Journal of Gastrointestinal Cancer最新文献

{"title":"Impact of DAA Treatment for HCV on Hepatocellular Carcinoma in a Predominately African American Population.","authors":"Mohamad I Itani, Bassem Farah, Margaret Wasvary, Anshu Wadehra, Tj Wilson, Brian Rutledge, Paul Naylor, Eliza W Beal, Milton Mutchnick","doi":"10.1007/s12029-024-01076-w","DOIUrl":"10.1007/s12029-024-01076-w","url":null,"abstract":"<p><strong>Purpose: </strong>This study tested the hypothesis that our predominately AA medical center population would demonstrate a decline in HCV-driven HCC diagnosis following the initiation of DAA treatment in 2014. Also evaluated was whether achieving an SVR prior to diagnosis of HCC improved outcomes in patients who had an HCV diagnosis after completion of treatment.</p><p><strong>Methods: </strong>All patients with HCC seen at the Detroit Medical Center from 2009 to 2021 were identified using ICD-10 codes, and medical records were evaluated. Outcomes were evaluated as either alive or death/hospice as of December of 2022.</p><p><strong>Results: </strong>There were 461 patients with HCC of whom 433 (94%) had racial information in the database (AA = 351; non-AA = 82). HCC incidence regardless of race peaked in 2017, with a subsequent decline through 2021. HCV as a risk factor was higher in AA as compared to non-AA (85% vs. 53% p = 0.0001). Outcome (alive vs. death/hospice) was better for SVR patients compared to untreated patients (54% vs. 19%; p = 0.0009). HCC patients who achieved SVR also had better liver function at diagnosis as defined by Child-Pugh score (74% vs. 49% Class A p = 0.04) at the time of diagnosis.</p><p><strong>Conclusions: </strong>Racial disparity in HCC etiology was confirmed with AA more likely to have HCV than non-AA. The reduction in HCC patients with HCV confirms the impact of DAA treatment and prior successful treatment of HCV yields better outcomes. Increasing HCV treatment rates especially in AA patients will have a major impact on HCC development and treatment outcomes.</p><p><strong>What is known: </strong>• African Americans are more likely to have HCV infection as compared to non-AA. • Hepatocellular carcinoma is increasing in incidence in the US. • The role of HCV in the development of HCC remains to be further investigated.</p><p><strong>What is new: </strong>• HCC diagnosis in a single urban medical center study increased from 2009 as a result of HCV as a risk factor. • HCC declined post 2018 due primarily to a reduction in HCV infection as the risk factor. • African Americans were more likely to have HCV as the risk factor as compared to non-AA patients who were more likely to have no known risk factor on record (i.e., cryptogenic).</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgery for Infrarenal Retroperitoneal Node Metastases from Colon Cancer.","authors":"Anne-Sophie Dulac, Pietro Genova, Olivier Benoit, Cindy Neuzillet, Mostapha El Hajjam, Jean-François Emile, Frédérique Peschaud, Renato Micelli Lupinacci","doi":"10.1007/s12029-024-01086-8","DOIUrl":"10.1007/s12029-024-01086-8","url":null,"abstract":"<p><strong>Purpose: </strong>Treatment of retroperitoneal lymph node metastases (RPN) from colon cancer (CC) is a therapeutic challenge. Available evidence supporting a curative approach is weak and uncertainties remain concerning the extent of the dissection, the optimal timing for surgery, and the role of adjuvant radiotherapy. We report the outcomes of a curative intent strategy in a recent monocentric series of patients.</p><p><strong>Methods: </strong>We did a retrospective review of all curative intent surgical treatment of RPN from CC performed consecutively in a French university hospital from June 2015 to April 2021. Demographics, clinicopathological, and molecular characteristics were evaluated. We describe recurrence-free and overall survival and factors related to recurrence.