Therapeutic Advances in Medical Oncology最新文献

{"title":"Early stereotactic body radiation therapy improves progression-free survival of first-generation EGFR tyrosine kinase inhibitors in EGFR-mutated lung cancer: an observational cohort study.","authors":"Hailing Xu, Rongbin Qi, Chao Zhou, Yingying Yu, Ling Lin, Xiaomai Wu, Dongqing Lv","doi":"10.1177/17588359241290133","DOIUrl":"10.1177/17588359241290133","url":null,"abstract":"<p><strong>Background: </strong>Stereotactic body radiation therapy (SBRT) in treating non-small-cell lung cancer (NSCLC) exhibits a remarkable therapeutic efficacy. However, its effectiveness in overcoming resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced EGFR mutations (EGFRm) NSCLC remains uncertain.</p><p><strong>Objective: </strong>We aimed to analyze the effect of SBRT on patients with first-line EGFR-TKIs.</p><p><strong>Design and methods: </strong>Eligible patients with advanced NSCLC initially diagnosed with EGFRm were enrolled. Patients in the EGFR-TKIs group received only the first-generation EGFR-TKIs until disease progression or death, while the others in the EGFR-TKIs + SBRT group received EGFR-TKIs and early SBRT (dose of 40-60 Gy/5-8 F) targeting the primary lung tumor at 1 month after EGFR-TKIs. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were treatment-related adverse effects, overall survival (OS), and sites of initial failure.</p><p><strong>Results: </strong>A total of 184 advanced NSCLC patients with EGFRm were enrolled, including 39 patients in the EGFR-TKIs + SBRT group and 145 patients in the EGFR-TKIs group. The median PFS was 15.50 months in the EGFR-TKIs + SBRT group compared to 9.33 months in the EGFR-TKIs group (<i>p</i> = 0.0020). However, the median OS was 29.10 months in the EGFR-TKIs + SBRT group and 26.33 months in the EGFR-TKIs group, with no significant difference observed (<i>p</i> = 0.22). SBRT is an independent positive prognostic factor for PFS in advanced EGFRm NSCLC. EGFR exon 19 deletion mutation (16.33 vs 11.55 months, <i>p</i> = 0.0087) and fewer metastases (0-5) (31.94 vs 9.59 months, <i>p</i> = 0.0059) were associated with improved PFS in EGFR-TKIs + SBRT versus EGFR-TKIs. Combination therapy increased radiation pneumonitis mainly in Grades 1-2 (89.74% vs 0.0%). The EGFR-TKIs + SBRT group mainly had new site failure (57.10% vs 32.10%) rather than the original site failure.</p><p><strong>Conclusion: </strong>Early SBRT for primary lung tumors may overcome targeted resistance in advanced EGFRm NSCLC patients combined with EGFR-TKIs without serious toxicities, especially for EGFR exon 19-del.</p><p><strong>Trial registration: </strong>ChiCTR-OIN-17013920.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241290133"},"PeriodicalIF":4.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583631","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":"The role of baseline ¹⁸F-FDG PET/CT for survival prognosis in NSCLC patients undergoing immunotherapy: a systematic review and meta-analysis.","authors":"Mingxing Huang, Yuheng Zou, Weichen Wang, Qianrui Li, Rong Tian","doi":"10.1177/17588359241293364","DOIUrl":"10.1177/17588359241293364","url":null,"abstract":"<p><strong>Background: </strong>The value of pretreatment baseline ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET)/computed tomography (CT) as a prognostic factor for survival of patients with non-small-cell lung cancer (NSCLC) receiving immunotherapy remained uncertain.</p><p><strong>Objectives: </strong>To investigate the prognostic ability of baseline ¹⁸F-FDG PET/CT in patients with NSCLC receiving immunotherapy.</p><p><strong>Design: </strong>A systematic review and meta-analysis.</p><p><strong>Data sources and methods: </strong>We searched the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases until May 7, 2024, and extracted data related to patient characteristics, semiquantitative parameters of ¹⁸F-FDG PET/CT, and survival. We pooled hazard ratios (HRs) to evaluate the prognostic value of the maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for overall survival (OS) and progression-free survival (PFS).