霜降已至，作为秋季的最后一个节气，意味着秋末冬初的到来。随着白昼渐短，黑夜渐长，早晚的温差让人感受到季节的更迭。在这样的气候条件下，我们更应该关注身体健康，适时增添衣物。愿每个人都能在这个季节里，享受秋日的宁静与冬日的温馨，健康快乐地迎接每一个清晨与夜晚。
01
J Clin Oncol (IF: 42.1; Q1). 2024 Oct 9:JCO2400795.
doi: 10.1200/JCO.24.00795. Online ahead of print.
Pathologic Response of Phase III Study: Perioperative Camrelizumab Plus Rivoceranib and Chemotherapy Versus Chemotherapy for Locally Advanced Gastric Cancer (DRAGON IV/CAP 05)
III 期研究的病理学反应：局部晚期胃癌围手术期 Camrelizumab 联合 Rivoceranib 和化疗与化疗对比 (DRAGON IV/CAP 05)
Purpose: This multicenter, randomized phase III trial evaluated the efficacy and safety of perioperative camrelizumab (an anti-PD-1 antibody) plus low-dose rivoceranib (a VEGFR-2 inhibitor) and S-1 and oxaliplatin (SOX) (SOXRC), high-dose rivoceranib plus SOX (SOXR), and SOX alone (SOX) for locally advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.
Methods: Patients with T3-4aN + M0 G/GEJ adenocarcinoma were randomly assigned (1:1:1) to receive perioperative treatment with SOXRC, SOXR, or SOX. The primary end points were pathologic complete response (pCR) and event-free survival. The Independent Data Monitoring Committee recommended stopping enrollment in the SOXR group on the basis of the safety data of the first 103 randomly assigned patients in the three groups. The patients were then randomly assigned 1:1 to the SOXRC or SOX groups. This report presents the pCR results obtained per protocol for the first 360 randomly assigned patients who had the opportunity for surgery in the SOXRC and SOX groups.
Results: In the SOXRC and SOX groups, of the 180 patients in each group, 99% and 98% of patients received neoadjuvant therapy, 91% and 94% completed planned neoadjuvant therapy, and 86% and 87% underwent surgery, respectively. The pCR was significantly higher in the SOXRC group at 18.3% (95% CI, 13.0 to 24.8) compared with 5.0% (95% CI, 2.3 to 9.3) in the SOX group (difference of 13.7%; 95% CI, 7.2 to 20.1; odds ratio of 4.5 [95% CI, 2.1 to 9.9]). The one-sided P value was <.0001, crossing the prespecified statistical significance threshold of P = .005. Surgical complications and grade ≥3 neoadjuvant treatment-related adverse events were 27% versus 33% and 34% versus 17% for SOXRC and SOX, respectively.
Conclusion: The SOXRC regimen significantly improved pCR compared with SOX alone in patients with G/GEJ adenocarcinoma with a tolerable safety profile.
2
J Clin Oncol (IF: 42.1; Q1). 2024 Oct 4:JCO2400055.
doi: 10.1200/JCO.24.00055. Online ahead of print.
INTEGRATE IIa Phase III Study: Regorafenib for Refractory Advanced Gastric Cancer
INTEGRATE IIa III 期研究：瑞戈非尼治疗难治性晚期胃癌
Abstract
Purpose: Treatment options for refractory advanced gastric and esophagogastric junction cancer (AGOC) are limited. Regorafenib, an oral multikinase inhibitor, prolonged progression-free survival (PFS) versus placebo in the INTEGRATE I phase II trial. INTEGRATE IIa was designed to examine whether regorafenib improved overall survival (OS).
