Background: Large type 3 (diameter ≥ 8 cm) and type 4 gastric cancers have been arbitrarily combined in Japan as a single entity. However, whether these two types are oncologically similar remain unclear. This study aimed to clarify this issue.
Methods: In this retrospective study, we analyzed a database of 3,575 patients from nine institutions who underwent gastrectomy between 2010 and 2014. Using propensity scores to balance significant variables, we compared prognoses and tumor recurrences.
Results: Of patients with clinical T3/T4 who underwent R0 resection, 75 and 73 had large type 3 and 4 tumors, respectively. Patients with type 4 tumors had significantly lower overall survival rates than those of patients with large type 3 tumors (hazard ratio [HR] 1.77; 95% confidence interval [CI] 1.14-2.74). However, among the large type 3 tumors, a remarkable difference in prognosis was observed between the differentiated and undifferentiated histological types. A comparison was made between large type 3 with undifferentiated phenotype and type 4, each with 39 patients after propensity score matching. Outcomes in both groups were similar in terms of overall survival (HR 1.28; 95% CI 0.73-2.25) and relapse-free survival (HR 1.34; 95% CI 0.80-2.27). No statistically significant differences were observed in the incidence of peritoneal recurrence (35.9% vs. 46.1%, P = 0.36) and lymph node recurrence (25.6% vs. 12.8%, P = 0.15).
Conclusions: Large type 3 tumors with undifferentiated phenotype and type 4 tumors were oncologically similar. This subgroup could be considered as a new entity for future clinical trials.
背景:在日本,大型 3 型(直径≥ 8 厘米)和 4 型胃癌被任意合并为一个实体。然而,这两种类型在肿瘤学上是否相似仍不清楚。本研究旨在澄清这一问题:在这项回顾性研究中,我们分析了来自九家医疗机构、在 2010 年至 2014 年间接受胃切除术的 3575 名患者的数据库。利用倾向评分平衡重要变量,我们比较了预后和肿瘤复发情况:在接受R0切除术的临床T3/T4患者中,分别有75人和73人患有3型和4型大肿瘤。4型肿瘤患者的总生存率明显低于3型大肿瘤患者(危险比[HR]1.77;95%置信区间[CI]1.14-2.74)。不过,在大型 3 型肿瘤中,分化型和未分化型组织学类型的预后差异明显。经过倾向评分匹配后,对具有未分化表型的大型3型肿瘤和4型肿瘤进行了比较,每组各有39名患者。两组患者的总生存期(HR 1.28;95% CI 0.73-2.25)和无复发生存期(HR 1.34;95% CI 0.80-2.27)结果相似。腹膜复发率(35.9% vs. 46.1%,P = 0.36)和淋巴结复发率(25.6% vs. 12.8%,P = 0.15)无统计学差异:结论:具有未分化表型的大型3型肿瘤与4型肿瘤在肿瘤学上相似。结论:表型未分化的大型3型肿瘤与4型肿瘤在肿瘤学上相似,可将这一亚组视为未来临床试验的新实体。
{"title":"Oncological similarities between large type 3 and type 4 tumors in patients with resectable gastric cancer: a propensity score-matched analysis of a multi-institutional dataset.","authors":"Koki Nakanishi, Mitsuro Kanda, Seiji Ito, Yoshinari Mochizuki, Hitoshi Teramoto, Kiyoshi Ishigure, Toshifumi Murai, Takahiro Asada, Akiharu Ishiyama, Hidenobu Matsushita, Dai Shimizu, Chie Tanaka, Michitaka Fujiwara, Kenta Murotani, Yasuhiro Kodera","doi":"10.1007/s10120-024-01546-x","DOIUrl":"10.1007/s10120-024-01546-x","url":null,"abstract":"<p><strong>Background: </strong>Large type 3 (diameter ≥ 8 cm) and type 4 gastric cancers have been arbitrarily combined in Japan as a single entity. However, whether these two types are oncologically similar remain unclear. This study aimed to clarify this issue.</p><p><strong>Methods: </strong>In this retrospective study, we analyzed a database of 3,575 patients from nine institutions who underwent gastrectomy between 2010 and 2014. Using propensity scores to balance significant variables, we compared prognoses and tumor recurrences.