</p><p><strong>Results: </strong>Records from 18 patients were reviewed. The median age was 69 years. Most of the patients were male (55%), ASA 1-2 (94%), had a left-sided primary colon cancer (73%), and had metachronous RPN (62%). Thirteen patients (72%) experienced recurrence. Recurrence was often limited to RPN (27%) or liver (22%). Four patients underwent a second surgery for RPN recurrence. Median disease-free and overall survival were 22 months and 50 months after RPN surgery. We did not find any factor associated with recurrence. Short-term recurrence (< 6 months) was associated with shorter overall survival (0.031).</p><p><strong>Conclusion: </strong>The current results suggest that RPN resection is feasible and associated with long survival in selected patients. Further studies evaluating the benefit of curative strategies including radical surgery for patients with potentially resectable RPN are warranted.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeat Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors: A NET Center of Excellence Experience.","authors":"Udhayvir S Grewal, Bradley T Loeffler, Alexander Paschke, Joseph S Dillon, Chandrikha Chandrasekharan","doi":"10.1007/s12029-024-01065-z","DOIUrl":"10.1007/s12029-024-01065-z","url":null,"abstract":"<p><strong>Introduction: </strong>The available data for the safety and efficacy of repeat peptide receptor radionuclide therapy (PRRT) are almost exclusively from European centers. We present an updated experience with repeat PRRT in a cohort of US patients with neuroendocrine tumors (NETs) at our NET center of excellence.</p><p><strong>Methods: </strong>We used our single-center longitudinal NET registry to identify patients who had been previously treated with at least one dose of PRRT (PRRT 1, either ¹⁷⁷Lu DOTATATE or ⁹⁰Y DOTATOC) and following radiographic disease progression were re-treated with a second course of PRRT (PRRT 2). We reviewed patient, tumor and treatment characteristics, objective response rates, and toxicities after PRRT 1 and PRRT 2.</p><p><strong>Results: </strong>A total of 11 patients were included in the analysis. 45.5% (5/11) of patients received ¹⁷⁷Lu DOTATATE PRRT only, both for PRRT1 and PRRT 2, while 54.5% (6/11) of patients received ⁹⁰Y DOTATOC PRRT for PRRT1. At first restaging scan after PRRT2 (3-6 months), 18.2% (2/11), 36.4% (4/11), and 27.3% (3/11) of patients had PR, SD, and PD, respectively; 2/11 patients (18.2%) died before the first restaging scan. Therefore, 5/11 (45.5%) patients were noted to have disease progression. Median PFS for PRRT1 was 25.4 months and median PFS for PRRT2 was 13.1 months (p = 0.0001). We did not find a statistically significant difference between the occurrence of short and long-term hematological toxicities as well as renal toxicity after PRRT1 and PRRT2.</p><p><strong>Conclusion: </strong>We show that repeat PRRT may benefit select patients and have an acceptable safety profile. In our cohort, PFS was significantly lower after PRRT2 as compared to PRRT1.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Clinical Efficacy and Quality of Life of Braun Anastomosis in Gastrointestinal Reconstruction in Totally Laparoscopic Distal Gastrectomy: A Single-Center Retrospective Study.","authors":"Yayan Fu, Jun Ren, Yue Ma, Jiajie Zhou, Wenzhe Shao, Guowei Sun, Qiannan Sun, Daorong Wang","doi":"10.1007/s12029-024-01079-7","DOIUrl":"10.1007/s12029-024-01079-7","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to compare the clinical efficacy and quality of life of B-IIB (Billroth-II with Braun anastomosis) and B-II (Billroth-II anastomosis) in the alimentary tract reconstruction postoperative totally laparoscopic distal gastrectomy (TLDG) for gastric cancer.</p><p><strong>Methods: </strong>From February 2016 to January 2022, 158 patients underwent totally laparoscopic distal gastrectomy and D2 lymphadenectomy in Northern Jiangsu People's Hospital, with Billroth-II with Braun anastomosis for 93 patients and Billroth-II anastomosis for 65 patients. The patients' data were collected prospectively and reviewed retrospectively.