Introduction: Gastric cancer with fusion genes involving the Rho GTPase-activating protein domain (RhoGAP-GC) is mainly included in the genomically stable type of The Cancer Genome Atlas classification. Clinical implications and histological characteristics of RhoGAP-GC in the early phase remain unclear.
Methods: We analyzed 878 consecutive pT1b GCs for RhoGAP and its partner genes using fluorescence in situ hybridization assay.
Results: RhoGAP fusion was detected in 57 (6.5%) GCs. Univariate analysis revealed that female sex, middle-lower third tumor location, advanced macroscopic type, tumor diameter > 2 cm, pT1b2, lymphatic invasion, venous invasion, negative EBER-ISH, and RhoGAP fusion were significantly associated with lymph node metastasis (LNM). Multivariate analysis presented RhoGAP fusion, lymphatic invasion, tumor diameter > 2 cm, advanced macroscopic type, venous invasion, and middle-lower third tumor location as independent risk factors for LNM. Notably, RhoGAP fusion had the highest odds ratio (3.92) for LNM among analyzed parameters (95% CI 2.12-7.27; p < 0.001). Compared to non-RhoGAP-GCs, RhoGAP-GCs were significantly frequent in younger females and showed the highest incidence of lymphatic invasion (56.2%) and LNM (49.1%) (p < 0.001). Histologically, microtubular architecture with pseudo-trabecular interconnection and small aggregations of tumor cells with a varied amount of cytoplasmic mucin, named "microtubular-mucocellular (MTMC) histology," was found in 93.0% (53 of 57) of RhoGAP-GCs in the intramucosal area. MTMC histology showed high sensitivity and negative predictive value (93.0% and 99.4%, respectively) for RhoGAP fusion, albeit positive predictive value is low (34.9%).
Conclusion: RhoGAP-GC is linked to a characteristic MTMC histology and a high incidence of LNM.
{"title":"Early gastric cancer with RhoGAP fusion is linked to frequent nodal metastasis and a part of microtubular-mucocellular histology.","authors":"Hiroto Noda, Seiji Sakata, Satoko Baba, Yuki Togashi, Kaoru Nakano, Toshiaki Hirasawa, Izuma Nakayama, Chiina Hata, Manabu Takamatsu, Emiko Sugawara, Noriko Yamamoto, Junko Fujisaki, Souya Nunobe, Katsuhiko Iwakiri, Kengo Takeuchi, Hiroshi Kawachi","doi":"10.1007/s10120-024-01507-4","DOIUrl":"10.1007/s10120-024-01507-4","url":null,"abstract":"<p><strong>Introduction: </strong>Gastric cancer with fusion genes involving the Rho GTPase-activating protein domain (RhoGAP-GC) is mainly included in the genomically stable type of The Cancer Genome Atlas classification. Clinical implications and histological characteristics of RhoGAP-GC in the early phase remain unclear.</p><p><strong>Methods: </strong>We analyzed 878 consecutive pT1b GCs for RhoGAP and its partner genes using fluorescence in situ hybridization assay.</p><p><strong>Results: </strong>RhoGAP fusion was detected in 57 (6.5%) GCs. Univariate analysis revealed that female sex, middle-lower third tumor location, advanced macroscopic type, tumor diameter > 2 cm, pT1b2, lymphatic invasion, venous invasion, negative EBER-ISH, and RhoGAP fusion were significantly associated with lymph node metastasis (LNM). Multivariate analysis presented RhoGAP fusion, lymphatic invasion, tumor diameter > 2 cm, advanced macroscopic type, venous invasion, and middle-lower third tumor location as independent risk factors for LNM. Notably, RhoGAP fusion had the highest odds ratio (3.92) for LNM among analyzed parameters (95% CI 2.12-7.27; p < 0.001). Compared to non-RhoGAP-GCs, RhoGAP-GCs were significantly frequent in younger females and showed the highest incidence of lymphatic invasion (56.2%) and LNM (49.1%) (p < 0.001). Histologically, microtubular architecture with pseudo-trabecular interconnection and small aggregations of tumor cells with a varied amount of cytoplasmic mucin, named \"microtubular-mucocellular (MTMC) histology,\" was found in 93.0% (53 of 57) of RhoGAP-GCs in the intramucosal area. MTMC histology showed high sensitivity and negative predictive value (93.0% and 99.4%, respectively) for RhoGAP fusion, albeit positive predictive value is low (34.9%).</p><p><strong>Conclusion: </strong>RhoGAP-GC is linked to a characteristic MTMC histology and a high incidence of LNM.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957145","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: Gastric cancer with peritoneal dissemination (PD) has a dismal prognosis, and current treatments have shown little efficacy. CLDN18.2-targeted therapies have shown promising efficacy against gastric cancers that express high levels of CLDN18. Because of the limited information regarding CLDN18.2 status in PD, we analyzed PD-positive gastric cancers for CLDN18 status in both primary and PD, along with HER2 and PD-L1 combined positive score (CPS).