</p><p><strong>Results: </strong>Of patients with clinical T3/T4 who underwent R0 resection, 75 and 73 had large type 3 and 4 tumors, respectively. Patients with type 4 tumors had significantly lower overall survival rates than those of patients with large type 3 tumors (hazard ratio [HR] 1.77; 95% confidence interval [CI] 1.14-2.74). However, among the large type 3 tumors, a remarkable difference in prognosis was observed between the differentiated and undifferentiated histological types. A comparison was made between large type 3 with undifferentiated phenotype and type 4, each with 39 patients after propensity score matching. Outcomes in both groups were similar in terms of overall survival (HR 1.28; 95% CI 0.73-2.25) and relapse-free survival (HR 1.34; 95% CI 0.80-2.27). No statistically significant differences were observed in the incidence of peritoneal recurrence (35.9% vs. 46.1%, P = 0.36) and lymph node recurrence (25.6% vs. 12.8%, P = 0.15).</p><p><strong>Conclusions: </strong>Large type 3 tumors with undifferentiated phenotype and type 4 tumors were oncologically similar. This subgroup could be considered as a new entity for future clinical trials.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"1331-1341"},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1007/s10120-024-01547-w
A Harris, J B Butterworth, P R Boshier, S Mavroveli, B Vadhwana, C J Peters, B W Eom, C-C Yeh, S Mikhail, M Sasako, Y-W Kim, G B Hanna
{"title":"Correction: Development of a reliable surgical quality assurance tool for gastrectomy in oncological trials.","authors":"A Harris, J B Butterworth, P R Boshier, S Mavroveli, B Vadhwana, C J Peters, B W Eom, C-C Yeh, S Mikhail, M Sasako, Y-W Kim, G B Hanna","doi":"10.1007/s10120-024-01547-w","DOIUrl":"10.1007/s10120-024-01547-w","url":null,"abstract":"","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"1350"},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-07-19DOI: 10.1007/s10120-024-01536-z
Chiara Molinari, Leonardo Solaini, Francesca Rebuzzi, Gianluca Tedaldi, Davide Angeli, Elisabetta Petracci, Dusan Prascevic, Jan Ewald, Erhard Rahm, Matteo Canale, Martinelli Giovanni, Anna Tomezzoli, Maria Bencivenga, Maria Raffaella Ambrosio, Daniele Marrelli, Paolo Morgagni, Giorgio Ercolani, Paola Ulivi, Luca Saragoni
Background: The purpose of the study was to conduct a comprehensive genomic characterization of gene alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) in submucosal-penetrating (Pen) early gastric cancers (EGCs) with varying prognoses.
Methods: Samples from EGC patients undergoing surgery and with 10-year follow-up data available were collected. Tissue genomic alterations were characterized using Trusight Oncology panel (TSO500). Pathway instability (PI) scores for a selection of 218 GC-related pathways were calculated both for the present case series and EGCs from the TCGA cohort.
Results: Higher age and tumor location in the upper-middle tract are significantly associated with an increased hazard of relapse or death from any cause (p = 0.006 and p = 0.032). Even if not reaching a statistical significance, Pen A tumors more frequently present higher TMB values, higher frequency of MSI-subtypes and an overall increase in PI scores, along with an enrichment in immune pathways. ARID1A gene was observed to be significantly more frequently mutated in Pen A tumors (p = 0.006), as well as in patients with high TMB (p = 0.027). Tumors harboring LRP1B alterations seem to have a higher hazard of relapse or death from any cause (p = 0.089), being mutated mainly in relapsed patients (p = 0.093).
Conclusions: We found that the most aggressive subtype Pen A is characterized by a higher frequency of ARID1A mutations and a higher genetic instability, while LRP1B alterations seem to be related to a lower disease-free survival. Further investigations are needed to provide a rationale for the use of these markers to stratify prognosis in EGC patients.
