OncologistPub Date : 2025-02-06DOI: 10.1093/oncolo/oyaf008
Martina Morini, Sebastiano Barco, Martina Ardito, Alessia Cafaro, Federica Pigliasco, Lucilla Rossi, Martina Fragola, Daniela Segalerba, Massimo Conte, Alberto Garaventa, Mirco Ponzoni, Giuliana Cangemi, Maria Valeria Corrias
{"title":"Detection of plasma circulating GD2 ganglioside in patients with neuroblastoma and age-matched healthy children. Diagnostic and prognostic evaluation.","authors":"Martina Morini, Sebastiano Barco, Martina Ardito, Alessia Cafaro, Federica Pigliasco, Lucilla Rossi, Martina Fragola, Daniela Segalerba, Massimo Conte, Alberto Garaventa, Mirco Ponzoni, Giuliana Cangemi, Maria Valeria Corrias","doi":"10.1093/oncolo/oyaf008","DOIUrl":"10.1093/oncolo/oyaf008","url":null,"abstract":"<p><strong>Background: </strong>GD2 ganglioside, a known specific marker for neuroblastoma (NB), exists in different lipoforms, including C18 and C20, which are distinguished by the length of their fatty acid chains. C18 and C20 GD2 lipoforms can be simultaneously measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We evaluated the diagnostic and prognostic performance of circulating GD2 levels in children with NB.</p><p><strong>Methods: </strong>Thirty microliters of peripheral blood (PB) plasma samples from 83 children with NB at diagnosis and 83 age-matched healthy controls were analyzed by LC-MS/MS. From stage M patients, 29 additional PB plasma samples were collected after induction therapy, 7 before and after immunotherapy, and 6 at relapse. For 22 stage M patients, bone marrow (BM) plasma samples were also collected at diagnosis.</p><p><strong>Results: </strong>C18 and C20 GD2 concentrations were significantly higher in children with NB than in controls. Receiver operating characteristic (ROC) analysis showed a cut-point of 44.1 and 0.47 nM for C18 and C20, respectively, able to discriminate with high specificity and sensitivity in patients with NB from controls. Circulating C18 and C20 levels in PB strongly correlated with those in BM. At diagnosis, C18 and C20 GD2 concentrations were significantly higher in stage M, deceased patients, and in those bearing tumors with MYCN amplification. ROC analysis identified prognostic cut points for the whole population, whereas only C20 concentrations above the cut points were significantly associated with a worse event-free survival of patients with stage M disease or with MYCN-amplified tumors. C18 and C20 plasma concentrations strongly decreased during treatment but increased at relapse.</p><p><strong>Conclusions: </strong>Measurement of circulating GD2 seems to have prognostic power in the subsets of patients with stage M disease and with MYCN-amplified tumors, and be able to early detect relapse, thus its ability to monitor disease should be prospectively evaluated in future studies.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411408","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}
OncologistPub Date : 2025-02-06DOI: 10.1093/oncolo/oyae268
Anna Kerkmann, Christian Schinke, Adam Dordevic, Johannes Kern, Nikola Bangemann, Josefine Finck, Jens-Uwe Blohmer, Klemens Ruprecht, Jens C Göpfert, Carolin Otto, Bianca Materne, Matthias Endres, Wolfgang Boehmerle, Petra Huehnchen
{"title":"Chemotherapy-induced cognitive impairment and its long-term development in patients with breast cancer: results from the observational CICARO study.","authors":"Anna Kerkmann, Christian Schinke, Adam Dordevic, Johannes Kern, Nikola Bangemann, Josefine Finck, Jens-Uwe Blohmer, Klemens Ruprecht, Jens C Göpfert, Carolin Otto, Bianca Materne, Matthias Endres, Wolfgang Boehmerle, Petra Huehnchen","doi":"10.1093/oncolo/oyae268","DOIUrl":"10.1093/oncolo/oyae268","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy-induced cognitive impairment (CICI) is a well-recognized side effect of breast cancer treatment. However, prospective long-term evaluations of CICI using standardized neuropsychological tests are scarce.</p><p><strong>Patients and methods: </strong>This prospective longitudinal cohort study investigated cognitive dysfunction and its impact on quality of life and everyday functioning in patients with breast cancer receiving first-line chemotherapy compared to patients with breast cancer without chemotherapy. Assessment occurred prior to chemotherapy, postchemotherapy (median 6 months), and 2-3 years later. We used standardized neuropsychological tests, questionnaires, and scales to assess patients' quality of life and functioning. Additionally, serum analysis for neurodegenerative markers and autoantibodies was conducted.