Methods: Immunohistochemical analyses were performed on 84 gastric cancer cases using paired primary and PD tissue samples.
Results: At 40% cut-off, CLDN18 was positive in 57% (48/84) primary tumors and in 44% (37/84) PDs. At 75% cut-off, 28.6% (24/84) primary tumors and 20.2% (17/84) PDs were CLDN18-positive. The concordance rate between primary tumors and PD was 79.8% at 40% cut-off and 75% at 75% cut-off. When comparing biopsy and surgical specimens, the concordance rates were 87.5% at 40% cut-off and 81.3% at 75% cut-off. Within a tumor, the superficial area tended to have a higher CLDN18-positive rate than the invasive front (P = 0.001). Although HER2 -positivity was only 11.9% in this cohort, CLDN18 positivity in HER2-negative tumors (n = 74) was relatively high: 60.8% at 40% cut-off and 28.4% at 75% cut-off. Among double-negative (HER2 - and PD-L1 CPS < 1) tumors, CLDN18 positivity was 67.6% at 40% cut-off and 26.5% at 75% cut-off.
Conclusions: CLDN18 expression is generally maintained in PD and is relatively high even in double-negative tumors, making it a promising therapeutic target for PD-positive gastric cancer.
{"title":"Claudin-18 status and its correlation with HER2 and PD-L1 expression in gastric cancer with peritoneal dissemination.","authors":"Haruki Ogawa, Hiroyuki Abe, Koichi Yagi, Yasuyuki Seto, Tetsuo Ushiku","doi":"10.1007/s10120-024-01505-6","DOIUrl":"10.1007/s10120-024-01505-6","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer with peritoneal dissemination (PD) has a dismal prognosis, and current treatments have shown little efficacy. CLDN18.2-targeted therapies have shown promising efficacy against gastric cancers that express high levels of CLDN18. Because of the limited information regarding CLDN18.2 status in PD, we analyzed PD-positive gastric cancers for CLDN18 status in both primary and PD, along with HER2 and PD-L1 combined positive score (CPS).</p><p><strong>Methods: </strong>Immunohistochemical analyses were performed on 84 gastric cancer cases using paired primary and PD tissue samples.</p><p><strong>Results: </strong>At 40% cut-off, CLDN18 was positive in 57% (48/84) primary tumors and in 44% (37/84) PDs. At 75% cut-off, 28.6% (24/84) primary tumors and 20.2% (17/84) PDs were CLDN18-positive. The concordance rate between primary tumors and PD was 79.8% at 40% cut-off and 75% at 75% cut-off. When comparing biopsy and surgical specimens, the concordance rates were 87.5% at 40% cut-off and 81.3% at 75% cut-off. Within a tumor, the superficial area tended to have a higher CLDN18-positive rate than the invasive front (P = 0.001). Although HER2 -positivity was only 11.9% in this cohort, CLDN18 positivity in HER2-negative tumors (n = 74) was relatively high: 60.8% at 40% cut-off and 28.4% at 75% cut-off. Among double-negative (HER2 - and PD-L1 CPS < 1) tumors, CLDN18 positivity was 67.6% at 40% cut-off and 26.5% at 75% cut-off.</p><p><strong>Conclusions: </strong>CLDN18 expression is generally maintained in PD and is relatively high even in double-negative tumors, making it a promising therapeutic target for PD-positive gastric cancer.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897166","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 : 2024-07-01Epub Date: 2024-03-31DOI: 10.1007/s10120-024-01483-9
Chung Ryul Oh, Eo Jin Kim, Heejung Chae, Young Soo Park, Min-Hee Ryu, Hyung-Don Kim, Yoon-Koo Kang
Background: We examined the impact of mismatch repair (MMR) status on efficacy of first-line fluoropyrimidine plus platinum (FP) chemotherapy in patients with HER2-negative metastatic, recurrent, or unresectable gastric cancer (mGC).
Methods: Patients with mGC receiving first-line FP between 2015 and 2018 at Asan Medical Center, Korea, were reviewed. We evaluated the clinical characteristics and the efficacy of chemotherapy according to MMR status in patients with available immunohistochemistry results.
Results: Of 895 patients, we analyzed 543 with available MMR protein expression results, and deficient MMR (dMMR) was detected in 4.4% (n = 24). Patients with dMMR exhibited a significantly higher median age than those with proficient MMR (pMMR) (64 vs. 58 years, p = 0.044). No signet ring cell carcinoma (SRCC) was detected among dMMR tumors, whereas SRCC was found in 17.5% of pMMR. Objective response rate was 27.3% in dMMR and 34.3% in pMMR (p = 0.556). No difference in progression-free survival was noted between patients with dMMR and pMMR (median, 5.6 vs. 5.8 months, p = 0.266). Patients with dMMR tended to have better overall survival than those with pMMR although this difference was not statistically significant (median, 17.9 vs. 12.2 months, p = 0.183).