研究背景该研究旨在对不同预后的粘膜下穿透性早期胃癌(EGC)的基因改变、微卫星不稳定性(MSI)和肿瘤突变负荷(TMB)进行全面的基因组学分析:方法:收集接受过手术且有10年随访数据的EGC患者样本。采用 Trusight Oncology 面板(TSO500)对组织基因组改变进行表征。针对本病例系列和TCGA队列中的EGC,计算了218条GC相关通路的通路不稳定性(PI)评分:结果:较高的年龄和肿瘤位于中上部与复发或死于任何原因的风险增加有显著相关性(p = 0.006 和 p = 0.032)。即使未达到统计学意义,Pen A 型肿瘤也更常出现较高的 TMB 值、较高的 MSI 亚型频率和 PI 评分的整体增加,以及免疫通路的富集。据观察,ARID1A 基因在 Pen A 型肿瘤(p = 0.006)和高 TMB 患者(p = 0.027)中的突变频率明显更高。携带LRP1B基因改变的肿瘤似乎有更高的复发或死于任何原因的风险(p = 0.089),主要在复发患者中发生突变(p = 0.093):我们发现,最具侵袭性的亚型 Pen A 的特点是 ARID1A 突变频率较高和遗传不稳定性较高,而 LRP1B 的改变似乎与较低的无病生存率有关。还需要进一步研究,为使用这些标记物对EGC患者的预后进行分层提供依据。
{"title":"Genomic events stratifying prognosis of early gastric cancer.","authors":"Chiara Molinari, Leonardo Solaini, Francesca Rebuzzi, Gianluca Tedaldi, Davide Angeli, Elisabetta Petracci, Dusan Prascevic, Jan Ewald, Erhard Rahm, Matteo Canale, Martinelli Giovanni, Anna Tomezzoli, Maria Bencivenga, Maria Raffaella Ambrosio, Daniele Marrelli, Paolo Morgagni, Giorgio Ercolani, Paola Ulivi, Luca Saragoni","doi":"10.1007/s10120-024-01536-z","DOIUrl":"10.1007/s10120-024-01536-z","url":null,"abstract":"<p><strong>Background: </strong>The purpose of the study was to conduct a comprehensive genomic characterization of gene alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) in submucosal-penetrating (Pen) early gastric cancers (EGCs) with varying prognoses.</p><p><strong>Methods: </strong>Samples from EGC patients undergoing surgery and with 10-year follow-up data available were collected. Tissue genomic alterations were characterized using Trusight Oncology panel (TSO500). Pathway instability (PI) scores for a selection of 218 GC-related pathways were calculated both for the present case series and EGCs from the TCGA cohort.</p><p><strong>Results: </strong>Higher age and tumor location in the upper-middle tract are significantly associated with an increased hazard of relapse or death from any cause (p = 0.006 and p = 0.032). Even if not reaching a statistical significance, Pen A tumors more frequently present higher TMB values, higher frequency of MSI-subtypes and an overall increase in PI scores, along with an enrichment in immune pathways. ARID1A gene was observed to be significantly more frequently mutated in Pen A tumors (p = 0.006), as well as in patients with high TMB (p = 0.027). Tumors harboring LRP1B alterations seem to have a higher hazard of relapse or death from any cause (p = 0.089), being mutated mainly in relapsed patients (p = 0.093).</p><p><strong>Conclusions: </strong>We found that the most aggressive subtype Pen A is characterized by a higher frequency of ARID1A mutations and a higher genetic instability, while LRP1B alterations seem to be related to a lower disease-free survival. Further investigations are needed to provide a rationale for the use of these markers to stratify prognosis in EGC patients.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"1189-1200"},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-07-30DOI: 10.1007/s10120-024-01540-3
Hea Lim Choi, Danbee Kang, Hyunsoo Kim, Juhee Cho, Keun Hye Jeon, Wonyoung Jung, Dong Wook Shin, Su-Min Jeong
Background: Previous studies have investigated cardiovascular disease (CVD) risks in cancer patients, but there is limited knowledge concerning the CVD risk in adult and young adolescent (AYA) survivors of gastric cancer.
Objectives: This study aims to investigate the incidence of CVD in AYA gastric cancer survivors, analyzing it by treatment type and identifying associated risk factors.
Methods: We conducted a retrospective cohort study using Korean National Health Insurance Service data collected from 2006 to 2019. Propensity score matching (1:3, caliper < 0.1) was performed using the variables age, sex, income, residential area, and presence of comorbidities, and we classified participants into gastric cancer (n = 6562) and non-cancer control (n = 19,678) groups. Cox regression models were used to calculate hazard ratios (HRs) for CVD incidence. The study assessed CVD incidence by cancer treatment and identified risk factors through multivariable Cox regression.
