Cancers最新文献

{"title":"A Contemporary Review of Resectability and Treatment Strategies for Colorectal Liver Metastases: Part 1-Diagnosis, Defining Resectability, and Management of Upfront Resectable and Synchronous Disease.","authors":"Jennifer A Kalil, René Adam, Nicholas Meti, Peter Metrakos","doi":"10.3390/cancers18193165","DOIUrl":"10.3390/cancers18193165","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Colorectal liver metastases (CRLMs) remain a major determinant of long-term outcome. Although hepatic resection offers the best chance of durable survival, the definition of resectability has evolved beyond technical feasibility alone. This review aims to provide a structured overview of contemporary management strategies for patients with upfront technically resectable or synchronous CRLM, with emphasis on patient selection, tumor biology, perioperative systemic therapy, margin strategy, and surgical sequencing. <b>Methods</b>: A structured literature search of PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library was performed to identify studies published between 2000 and 2026. Eligible studies evaluated surgical, liver-directed, or systemic treatment strategies for CRLMs and reported outcomes including overall survival, disease-free survival, recurrence, margin status, or perioperative morbidity. Given the heterogeneity of the available evidence, findings were synthesized narratively. <b>Results</b>: Contemporary management of CRLMs requires integration of patient fitness, technical resectability, and tumor biology. In upfront technically resectable disease, routine neoadjuvant chemotherapy has not consistently improved overall survival, whereas selected high-risk patients may benefit from short-course preoperative therapy. Margin strategy is increasingly biology-informed rather than based on a universal margin width. In synchronous disease, no single operative sequence is superior for all patients; treatment should be selected according to disease burden, operative complexity, and the need to preserve access to systemic therapy. <b>Conclusions</b>: Management of upfront resectable and synchronous CRLMs should be individualized through multidisciplinary assessment. Current evidence supports a risk-adapted strategy that integrates technical feasibility, patient factors, and tumor biology while recognizing persistent uncertainty regarding optimal chemotherapy timing and surgical sequencing.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191219","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":"SOX17 in Gynecologic Tumors: Biology and Diagnostic Applications.","authors":"Wenfang Liu, Maryam Tahir, Anil V Parwani, Qingqing Ding, Zaibo Li","doi":"10.3390/cancers18193162","DOIUrl":"10.3390/cancers18193162","url":null,"abstract":"<p><p>SOX17 is a developmental transcription factor that regulates endoderm formation, vascular development, germ cell specification, and tissue differentiation. Recent studies have identified SOX17 as a highly informative immunohistochemical marker and lineage-associated regulator in gynecologic pathology. This review summarizes the physiological functions of SOX17, its expression in normal and neoplastic tissues, and its expanding diagnostic and translational applications. SOX17 demonstrates high sensitivity for most ovarian and endometrial epithelial carcinomas while exhibiting substantially greater specificity than PAX8 because it is consistently absent in the vast majority of renal, thyroid, breast, pulmonary, gastrointestinal, and other nongynecologic carcinomas. These characteristics make SOX17 particularly valuable for supporting Müllerian origin in metastatic tumors and cytology specimens. Emerging evidence also supports its utility in diagnostically challenging settings, including mesonephric-like adenocarcinoma, seminomatous germ cell tumors, yolk sac tumors, angiosarcoma, and selected mesothelial proliferations, where awareness of potential diagnostic pitfalls is essential. Beyond its diagnostic role, SOX17 functions in a context-dependent manner, acting either as a tumor suppressor or as a lineage-survival transcription factor through interactions with signaling pathways such as Wnt/β-catenin and the PAX8 transcriptional network. These biological insights underscore its role in lineage maintenance, angiogenesis, and tumor progression and suggest potential therapeutic relevance. Collectively, current evidence establishes SOX17 as a lineage biomarker with both diagnostic and biologic relevance.