900","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}