</p><p><strong>Results: </strong>We included n = 53 patients. Overall cognitive function declined statistically significantly (P = .046) postchemotherapy compared to control patients, mostly driven by a reduced figural memory (P = .011). Patients who received chemotherapy showed a greater reduction in quality of life (increased fatigue symptoms, P = .023; reduced Karnofsky index, P < .001); however, without a statistically significant effect on cognitive decline. The neurodegenerative markers Neurofilament light chain (NfL) and phosphorylated Neurofilament heavy chain (pNfH) increased statistically significantly (P < .001) postchemotherapy and pNfH correlated with overall cognitive function. After 2-3 years, both cognitive performance and quality of life were comparable between chemotherapy-treated and control patients.</p><p><strong>Conclusion: </strong>Our findings suggest that chemotherapy statistically significantly contributes to overall cognitive dysfunction in patients with breast cancer, which disappears after 2-3 years, indicating a recovery in both objectively measurable cognitive function and subjective quality of life. Future research should examine larger sample sizes and explore screening indicators, particularly pNfH.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481134","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 microvascular invasion risk on tumor progression of hepatocellular carcinoma after conventional transarterial chemoembolization.","authors":"Guanhua Yang, Yuxin Chen, Minglei Wang, Hongfang Wang, Yong Chen","doi":"10.1093/oncolo/oyae286","DOIUrl":"10.1093/oncolo/oyae286","url":null,"abstract":"<p><strong>Objective: </strong>To assess tumor progression in patients with hepatocellular carcinoma (HCC) without macrovascular invasion who underwent treatment with conventional transarterial chemoembolization (cTACE) based on microvascular invasion (MVI) risk within 2 years.</p><p><strong>Methods: </strong>This retrospective investigation comprised adult patients with HCC who had either liver resection or cTACE as their first treatment from January 2016 to December 2021. A predictive model for MVI was developed and validated using preoperative clinical and MRI data from patients with HCC treated with liver resection. The MVI predictive model was applied to patients with HCC receiving cTACE, and differences in tumor progression between the MVI high- and low-risk groups were examined throughout 2 years.</p><p><strong>Results: </strong>The MVI prediction model incorporated nonsmooth margin, intratumoral artery, incomplete or absent tumor capsule, and tumor DWI/T2WI mismatch. The area under the receiver operating characteristic curve (AUC) for the prediction model, in the training cohort, was determined to be 0.904 (95% CI, 0.862-0.946), while in the validation cohort, it was 0.888 (0.782-0.994). Among patients with HCC undergoing cTACE, those classified as high risk for MVI possessed a lower rate of achieving a complete response after the first tumor therapy and a higher risk of tumor progression within 2 years.</p><p><strong>Conclusions: </strong>The MVI prediction model developed in this study demonstrates a considerable degree of accuracy. Patients at high risk for MVI who underwent cTACE treatment exhibited a higher risk of tumor progression within 2 years.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548954","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":"Radiotherapy with targeted and immunotherapy improved overall survival and progression-free survival for hepatocellular carcinoma with portal vein tumor thrombosis.","authors":"Jianing Ma, Haifeng Zhang, Ruipeng Zheng, Shudong Wang, Lijuan Ding","doi":"10.1093/oncolo/oyae209","DOIUrl":"10.1093/oncolo/oyae209","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of radiotherapy (RT) combined with targeted therapy and immunotherapy in treating hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) is still unclear. This study investigated the efficacy and safety of RT combined with targeted therapy and immunotherapy in HCC with PVTT.</p><p><strong>Materials and methods: </strong>Seventy-two patients with HCC with PVTT treated with tyrosine kinase inhibitor (TKI) plus programmed cell death protein-1 (PD-1) inhibitor with or without RT from December 2019 to December 2023 were included. After propensity score matching (PSM) for adjusting baseline differences, 32 pairs were identified in RT + TKI + PD-1 group (n = 32) and TKI + PD-1 group (n = 32). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs).</p><p><strong>Results: </strong>Median OS (mOS) in RT + TKI + PD-1 group was significantly longer than TKI + PD-1 group (15.6 vs. 8.2 months, P = .008). Median PFS (mPFS) in RT + TKI + PD-1 group was dramatically longer than TKI + PD-1 group (8.1 vs. 5.2 months, P = .011). Patients in TKI + PD-1 + RT group showed favorable ORR and DCR compared with TKI + PD-1 group (78.1% vs. 56.3%, P = .055; 93.8% vs. 81.3%, P = .128). Subgroup analysis demonstrated a remarkable OS and PFS benefit with TKI + PD-1 + RT for patients with main PVTT (type III/IV) and those of Child-Pugh class A. Multivariate analysis confirmed RT + TKI + PD-1 as an independent prognostic factor for longer OS (HR 0.391, P = .024) and longer PFS (HR 0.487, P = .013), with no mortality or severe TRAEs.</p><p><strong>Conclusion: </strong>RT combined with TKI and PD-1 inhibitor could significantly improve mOS and mPFS without inducing severe TRAEs or mortality.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134480","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}
OncologistPub Date : 2025-02-06DOI: 10.1093/oncolo/oyae220
Fernando Sabino Marques Monteiro, Antonio Machado Alencar Junior, Karine Martins da Trindade, Taiane Francieli Rebelatto, Fernando C Maluf, Antonia A Gazzola, Pablo M Barrios, Joaquim Bellmunt, Rafaela Gomes de Jesus, Gyl Eanes Barros Silva, Antonio Augusto Lima Teixeira Junior, Philippe E Spiess, Andre P Fay
{"title":"Molecular characterization of metastatic penile squamous cell carcinoma in developing countries and its impact on clinical outcomes: LACOG 2018 translational study.","authors":"Fernando Sabino Marques Monteiro, Antonio Machado Alencar Junior, Karine Martins da Trindade, Taiane Francieli Rebelatto, Fernando C Maluf, Antonia A Gazzola, Pablo M Barrios, Joaquim Bellmunt, Rafaela Gomes de Jesus, Gyl Eanes Barros Silva, Antonio Augusto Lima Teixeira Junior, Philippe E Spiess, Andre P Fay","doi":"10.1093/oncolo/oyae220","DOIUrl":"10.1093/oncolo/oyae220","url":null,"abstract":"<p><strong>Background: </strong>Penile squamous cell carcinoma (PSCC) is a rare malignancy. However, in developing countries the incidence rate is higher. The understanding of molecular alterations is essential for evaluating possible targets for more effective systemic therapies.</p><p><strong>Methods: </strong>We retrospectively collected clinical data of metastatic PSCC (mPSCC) patients who had received at least one prior systemic treatment from 3 Brazilian hospitals. Tumor samples were evaluated using the next-generation sequencing (NGS) Foundation One DX and immunohistochemistry (IHC). The objective was to identify and describe somatic genomic alterations known to be functional or pathogenic and their association with survival outcomes.</p><p><strong>Results: </strong>Twenty-three patients were identified, 22 and 18 patients had tumor samples analyzed by IHC and NGS, respectively. PD-L1 expression (CPS ≥ 1%) was positive in 14 patients (63.6%). Regarding the genomic alterations, 16 patients (88.9%) had some clinically relevant genomic alterations. TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and CDKN2B loss were identified in 66.7%, 50%, 50%, 33.3%, 27.8%, and 22.2% of the patients, respectively. No MSI or TMB high (≥10 mutations/MB) cases were identified. NOTCH1 mutation was identified only in HPV-negative patients and it was associated with worse OS (yes: 5.5 vs no: 12.8 months, P = .049) and progression-free survival (yes: 5.5 vs no: 11.7 months, P = .032).</p><p><strong>Conclusion: </strong>This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121183","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":"Colorectal cancer harboring EGFR kinase domain duplication response to EGFR tyrosine kinase inhibitors.","authors":"Tomohiro Kondo, Osamu Kikuchi, Yoshihiro Yamamoto, Tomohiko Sunami, Yafeng Wang, Keita Fukuyama, Tomoki Saito, Hideto Nakahara, Sachiko Minamiguchi, Masashi Kanai, Atsushi Sueyoshi, Manabu Muto","doi":"10.1093/oncolo/oyae113","DOIUrl":"10.1093/oncolo/oyae113","url":null,"abstract":"<p><p>Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare, recurrent oncogenic variant that constitutively activates EGFR in non-small-cell lung cancer. Herein, we report the case of a 70-year-old man with resectable colorectal adenocarcinoma who underwent surgery followed by adjuvant therapy. He relapsed with multiple liver metastases and received standard chemotherapy until his disease became refractory. Comprehensive genomic profiling of his postoperative colorectal cancer tissue revealed EGFR-KDD. He was treated with an EGFR tyrosine kinase inhibitor (TKI), afatinib and achieved a partial response (- 55%) after 8 weeks; however, he developed massive malignant ascites after 13 weeks. Osimertinib, another EGFR-TKI, controlled his tumors for 9 months. Patient-derived cancer organoids from his malignant ascites confirmed sensitivity to EGFR-TKIs. The findings suggest that EGFR-TKIs can be a potential treatment option for this molecular subgroup.