Conclusions: Efficacy of first-line FP was not different by MMR status in mGC patients.
{"title":"Prognostic value of mismatch repair deficiency in patients receiving first-line fluoropyrimidine plus platinum for metastatic, recurrent, or unresectable gastric cancer.","authors":"Chung Ryul Oh, Eo Jin Kim, Heejung Chae, Young Soo Park, Min-Hee Ryu, Hyung-Don Kim, Yoon-Koo Kang","doi":"10.1007/s10120-024-01483-9","DOIUrl":"10.1007/s10120-024-01483-9","url":null,"abstract":"<p><strong>Background: </strong>We examined the impact of mismatch repair (MMR) status on efficacy of first-line fluoropyrimidine plus platinum (FP) chemotherapy in patients with HER2-negative metastatic, recurrent, or unresectable gastric cancer (mGC).</p><p><strong>Methods: </strong>Patients with mGC receiving first-line FP between 2015 and 2018 at Asan Medical Center, Korea, were reviewed. We evaluated the clinical characteristics and the efficacy of chemotherapy according to MMR status in patients with available immunohistochemistry results.</p><p><strong>Results: </strong>Of 895 patients, we analyzed 543 with available MMR protein expression results, and deficient MMR (dMMR) was detected in 4.4% (n = 24). Patients with dMMR exhibited a significantly higher median age than those with proficient MMR (pMMR) (64 vs. 58 years, p = 0.044). No signet ring cell carcinoma (SRCC) was detected among dMMR tumors, whereas SRCC was found in 17.5% of pMMR. Objective response rate was 27.3% in dMMR and 34.3% in pMMR (p = 0.556). No difference in progression-free survival was noted between patients with dMMR and pMMR (median, 5.6 vs. 5.8 months, p = 0.266). Patients with dMMR tended to have better overall survival than those with pMMR although this difference was not statistically significant (median, 17.9 vs. 12.2 months, p = 0.183).</p><p><strong>Conclusions: </strong>Efficacy of first-line FP was not different by MMR status in mGC patients.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329769","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 : 2024-07-01Epub Date: 2024-04-25DOI: 10.1007/s10120-024-01498-2
Sung Eun Oh, Soomin Ahn, Kyoung-Mee Kim, Min-Gew Choi, Jun Ho Lee, Tae Sung Sohn, Jae Moon Bae, Ji Yeong An
Background and aims: When treating undifferentiated-type early gastric cancer (UD-EGC) that is limited to the mucosa (clinically T1a), endoscopic submucosal dissection (ESD) can be considered if the tumor is 2 cm or less and is not ulcerated. However, there is insufficient evidence to determine the relationships between tumor size and oncological safety of ESD in UD-EGC.
Methods: The pathology reports of Korean patients who were diagnosed with UD-EGC (n = 5286) were retrospectively reviewed. The cumulative incidence of lymph node metastasis (LNM) according to tumor size was evaluated in subgroups. The tumor-size cut-off was identified as the upper limit of the 95% confidence interval (CI) of cumulative LNM incidence that did not exceed 1.0%.
Results: We identified 1516 patients with non-ulcerated T1a tumors ≤2 cm in size. Among patients without lymphatic invasion, 1.5% (95% CI 0.91-2.16%) had LNM. In patients with poorly differentiated tubular adenocarcinoma (PD), LNM increased from 0 to 0.74% based on a tumor size of 1.0 cm. Regardless of tumor size, smaller percentages of undifferentiated-type (UD) and poorly cohesive carcinoma (PCC) patients experienced LNM than did those with PD. In non-ulcerated mucosal cancer without lymphatic invasion and tumor size ≤0.9 cm, no LNM was observed in patients with UD (95% CI 0-0.53%), PCC (95% CI 0-0.59%), or PD (95% CI 0-0.86%) histologic type.
Conclusion: In patients diagnosed with non-ulcerated T1a UD-EGC, ESD can be performed if the tumor size is 0.9 cm or less, regardless of histologic type.