Methods: A double-blind placebo-controlled phase III trial compared regorafenib and best supportive care (BSC) versus placebo and BSC for participants with confirmed evaluable metastatic/advanced AGOC who failed ≥two prior therapies on a 2:1 random assignment, stratified by tumor location, geographic region (Asia v rest of world), and prior vascular endothelial growth factor inhibitors. The primary end point was OS. Treatment efficacy on OS was first tested in the pooled INTEGRATE I + INTEGRATE IIa cohort and, if significant, then in the INTEGRATE IIa cohort. Secondary end points were PFS, objective response rate, safety, and quality of life (QoL).
Results: INTEGRATE IIa enrolled 251 participants: 157 from Asia and 94 from rest of world and 169 received regorafenib and 82 received placebo. No significant heterogeneity was observed between INTEGRATE I and INTEGRATE IIa studies on OS. Pooled OS analysis hazard ratio (HR) was 0.70 (95% CI, 0.56 to 0.87; P = .001; 361 events). INTEGRATE IIa alone OS HR was 0.68 (95% CI, 0.52 to 0.90; P = .006; 238 events), the median OS was 4.5 months versus 4.0 months, and 12-month survival rates were 19% and 6%, for regorafenib versus placebo, respectively. After a preplanned adjustment for multiplicity, there were no statistically significant differences across regions or other prespecified subgroups. Regorafenib improved PFS (HR, 0.53 [95% CI, 0.40 to 0.70]; P < .0001) and delayed deterioration in global QoL (HR, 0.68 [95% CI, 0.52 to 0.89]; P = .0043). The toxicity profile was consistent with that of previous reports.
Conclusion: Regorafenib improves survival compared with placebo in refractory AGOC.
3
J Clin Oncol (IF: 42.1; Q1). 2024 Oct 21:JCO2400410.
doi: 10.1200/JCO.24.00410. Online ahead of print.
DKN-01 in Combination With Tislelizumab and Chemotherapy as First-Line Therapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: DisTinGuish
DKN-01 联合替雷利珠单抗和化疗作为晚期胃或胃食管结合部腺癌的一线治疗：DisTinGuish
Abstract
Purpose: The outcomes of anti-PD-1 agents plus fluoropyrimidine/platinum in frontline advanced gastroesophageal adenocarcinomas (aGEAs) remain poor. We investigated the safety, tolerability, and activity of fluoropyrimidine/oxaliplatin and tislelizumab with the DKK1-neutralizing antibody DKN-01 in aGEAs in a phase IIa open-label study.
Patients and methods: Patients had untreated human epidermal growth factor receptor 2-negative aGEAs, RECIST v1.1 measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and adequate organ function. Patients received intravenous DKN-01 300 mg once every 2 weeks, tislelizumab 200 mg once every 3 weeks, oxaliplatin 130 mg/m2 once every 3 weeks, and capecitabine 1,000 mg/m2 twice daily on days 1-15 of each 21-day cycle. The primary end point was safety and tolerability. Key secondary end points included objective response rate (ORR) by RECISTv1.1, progression-free survival (PFS), and overall survival (OS).
Results: Between September 18, 2020, and April 8, 2021, 25 patients were enrolled. All patients who received at least one dose of DKN-01 were included in the safety analysis. Most patients had gastroesophageal junction tumors, median age was 61 years, 76% were male, and 55% were ECOG of 0. All patients reported at least one treatment-emergent adverse event. The ORR was 73% (95% CI, 49.8 to 89.3), with a disease control rate of 95%. The ORR was 90% (95% CI, 55.5 to 99.7) in the DKK1-high tumor patients and 67% (95% CI, 29.9 to 92.5) in the DKK1-low tumor patients. The median PFS was 11.3 months (95% CI, 5.8 to 12.0) and the 12-month PFS rate was 33%. The median OS was 19.5 months (95% CI, 15.2 to 24.4) with a 12-month OS rate of 76% and an 18-month OS rate of 55%.
Conclusion: DKN-01 can be safely combined with frontline fluoropyrimidine/oxaliplatin and tislelizumab and demonstrates encouraging activity independent of PD-L1 expression levels. A randomized phase II trial is ongoing (ClinicalTrials.gov identifier: NCT04363801).