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191519","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":"Prediction of Response to Immunotherapy in Hepatocellular Carcinoma: Where Do We Stand?","authors":"Mariana Verdelho Machado","doi":"10.3390/cancers18193167","DOIUrl":"10.3390/cancers18193167","url":null,"abstract":"<p><p>Worldwide, liver cancer is the seventh most common cancer and the third leading cause of cancer-related mortality, reflecting its dismal prognosis, with only approximately 20% of patients alive 5 years after diagnosis. At least 50% of patients ultimately require systemic treatment. In 2020, the systemic treatment landscape changed dramatically with the introduction of immune checkpoint inhibitor (ICI)-based therapies, which have demonstrated improved overall survival and longer preservation of quality of life compared with tyrosine kinase inhibitor (TKI)-based approaches. However, fewer than one third of patients achieve objective response, 10-25% experience severe immune-related adverse events, and ICI-based treatments represent a substantial economic burden for health systems. Importantly, robust and clinically validated predictive biomarkers of response to ICI remain an unmet need. This review summarizes current efforts to identify predictive biomarkers of ICI response in hepatocellular carcinoma (HCC), integrating clinical, pathological, molecular, microbiome, and imaging approaches, and discusses how these developments may shape the future of treatment selection.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191547","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":"Preoperative Systemic Inflammatory Indices as Adjunctive Biomarkers for Malignancy Prediction in Bethesda III (AUS) Thyroid Nodules.","authors":"Gökhan Rıza Baykal, Müge Keskin, Kübra Katipoğlu, Ersin Gürkan Dumlu, Didem Özdemir, Oya Topaloğlu, Reyhan Ersoy, Bekir Çakır","doi":"10.3390/cancers18193170","DOIUrl":"10.3390/cancers18193170","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Atypia of undetermined significance (AUS; Bethesda category III) remains a challenging thyroid cytological diagnosis because of its heterogeneous malignancy risk and limited preoperative certainty. Molecular testing can improve risk stratification but is not universally available. This study evaluated the diagnostic and incremental predictive value of preoperative complete blood count-derived systemic inflammatory indices in surgically treated Bethesda III thyroid nodules. <b>Methods:</b> This retrospective cohort included 352 patients who underwent thyroidectomy for Bethesda III thyroid nodules. Preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were evaluated. Postoperative histopathology served as the reference standard. Receiver operating characteristic analysis and multivariable logistic regression were performed, followed by incremental model assessment, bootstrap internal validation, Hashimoto thyroiditis interaction analysis, and exploratory molecular subgroup analysis. <b>Results:</b> Among 352 patients, 197 (56.0%) had malignant histopathology. Malignant nodules showed higher NLR, PLR, SII, SIRI, and AISI and lower LMR. All six indices remained independently associated with malignancy after multivariable adjustment, with the strongest positive associations observed for SII (adjusted OR, 2.09; 95% CI, 1.60-2.72) and NLR (adjusted OR, 1.96; 95% CI, 1.51-2.54). SII demonstrated the numerically highest individual discrimination (AUC 0.687; 95% CI, 0.631-0.740), followed by NLR (AUC 0.661) and AISI (AUC 0.659); SII and NLR did not differ significantly (DeLong <i>p</i> = 0.182). Addition of SII increased the AUC of the clinico-ultrasonographic model from 0.695 to 0.761, with an optimism-corrected AUC of 0.721. Hashimoto thyroiditis did not significantly modify these associations. In the molecular subgroup, mutation status increased model discrimination from 0.765 to 0.824, whereas no statistically significant additional improvement with SII was detected in the exploratory molecular subgroup. <b>Conclusions:</b> Preoperative systemic inflammatory indices, particularly SII, provide modest but incremental predictive information beyond conventional clinical and ultrasonographic variables in surgically treated Bethesda III thyroid nodules. Their role appears complementary rather than diagnostic when used in isolation, particularly when comprehensive molecular testing is unavailable. Prospective external validation is required before clinical implementation.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191568","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":"Association of Body Composition with Tumor Proteomics and Survival in Patients with Clear Cell Renal Cell Carcinoma.","authors":"Cuthbert Mario Mahenge, Rand Talal Akasheh, Xuan V Nguyen, Ting-Yuan David Cheng","doi":"10.3390/cancers18193161","DOIUrl":"10.3390/cancers18193161","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Prognoses for patients with clear cell renal cell carcinoma (ccRCC) are associated with complex interactions between tumor and patient characteristics. This cross-sectional study investigated associations between body composition and tumor proteomics and their interaction with survival among patients with ccRCC. <b>Methods</b>: Data from 178 patients in the TCGA-KIRC project were analyzed to assess