背景和目的:在治疗局限于粘膜(临床上为T1a)的未分化型早期胃癌(UD-EGC)时,如果肿瘤小于或等于2厘米且没有溃疡,可以考虑进行内镜下粘膜下剥离术(ESD)。然而,目前还没有足够的证据来确定 UD-EGC 中肿瘤大小与 ESD 的肿瘤学安全性之间的关系:方法:对确诊为 UD-EGC 的韩国患者(n = 5286)的病理报告进行了回顾性研究。根据肿瘤大小对亚组淋巴结转移(LNM)的累积发生率进行评估。肿瘤大小的临界值被确定为累计淋巴结转移发生率不超过1.0%的95%置信区间(CI)的上限:我们发现了1516名非溃疡性T1a肿瘤大小≤2厘米的患者。在无淋巴管侵犯的患者中,1.5%(95% CI 0.91-2.16%)的患者有LNM。在分化不良的管状腺癌(PD)患者中,以肿瘤大小为1.0厘米为基准,LNM从0%增加到0.74%。无论肿瘤大小如何,未分化型(UD)和粘连性差的腺癌(PCC)患者出现 LNM 的比例都低于分化型腺癌患者。在无淋巴侵犯、肿瘤大小≤0.9厘米的非溃疡性粘膜癌中,组织学类型为UD(95% CI 0-0.53%)、PCC(95% CI 0-0.59%)或PD(95% CI 0-0.86%)的患者未观察到LNM:结论:对于确诊为非溃疡性T1a UD-EGC的患者,如果肿瘤大小在0.9厘米或以下,无论组织学类型如何,都可以进行ESD治疗。
{"title":"Identification of maximal tumor size associated with negligible lymph node metastasis for endoscopic submucosal dissection of undifferentiated-type early gastric cancer.","authors":"Sung Eun Oh, Soomin Ahn, Kyoung-Mee Kim, Min-Gew Choi, Jun Ho Lee, Tae Sung Sohn, Jae Moon Bae, Ji Yeong An","doi":"10.1007/s10120-024-01498-2","DOIUrl":"10.1007/s10120-024-01498-2","url":null,"abstract":"<p><strong>Background and aims: </strong>When treating undifferentiated-type early gastric cancer (UD-EGC) that is limited to the mucosa (clinically T1a), endoscopic submucosal dissection (ESD) can be considered if the tumor is 2 cm or less and is not ulcerated. However, there is insufficient evidence to determine the relationships between tumor size and oncological safety of ESD in UD-EGC.</p><p><strong>Methods: </strong>The pathology reports of Korean patients who were diagnosed with UD-EGC (n = 5286) were retrospectively reviewed. The cumulative incidence of lymph node metastasis (LNM) according to tumor size was evaluated in subgroups. The tumor-size cut-off was identified as the upper limit of the 95% confidence interval (CI) of cumulative LNM incidence that did not exceed 1.0%.</p><p><strong>Results: </strong>We identified 1516 patients with non-ulcerated T1a tumors ≤2 cm in size. Among patients without lymphatic invasion, 1.5% (95% CI 0.91-2.16%) had LNM. In patients with poorly differentiated tubular adenocarcinoma (PD), LNM increased from 0 to 0.74% based on a tumor size of 1.0 cm. Regardless of tumor size, smaller percentages of undifferentiated-type (UD) and poorly cohesive carcinoma (PCC) patients experienced LNM than did those with PD. In non-ulcerated mucosal cancer without lymphatic invasion and tumor size ≤0.9 cm, no LNM was observed in patients with UD (95% CI 0-0.53%), PCC (95% CI 0-0.59%), or PD (95% CI 0-0.86%) histologic type.</p><p><strong>Conclusion: </strong>In patients diagnosed with non-ulcerated T1a UD-EGC, ESD can be performed if the tumor size is 0.9 cm or less, regardless of histologic type.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858442","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 : 2024-07-01Epub Date: 2024-04-26DOI: 10.1007/s10120-024-01492-8
S C Sodergren, A Hurley-Wallace, V Vassiliou, B Alkhaffaf, B Batsaikhan, A S Darlington, T Fleitas-Kanonnikof, M G Guren, M Honda, Y W Kim, S Kim, M N Krishnamurthy, S Y Loh, N S Turhal, J Zhou, K Dennis, R Krishnatry, M Terashima, G Tsironis, T Yoshikawa, M Terada
Background: The EORTC QLQ-STO22 (QLQ-STO22) is a firmly established and validated measure of health-related quality of life (HRQoL) for people with gastric cancer (GC), developed over two decades ago. Since then there have been dramatic changes in treatment options for GC. Also, East Asian patients were not involved in the development of QLQ-STO22, where GC is most prevalent and the QLQ-STO22 is widely used. A review with appropriate updating of the measure was planned. This study aims to capture HRQoL issues associated with new treatments and the perspectives of patients and health care professionals (HCPs) from different cultural backgrounds, including East Asia.
Methods: A systematic literature review and open-ended interviews were preformed to identify potential new HRQoL issues relating to GC. This was followed by structured interviews where HCPs and patients reviewed the QLQ-STO22 alongside new issues regarding relevance, importance, and acceptability.