</p><p><strong>Results: </strong>A total of 22 studies (1363 patients, average age range 30-88 years) were included. Baseline ¹⁸F-FDG PET/CT-derived MTV was significantly associated with both OS (HR: 1.124, 95% confidence interval (CI) 1.058-1.195, <i>I</i> ² = 81.70%) and PFS (HR: 1.069, 95% CI: 1.016-1.124, <i>I</i> ² = 71.80%). Other baseline ¹⁸F-FDG PET/CT-derived parameters, including SUV_max (OS: HR: 0.930, 95% CI: 0.718-1.230; PFS: HR: 0.979, 95% CI: 0.759-1.262), SUV_mean (OS: HR: 0.801, 95% CI: 0.549-1.170; PFS: HR: 0.688, 95% CI: 0.464-1.020), and TLG (OS: HR: 0.999, 95% CI: 0.980-1.018; PFS: HR: 0.995, 95% CI: 0.980-1.010), were not associated with survival. Sensitivity analyses by removing one study at a time did not significantly alter the association between MTV and PFS or between MTV and OS. There was no evidence of publication bias.</p><p><strong>Conclusion: </strong>Pretreatment baseline ¹⁸F-FDG PET/CT-derived MTV might be a prognostic biomarker in NSCLC patients receiving immunotherapy. Further studies are needed to support routine use.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241293364"},"PeriodicalIF":4.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583741","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":"Unveiling the prognostic significance of malignant ascites in advanced gastrointestinal cancers: a marker of peritoneal carcinomatosis burden.","authors":"Leonardo Provenzano, Yong Xiang Gwee, Veronica Conca, Sara Lonardi, Silvia Bozzarelli, Emiliano Tamburini, Alessandro Passardi, Alberto Zaniboni, Federica Tosi, Giuseppe Aprile, Vincenzo Nasca, Alessandra Boccaccino, Margherita Ambrosini, Guglielmo Vetere, Martina Carullo, Marcello Guaglio, Luigi Battaglia, Joseph Jonathan Zhao, Daryl Kai Ann Chia, Wei Peng Yong, Patrick Tan, Jimmy So, Guowei Kim, Asim Shabbir, Chin-Ann Johnny Ong, Francesco Casella, Chiara Cremolini, Maria Bencivenga, Raghav Sundar, Filippo Pietrantonio","doi":"10.1177/17588359241289517","DOIUrl":"10.1177/17588359241289517","url":null,"abstract":"<p><strong>Background: </strong>Ascites is common in advanced gastrointestinal cancers with peritoneal metastases (PM) and negatively impacts patient survival. No study to date has specifically evaluated the relationship between ascites, PM and survival outcomes in metastatic colorectal cancer (mCRC) and metastatic gastric cancer (mGC).</p><p><strong>Objectives: </strong>This study aims to investigate and elucidate the relationship between malignant ascites, PM and survival outcomes in both mCRC and mGC patients.</p><p><strong>Design: </strong>This is a retrospective analysis of prospectively collected clinical trial data of mCRC and mGC patients with PM.</p><p><strong>Methods: </strong>We performed two pooled analyses, firstly of two Italian randomized trials enrolling patients with mCRC eligible for systemic therapy (TRIBE2; VALENTINO), and secondly of gastric cancer and peritoneal metastasis (GCPM) patients who underwent bi-directional therapeutic treatment comprising systemic and peritoneal-directed therapies.</p><p><strong>Results: </strong>Of 900 mCRC patients, 39 (4.3%) had PM with malignant ascites. Compared to the group without PM, median progression-free and overall survival were significantly inferior in the ascites group (hazard ratio (HR) for progression-free survival (PFS) 1.68, 95% confidence interval (CI): 1.21-2.35, <i>p</i> = 0.007; HR for overall survival (OS) 2.14, 95% CI: 1.57-3.01, <i>p</i> < 0.001), but not in the group of PM without ascites (HR for PFS 1.10, 95% CI: 0.91 - 1.34; HR for OS 1.04, 95% CI: 0.84 - 1.30). Of 170 patients with GCPM, those with ascites had higher median Peritoneal Cancer Index scores (23 vs 9, <i>p</i> < 0.001). Median OS was significantly inferior among those with ascites compared to those without (13.0 vs 21.0 months, HR 1.71, 95% CI: 1.16-2.52, <i>p</i> = 0.007).</p><p><strong>Conclusion: </strong>Ascites identifies a subgroup of patients with PM and poor outcomes, for whom tailored research are needed.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241289517"},"PeriodicalIF":4.