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Nat Commun (IF: 14.7; Q1). 2024 Oct 15;15(1):8876.
doi: 10.1038/s41467-024-53109-4.
Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial
纳武利尤单抗联合盐酸安罗替尼治疗晚期胃腺癌和食管鳞状细胞癌：II 期 OASIS 试验
Abstract
Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs), possess immunomodulatory properties and have shown promising outcomes when combined with anti-PD-1 antibodies. The OASIS phase II trial (NCT04503967) is designed to determine the clinical activity and safety of nivolumab (anti-PD-1) and anlotinib hydrochloride (a multi-targets TKI) as second-line or above therapy in patients with advanced gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC). From December 2020 to September 2022, 45 patients with GAC and 3 with ESCC were enrolled in this study. The pre-specified endpoints were reached, with the primary endpoint of overall response rate achieving 29.2%. For secondary objectives, disease control rate was 64.6%; median progression-free survival was 4.0 months; and median overall survival was 11.1 months with a manageable toxicity profile. The exploratory analyses unveiled that the balance of gut bacteria and the presence of a pre-existing immune signature characterized by a high percentage of CD68+ PD-L1+ PD-1+ macrophages and low pretreatment variant allele frequencies (VAF), as well as low expression of certain cytokines were significantly associated with improved clinical outcomes in patients with GAC.
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Ageing Res Rev (IF: 12.5; Q1). 2024 Oct 2:101:102528.
doi: 10.1016/j.arr.2024.102528. Online ahead of print.
Frailty as a predictor of adverse outcomes in patients with gastric cancer: A systematic review and meta-analysis of 75,357 patients
虚弱是胃癌患者不良结局的预测因子：对 75,357 名患者的系统回顾和荟萃分析
Abstract
Background: Frailty is the most problematic expression of population ageing, which has been associated with increased mortality and complications among patients with gastric cancer (GC). However, previous evidence about the frailty prevalence and outcomes in frail populations with gastric cancer remains unknown.
Methods: Eligible studies were searched in Embase, PubMed, Scopus, and Web of Science to explore the prevalence and impact of frailty in patients with gastric cancer from inception until November 25, 2023. The pooled prevalence of frailty, hazard ratio (HR), and odds ratio (OR) corresponding 95 % confidence intervals (CI) in mortality and postoperative complications estimates were analyzed.
Results: A total of 24 studies containing 75,357 GC patients were involved. The prevalence of frailty in gastric cancer was 27 % (95 % CI = 24-30; I2= 96.7 %; p = 0.000). Frailty was independently associated with an increased hazard ratio for mortality (adjusted HR = 2.14; 95 % CI = 1.60-2.86; I2= 67.3 %, p = 0.000). Furthermore, frailty was significantly associated with an increased odds ratio for postoperative complication in GC patients (adjusted OR = 2.65; 95 % CI = 2.17-3.25; I2= 0.0 %, Cochran's Q = 1.20, p = 0.878).
Conclusion: The prevalence of frailty in gastric cancer is common and has a significant adverse effect on GC patients' outcomes. Our findings highlight the importance of routine frailty assessment in GC patients, which may provide prognostic outcomes.
6
Clin Gastroenterol Hepatol (IF: 11.6; Q1). 2024 Oct 1:S1542-3565(24)00864-4.
doi: 10.1016/j.cgh.2024.09.003. Online ahead of print.
Global Progression Rates of Precursor Lesions for Gastric Cancer: A Systematic Review and Meta-Analysis
胃癌前体病灶的全球进展率：系统回顾和荟萃分析
Abstract
Background and aims: Whether gastric cancer (GC) precursor lesions progress to invasive cancer at similar rates globally remains unknown. We conducted a systematic review and meta-analysis to determine the progression of precursor lesions to GC in countries with low versus medium/high incidence.