Results: The review of 267 publications and interviews with 104 patients and 18 HCPs (48 and 9 from East Asia, respectively) generated a list of 58 new issues. Three of these relating to eating small amounts, flatulence, and neuropathy were recommended for inclusion in an updated version of the QLQ-STO22 and covered by five additional questions.
Conclusions: This study supports the content validity of the QLQ-STO22, suggesting its continued relevance to patients with GC, including those from East Asia. The updated version with additional questions and linguistic changes will enhance its specificity, but further testing is required.
{"title":"Revisiting the use of the EORTC QLQ-STO22 to assess health-related quality of life of patients with gastric cancer: incorporating updated treatment options and cross-cultural perspectives.","authors":"S C Sodergren, A Hurley-Wallace, V Vassiliou, B Alkhaffaf, B Batsaikhan, A S Darlington, T Fleitas-Kanonnikof, M G Guren, M Honda, Y W Kim, S Kim, M N Krishnamurthy, S Y Loh, N S Turhal, J Zhou, K Dennis, R Krishnatry, M Terashima, G Tsironis, T Yoshikawa, M Terada","doi":"10.1007/s10120-024-01492-8","DOIUrl":"10.1007/s10120-024-01492-8","url":null,"abstract":"<p><strong>Background: </strong>The EORTC QLQ-STO22 (QLQ-STO22) is a firmly established and validated measure of health-related quality of life (HRQoL) for people with gastric cancer (GC), developed over two decades ago. Since then there have been dramatic changes in treatment options for GC. Also, East Asian patients were not involved in the development of QLQ-STO22, where GC is most prevalent and the QLQ-STO22 is widely used. A review with appropriate updating of the measure was planned. This study aims to capture HRQoL issues associated with new treatments and the perspectives of patients and health care professionals (HCPs) from different cultural backgrounds, including East Asia.</p><p><strong>Methods: </strong>A systematic literature review and open-ended interviews were preformed to identify potential new HRQoL issues relating to GC. This was followed by structured interviews where HCPs and patients reviewed the QLQ-STO22 alongside new issues regarding relevance, importance, and acceptability.</p><p><strong>Results: </strong>The review of 267 publications and interviews with 104 patients and 18 HCPs (48 and 9 from East Asia, respectively) generated a list of 58 new issues. Three of these relating to eating small amounts, flatulence, and neuropathy were recommended for inclusion in an updated version of the QLQ-STO22 and covered by five additional questions.</p><p><strong>Conclusions: </strong>This study supports the content validity of the QLQ-STO22, suggesting its continued relevance to patients with GC, including those from East Asia. The updated version with additional questions and linguistic changes will enhance its specificity, but further testing is required.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874586","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 : 2024-07-01Epub Date: 2024-04-18DOI: 10.1007/s10120-024-01479-5
Paolo Morgagni, Maria Bencivenga, Fatima Carneiro, Stefano Cascinu, Sarah Derks, Maria Di Bartolomeo, Claire Donohoe, Clarisse Eveno, Suzanne Gisbertz, Peter Grimminger, Ines Gockel, Heike Grabsch, Paulo Kassab, Rupert Langer, Sara Lonardi, Marco Maltoni, Sheraz Markar, Markus Moehler, Daniele Marrelli, Maria Antonietta Mazzei, Davide Melisi, Carlo Milandri, Paul Stefan Moenig, Bianca Mostert, Gianni Mura, Wojciech Polkowski, John Reynolds, Luca Saragoni, Mark I Van Berge Henegouwen, Richard Van Hillegersberg, Michael Vieth, Giuseppe Verlato, Lorena Torroni, Bas Wijnhoven, Guido Alberto Massimo Tiberio, Han-Kwang Yang, Franco Roviello, Giovanni de Manzoni
Background: Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible.
Methods: A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement.
Results: The assembly agreed to define oligometastases as a "dynamic" disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy.
Conclusion: As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.