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583952","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":"Exploratory analysis of immunomodulatory factors identifies L1CAM as a prognostic marker in alveolar soft-part sarcoma.","authors":"José L Mondaza-Hernandez, Nadia Hindi, Antonio Fernandez-Serra, Rafael Ramos, Ricardo Gonzalez-Cámpora, María Carmen Gómez-Mateo, Javier Martinez-Trufero, Javier Lavernia, Antonio Lopez-Pousa, Nuria Laínez, Jeronimo Martinez-Garcia, Claudia Valverde, María Ángeles Vaz-Salgado, Gabriel Garcia-Plaza, Isabel Marin-Borrero, Jaime Carrillo-Garcia, Marta Martin-Ruiz, Pablo Romero, Antonio Gutierrez, Jose A López-Guerrero, David S Moura, Javier Martin-Broto","doi":"10.1177/17588359241293951","DOIUrl":"10.1177/17588359241293951","url":null,"abstract":"<p><strong>Background: </strong>Alveolar soft-part sarcoma (ASPS) is a rare tumor driven by the ASPSCR1-TFE3 fusion protein, with a propensity for metastasis. Prognostic factors remain poorly understood, and traditional chemotherapies are largely ineffective. Recent interest lies in immune checkpoint inhibitors (ICIs), yet predictive biomarkers for treatment response are lacking. Previous studies have shown promising results with ICIs in ASPS, indicating a need for further investigation into biomarkers associated with immune response.</p><p><strong>Objectives: </strong>To identify prognostic biomarkers in ASPS and to explore the role of immune-related markers, particularly L1CAM, in predicting patient outcomes.</p><p><strong>Design: </strong>A retrospective cohort study of 19 ASPS patients registered in the GEIS database. The study involved the collection of clinical and histopathological data, followed by an analysis of immune markers and gene expression profiles to identify potential prognostic indicators.</p><p><strong>Methods: </strong>Clinical and histopathological data were retrospectively collected from the GEIS-26 study cohort of 19 ASPS patients. Immunohistochemistry was performed to evaluate immune markers programmed death-1 ligand (PD-L1), programmed death-1, FAS, FASL, CD8, CD3, and CD4. An HTG ImmunOncology panel was conducted on formalin-fixed paraffin-embedded samples to explore gene expression. Effects of differentially expressed genes on survival were explored by Kaplan-Meier.</p><p><strong>Results: </strong>PD-L1 positivity was widely observed (63%) in tumors, and CD8+ lymphocytic infiltration was common. High CD8 density correlated with greater overall survival (OS) while not statistically significant. No associations were found for other immune markers. <i>L1CAM</i> was identified as differentially expressed in patients with low CD8 infiltration and correlated negatively with OS.</p><p><strong>Conclusion: </strong>High <i>L1CAM</i> expression correlated with poorer OS, highlighting its potential as a prognostic marker and therapeutic target in ASPS. Immunomodulatory interventions may hold promise, as evidenced by PD-L1 expression and CD8+ infiltration. Further research, including larger cohorts and international collaborations, is needed to validate these findings and explore therapeutic strategies targeting <i>L1CAM</i> in ASPS.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241293951"},"PeriodicalIF":4.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583636","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":"Second-line treatment of PD-1 and CTLA-4 blockade combined with liposomal irinotecan plus leucovorin and fluorouracil for advanced cholangiocarcinoma: study protocol of a single-arm, prospective phase II trial.","authors":"Heqi Yang, Linjuan Li, Xiaofen Li, Yuhang Ma, Yu Yang, Dan Cao","doi":"10.1177/17588359241292264","DOIUrl":"10.1177/17588359241292264","url":null,"abstract":"<p><strong>Background: </strong>Cholangiocarcinoma is a kind of malignant tumor that originates in the epithelium of the biliary tract. Although there are several options for second-line treatment for patients without specific genetic mutations, the overall treatment efficacy is disappointing. Second-line treatment which is composed of liposomal irinotecan plus fluorouracil and leucovorin significantly improved the treatment efficacy for advanced biliary tract cancer and extended patient survival. This study aims to evaluate the efficacy and safety of the combination of cadonilimab with liposomal irinotecan plus fluorouracil and leucovorin for advanced biliary tract cancer.