Methods: We searched relevant databases for studies reporting the progression of endoscopically confirmed precursor lesions to GC. Studies were stratified by low (<6 per 100,000) or medium/high (≥6 per 100,000) GC incidence countries. Random-effects models were used to estimate the progression rates of atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia to GC per 1,000 person-years.
Results: Among the 5,829 studies identified, 44 met our inclusion criteria. The global pooled estimates of the progression rate per 1,000 person-years were 2.09 (95% CI 1.46-2.99), 2.89 (2.03-4.11) and 10.09 (5.23-19.49) for AG, IM, and dysplasia respectively. The estimated progression rates per 1,000 person-years for low versus medium/high GC incidence countries, respectively, were 0.97 (0.86-1.10) vs. 2.47 (1.70-2.99) for AG (p<0.01); 2.37 (1.43-3.92) vs. 3.47 (2.13-5.65) for IM (p=0.29); and 5.51 (2.92-10.39) vs. 14.80 (5.87-37.28) for dysplasia (p=0.08). There were no differences for progression of AG between groups when high quality studies were compared.
Conclusion: Similar progression rates of IM and dysplasia were observed among low and medium/high GC incidence countries. This suggests that the potential benefits of surveillance for these lesions in low-risk regions may be comparable to those of population-wide interventions in high-risk regions. Further prospective studies are needed to confirm these findings and inform global screening and surveillance guidelines.
7
MedComm (2020) (IF: 10.7; Q1). 2024 Oct 28;5(11):e762.
doi: 10.1002/mco2.762IF: 10.7 Q1 . eCollection 2024 Nov.
Reduced intestinal-to-diffuse conversion and immunosuppressive responses underlie superiority of neoadjuvant immunochemotherapy in gastric adenocarcinoma
肠道向弥漫性转化的减少和免疫抑制反应是新辅助免疫化疗在胃腺癌中优效性的基础
Abstract
Neoadjuvant immunochemotherapy (NAIC) achieves superior clinical benefits over neoadjuvant chemotherapy (NAC) in multiple types of human cancers, including gastric adenocarcinoma (GAC). However, it is poorly understood how the malignant epithelial cells and tumor immune microenvironment (TIME) might respond distinctly to NAIC and NAC that underlies therapeutic efficacy. Here treatment-naive and paired tumor tissues from multiple centers were subjected to pathological, immunological, and transcriptomic analysis. NAIC demonstrated significantly increased rate of pathological complete response compared to NAC (pCR: 25% vs. 4%, p < 0.05). Interestingly, pretreatment intestinal subtype of Lauren's classification was predictive of pathologic regression following NAIC, but not NAC. A substantial portion of cancers underwent intestinal-to-diffuse transition, which occurred less following NAIC and correlated with treatment failure. Moreover, NAIC prevented reprogramming to an immunosuppressive TIME with less active fibroblasts and exhausted CD8+ T cells, and increased numbers of mature tertiary lymphoid structures. Mechanistically, activation of the tumor necrosis factor alpha (TNFα)/nuclear factor-kappa B (NF-κB) signaling pathway was associated with response to NAIC. Together, NAIC is superior to NAC for locally advanced GAC, likely due to reduced intestinal-to-diffuse conversion and reprogramming to an immuno-active TIME. Modulation of the histological conversion and immunosuppressive TIME could be translatable approaches to improve neoadjuvant therapeutic efficacy.
8
Radiol Med (IF: 9.7; Q1). 2024 Oct 1.
doi: 10.1007/s11547-024-01892-x. Online ahead of print.