adipose and skeletal muscle tissue areas at the third lumbar vertebra of diagnostic computed tomography scan images. Patients were classified into four body composition types: high muscle with low adiposity; high muscle with high adiposity; low muscle with low adiposity; and low muscle with high adiposity. Proteins with differential expression (<i>p</i> < 0.05) were screened for interactions with body composition type on survival. Linear regression was used to assess associations, and Cox regression models-adjusted for age, tumor stage, sex, race, and ethnicity-were utilized for survival analysis. <b>Results</b>: Patients with low muscle with low adiposity exhibited worse survival than those having high muscle with high adiposity (hazard ratio, 3.74 [95% CI, 1.69-8.27]). Low muscle with low adiposity was also associated with increased expression of P-cadherin and decreased expression of DIRAS3 (<i>p</i> < 0.05; false discovery rate-corrected <i>p</i> < 0.1), both associated with poor survival in the entire TCGA-KIRC cohort. Among patients having low muscle with high adiposity, high (vs. low) PREX1 expression was associated with 15.8-fold (95% CI, 3.08-80.78) increased mortality. <b>Conclusions</b>: Body composition is associated with differential protein expressions and survival in ccRCC. Therefore, body composition and its associated tumor proteomics may serve as prognostic biomarkers and therapeutic targets in ccRCC.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191318","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":"From Bile Dysmetabolism to Lipid-Metabolic Remodeling of the Distal Colon: A Vectorial Concept of Colorectal Carcinogenesis (Part I).","authors":"Maria A Sukhanova, Zakhar A Akulov, Zelimkhan G M Berikkhanov, Alexey L Shestakov, Aleksey G Kotelnikov, Andrey M Nikolaev, Vadim S Razumovsky, Evgeniy A Tarabrin, Milena Yu Ivanova, Mehrshad Ebrahimnezhad, Sergey Yu Muraviev","doi":"10.3390/cancers18193160","DOIUrl":"10.3390/cancers18193160","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is traditionally viewed as the result of the sequential accumulation of molecular alterations and the clonal expansion of transformed cells. However, the state of morphologically non-neoplastic mucosa preceding the development of neoplasia remains considerably less well characterized. This narrative review aims to integrate evidence on biliary and lipid metabolism, intestinal transit, microbial metabolism, and field cancerization and to formulate a testable model of early metabolic remodeling in the distal colon. We propose that a chronically altered biliary-metabolic environment, combined with prolonged luminal and mucosa-associated exposure, may promote lipid-metabolic remodeling of morphologically non-neoplastic mucosa. This state is considered not as a new disease entity but as a potential tissue phenotype capable of altering the barrier, metabolic, and regenerative properties of the epithelium. Subsequent exposure to nitrogen-containing products of microbial metabolism may sustain repeated cycles of injury and regeneration, thereby creating conditions for clonal selection. Following the emergence of a neoplastic clone, the same local environment may potentially assume a different biological role and become part of a metabolic niche that supports further clonal expansion. The proposed model extends the concept of field cancerization by incorporating a metabolic dimension and generates a series of spatial and temporal predictions amenable to experimental and prospective clinical testing. Validation of this model may provide a basis for investigating morphologically non-neoplastic mucosa as potential tissue at risk and for developing earlier preventive and diagnostic approaches.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191099","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":"Early and Late Prognostic Factors in Patients with Resected Brain Metastases.","authors":"Dan M Visarion, Ioana Petrescu, Viorel M Pruna, Radu M Gorgan","doi":"10.3390/cancers18193157","DOIUrl":"10.3390/cancers18193157","url":null,"abstract":"<p><strong>Background: </strong>Brain metastases are the most common malignant intracranial tumors and remain associated with poor survival despite advances in multimodal treatment. This study aimed to evaluate the associations between clinical, radiological, surgical, and perioperative characteristics and outcomes in patients undergoing surgical resection of brain metastases.</p><p><strong>Materials and methods: </strong>This retrospective single-center cohort study included 378 consecutive adult patients who underwent resection of histopathologically confirmed brain metastases between 2015 and 2023. Overall survival was estimated using the Kaplan-Meier method, and differences between groups were assessed using the log-rank test. Factors associated with overall survival were evaluated using univariable and multivariable Cox proportional hazards regression. Binary logistic regression was used to evaluate factors associated with 30-day mortality.