</p><p><strong>Objectives: </strong>The primary objective of this study is to determine the objective response rate. The second objectives of this study are overall survival, progression-free survival, disease control rate, and adverse event incidence rate.</p><p><strong>Design: </strong>The study is a single-arm, prospective phase II clinical trial. In all, 51 patients who are diagnosed with locally advanced or metastatic bile tract cancer will be enrolled.</p><p><strong>Methods and analysis: </strong>Eligible participants will receive cadonilimab at a dosage of 6 mg/kg on day 1 of each 21-day cycle combined with intravenous liposomal irinotecan at a dosage of 70 mg/m² for 90 min on day 1 plus leucovorin at a dosage of 400 mg/m² for 30 min on day 1 and fluorouracil at a dosage of 400 mg/m² for 46 h every 2 weeks.</p><p><strong>Discussion: </strong>Previous studies have suggested that there is a synergistic effect between the two treatment modalities. However, the potential of cadonilimab in bile tract cancer has not been explored. Hence, this trial is the first to investigate its efficacy and toxicity. In addition, the trial is also willing to explore potential biomarkers in patients with locally advanced and metastatic bile tract cancer.</p><p><strong>Trial registration: </strong>This study was registered on ClinicalTrials.gov with NCT06438822.</p><p><strong>Ethics: </strong>This study protocol and amendments have been approved by the Ethics Committee of West China Hospital (2024(791)).</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241292264"},"PeriodicalIF":4.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569710","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":"Pre-treatment pan-immune-inflammation value as a prognostic marker of pazopanib in soft tissue sarcoma.","authors":"Cheng-Han Wu, Cheng-Lun Lai, Yong-Chen Hsu, Chiann-Yi Hsu, Yu-Chao Wang, Hsin-Chen Lin","doi":"10.1177/17588359241292255","DOIUrl":"10.1177/17588359241292255","url":null,"abstract":"<p><strong>Background: </strong>Increasingly, more evidence has shown that inflammation stress and the tumor microenvironment pose a negative effect on targeted therapy. The neutrophil-to-lymphocyte ratio is considered to be a surrogate biomarker of inflammation and can predict pazopanib treatment effect in non-adipocytic soft-tissue sarcoma (STS). The role of the pan-immune-inflammation value (PIV) in STS is still yet to be determined.</p><p><strong>Objectives: </strong>We sought whether the pre-treatment PIV could be applied to predict the response of pazopanib in STS.</p><p><strong>Design: </strong>We conducted a retrospective analysis of 75 patients who had been treated with pazopanib for recurrent or metastatic non-adipocytic STS.</p><p><strong>Methods: </strong>Our cohort was stratified into either a pre-treatment high PIV group with PIV ⩾310 (<i>n</i> = 45) or a low PIV group with PIV <310 (<i>n</i> = 30). We compared their clinical features and outcomes. Cox regression analysis was employed to determine the risk factors of disease progression and mortality. Kaplan-Meier survival curves were utilized to assess both the progression-free survival (PFS) and overall survival (OS).</p><p><strong>Results: </strong>The results revealed that a pre-treatment high PIV (⩾310) is a risk factor for progression under pazopanib (hazard ratio: 1.91; 95% confidence interval: 1.08-3.36; <i>p</i> = 0.025). The median PFS and OS of the pre-treatment high PIV group were found to be significantly lower than the low PIV group (0.33 vs 0.75 years; <i>p</i> = 0.023, 0.46 vs 1.63 years; <i>p</i> = 0.025).</p><p><strong>Conclusion: </strong>High pre-treatment PIV in STS patients may indicate an elevated risk of disease progression and mortality. Pre-treatment PIV reflects inflammation stress and acts as a practical biomarker for STS patients treated with pazopanib.