From twilight to starlight? Debating the role of chemoradiotherapy in gastric cancer in the D2 dissection era
从黄昏到星光闪耀？ D2切除时代放化疗在胃癌中的作用争论
Abstract
Patients affected by resectable locally advanced gastric cancer (GC) should receive perioperative chemotherapy as a standard of care. However, an additional benefit of adjuvant chemoradiation (CRT) has been negated by modern trials in the era of extended surgical dissection, and CRT is currently only considered on an individual basis in case of suboptimal resection. However, the dismal prognosis of GC and the modest treatment completion rates of perioperative chemotherapy have pushed to reconsider CRT, particularly as a preoperative treatment, in light of modern treatment techniques, advances in the understanding of the immune landscape and development of targeted agents. The aim of this review is to critically assess the historical role of CRT, the limitations of current evidence and to debate its potential role in an integrated neoadjuvant strategy for patients with resectable GC.
9
J Nucl Med (IF: 9.1; Q1). 2024 Oct 10:jnumed.124.267529.
doi: 10.2967/jnumed.124.267529. Online ahead of print.
Granzyme B PET/CT Imaging Evaluates Early Response to Immunotherapy in Gastric Cancer
颗粒酶 B PET/CT 成像评估胃癌免疫治疗的早期反应
Abstract
In several malignancies, only a limited number of patients respond to immune checkpoint inhibitors. Predicting and monitoring responses to these inhibitors represent an unmet clinical need. Here, we developed a PET/CT probe targeting granzyme B, [68Ga]Ga-NOTA-Gly-Gly-Gly-Ile-Glu-Pro-Asp-CHO (GSI), and aimed to investigate whether it can be used to monitor the effects of immune checkpoint inhibitors early in the course of therapy.
Methods: Seventy-two patients with gastric cancer (stages III-IV) were recruited for [68Ga]Ga-DOTA-GSI PET/CT imaging after 2 or 3 cycles of the immunotherapy, and 40 patients were included in the final analysis. The SUVmax of primary tumors (SUVmax-t), SUVmax of metastatic lymph nodes (SUVmax-LN), and SUVmax of normal tissues (liver and blood pool) were measured, and their target-to-liver background ratio (TLR) and target-to-blood background ratio (TBR) were denoted for primary tumors as TLRtumor and TBRtumor and for metastatic lymph nodes as TLRLN and TBRLN, respectively. The treatment responses were assessed within 1 wk after full-course treatment according to RECIST version 1.1. Wilcoxon rank-sum tests were used to compare the PET/CT parameters between responders and nonresponders. Receiver operating characteristic curve analysis was used to assess the diagnostic efficacy of [68Ga]Ga-DOTA-GSI PET/CT parameters in identifying responders. Two-tailed P value of less than 0.05 was considered statistically significant.
Results: We found that SUVmax-t, TLRtumor, TBRtumor, SUVmax-LN, and TBRLN were higher in responders than in nonresponders (2.49 ± 0.58 vs. 1.55 ± 0.48, P = 0.000; 2.24 ± 0.48 vs. 1.74 ± 0.67, P = 0.007; 1.38 ± 0.43 vs. 0.90 ± 0.23, P = 0.000; 2.24 ± 0.99 vs. 1.42 ± 0.55, P = 0.003; and 1.28 ± 0.68 vs. 0.83 ± 0.32, P = 0.012, respectively). According to receiver operating characteristic curve analysis, the area under the curve for SUVmax-t, TBRtumor, TLRtumor, SUVmax-LN, TLRLN, and TBRLN was 0.886, 0.866, 0.746, 0.772, 0.648, and 0.731, respectively. The threshold of SUVmax-t was 2.05, and its sensitivity and specificity were 81.0% and 84.2%, respectively. In addition, multivariate logistic regression indicated that TBRtumor was an independent predictor of treatment response (P = 0.03).
Conclusion: Our results indicated that [68Ga]Ga-DOTA-GSI PET/CT is a promising tool for predicting early response to combined immunotherapy in gastric cancer patients.
10
Cell Commun Signal (IF: 8.2; Q1). 2024 Oct 24;22(1):518.
doi: 10.1186/s12964-024-01893-3.