Results: During a median 6.5-year follow-up, AYA gastric cancer survivors consistently exhibited greater CVD incidence. Their risk of CVD was significantly elevated compared to that of controls (HR, 1.18; 95% confidence interval [CI] 1.05-1.33). In particular, deep vein thrombosis (HR, 3.93; 95% CI 3.06-14.67) and pulmonary embolism (HR, 6.58; 95% CI 3.06-14.67) risks were notably increased. Chemotherapy was associated with an increased risk of stroke, heart failure, atrial fibrillation, deep vein thrombosis, and pulmonary embolism. Hypertension (HR, 1.58; 95% CI 1.10-2.26) and dyslipidemia (HR, 1.46; 95% CI 1.06-2.20) emerged as risk factors for CVD development.
Conclusion: This study reports elevated risks of CVD in AYA gastric cancer survivors and emphasizes the need for vigilant monitoring of CVD in this population.
{"title":"Increased cardiovascular disease risk among adolescents and young adults with gastric cancer.","authors":"Hea Lim Choi, Danbee Kang, Hyunsoo Kim, Juhee Cho, Keun Hye Jeon, Wonyoung Jung, Dong Wook Shin, Su-Min Jeong","doi":"10.1007/s10120-024-01540-3","DOIUrl":"10.1007/s10120-024-01540-3","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have investigated cardiovascular disease (CVD) risks in cancer patients, but there is limited knowledge concerning the CVD risk in adult and young adolescent (AYA) survivors of gastric cancer.</p><p><strong>Objectives: </strong>This study aims to investigate the incidence of CVD in AYA gastric cancer survivors, analyzing it by treatment type and identifying associated risk factors.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using Korean National Health Insurance Service data collected from 2006 to 2019. Propensity score matching (1:3, caliper < 0.1) was performed using the variables age, sex, income, residential area, and presence of comorbidities, and we classified participants into gastric cancer (n = 6562) and non-cancer control (n = 19,678) groups. Cox regression models were used to calculate hazard ratios (HRs) for CVD incidence. The study assessed CVD incidence by cancer treatment and identified risk factors through multivariable Cox regression.</p><p><strong>Results: </strong>During a median 6.5-year follow-up, AYA gastric cancer survivors consistently exhibited greater CVD incidence. Their risk of CVD was significantly elevated compared to that of controls (HR, 1.18; 95% confidence interval [CI] 1.05-1.33). In particular, deep vein thrombosis (HR, 3.93; 95% CI 3.06-14.67) and pulmonary embolism (HR, 6.58; 95% CI 3.06-14.67) risks were notably increased. Chemotherapy was associated with an increased risk of stroke, heart failure, atrial fibrillation, deep vein thrombosis, and pulmonary embolism. Hypertension (HR, 1.58; 95% CI 1.10-2.26) and dyslipidemia (HR, 1.46; 95% CI 1.06-2.20) emerged as risk factors for CVD development.</p><p><strong>Conclusion: </strong>This study reports elevated risks of CVD in AYA gastric cancer survivors and emphasizes the need for vigilant monitoring of CVD in this population.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"1169-1179"},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-07-04DOI: 10.1007/s10120-024-01531-4
Kuan-Fu Liao, Shih-Wei Lai
{"title":"Comment on \"Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for new-onset gastric cancer and gastric diseases in patients with type 2 diabetes mellitus: a population-based cohort study\".","authors":"Kuan-Fu Liao, Shih-Wei Lai","doi":"10.1007/s10120-024-01531-4","DOIUrl":"10.1007/s10120-024-01531-4","url":null,"abstract":"","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"1342-1343"},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Homologous recombination deficiency (HRD) is one of the crucial hallmarks of cancer. It is associated with a favorable response to platinum-based chemotherapy. We explored the distinctive clinicopathological features of gastric cancer (GC) with HRD and the clinical significance of HRD in platinum-based first-line chemotherapy for unresectable metastatic GC.