</p><p><strong>Results: </strong>In this study, the post-op hospital stay of B-IIB group were shorter than B-II group (12.70 ± 3.08 days in the B-IIB group versus 14.12 ± 4.90 days in the B-II group, p < 0.05) and the first post-op flatus time of the B-IIB group were shorter than B-II group (3.49 ± 1.02 days versus 4.08 ± 1.85 days, p < 0.05). Two groups did differ significantly in hemoglobin on postoperative 3 months, albumin at 3 months after operation, and serum sodium on postoperative 3 days and 3 months (p < 0.05), and the B-IIB had an advantage; the complications incidence (Clavien-Dindo grade II or even a higher grade) of the B-IIB group and B-II group were 10.75% and 29.23%, respectively. There being a statistical difference between the two groups. The B-IIB group and the B-II group both had different degrees of weight loss at 3 months after operation compared with preoperative weight. The weight of B-IIB group was 4.04 ± 1.33 kg, which was less than B-II group (8.08 ± 1.47 kg). The difference was statistically significant (p < 0.05). According to the PGSAS (Postgastrectomy Syndrome Assessment Scale), the score of the B-IIB group is lower than that of the B-II group for esophageal reflux gastritis, dyspepsia, and dumping syndrome group (1.84 ± 0.92 VS 2.15 ± 0.85, P = 0.031; 1.86 ± 1.10 VS 2.22 ± 0.91, P = 0.034; 1.98 ± 1.06 VS 2.32 ± 0.94, P = 0.037, respectively).</p><p><strong>Conclusion: </strong>Totally laparoscopic distal gastrectomy with Billroth-II Braun reconstruction is a safe and technically feasible method for gastric cancer patients, which can reduce the incidence of postoperative reflux esophagitis and dumping syndrome. Compared with Billroth-II reconstruction, it has advantages in maintaining postoperative nutritional status and electrolyte balance and improving quality of life.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Defense Mechanism Styles on Disease Progression in Patients with Gastrointestinal Cancer: Focusing on Clinical Staging.","authors":"Vahid Moazed, Daryoush Yousofi Zadeh, Amineh Jalali, Fatemeh Yahyazadeh Gooki, Zahra Karbakhsh Ravari","doi":"10.1007/s12029-024-01088-6","DOIUrl":"10.1007/s12029-024-01088-6","url":null,"abstract":"<p><strong>Background: </strong>The escalating incidence of cancer and the concurrent rise in mental health issues necessitate investigation into the potential for psychological factors to impede timely and effective treatment. This study examines the association between defense mechanism styles and disease progression, specifically focusing on clinical staging, in patients diagnosed with gastrointestinal (GI) cancer.</p><p><strong>Methods: </strong>Employing a descriptive correlational design, the study recruited 205 patients with GI cancer admitted to Javad Al-Aeme Hospital in Kerman, Iran, during the year 2022. Convenience sampling was utilized for participant selection. Data collection instruments included the Defense Style Questionnaire-40 (DSQ-40) and patients' documented clinical stage information. Correlation coefficients and ordinal logistic regression were employed for data analysis.</p><p><strong>Results: </strong>Over half of 205 GI cancer patients were female (53.2%). The majority were married (85.8%) with an average age of 53.86 ± 8.21 years. Nearly a quarter (23.9%) were in disease stage 1, with similar proportions in stages 2 (25.4%), 3 (27.3%), and 4 (23.4%). The findings revealed a significant inverse correlation between mature defense mechanism styles and clinical stage (r =  - 0.55, p < 0.001), indicating that patients who employed more adaptive defense mechanisms had lower-stage cancer. Conversely, a significant positive correlation was observed between immature defense mechanism styles and clinical stage (r =  - 0.49, p < 0.001), suggesting that patients who relied on less effective defense mechanisms had more advanced-stage cancer. However, no significant association was found between neurotic defense mechanism styles and clinical stage (r =  - 0.12, p = 0.079).