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185025","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":"Prophylactic antibiotic use is associated with better clinical outcomes in gastric cancer patients receiving immunotherapy.","authors":"Fangyuan Zhang, Zixuan Ding, Yongping Lian, Xiao Yang, Pengbo Hu, Yongqing Liu, Liang Xu, Zhou Li, Hong Qiu","doi":"10.1093/oncolo/oyae362","DOIUrl":"10.1093/oncolo/oyae362","url":null,"abstract":"<p><strong>Background: </strong>The relationship between antibiotic treatment and immunotherapy efficacy is complex.</p><p><strong>Methods: </strong>This study was a single-center study. History of antibiotic use in gastric cancer (GC) patients within 1 or 3 months prior to immunotherapy was collected. Patients were categorized into 3 groups according to whether they had used antibiotics prior to immunotherapy: none, prophylactic use, and infection.</p><p><strong>Results: </strong>A total of 252 GC patients received immunotherapy, of which 38.5% (97/252) received antibiotic treatment within 1 month before immunotherapy (prophylactic use in 72.2% of patients) and 48.8% (123/252) received antibiotic treatment within 3 months before immunotherapy (prophylactic use in 74.8% of patients). The prophylactic use of antibiotic within 1 month prior to immunotherapy significantly improved overall survival (OS) compared with patients who received anti-infective therapy and had no history of antibiotic use (prophylactic vs infection: OS, 22.6 vs 9.7 m, HR, 0.53, 95% CI, 0.27-1.07; prophylactic vs none: OS, 22.6 vs 14.7 m, HR, 0.57; 95% CI, 0.39-0.83). The use of antibiotics in infected patients did not increase the risk of death in patients compared with those who did not use antibiotics. Prophylactic antibiotic use within 1 month before immunotherapy is an independent prognostic factor for OS.</p><p><strong>Conclusions: </strong>Prophylactic use of antibiotics is associated with better prognosis in GC patients receiving immunotherapy. Therefore, there is no necessity to delay the use of immune checkpoint inhibitors in this group of patients.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557723","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}
OncologistPub Date : 2025-02-06DOI: 10.1093/oncolo/oyae227
Simon Khagi, Rupesh Kotecha, Na Tosha N Gatson, Suriya Jeyapalan, Huda Ismail Abdullah, Nicholas G Avgeropoulos, Eleni T Batzianouli, Moshe Giladi, Leonardo Lustgarten, Samuel A Goldlust
{"title":"Recent advances in Tumor Treating Fields (TTFields) therapy for glioblastoma.","authors":"Simon Khagi, Rupesh Kotecha, Na Tosha N Gatson, Suriya Jeyapalan, Huda Ismail Abdullah, Nicholas G Avgeropoulos, Eleni T Batzianouli, Moshe Giladi, Leonardo Lustgarten, Samuel A Goldlust","doi":"10.1093/oncolo/oyae227","DOIUrl":"10.1093/oncolo/oyae227","url":null,"abstract":"<p><p>Tumor Treating Fields (TTFields) therapy is a locoregional, anticancer treatment consisting of a noninvasive, portable device that delivers alternating electric fields to tumors through arrays placed on the skin. Based on efficacy and safety data from global pivotal (randomized phase III) clinical studies, TTFields therapy (Optune Gio) is US Food and Drug Administration-approved for newly diagnosed (nd) and recurrent glioblastoma (GBM) and Conformité Européenne-marked for grade 4 glioma. Here we review data on the multimodal TTFields mechanism of action that includes disruption of cancer cell mitosis, inhibition of DNA replication and damage response, interference with cell motility, and enhancement of systemic antitumor immunity (adaptive immunity). We describe new data showing that TTFields therapy has efficacy in a broad range of patients, with a tolerable safety profile extending to high-risk subpopulations. New analyses of clinical study data also confirmed that overall and progression-free survival positively correlated with increased usage of the device and dose of TTFields at the tumor site. Additionally, pilot/early phase clinical studies evaluating TTFields therapy in ndGBM concomitant with immunotherapy as well as radiotherapy have shown promise, and new pivotal studies will explore TTFields therapy in these settings. Finally, we review recent and ongoing studies in patients in pediatric care, other central nervous system tumors and brain metastases, as well as other advanced-stage solid tumors (ie, lung, ovarian, pancreatic, gastric, and hepatic cancers), that highlight the broad potential of TTFields therapy as an adjuvant treatment in oncology.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481147","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}