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241292255"},"PeriodicalIF":4.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of the <i>TP53</i> mutation in patients with pancreatic ductal adenocarcinoma receiving FOLFIRINOX.","authors":"Min Kyu Kim, In Rae Cho, Yooeun Kim, Jin Ho Choi, Kwangrok Jung, Jaihwan Kim, Sheehyun Kim, Hongseok Yun, Jeesun Yoon, Do-Youn Oh, Kwangsoo Kim, Sang Hyub Lee","doi":"10.1177/17588359241290482","DOIUrl":"https://doi.org/10.1177/17588359241290482","url":null,"abstract":"<p><strong>Background: </strong><i>KRAS</i>, <i>TP53</i>, <i>CDKN2A</i>, and <i>SMAD4</i> have been the main driver mutations in pancreatic ductal adenocarcinoma (PDAC). Studies on the clinical significance and treatment response to 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) regimen in terms of the presence of these mutations remain inconclusive.</p><p><strong>Objectives: </strong>This study aimed to compare the survival outcome and response to FOLFIRINOX chemotherapy based on the presence of four driver mutation genes.</p><p><strong>Design: </strong>A multi-center retrospective study conducted at two tertiary medical centers.</p><p><strong>Methods: </strong>This study analyzed PDAC patients who were treated with FOLFIRINOX chemotherapy as the initial treatment. Tumor specimens were analyzed by a targeted next-generation sequencing platform at two tertiary referral hospitals from January 2016 to March 2022. Patients' demographics, survival outcomes, and chemotherapeutic response were investigated and compared according to the presence of driver mutations.</p><p><strong>Results: </strong>The analysis included 100 patients. <i>KRAS</i> mutation was identified in 92 (92.0%) patients, followed by <i>TP53</i>, <i>CDKN2A</i>, and <i>SMAD4</i> in 63 (63.0%), 18 (18.0%), and 17 (17.0%) patients, respectively. The <i>TP53</i> wild-type group demonstrated longer overall survival (OS) than the <i>TP53</i> mutated group (median OS: 29 vs 19 months, <i>p</i> = 0.03), and <i>TP53</i> served as a prognostic factor for survival (hazard ratio = 1.74, 95% confidence interval: 1.00-3.00, <i>p</i> = 0.048). The difference in OS according to <i>TP53</i> mutation was intensified in localized pancreatic adenocarcinoma (37 vs 19 months, <i>p</i> = 0.01). The <i>TP53</i> wild-type group demonstrated a higher objective response rate to FOLFIRINOX chemotherapy than the <i>TP53</i> mutation group in localized pancreatic adenocarcinoma (50.0% vs 17.6%, <i>p</i> = 0.024).</p><p><strong>Conclusion: </strong>PDAC patients with wild-type <i>TP53</i> demonstrated longer OS than those with <i>TP53</i> mutation, and this trend was intensified in patients with localized disease. This result may be due to an impaired response to FOLFIRINOX chemotherapy in patients with <i>TP53</i> mutation.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241290482"},"PeriodicalIF":4.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508536","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":"Deciphering HER2-low breast cancer (BC): insights from real-world data in early stage breast cancer.","authors":"Anna Pous, Adrià Bernat-Peguera, Assumpció López-Paradís, Beatriz Cirauqui, Vanesa Quiroga, Iris Teruel, Eudald Felip, Angelica Ferrando-Díez, Milana Bergamino, Laia Boronat, Margarita Romeo, Gemma Soler, Christian Mariño, Paula Rodríguez-Martínez, Laura Pons, Ester Ballana, Anna Martinez-Cardús, Mireia Margelí","doi":"10.1177/17588359241290720","DOIUrl":"https://doi.org/10.1177/17588359241290720","url":null,"abstract":"<p><strong>Background: </strong>Human epidermal growth factor receptor 2 (HER2)-low has emerged as a potential new entity in breast cancer (BC). Data on this subset are limited, and prognostic results are controversial, evidencing the need of further data in a BC real-world cohort.