Immunomodulatory effects of trastuzumab deruxtecan through the cGAS-STING pathway in gastric cancer cells
德曲妥珠单抗通过 cGAS-STING 通路对胃癌细胞的免疫调节作用
11
Clin Transl Med (IF: 7.9; Q1). 2024 Oct;14(10):e70054.
doi: 10.1002/ctm2.70054.
Single-cell characterization of differentiation trajectories and drug resistance features in gastric cancer with peritoneal metastasis
胃癌腹膜转移分化轨迹的单细胞特征和耐药特征
Background: Gastric cancer patients with peritoneal metastasis (GCPM) experience a rapidly deteriorating clinical trajectory characterized by therapeutic resistance and dismal survival, particularly following the development of malignant ascites. However, the intricate dynamics within the peritoneal microenvironment (PME) during the treatment process remain largely unknown.
Methods: Matched samples from primary tumours (PT), peritoneal metastases (PM), and paired pre-treatment and post-chemo/immunotherapy (anti-PD-1/PD-L1) progression malignant ascites samples, were collected from 48 patients. These samples were subjected to single-cell RNA sequencing (n = 30), multiplex immunofluorescence (n = 30), and spatial transcriptomics (n = 3). Furthermore, post hoc analyses of a phase 1 clinical trial (n = 20, NCT03710265) and an in-house immunotherapy cohort (n = 499) were conducted to validate the findings.
Results: Tracing the evolutionary trajectory of epithelial cells unveiled the terminally differentially MUC1+ cancer cells with a high epithelial-to-mesenchymal transition potential, and they demonstrated spatial proximity with fibroblasts and endothelial cells, correlating with poor prognosis. A significant expansion of macrophage infiltrates, which exhibited the highest proangiogenic activity, was observed in the ascites compared with PT and PM. Besides, higher C1Q+ macrophage infiltrates correlated with significantly lower GZMA+ T-lymphocyte infiltrates in therapeutic failure cases, potentially mediated by the LGALS9-CD45 and SPP1-CD44 ligand-receptor interactions. In the chemoresistant group, intimate interactions between C1Q+ macrophages and fibroblasts through the complement activation pathway were found. In the group demonstrating immunoresistance, heightened TGF-β production activity was detected in MUC1+ cancer cells, and they were skewed to interplay with C1Q+ macrophages through the GDF15-TGF-βR2 axis. Ultimately, post hoc analyses indicated that co-targeting TGF-β and PDL1 pathways may confer superior clinical benefits than sole anti-PD-1/PD-L1 therapy for patients presenting with GCPM at the time of diagnosis.
Conclusions: Our findings elucidated the cellular differentiation trajectories and crucial drug resistance features within PME, facilitating the exploration of effective targets for GCPM treatment.
Highlights: MUC1+ cancer cells with a high epithelial-to-mesenchymal transition potential and exhibiting spatial proximity to fibroblasts and endothelial cells constitute the driving force of gastric cancer peritoneal metastasis (GCPM). Higher C1Q+ macrophage infiltrates correlated with significantly lower GZMA+ T-lymphocyte infiltrates within the peritoneal microenvironment in therapeutic failure cases. Co-targeting TGF-β and PDL1 pathways may confer superior clinical benefits than sole anti-PD-1/PD-L1 therapy for patients presenting with GCPM at diagnosis.
12
Cell Rep (IF: 7.5; Q1). 2024 Oct 22;43(10):114774.
doi: 10.1016/j.celrep.2024.114774. Epub 2024 Oct 1.