</p><p><strong>Results: </strong>Median overall survival was 11.3 months, the one-year survival rate was 45.5%, and 18 patients (4.8%) died within 30 days after surgery. In the adjusted logistic regression model, preoperative KPS < 80, hydrocephalus, postoperative hematoma, and postoperative pneumonia were associated with higher odds of 30-day mortality. In the multivariable Cox regression analysis, increasing age, preoperative KPS < 80, tumor volume ≥ 9 cm³, hydrocephalus, wound complications, and postoperative KPS deterioration were independently associated with shorter overall survival. Subtotal versus total resection was not significantly associated with overall survival after adjustment.</p><p><strong>Conclusions: </strong>Several preoperative and postoperative characteristics were associated with early mortality and overall survival in this surgically selected cohort. These findings emphasize the importance of careful patient selection, preservation of functional status, optimization of perioperative care, and prevention of postoperative complications.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Web-Based Nomogram for Predicting Survival in Patients with Esthesioneuroblastoma Using SEER Database.","authors":"Julianna L Barbaro, Abhishek S Bhutada, Srijan Adhikari, Kristine Ravina, Eric A Marvin","doi":"10.3390/cancers18193145","DOIUrl":"10.3390/cancers18193145","url":null,"abstract":"<p><p><b>Background</b>: Esthesioneuroblastoma (ENB) is a rare neuroectodermal tumor arising from the olfactory epithelium. This study aimed to identify survival determinants and construct a prognostic web-based nomogram to provide individualized survival predictions for ENB patients. <b>Methods</b>: Patients diagnosed with ENB between 2000 and 2022 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Patient demographics, tumor characteristics, and treatment data were analyzed using Cox proportional hazards models and Kaplan-Meier survival curves. A web-based nomogram was constructed to predict 5- and 10-year survival probabilities individualized to a specific patient. <b>Results</b>: Nine hundred and forty-one ENB patients were analyzed. Overall survival (OS) rates at 1-, 2-, 5-, and 10-years were 89%, 85%, 75%, and 58%, respectively. Multivariable analysis revealed that age over 50 (<i>p</i> < 0.001) and tumor size over 6.0 cm (<i>p</i> < 0.01) were independent predictors of worse OS. Compared to patients treated with gross total resection (GTR) alone, worse OS was observed in those treated with chemotherapy (CT) only (<i>p</i> < 0.01), CT and radiation (RT, <i>p</i> < 0.01), GTR + CT (<i>p</i> < 0.05), RT only (<i>p</i> < 0.01), or no treatment (<i>p</i> < 0.001). No statistically significant differences in OS were found between GTR alone and GTR + RT, GTR + RT + CT, subtotal resection (STR), or STR with adjuvant therapies. The resulting ENB prognostic nomogram demonstrated acceptable predictive performance, with a C-index of 0.733 ± 0.041 and AUC of 0.749. <b>Conclusions</b>: Age and tumor size are critical survival determinants in ENB, and GTR continues to be the foundational treatment. The developed prognostic web-based nomogram successfully quantifies individualized survival probabilities, providing clinicians with a tailored tool to guide evidence-based counseling and management for ENB patients.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191313","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":"Sequencing BCMA-Directed Therapies in Relapsed/Refractory Multiple Myeloma: A Real-World Comparison of CAR T-Cell Therapy and Bispecific Antibodies.","authors":"Osama M Younis, Sencer Goklemez, Carmel Awadallah, Shebli Atrash, Barry Paul, Hira Shaikh, Christopher Strouse, Andrew Vegel, Emily Struble, Anita Mazloom, Omar Alkharabsheh, Prerna Mewawalla, Mansi R Shah, Abhiraj Saxena, Zahra Mahmoudjafari, Jordan Snyder, Muhammad Umair Mushtaq, Jeries Kort, Alma Habib, Joseph McGuirk, Al-Ola Abdallah, Abdullah Mohammad Khan","doi":"10.3390/cancers18193147","DOIUrl":"10.3390/cancers18193147","url":null,"abstract":"<p><strong>Background: </strong>Several B-cell maturation antigen (BCMA)-directed therapy (BDT) modalities have been approved by the US Food and Drug Administration (FDA) for relapsed-refractory multiple myeloma (RRMM). Ideal sequencing of these therapies remains unknown.</p><p><strong>Methods: </strong>We report one of the largest multicenter retrospective patient cohorts in this real-world analysis of patients receiving a BDT in both BDT-naïve and exposed settings at major academic centers.