</p><p><strong>Methods: </strong>Patients with HER2-negative stage I-III BC diagnosed between 2006 and 2016 were retrospectively reviewed in a single cohort from the Catalan Institute of Oncology Badalona. Demographics and clinicopathological characteristics were examined via medical charts/electronic health records. We aim to describe and compare HER2-0/HER2-low populations through Chi-square or Fisher test, and explore its prognostic impact using Kaplan-Meier curves and Cox regression models.</p><p><strong>Results: </strong>From a cohort of 1755 BC patients, 1401 invasive HER2-negative, stage I-III cases were evaluated. 87% were hormone receptor (HR)-positive versus 13% triple negative (TNBC). Overall, 43% were HER2-0 and 57% HER2-low (61% immunohistochemistry (IHC) 1+ and 39% IHC 2+). Comparing HER2-low versus HER2-0, HER2-low showed higher proportion of estrogen receptor (ER)-positive (91.6% vs 79.9%, <i>p</i> ⩽ 0.001) and progesterone receptor (PR)-positive (79.8% vs 68.9%, <i>p</i> ⩽ 0.001) cases. HER2-0 exhibited higher proportion of TNBC (20.1% vs 8.4%, <i>p</i> = 0.001), grade III tumors (28.8% vs 23.5%, <i>p</i> = 0.039), and higher Ki67 median value (26.47% vs 23.88%, <i>p</i> = 0.041). HER2-low was associated with longer time to distant recurrence (TTDR) compared to HER2-0 (67.8 vs 54.1 months; <i>p</i> = 0.015) and better BC-related survival (19.2 vs 16.3 years; <i>p</i> = 0.033). In the multivariable analysis, HER2-low was not an independent prognostic factor for TTDR and BC-related survival. ER expression showed a strong association with longer TTDR (Hazard Ratio: 0.425, <i>p</i> ⩽ 0.001) and improved BC-related survival (Hazard Ratio: 0.380, <i>p</i> ⩽ 0.001). PR expression was also associated with longer TTDR (Hazard Ratio: 0.496, <i>p</i> ⩽ 0.001), and improved BC-related survival (Hazard Ratio: 0.488, <i>p</i> ⩽ 0.001). Histological grade III was significantly associated with shorter TTDR (Hazard Ratio: 1.737, <i>p</i> = 0.002). Positive nodal status was the strongest factor correlated with worse BC-related survival (Hazard Ratio: 2.747, <i>p</i> ⩽ 0.001).</p><p><strong>Conclusion: </strong>HER2-low was significantly associated with HR-positive disease, whereas HER2-0 group had higher incidence of TNBC, histological grade III and higher Ki67%. Although HER2-low group was associated with longer TTDR and improved BC-related survival, these findings could be explained by the greater proportion of favorable prognostic features in this subgroup compared to HER2-0.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241290720"},"PeriodicalIF":4.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508534","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":"Abemaciclib combined with endocrine therapy as adjuvant treatment for hormone-receptor-positive, HER2-, high-risk early breast cancer: 5-year Chinese population analysis of the phase III randomized monarchE study.","authors":"Qingyuan Zhang, Kunwei Shen, Chuan-Gui Song, Quchang Ouyang, Zhenzhen Liu, Qiang Liu, Jifeng Feng, Joanne W Y Chiu, Jinhai Tang, Zefei Jiang, Ling-Ming Tseng, Xiaojia Wang, Liu Yang, Chenxi Qian, Zhimin Shao","doi":"10.1177/17588359241286775","DOIUrl":"10.1177/17588359241286775","url":null,"abstract":"<p><strong>Background: </strong>Abemaciclib was the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor approved globally in the adjuvant setting for high-risk hormone-receptor positive (HR+)/human epidermal growth factor 2 negative (HER2-) early breast cancer (EBC), based on the phase III monarchE trial.</p><p><strong>Objective: </strong>To report an exploratory Chinese population analysis based on the preplanned overall survival (OS) interim analysis with 5-year efficacy results of monarchE.</p><p><strong>Design and methods: </strong>Patients with HR+/HER2-, high-risk (⩾4 positive lymph nodes, or 1-3 nodes and either tumor size ⩾5 cm, histologic grade 3, or Ki-67 ⩾20%) EBC were randomized (1:1) to abemaciclib (150 mg twice daily for 2 years) plus endocrine therapy (ET), or ET alone. This analysis included Chinese patients enrolled in mainland China, Hong Kong, and Taiwan. The primary endpoint was invasive disease-free survival (IDFS); key secondary endpoints included distant relapse-free survival (DRFS), safety, and patient-reported outcomes (PROs).