Phosphoproteomic subtyping of gastric cancer reveals dynamic transformation with chemotherapy and guides targeted cancer treatmen
胃癌的磷酸化蛋白质组亚型揭示化疗的动态转变并指导靶向癌症治疗
There are only a few effective molecular targeted agents for advanced unresectable or recurrent advanced gastric cancer (AGC), which has a poor prognosis with a median survival time of less than 14 months. Focusing on phosphorylation signaling in cancer cells, we have been developing deep phosphoproteome analysis from minute endoscopic biopsy specimens frozen within 20 s of collection. Phosphoproteomic analysis of 127 fresh-frozen endoscopic biopsy samples from untreated patients with AGC revealed three subtypes reflecting different cellular signaling statuses. Subsequent serial biopsy analysis has revealed the dynamic mesenchymal transitions within cancer cells, along with the concomitant rewiring of the kinome network, ultimately resulting in the conversion to the epithelial-mesenchymal transition (EMT) subtype throughout treatment. We present our investigation of intracellular signaling related to the EMT in gastric cancer and propose therapeutic approaches targeting AXL. This study also provides a wealth of resources for the future development of treatments and biomarkers for AGC.
13
Comput Biol Med (IF: 7.0; Q1). 2024 Oct 23:183:109276.
doi: 10.1016/j.compbiomed.2024.109276. Online ahead of print.
Molecular characterization and biomarker discovery in gastric cancer progression through transcriptome meta-analysis
通过转录组荟萃分析发现胃癌进展的分子特征和生物标志物
Gastric cancer (GC) is a leading cause of cancer-related deaths globally. It is a multifactorial, molecularly heterogeneous disease whose carcinogenic patterns are not yet well established, requiring the development of new tools for better understanding and identifying gastric carcinogenesis. From this point of view, this study aims to compare transcriptome profiles from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) and a human-merged dataset to identify potential biomarkers and therapeutic targets. Principal component analysis (PCA) revealed shared and distinct gene expression patterns between datasets. Differential expression analysis identified key genes with altered expression across non-malignant and malignant samples. Six genes, including SERPINE1 and CLDN9, were significantly associated with patient survival. The findings underscore the molecular diversity of GC and highlight novel biomarkers for early diagnosis and therapeutic strategies. Further validation in clinical specimens is necessary.
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Gastric Cancer (IF: 6.0; Q1). 2024 Oct 10.
doi: 10.1007/s10120-024-01558-7. Online ahead of print.
Neoadjuvant chemotherapy in relation to long-term mortality in individuals cured of gastric adenocarcinoma
新辅助化疗与胃腺癌治愈患者长期死亡率的关系
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.
15
Gastric Cancer (IF: 6.0; Q1). 2024 Oct 10.
doi: 10.1007/s10120-024-01555-w. Online ahead of print.
Real-world effectiveness and safety of trastuzumab-deruxtecan in Japanese patients with HER2-positive advanced gastric cancer (EN-DEAVOR study)
德曲妥珠单抗治疗HER2 阳性晚期胃癌日本患者的真实世界有效性和安全性（EN-DEAVOR 研究）
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.
Clinical trial registration: UMIN000049032.
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Gastric Cancer (IF: 6.0; Q1). 2024 Oct 5.
doi: 10.1007/s10120-024-01556-9. Online ahead of print.
Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer
循环肿瘤DNA预测可切除胃癌和胃食管交界癌患者的复发和生存
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.
17
Cancer Biol Med (IF: 5.6; Q1). 2024 Oct 30;21(10):j.issn.2095-3941.2024.0224.
doi: 10.20892/j.issn.2095-3941.2024.0224.
Intricate roles of estrogen and estrogen receptors in digestive system cancers: a systematic review
雌激素和雌激素受体在消化系统肿瘤中的复杂作用：系统评价
Gender disparities are evident across different types of digestive system cancers, which are typically characterized by a lower incidence and mortality rate in females compared to males. This finding suggests a potential protective role of female steroid hormones, particularly estrogen, in the development of these cancers. Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors (ERs), including the classic (ERα and ERβ) and non-traditional ERs [G protein-coupled estrogen receptor (GPER)]. Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers. In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers, including hepatocellular, pancreatic, esophageal, gastric, and colorectal carcinoma. Furthermore, we discuss the potential molecular mechanisms underlying ERα, ERβ, and GPER effects, and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs. The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved. Additionally, deciphering the intricate roles of estrogen, ERs, and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers, eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.
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