{"title":"International consensus on the management of metastatic gastric cancer: step by step in the foggy landscape : Bertinoro Workshop, November 2022.","authors":"Paolo Morgagni, Maria Bencivenga, Fatima Carneiro, Stefano Cascinu, Sarah Derks, Maria Di Bartolomeo, Claire Donohoe, Clarisse Eveno, Suzanne Gisbertz, Peter Grimminger, Ines Gockel, Heike Grabsch, Paulo Kassab, Rupert Langer, Sara Lonardi, Marco Maltoni, Sheraz Markar, Markus Moehler, Daniele Marrelli, Maria Antonietta Mazzei, Davide Melisi, Carlo Milandri, Paul Stefan Moenig, Bianca Mostert, Gianni Mura, Wojciech Polkowski, John Reynolds, Luca Saragoni, Mark I Van Berge Henegouwen, Richard Van Hillegersberg, Michael Vieth, Giuseppe Verlato, Lorena Torroni, Bas Wijnhoven, Guido Alberto Massimo Tiberio, Han-Kwang Yang, Franco Roviello, Giovanni de Manzoni","doi":"10.1007/s10120-024-01479-5","DOIUrl":"10.1007/s10120-024-01479-5","url":null,"abstract":"<p><strong>Background: </strong>Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible.</p><p><strong>Methods: </strong>A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement.</p><p><strong>Results: </strong>The assembly agreed to define oligometastases as a \"dynamic\" disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy.</p><p><strong>Conclusion: </strong>As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853716","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 : 2024-07-01Epub Date: 2024-05-23DOI: 10.1007/s10120-024-01509-2
Young-Gyu Park, Hyung-Don Kim, Jaewon Hyung, Young Soo Park, Min-Hee Ryu
Background: We aimed to investigate clinicopathologic factors leading to different clinical outcomes in patients with deficient mismatch repair protein (d-MMR) gastric cancer (GC) treated with nivolumab plus chemotherapy (nivolumab chemotherapy).
Methods: This retrospective study included 28 patients with d-MMR advanced GC treated with first-line nivolumab chemotherapy. As a control group, 68 treated with first-line chemotherapy alone were included. Clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and PD-L1 combined positive score (CPS), were analyzed with regards to the efficacy outcomes.
Results: Progression-free survival (PFS) was longer (median PFS; not reached [NR] vs. 5.2 months, hazard ratio [HR] 0.28, P < 0.001), and overall survival (OS) tended to be longer (median OS; NR vs. 17.9 months, HR 0.43, P = 0.057) in patients treated with nivolumab chemotherapy than those treated with chemotherapy. The PFS benefit of nivolumab chemotherapy over chemotherapy was pronounced in the subgroup with a lower NLR (< 3.80 [median NLR]) (HR 0.10), whereas it was less prominent in patients with a high NLR (≥ 3.80) (HR 0.58). Among patients treated with nivolumab chemotherapy, PFS was worse in patients with a higher NLR (≥ 3.80) than in those with a lower NLR (< 3.80), and survival outcomes were similar between those with PD-L1 CPS ≥ 5 and < 5.
Conclusion: Nivolumab chemotherapy was associated with better efficacy outcomes than chemotherapy alone among patients with d-MMR GC, but survival outcomes were poor even with nivolumab chemotherapy for those with a high NLR. Survival outcomes were not different according to PD-L1 CPS among d-MMR patients treated with nivolumab chemotherapy.
{"title":"Factors associated with the efficacy of first-line nivolumab plus chemotherapy in advanced gastric cancer patients with deficient mismatch repair.","authors":"Young-Gyu Park, Hyung-Don Kim, Jaewon Hyung, Young Soo Park, Min-Hee Ryu","doi":"10.1007/s10120-024-01509-2","DOIUrl":"10.1007/s10120-024-01509-2","url":null,"abstract":"<p><strong>Background: </strong>We aimed to investigate clinicopathologic factors leading to different clinical outcomes in patients with deficient mismatch repair protein (d-MMR) gastric cancer (GC) treated with nivolumab plus chemotherapy (nivolumab chemotherapy).</p><p><strong>Methods: </strong>This retrospective study included 28 patients with d-MMR advanced GC treated with first-line nivolumab chemotherapy. As a control group, 68 treated with first-line chemotherapy alone were included. Clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and PD-L1 combined positive score (CPS), were analyzed with regards to the efficacy outcomes.</p><p><strong>Results: </strong>Progression-free survival (PFS) was longer (median PFS; not reached [NR] vs. 5.2 months, hazard ratio [HR] 0.28, P < 0.001), and overall survival (OS) tended to be longer (median OS; NR vs. 17.9 months, HR 0.43, P = 0.057) in patients treated with nivolumab chemotherapy than those treated with chemotherapy. The PFS benefit of nivolumab chemotherapy over chemotherapy was pronounced in the subgroup with a lower NLR (< 3.80 [median NLR]) (HR 0.10), whereas it was less prominent in patients with a high NLR (≥ 3.80) (HR 0.58). Among patients treated with nivolumab chemotherapy, PFS was worse in patients with a higher NLR (≥ 3.80) than in those with a lower NLR (< 3.80), and survival outcomes were similar between those with PD-L1 CPS ≥ 5 and < 5.</p><p><strong>Conclusion: </strong>Nivolumab chemotherapy was associated with better efficacy outcomes than chemotherapy alone among patients with d-MMR GC, but survival outcomes were poor even with nivolumab chemotherapy for those with a high NLR. Survival outcomes were not different according to PD-L1 CPS among d-MMR patients treated with nivolumab chemotherapy.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081224","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: Although endoscopy is commonly used for gastric cancer screening in South Korea, predictive models that integrate endoscopy results are scarce. We aimed to develop a 5-year gastric cancer risk prediction model using endoscopy results as a predictor.