Methods: We enrolled 160 patients with GC in this study. Their tumor samples were subjected to genomic profiling utilizing targeted tumor sequencing. HRD was defined as the presence of alterations in any of 16 HR genes (BARD1, BLM, BRCA1, BRCA2, BRIP1, MRE11A, NBN, PALB2, PARP1, POLD1, RAD50, RAD51, RAD51C, RAD51D, WRN, and XRCC2). The clinicopathological features and treatment outcomes of first-line chemotherapy for unresectable metastatic GC were compared between HRD and non-HRD groups.
Results: Forty-seven patients (29.4%) were classified into the HRD group. This group had a significantly lower proportion of macroscopic type 3 or 4 tumors and higher TMB than the non-HRD group. Among patients who underwent platinum-based first-line chemotherapy, the HRD group had a greater response rate and longer progression-free survival after treatment (median 8.0 months vs. 3.0 months, P = 0.010), with an adjusted hazard ratio of 0.337 (95% confidence interval 0.151-0.753). HRD status was not associated with treatment outcomes in patients who did not undergo platinum-based chemotherapy.
Conclusions: Low proportion of macroscopic type 3 or 4 tumors and a high TMB are distinctive features of GC with HRD. HRD status is a potential predictive marker in platinum-based first-line chemotherapy for unresectable metastatic GC.
{"title":"Landscape of homologous recombination deficiency in gastric cancer and clinical implications for first-line chemotherapy.","authors":"Hiroshi Ichikawa, Masaki Aizawa, Yosuke Kano, Takaaki Hanyu, Yusuke Muneoka, Sou Hiroi, Hiroto Ueki, Kazuki Moro, Yuki Hirose, Kohei Miura, Yoshifumi Shimada, Jun Sakata, Hiroshi Yabusaki, Satoru Nakagawa, Takashi Kawasaki, Shujiro Okuda, Toshifumi Wakai","doi":"10.1007/s10120-024-01542-1","DOIUrl":"10.1007/s10120-024-01542-1","url":null,"abstract":"<p><strong>Background: </strong>Homologous recombination deficiency (HRD) is one of the crucial hallmarks of cancer. It is associated with a favorable response to platinum-based chemotherapy. We explored the distinctive clinicopathological features of gastric cancer (GC) with HRD and the clinical significance of HRD in platinum-based first-line chemotherapy for unresectable metastatic GC.</p><p><strong>Methods: </strong>We enrolled 160 patients with GC in this study. Their tumor samples were subjected to genomic profiling utilizing targeted tumor sequencing. HRD was defined as the presence of alterations in any of 16 HR genes (BARD1, BLM, BRCA1, BRCA2, BRIP1, MRE11A, NBN, PALB2, PARP1, POLD1, RAD50, RAD51, RAD51C, RAD51D, WRN, and XRCC2). The clinicopathological features and treatment outcomes of first-line chemotherapy for unresectable metastatic GC were compared between HRD and non-HRD groups.</p><p><strong>Results: </strong>Forty-seven patients (29.4%) were classified into the HRD group. This group had a significantly lower proportion of macroscopic type 3 or 4 tumors and higher TMB than the non-HRD group. Among patients who underwent platinum-based first-line chemotherapy, the HRD group had a greater response rate and longer progression-free survival after treatment (median 8.0 months vs. 3.0 months, P = 0.010), with an adjusted hazard ratio of 0.337 (95% confidence interval 0.151-0.753). HRD status was not associated with treatment outcomes in patients who did not undergo platinum-based chemotherapy.</p><p><strong>Conclusions: </strong>Low proportion of macroscopic type 3 or 4 tumors and a high TMB are distinctive features of GC with HRD. HRD status is a potential predictive marker in platinum-based first-line chemotherapy for unresectable metastatic GC.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"1273-1286"},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Trastuzumab-deruxtecan (T-DXd) was approved for the treatment of HER2-positive patients with advanced gastric cancer in Japan based on the results of the DESTINY-Gastric01 trial. This study aimed to collect real-world data and evaluate the effectiveness and safety of T-DXd.
Methods: Patients aged ≥ 20 years at the start of T-DXd administration with a histopathologically confirmed diagnosis of HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma that had worsened after chemotherapy were enrolled in this retrospective cohort study. Key outcomes included T-DXd treatment status, overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate and frequency of grade ≥ 3 adverse events (AEs).