</p><p><strong>Conclusions: </strong>This study provides preliminary evidence that defense mechanism styles are associated with disease progression in patients with GI cancer. Mature defense mechanisms may promote slower disease progression, while immature defense mechanisms may contribute to more advanced disease stages. Further research is needed to confirm these findings and develop interventions to improve psychological well-being in this patient population.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T Cell Therapy in Pancreatic and Biliary Tract Cancers: An Updated Review of Clinical Trials.","authors":"Konstantinos Drougkas, Konstantinos Karampinos, Ioannis Karavolias, Georgia Gomatou, Ioannis-Alexios Koumprentziotis, Ioanna Ploumaki, Efthymios Triantafyllou, Elias Kotteas","doi":"10.1007/s12029-024-01054-2","DOIUrl":"10.1007/s12029-024-01054-2","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic and biliary tract cancers are digestive system tumors with dismal prognosis and limited treatment options. The effectiveness of conventional surgical interventions, radiation therapy, and systemic therapy is restricted in these cases. Furthermore, clinical trials have shown that immunotherapy using immune checkpoint inhibitors has only demonstrated modest clinical results when applied to patients with pancreatobiliary tumors. This highlights the importance of implementing combination immunotherapy approaches or exploring alternative therapeutic strategies to improve treatment outcomes.</p><p><strong>Materials and methods: </strong>We reviewed the relevant literature on chimeric antigen receptor (CAR)-T cell therapy for pancreatobiliary cancers from PubMed/Medline and ClinicalTrials.gov and retrieved the relevant data accordingly. Attention was additionally given to the examination of grey literature with the aim of obtaining additional details regarding ongoing clinical trials. We mainly focused on abstracts and presentations and e-posters and slides of recent important annual meetings (namely ESMO Immuno-Oncology Congress, ESMO Congress, ASCO Virtual Scientific Program, ASCO Gastrointestinal Cancers Symposium).</p><p><strong>Results: </strong>CAR-T cell therapy has emerged as a promising and evolving treatment approach for pancreatic and biliary tract cancer. This form of adoptive cell therapy utilizes genetic engineering to modify the expression of specific antibodies on the surface of T cells enabling them to target specific cancer-associated antigens and to induce potent anti-tumor activity. The aim of this review is to provide an updated summary of the available evidence from clinical trials that have explored the application of CAR-T cell therapy in treating pancreatobiliary cancers.</p><p><strong>Conclusions: </strong>While the utilization of CAR-T cell therapy in pancreatobiliary cancers is still in its initial phases with only a limited amount of clinical data available, the field is advancing rapidly, incorporating novel technologies to mitigate potential toxicities and enhance antigen-directed tumor eradication.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Relationship Between KRAS, NRAS, and BRAF Mutations and Clinical Characteristics in Iranian Colorectal Cancer Patients.","authors":"Zahra Mosaferi, Majid Pirestani, Ehsan Arefian, Goli Gojani, Nastaran Kavousinasab, Parto Karimi, Azam Deilami, Zahra Abrehdari-Tafreshi","doi":"10.1007/s12029-024-01064-0","DOIUrl":"10.1007/s12029-024-01064-0","url":null,"abstract":"<p><strong>Background: </strong>Patients with colorectal cancer can benefit from anti-EGFR (epidermal growth factor receptor) therapy. However, this therapy is not effective for treating colorectal cancers with constitutive activating mutations in the KRAS, NRAS, and BRAF genes. Molecular analysis of tumor tissue frequently informs treatment decisions for colorectal cancer. This study aims to identify KRAS, NRAS, and BRAF mutations in Iranian patients diagnosed with colorectal cancer and to assess the prevalence of these mutations relative to the tumor differentiation stage within these populations.