Methods: We developed a predictive model using the cohort data of the Kangbuk Samsung Health Study from 2011 to 2019. Among the 260,407 participants aged ≥20 years who did not have any previous history of cancer, 435 cases of gastric cancer were observed. A Cox proportional hazard regression model was used to evaluate the predictors and calculate the 5-year risk of gastric cancer. Harrell's C-statistics and Nam-D'Agostino χ2 test were used to measure the quality of discrimination and calibration ability, respectively.
Results: We included age, sex, smoking status, alcohol consumption, family history of cancer, and previous results for endoscopy in the risk prediction model. This model showed sufficient discrimination ability [development cohort: C-Statistics: 0.800, 95% confidence interval (CI) 0.770-0.829; validation cohort: C-Statistics: 0.799, 95% CI 0.743-0.856]. It also performed well with effective calibration (development cohort: χ2 = 13.65, P = 0.135; validation cohort: χ2 = 15.57, P = 0.056).
Conclusion: Our prediction model, including young adults, showed good discrimination and calibration. Furthermore, this model considered a fixed time interval of 5 years to predict the risk of developing gastric cancer, considering endoscopic results. Thus, it could be clinically useful, especially for adults with endoscopic results.
{"title":"Risk prediction model for gastric cancer within 5 years in healthy Korean adults.","authors":"Hyungseok Oh, Sunwoo Cho, Jung Ah Lee, Seungho Ryu, Yoosoo Chang","doi":"10.1007/s10120-024-01488-4","DOIUrl":"10.1007/s10120-024-01488-4","url":null,"abstract":"<p><strong>Background: </strong>Although endoscopy is commonly used for gastric cancer screening in South Korea, predictive models that integrate endoscopy results are scarce. We aimed to develop a 5-year gastric cancer risk prediction model using endoscopy results as a predictor.</p><p><strong>Methods: </strong>We developed a predictive model using the cohort data of the Kangbuk Samsung Health Study from 2011 to 2019. Among the 260,407 participants aged ≥20 years who did not have any previous history of cancer, 435 cases of gastric cancer were observed. A Cox proportional hazard regression model was used to evaluate the predictors and calculate the 5-year risk of gastric cancer. Harrell's C-statistics and Nam-D'Agostino χ<sup>2</sup> test were used to measure the quality of discrimination and calibration ability, respectively.</p><p><strong>Results: </strong>We included age, sex, smoking status, alcohol consumption, family history of cancer, and previous results for endoscopy in the risk prediction model. This model showed sufficient discrimination ability [development cohort: C-Statistics: 0.800, 95% confidence interval (CI) 0.770-0.829; validation cohort: C-Statistics: 0.799, 95% CI 0.743-0.856]. It also performed well with effective calibration (development cohort: χ<sup>2</sup> = 13.65, P = 0.135; validation cohort: χ<sup>2</sup> = 15.57, P = 0.056).</p><p><strong>Conclusion: </strong>Our prediction model, including young adults, showed good discrimination and calibration. Furthermore, this model considered a fixed time interval of 5 years to predict the risk of developing gastric cancer, considering endoscopic results. Thus, it could be clinically useful, especially for adults with endoscopic results.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335308","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 : 2024-07-01DOI: 10.1007/s10120-024-01520-7
Paolo Morgagni, Maria Bencivenga, Fatima Carneiro, Stefano Cascinu, Sarah Derks, Maria Di Bartolomeo, Claire Donohoe, Clarisse Eveno, Suzanne Gisbertz, Peter Grimminger, Ines Gockel, Heike Grabsch, Paulo Kassab, Rupert Langer, Sara Lonardi, Marco Maltoni, Sheraz Markar, Markus Moehler, Daniele Marrelli, Maria Antonietta Mazzei, Davide Melisi, Carlo Milandri, Paul Stefan Moenig, Bianca Mostert, Gianni Mura, Wojciech Polkowski, John Reynolds, Luca Saragoni, Mark I Van Berge Henegouwen, Richard Van Hillegersberg, Michael Vieth, Giuseppe Verlato, Lorena Torroni, Bas Wijnhoven, Guido Alberto Massimo Tiberio, Han-Kwang Yang, Franco Roviello, Giovanni de Manzoni
{"title":"Correction: International consensus on the management of metastatic gastric cancer: step by step in the foggy landscape.","authors":"Paolo Morgagni, Maria Bencivenga, Fatima Carneiro, Stefano Cascinu, Sarah Derks, Maria Di Bartolomeo, Claire Donohoe, Clarisse Eveno, Suzanne Gisbertz, Peter Grimminger, Ines Gockel, Heike Grabsch, Paulo Kassab, Rupert Langer, Sara Lonardi, Marco Maltoni, Sheraz Markar, Markus Moehler, Daniele Marrelli, Maria Antonietta Mazzei, Davide Melisi, Carlo Milandri, Paul Stefan Moenig, Bianca Mostert, Gianni Mura, Wojciech Polkowski, John Reynolds, Luca Saragoni, Mark I Van Berge Henegouwen, Richard Van Hillegersberg, Michael Vieth, Giuseppe Verlato, Lorena Torroni, Bas Wijnhoven, Guido Alberto Massimo Tiberio, Han-Kwang Yang, Franco Roviello, Giovanni de Manzoni","doi":"10.1007/s10120-024-01520-7","DOIUrl":"10.1007/s10120-024-01520-7","url":null,"abstract":"","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330723","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}
Background: Microsatellite instability-high (MSI-H) tumors are distinct molecular subtypes in gastric cancer. However, a few studies have comprehensively reported the molecular features of MSI-H tumors and their prognostic factors in locally advanced gastric cancer. This study aimed to clarify the molecular features and prognostic factors of locally advanced MSI-H gastric cancer.