Results: Of the 312 patients included in the analysis, 75.3% were male, the median (range) age was 70.0 (27.0-89.0) years, 12.2% had an ECOG PS ≥ 2, 43.3% had ascites and the initial T-DXd dose was > 5.4- ≤ 6.4 mg/kg in 78.2% of patients. The median (95% confidence interval) OS, rwPFS and TTF (months) was 8.9 (8.0-11.0), 4.6 (4.0-5.1) and 3.9 (3.4-4.2), respectively. The response rate was 42.9% in patients with a target lesion. In total, 48.4% of patients experienced a grade ≥ 3 AE, 2.6% experienced grade 5 AEs and 60.9% experienced AEs leading to T-DXd dose adjustments (reduction: 36.9%, interruption: 34.0% or discontinuation: 23.7%). No new safety signals were detected.
Conclusions: T-DXd was effective and had a manageable safety profile as a third- or later-line treatment for patients with HER2-positive gastric or GEJ cancer in Japanese clinical practice.
{"title":"Real-world effectiveness and safety of trastuzumab-deruxtecan in Japanese patients with HER2-positive advanced gastric cancer (EN-DEAVOR study).","authors":"Hisato Kawakami, Koki Nakanishi, Akitaka Makiyama, Hirotaka Konishi, Satoshi Morita, Yukiya Narita, Naotoshi Sugimoto, Keiko Minashi, Motohiro Imano, Rin Inamoto, Yasuhiro Kodera, Hiroki Kume, Keita Yamaguchi, Wataru Hashimoto, Kei Muro","doi":"10.1007/s10120-024-01555-w","DOIUrl":"https://doi.org/10.1007/s10120-024-01555-w","url":null,"abstract":"<p><strong>Background: </strong>Trastuzumab-deruxtecan (T-DXd) was approved for the treatment of HER2-positive patients with advanced gastric cancer in Japan based on the results of the DESTINY-Gastric01 trial. This study aimed to collect real-world data and evaluate the effectiveness and safety of T-DXd.</p><p><strong>Methods: </strong>Patients aged ≥ 20 years at the start of T-DXd administration with a histopathologically confirmed diagnosis of HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma that had worsened after chemotherapy were enrolled in this retrospective cohort study. Key outcomes included T-DXd treatment status, overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate and frequency of grade ≥ 3 adverse events (AEs).</p><p><strong>Results: </strong>Of the 312 patients included in the analysis, 75.3% were male, the median (range) age was 70.0 (27.0-89.0) years, 12.2% had an ECOG PS ≥ 2, 43.3% had ascites and the initial T-DXd dose was > 5.4- ≤ 6.4 mg/kg in 78.2% of patients. The median (95% confidence interval) OS, rwPFS and TTF (months) was 8.9 (8.0-11.0), 4.6 (4.0-5.1) and 3.9 (3.4-4.2), respectively. The response rate was 42.9% in patients with a target lesion. In total, 48.4% of patients experienced a grade ≥ 3 AE, 2.6% experienced grade 5 AEs and 60.9% experienced AEs leading to T-DXd dose adjustments (reduction: 36.9%, interruption: 34.0% or discontinuation: 23.7%). No new safety signals were detected.</p><p><strong>Conclusions: </strong>T-DXd was effective and had a manageable safety profile as a third- or later-line treatment for patients with HER2-positive gastric or GEJ cancer in Japanese clinical practice.</p><p><strong>Clinical trial registration: </strong>UMIN000049032.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1007/s10120-024-01558-7
Wilhelm Leijonmarck, Fredrik Mattsson, Jesper Lagergren
Background: Late effects of chemotherapy could affect mortality amongst cancer survivors. This study aimed to clarify if neoadjuvant chemotherapy for gastric adenocarcinoma influences the long-term survival in individuals cured of this tumour.
Methods: This was a nationwide and population-based cohort study that included all individuals who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 and survived for ≥ 5 years after surgery. The cohort was followed up until death or end of study period (31 December 2020). Multivariable Cox proportional hazards regression was used to provide hazard ratios (HR) with 95% confidence intervals (CI). The HR were adjusted for age, sex, comorbidity, education, calendar year, tumour sub-location, in-hospital complications, and splenectomy. Data came from medical records and nationwide registers.