</p><p><strong>Methods: </strong>From April 2018 to December 2022, 2000 specimens from patients with colorectal cancer were collected. Data on sex, age, and tumor differentiation stage were recorded for all samples. For mutation detection, the KRAS and NRAS exons (2, 3, and 4) were amplified using the Diatech kit, and a specific primer was used to amplify BRAF exon 15. Pyrosequencing was then performed.</p><p><strong>Results: </strong>Analysis of samples revealed that 1105 specimens (55.3%) contained mutations in at least one of the screened genes. Among the genes studied, the highest occurrence was the KRAS mutation at 47.4%, followed by NRAS at 5.3% and BRAF at 2.7%. Most KRAS mutations were found in exon 2 (89.7%), with the G12D mutation being the most prevalent at 32% of cases. There was a significant difference in the rate of KRAS mutations in women (52.5%) compared to men (43.5%) (P =  0.02). For NRAS, the majority mutations were observed in exon 3 (76.2%), with the Q61H mutation being the most prevalent at 28.5% of cases. There were no significant associations between the clinicopathological parameters and mutations.</p><p><strong>Conclusion: </strong>The study's findings indicate a rising frequency of mutations in these genes in Iran, highlighting the need to screening mutations in the main exons of all three genes for effective colorectal cancer treatment strategies.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Influence of T Cell Marker Gene Expression on the Pathobiology and Clinical Prognostic Outcomes in Intestinal-Type Gastric Carcinoma.","authors":"Yixuan Chen, Wenbin Wang","doi":"10.1007/s12029-024-01104-9","DOIUrl":"10.1007/s12029-024-01104-9","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) poses a significant global health challenge. This study is aimed at elucidating the role of the immune system, particularly T cells and their subtypes, in the pathogenesis and progression of intestinal-type gastric carcinoma (GC), and at evaluating the predictive utility of a T cell marker gene-based risk score for overall survival.</p><p><strong>Methods: </strong>We performed an extensive analysis using single-cell RNA sequencing data to map the diversity of immune cells and identify specific T cell marker genes within GC. Pseudotime trajectory analysis was employed to observe the expression patterns of tumor-related pathways and transcription factors (TFs) at various disease stages. We developed a risk score using data from The Cancer Genome Atlas (TCGA) as a training set and validated it with the GSE15459 dataset.</p><p><strong>Results: </strong>Our analysis revealed distinct patterns of T cell marker gene expression associated with different stages of GC. The risk score, based on these markers, successfully stratified patients into high-risk and low-risk groups with significantly different overall survival prospects. High-risk patients exhibited poorer survival outcomes compared to low-risk patients (p < 0.05). Additionally, the risk score was capable of identifying patients across a spectrum from chronic atrophic gastritis to early GC.</p><p><strong>Conclusion: </strong>The findings enhance the understanding of the tumor immune microenvironment in GC and propose new immunotherapeutic targets. The T cell marker gene-based risk score offers a potential tool for gastroenterologists to tailor treatment plans more precisely according to the cancer's severity.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Salvage-line Nivolumab Monotherapy for Advanced Esophageal Squamous Cell Carcinoma: Comparison of 240 mg Versus 480 mg Doses.","authors":"Yuko Murashima, Shun Yamamoto, Toshiharu Hirose, Toru Kadono, Go Ikeda, Akihiro Ohara, Mai Itoyama, Kazuki Yokoyama, Yoshitaka Honma, Koshiro Ishiyama, Jyunya Oguma, Hiroyuki Daiko, Ken Kato","doi":"10.1007/s12029-024-01092-w","DOIUrl":"10.1007/s12029-024-01092-w","url":null,"abstract":"<p><strong>Background: </strong>Nivolumab monotherapy is the standard second-line treatment for advanced esophageal squamous cell carcinoma (ESCC) after failure of platinum-based chemotherapy without anti-PD-1 antibody. Fixed dosing with 240 mg every 2 weeks was approved initially, followed by fixed dosing with 480 mg every 4 weeks based on pharmacokinetics data. However, information on the comparative efficacy and safety of the two doses remains limited.