</p><p><strong>Results: </strong>In the BDT-naïve setting, which included 276 patients, 169 (61%) received chimeric antigen receptor T-cell therapy (CAR-T), whereas 107 (39%) received bispecific antibodies (BsAbs). Median progression-free survival (PFS) in the BDT-naïve setting was significantly longer with CAR-T than with BsAbs (16.1 vs. 13.5 months, <i>p</i> = 0.007) with a higher overall response rate (ORR) (87 vs. 68%). Multivariable Cox regression analysis revealed that receiving CAR-T (hazard ratio [HR] = 0.41), cytokine release syndrome (CRS) of any grade (HR = 0.50), achieving a best response of ≥very good partial response (VGPR) (HR = 0.12), and high-risk cytogenetic abnormalities (HRCA) (HR = 2.29) were all significant prognostic indicators of PFS. Similarly, HRCA (HR = 2.32), CRS (HR = 0.36), and a best response of ≥VGPR (HR = 0.16) were all independent prognostic factors of overall survival (OS). Of the 80 patients who received prior BDT, 22 received CAR-T (28%) and 58 (72%) received BsAbs. The median PFS was 6.3 months in the CAR-T group, with 64% ORR, vs. 4.4 months in the BsAb group, with 53% ORR (PFS HR, 0.93). Only the best response, ≥VGPR (HR = 0.20), achieved significance in the multivariable model.</p><p><strong>Conclusions: </strong>CAR-T led to more durable responses in the BDT-naïve setting than BsAbs. Responses to either modality were weaker in the BDT-exposed setting. These results highlight the importance of sequencing BDT in RRMM.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191539","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":"A Pilot Head-to-Head Comparison of Two Bisulfite Conversion Kits for NGS-Based DNA Methylation Analysis of Liquid Biopsy Samples from Colorectal Cancer.","authors":"Omayma Mazouji, Abdelhak Ouhajjou, Roberto Incitti, Chakib Nejjari, Menter David, Morris Van Karlyle, Raghav Kanwal Pratap Singh, Scott Kopetz, Hicham Mansour","doi":"10.3390/cancers18193148","DOIUrl":"10.3390/cancers18193148","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Given the important role of early detection in improving cancer outcomes, epigenetic alterations, particularly DNA methylation, have emerged as powerful biomarkers for cancer screening and diagnosis. However, methylation profiling of cfDNA (circulating free DNA) presents particular technical challenges because cfDNA is typically present at very low concentrations and is highly fragmented. Bisulfite conversion, although essential for distinguishing methylated from unmethylated cytosines, can further compromise DNA integrity through chemical-induced loss of DNA during purification steps. Inadequate conversion or excessive DNA loss may consequently reduce library complexity, increase DNA duplication rates, and negatively affect mapping efficiency and downstream sequencing quality. Therefore, optimizing bisulfite conversion is particularly important for reliable methylation profiling of low-input cfDNA. The effectiveness of these diagnostic approaches relies on the accurate detection of DNA methylation patterns, which is fundamentally dependent on the efficiency of bisulfite conversion of genomic DNA. This pilot study aims to compare the performance of two widely used bisulfite conversion kits, namely the EpiTect Bisulfite (EpiTect) Kit (Qiagen, Hilden, Germany) and the EZ DNA Methylation (Zymo) Kit (Zymo Research, Irvine, CA, USA), in the context of plasma-derived cfDNA methylation profiling using five samples, including two plasma samples from metastatic colorectal cancer (mCRC) patients collected at the Department of Gastrointestinal Oncology at The University of Texas MD Anderson Cancer Center, in Houston, TX, USA, and two plasma samples from healthy donors (controls) purchased from Innovative Research (Novi, MI, USA), along with one control DNA sample (Corriel NA12878-N88). Our objective was to evaluate and compare their conversion efficiency, mapping efficiency (percentage of mapped and unmapped reads), duplication rate, and distribution of methylated cytosines in CpG, CHG, and CHH contexts. Our results indicate that samples processed using the Zymo kit consistently outperformed those treated with the EpiTect kit across multiple performance metrics. The Zymo-treated samples yielded a higher concentration of cfDNA following bisulfite conversion (125.34 nM vs. 45.60 nM in samples processed with the Epitect kit). Additionally, the Zymo kit achieved a higher average bisulfite conversion efficiency (99.3% vs. 95.7%), as well as a significantly higher average mapping rate (94.86% vs. 72.4%), with fewer unmapped reads and lower duplication rates. Head-to-head comparison of Bismark methylation calls across the same reference regions showed high concordance between the two protocols. The SEPT9 region was strongly hypermethylated with both protocols (100% with EpiTect and approximately 94% with Zymo), whereas the BMP3 region was predominantly unmethylated (approximately 4% with EpiTect and 7% with Zymo). These findings suggest that the Zymo kit dem","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"18 19","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191200","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}