Results: Amongst 613 gastric adenocarcinoma survivors, neoadjuvant chemotherapy (used in 269 patients; 43.9%) was associated with a decreased crude mortality rate (HR 0.66, 95% CI 0.46-0.96). However, the association attenuated and became statistically non-significant after adjustment for all confounders (HR 0.83, 95% CI 0.56-1.23) and after adjustments solely for age and comorbidity (HR 0.82, 95% CI 0.56-1.20). Stratified analyses did not reveal any statistically significant associations between neoadjuvant chemotherapy and long-term mortality in categories of age, sex, comorbidity, calendar year and tumour sub-location.
Conclusion: Neoadjuvant chemotherapy did not decrease the long-term survival amongst gastric adenocarcinoma survivors. Patients who received neoadjuvant chemotherapy were a selected group characterised by younger age and fewer severe comorbidities and therefore with better chances of long-term survival.
背景:化疗的晚期效应可能会影响癌症幸存者的死亡率。本研究旨在明确胃腺癌新辅助化疗是否会影响该肿瘤治愈者的长期生存:这是一项基于人口的全国性队列研究,研究对象包括2006年至2015年间在瑞典因胃腺癌接受胃切除术且术后存活≥5年的所有患者。队列随访至死亡或研究期结束(2020 年 12 月 31 日)。采用多变量考克斯比例危险度回归法得出危险度比 (HR),并得出 95% 的置信区间 (CI)。HR已根据年龄、性别、合并症、教育程度、日历年、肿瘤亚位置、院内并发症和脾切除术进行了调整。数据来自医疗记录和全国范围内的登记:结果:在 613 名胃癌幸存者中,新辅助化疗(269 名患者,43.9%)与粗死亡率的降低有关(HR 0.66,95% CI 0.46-0.96)。然而,在对所有混杂因素进行调整后(HR 0.83,95% CI 0.56-1.23),以及仅对年龄和合并症进行调整后(HR 0.82,95% CI 0.56-1.20),这种关联性减弱,在统计学上变得不显著。分层分析未发现新辅助化疗与年龄、性别、合并症、日历年和肿瘤亚定位等类别的长期死亡率有任何统计学意义:结论:新辅助化疗不会降低胃腺癌幸存者的长期生存率。接受新辅助化疗的患者是经过筛选的群体,他们的特点是年龄较小、严重合并症较少,因此长期生存的机会更大。
{"title":"Neoadjuvant chemotherapy in relation to long-term mortality in individuals cured of gastric adenocarcinoma.","authors":"Wilhelm Leijonmarck, Fredrik Mattsson, Jesper Lagergren","doi":"10.1007/s10120-024-01558-7","DOIUrl":"https://doi.org/10.1007/s10120-024-01558-7","url":null,"abstract":"<p><strong>Background: </strong>Late effects of chemotherapy could affect mortality amongst cancer survivors. This study aimed to clarify if neoadjuvant chemotherapy for gastric adenocarcinoma influences the long-term survival in individuals cured of this tumour.</p><p><strong>Methods: </strong>This was a nationwide and population-based cohort study that included all individuals who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 and survived for ≥ 5 years after surgery. The cohort was followed up until death or end of study period (31 December 2020). Multivariable Cox proportional hazards regression was used to provide hazard ratios (HR) with 95% confidence intervals (CI). The HR were adjusted for age, sex, comorbidity, education, calendar year, tumour sub-location, in-hospital complications, and splenectomy. Data came from medical records and nationwide registers.</p><p><strong>Results: </strong>Amongst 613 gastric adenocarcinoma survivors, neoadjuvant chemotherapy (used in 269 patients; 43.9%) was associated with a decreased crude mortality rate (HR 0.66, 95% CI 0.46-0.96). However, the association attenuated and became statistically non-significant after adjustment for all confounders (HR 0.83, 95% CI 0.56-1.23) and after adjustments solely for age and comorbidity (HR 0.82, 95% CI 0.56-1.20). Stratified analyses did not reveal any statistically significant associations between neoadjuvant chemotherapy and long-term mortality in categories of age, sex, comorbidity, calendar year and tumour sub-location.</p><p><strong>Conclusion: </strong>Neoadjuvant chemotherapy did not decrease the long-term survival amongst gastric adenocarcinoma survivors. Patients who received neoadjuvant chemotherapy were a selected group characterised by younger age and fewer severe comorbidities and therefore with better chances of long-term survival.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-05DOI: 10.1007/s10120-024-01556-9
Cecilie Riis Iden, Salah Mohammad Mustafa, Nadia Øgaard, Tenna Henriksen, Sarah Østrup Jensen, Lise Barlebo Ahlborn, Kristian Egebjerg, Lene Baeksgaard, Rajendra Singh Garbyal, Mette Kjølhede Nedergaard, Michael Patrick Achiam, Claus Lindbjerg Andersen, Morten Mau-Sørensen
Background: Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC).