</p><p><strong>Results: </strong>Overall, 501 Chinese patients were included (abemaciclib + ET, <i>n</i> = 259; ET, <i>n</i> = 242). With a median follow-up of 53 months, the addition of abemaciclib to ET resulted in improvements in IDFS (estimated 5-year IDFS rate: 85.9% vs 79.1%; hazard ratio (HR), 0.65 (95% confidence interval (CI) 0.41-1.03)) and DRFS (estimated 5-year DRFS rate: 88.4% vs 82.3%; HR, 0.65 (95% CI, 0.39-1.07)). The most common grade ⩾3 treatment-emergent adverse events in the abemaciclib + ET versus ET groups were neutropenia (24.7% vs 0.8%) and leukopenia (22.4% vs 0.4%). Generally, no clinically meaningful difference in PROs (endocrine symptoms and fatigue) was observed between groups, except for diarrhea.</p><p><strong>Conclusion: </strong>At this prespecified OS interim analysis, which provides 5-year data, the addition of abemaciclib to ET in Chinese patients with high-risk HR+, HER2- EBC was associated with sustained and clinically meaningful improvements in IDFS and DRFS, with acceptable safety and tolerability profiles and minimal impact on PROs. These results represent the first full report of a CDK4/6 inhibitor in Chinese patients with EBC and support the positive benefit-risk profile of adjuvant abemaciclib + ET in Chinese patients.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03155997 (first posted: May 16, 2017).</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241286775"},"PeriodicalIF":4.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508532","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 biopsy-based Immunoscore in patients with treatment-naïve resectable gastric cancer.","authors":"Tanya T D Soeratram, Isis Beentjes, Jacqueline M P Egthuijsen, Aart Mookhoek, Marilyne M Lange, Elma Meershoek-Klein Kranenbarg, Henk H Hartgrink, Cornelis J H van de Velde, Bauke Ylstra, Hanneke W M van Laarhoven, Nicole C T van Grieken","doi":"10.1177/17588359241287747","DOIUrl":"https://doi.org/10.1177/17588359241287747","url":null,"abstract":"<p><strong>Background: </strong>The prognostic significance of T-cell densities in gastric cancer (GC) was previously demonstrated in surgical resection specimens. For prognosis or response prediction, it is preferable to identify biomarkers in pre-treatment biopsies; yet, its representativeness of the tumor immune microenvironment is unclear.</p><p><strong>Objectives: </strong>This study aimed to evaluate the concordance and prognostic value of T-cell densities in paired biopsies and resections.</p><p><strong>Methods: </strong>Paired diagnostic biopsies and surgical resections were available for 131 patients with resectable GC who were treated with surgery alone in the D1/D2 trial. T-cell markers such as CD3, CD45RO, CD8, FOXP3, and Granzyme B were assessed by immunohistochemistry and digitally quantified. Tumors were categorized into high and low subgroups for each marker. The concordance between biopsies and resections was determined for each marker with Cohen's κ. To determine the prognostic value of T cells in biopsies, Cox regression was performed.</p><p><strong>Results: </strong>The concordance of T-cell high and low tumors was moderate for CD8 (κ = 0.58) and weak for other markers (κ < 0.3). CD8 and FOXP3 densities in biopsies were significantly associated with cancer-specific survival. Multivariable analysis showed that an Immunoscore incorporating CD8 and FOXP3 served as an independent prognostic marker (low vs high: hazard ratio 3.40, 95% confidence interval: 1.27-9.10; <i>p</i> = 0.015).</p><p><strong>Conclusion: </strong>Although the concordance in T-cell densities between biopsy and resection specimens is modest, a biopsy-based Immunoscore identified distinct biological subgroups with prognostic potential. To fully evaluate the prognostic performance of this biopsy Immunoscore, additional studies are warranted.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241287747"},"PeriodicalIF":4.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508531","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}