OncologistPub Date : 2025-02-06DOI: 10.1093/oncolo/oyae269
Leontios Pappas, Julia C F Quintanilha, Richard S P Huang, Aparna R Parikh
{"title":"Genomic alterations associated with early-stage disease and early recurrence in patients with colorectal cancer.","authors":"Leontios Pappas, Julia C F Quintanilha, Richard S P Huang, Aparna R Parikh","doi":"10.1093/oncolo/oyae269","DOIUrl":"10.1093/oncolo/oyae269","url":null,"abstract":"<p><strong>Background: </strong>The molecular characterization of early-stage (1-3) colorectal cancer (CRC) remains incomplete, as opposed to metastatic disease, where comprehensive genomic profiling (CGP) is routinely performed. This study aimed to characterize the genomics of stages 1-3 versus IV CRC, and the genomics of patients recurring within 1 year of diagnosis.</p><p><strong>Patients and methods: </strong>Patients from a de-identified CRC clinico-genomic database who received Foundation Medicine testing (FoundationOne/FoundationOne CDx) during routine clinical care at approximately 280 US cancer clinics between March 2014 and June 2023 were included. Genomic alterations (GA) were compared by Fisher's exact test.</p><p><strong>Results: </strong>A total of 4702 patients were included; 1902 with stages 1-3 and 2800 with stage 4 disease. Among patients with stages 1-3 disease, 546 recurred within 1 year. Patients staged 1-3 had higher prevalence of microsatellite instability (MSI-H, 11.4% vs 4.5%, P < .001), tumor mutational burden (TMB) ≥ 10 Mut/Mb (14.6% vs 6.8%, P < .001), GA in RNF43 (11.2% vs 5.7%, P < .001), MSH6 (3.9% vs 1.7%, P < .001), MLH1 (2.3% vs 0.7%, P < .001), and MSH2 (1.5% vs 0.6%, P < .01) compared to those with stage 4 disease. Patients who recurred within 1 year had higher prevalence of MSI-H (13.2% vs 4.4%, P < .001), TMB ≥ 10 Mut/Mb (16.2% vs 6.9%, P < .001), BRAF V600E (17.2% vs 7.9%, P < .003), GA in RNF43 (13.7% vs 5.3%, P < .001), MSH6 (4.2% vs 1.6%, P = .035), and BRCA1/2 (6.2% vs 3.0%, P = .030). On recurrence, more patients received targeted therapy when CGP was performed before versus after first-line therapy (43% vs 19%, P < .001).</p><p><strong>Conclusions: </strong>Early-stage CRC patients can have distinct genomic profiles and CGP in this population can help expand access to targeted therapies.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632627","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}
OncologistPub Date : 2025-02-06DOI: 10.1093/oncolo/oyae229
Maria J Fernandez Turizo, Eunice Kim, Cancan Zhang, Tuyen Yankama, Gottfried Von Keudell, David J Sermer, Caroline Mejías-De Jesús, Aarti Asnani
{"title":"Pre-existing cardiovascular disease is associated with an increased risk of cardiovascular events during Bruton tyrosine kinase inhibitor therapy.","authors":"Maria J Fernandez Turizo, Eunice Kim, Cancan Zhang, Tuyen Yankama, Gottfried Von Keudell, David J Sermer, Caroline Mejías-De Jesús, Aarti Asnani","doi":"10.1093/oncolo/oyae229","DOIUrl":"10.1093/oncolo/oyae229","url":null,"abstract":"<p><p>The association between pre-existing cardiovascular disease (CVD) and the development of cardiovascular adverse events (CVAE) during Bruton tyrosine kinase inhibitor (BTKi) therapy is not well established. We compared the rate of CVAE, such as new onset or worsening atrial fibrillation (AF), supraventricular tachycardia, ventricular tachycardia, hypertension, myocardial infarction, and sudden cardiac death, between individuals with and without pre-existing CVD, during BTKi treatment. Secondary objectives were to compare the outcomes of patients treated with first generation BTKi versus second generation BTKi and characterize management decisions. A single-center retrospective review was conducted on patients treated with BTKi from 2013 to 2022 at Beth Israel Deaconess Medical Center. Adjusted logistic regression analyses were performed to evaluate the association between pre-existing CVD and CVAE. In this cohort, 11 out of 54 patients (20.4%) with pre-existing CVD developed CVAE, compared to 11 out of 135 patients (8.1%) without pre-existing CVD [age- and sex-adjusted OR 2.79; 95% CI (1.09, 7.25), P = .03]. Patients with pre-existing CVD had higher odds of developing new or worsening AF [age- and sex-adjusted OR 3.36; 95% CI (1.09, 10.71), P = .03]. Results remained robust after further adjustment of comorbidities, type of BTKi, and baseline medications. These results highlight the need for standardized approaches to prevent and promptly detect CVAE during BTKi treatment, particularly in patients with pre-existing CVD.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156701","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}