Methods: This study included 499 patients with locally advanced gastric cancer who underwent radical gastrectomy. We evaluated the MSI status and compared with previously published whole-exome sequencing, panel sequencing, and gene expression profiling data. Clinicopathological characteristics and molecular profiles were compared between patients with MSI-H and microsatellite stable (MSS) gastric cancer. A subgroup analysis of survival was performed in patients with MSI-H gastric cancer.
Results: MSI-H tumors were detected in 79 of 499 patients (15.8%). MSI-H tumors were associated with an increased tumor mutational burden, MLH1 downregulation, CD274 (PD-L1) upregulation, and enrichment of cell cycle pathways. Among patients with MSI-H gastric cancer, the disease-specific survival (DSS) tended to be better in the surgery plus tegafur, gimeracil, and oteracil potassium (S-1) adjuvant chemotherapy group than in the surgery alone group, especially for stage III patients. Furthermore, DSS was better in the T cell-inflamed gene expression signature-high group, and it tended to be worse in the non-solid type poorly differentiated adenocarcinoma group.
Conclusions: The molecular features and prognostic factors of locally advanced MSI-H gastric cancer were clarified. S-1 adjuvant chemotherapy appears to be beneficial, and the T cell-inflamed gene expression signature and histopathological type are prognostic factors in MSI-H tumors.
{"title":"Molecular features and prognostic factors of locally advanced microsatellite instability-high gastric cancer.","authors":"Kenichiro Furukawa, Keiichi Hatakeyama, Masanori Terashima, Kenichi Urakami, Yusuke Koseki, Keiichi Fujiya, Yutaka Tanizawa, Etsuro Bando, Ken Yamaguchi","doi":"10.1007/s10120-024-01506-5","DOIUrl":"10.1007/s10120-024-01506-5","url":null,"abstract":"<p><strong>Background: </strong>Microsatellite instability-high (MSI-H) tumors are distinct molecular subtypes in gastric cancer. However, a few studies have comprehensively reported the molecular features of MSI-H tumors and their prognostic factors in locally advanced gastric cancer. This study aimed to clarify the molecular features and prognostic factors of locally advanced MSI-H gastric cancer.</p><p><strong>Methods: </strong>This study included 499 patients with locally advanced gastric cancer who underwent radical gastrectomy. We evaluated the MSI status and compared with previously published whole-exome sequencing, panel sequencing, and gene expression profiling data. Clinicopathological characteristics and molecular profiles were compared between patients with MSI-H and microsatellite stable (MSS) gastric cancer. A subgroup analysis of survival was performed in patients with MSI-H gastric cancer.</p><p><strong>Results: </strong>MSI-H tumors were detected in 79 of 499 patients (15.8%). MSI-H tumors were associated with an increased tumor mutational burden, MLH1 downregulation, CD274 (PD-L1) upregulation, and enrichment of cell cycle pathways. Among patients with MSI-H gastric cancer, the disease-specific survival (DSS) tended to be better in the surgery plus tegafur, gimeracil, and oteracil potassium (S-1) adjuvant chemotherapy group than in the surgery alone group, especially for stage III patients. Furthermore, DSS was better in the T cell-inflamed gene expression signature-high group, and it tended to be worse in the non-solid type poorly differentiated adenocarcinoma group.</p><p><strong>Conclusions: </strong>The molecular features and prognostic factors of locally advanced MSI-H gastric cancer were clarified. S-1 adjuvant chemotherapy appears to be beneficial, and the T cell-inflamed gene expression signature and histopathological type are prognostic factors in MSI-H tumors.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921868","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}