</p><p><strong>Methods: </strong>We compared progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and the incidence of adverse events (AEs) between the two doses in 117 patients who received second-line (n = 85) or later-line (n = 32) nivolumab monotherapy at our institution between January 2016 and December 2021.</p><p><strong>Results: </strong>In the second-line group, patient characteristics for the 240 mg and 480 mg groups were as follows (240 mg vs. 480 mg): performance status (PS) 0/1/2 was 34/61/5% vs. 54/42/4%, and prior fluoropyrimidine plus platinum therapy (FP) was 81.3% vs. 42.3%. In the later-line group, the characteristics were: PS 0/1/2 was 28/60/12% vs. 14/86/0%, and prior FP was 60.0% vs. 42.8%. ORR was 11.9 vs. 24.0% in the second-line group (p = 0.19) and 0 vs. 14.3% in the later-line group (p = 0.22). Median PFS was 1.7 vs. 4.1 months on second-line (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.35-1.01, p = 0.056) and 1.4 vs. 1.8 months on later-line (HR 0.58, 95% CI 0.23-1.46, p = 0.25); AEs of any grade were observed in 58.3 vs. 69.7%, respectively.</p><p><strong>Conclusions: </strong>The efficacy and safety of the two doses of nivolumab monotherapy were comparable in patients with advanced ESCC.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Changes in Circulating Methylated Markers in Response to Antitumor Therapy of Rectal Cancer.","authors":"Anastasia A Ponomaryova, Elena Yu Rykova, Anastasia I Solovyova, Anna S Tarasova, Dmitry N Kostromitsky, Alexey Yu Dobrodeev, Sergey A Afanasiev, Nadezhda V Cherdyntseva","doi":"10.1007/s12029-024-01066-y","DOIUrl":"10.1007/s12029-024-01066-y","url":null,"abstract":"<p><strong>Background: </strong>Rectal cancer (RC) occupies a leading position in the structure of oncological morbidity and mortality. Aberrant methylation of tumor-suppressor genes and hypomethylation of retrotransposons were shown to be detectable in cell-free DNA, circulating in the blood (cfDNA) of cancer patients, indicating the possibility to use them as diagnostic and prognosis markers.</p><p><strong>Purpose: </strong>Evaluation of the changes in the methylation level of LINE-1 elements and SEPTIN9 and IKZF1 genes in the cell-surface-bound cfDNA (csb-cfDNA) from the blood of RC patients after antitumor therapy at a long-term follow-up.</p><p><strong>Methods: </strong>Blood samples were obtained from RC patients (n = 25) before treatment, after preoperative chemotherapy (3 courses according to the XELOX scheme), 10-15 days after surgery, and every 3 months during 12 months of dynamic observation. The methylation level of LINE-1, SEPTIN9, and IKZF1 in the csb-cfDNA was evaluated by quantitative methyl-specific PCR.</p><p><strong>Results: </strong>The LINE-1 methylation level in the csb-cfDNA increased 1.6 times in RC patients after chemotherapy and 3 times after tumor resection versus methylation level before therapy. The SEPTIN9 gene methylation level in the csb-cfDNA decreased by 1.7 times in RC patients after chemotherapy and by 2.3 times after tumor resection compared with the values before the treatment. The IKZF1 gene methylation level decreased by 2 times in RC patients after combined therapy. Notably, all patients with relapses (n = 5) showed an increase in methylation level for the SEPTIN9 and IKZF1 genes and a decrease of methylation level for the LINE-1 elements by 2 times or more in comparison with the level 10-15 days after surgery. There were no changes in the circulating SEPTIN9, IKZF1, and LINE-1 methylation levels during the 12-month follow-up period after the combined therapy of RC patients (n = 20) without relapses.</p><p><strong>Conclusion: </strong>The results indicate that SEPTIN9, IKZF1, and LINE-1 methylation levels in the csb-cfDNA are potential markers of the effectiveness of antitumor therapy and early detection of relapse in RC patients.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}