Methods: Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled. Serial plasma samples were collected at baseline, after one cycle of chemotherapy, after preoperative chemotherapy, and after surgery. ctDNA was assessed by a ddPCR test (TriMeth), which targets the gastrointestinal cancer-specific methylation patterns of the genes C9orf50, KCNQ5, and CLIP4.
Results: ctDNA analysis was performed on 229 plasma samples from 86 patients. At baseline, ctDNA was detected in 56% of patients, which decreased to 37% following one cycle of chemotherapy, 25% after preoperative chemotherapy and 15% after surgical resection. The presence of ctDNA after one cycle of chemotherapy was associated with reduced recurrence-free survival (RFS) (HR = 2.54, 95% confidence interval (CI) 1.33-4.85, p = 0.005) and overall survival (OS) (HR = 2.23, 95% CI 1.07-4.62, p = 0.032). Similarly, ctDNA after surgery was associated with significantly shorter RFS (HR = 6.22, 95% CI 2.39-16.2, p < 0.001) and OS (HR = 6.37, 95% CI 2.10-19.3, p = 0.001). Multivariable regression analysis confirmed ctDNA after surgery as an independent prognostic factor (p < 0.001).
Conclusion: ctDNA analysis has the potential to identify patients at elevated risk of recurrence, thus providing personalized treatment strategies for patients with resectable gastric and GEJ cancer. Further validation in larger cohorts and ctDNA-guided interventions are needed for future clinical use.
{"title":"Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer.","authors":"Cecilie Riis Iden, Salah Mohammad Mustafa, Nadia Øgaard, Tenna Henriksen, Sarah Østrup Jensen, Lise Barlebo Ahlborn, Kristian Egebjerg, Lene Baeksgaard, Rajendra Singh Garbyal, Mette Kjølhede Nedergaard, Michael Patrick Achiam, Claus Lindbjerg Andersen, Morten Mau-Sørensen","doi":"10.1007/s10120-024-01556-9","DOIUrl":"https://doi.org/10.1007/s10120-024-01556-9","url":null,"abstract":"<p><strong>Background: </strong>Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC).</p><p><strong>Methods: </strong>Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled. Serial plasma samples were collected at baseline, after one cycle of chemotherapy, after preoperative chemotherapy, and after surgery. ctDNA was assessed by a ddPCR test (TriMeth), which targets the gastrointestinal cancer-specific methylation patterns of the genes C9orf50, KCNQ5, and CLIP4.</p><p><strong>Results: </strong>ctDNA analysis was performed on 229 plasma samples from 86 patients. At baseline, ctDNA was detected in 56% of patients, which decreased to 37% following one cycle of chemotherapy, 25% after preoperative chemotherapy and 15% after surgical resection. The presence of ctDNA after one cycle of chemotherapy was associated with reduced recurrence-free survival (RFS) (HR = 2.54, 95% confidence interval (CI) 1.33-4.85, p = 0.005) and overall survival (OS) (HR = 2.23, 95% CI 1.07-4.62, p = 0.032). Similarly, ctDNA after surgery was associated with significantly shorter RFS (HR = 6.22, 95% CI 2.39-16.2, p < 0.001) and OS (HR = 6.37, 95% CI 2.10-19.3, p = 0.001). Multivariable regression analysis confirmed ctDNA after surgery as an independent prognostic factor (p < 0.001).</p><p><strong>Conclusion: </strong>ctDNA analysis has the potential to identify patients at elevated risk of recurrence, thus providing personalized treatment strategies for patients with resectable gastric and GEJ cancer. Further validation in larger cohorts and ctDNA-guided interventions are needed for future clinical use.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}