Mid-term follow-up results of neoadjuvant sintilimab combined with chemotherapy for locally advanced resectable esophageal squamous cell carcinoma.

The study was conducted in order to investigate whether neoadjuvant immunotherapy combined with chemotherapy can bring survival benefits to patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) in the real world. We retrospectively analysed patients with locally advanced resectable ESCC who underwent surgery at the Jining First People's Hospital from April 2020 to April 2022. Based on their medical history, the enrolled patients were divided into a neoadjuvant immunochemotherapy plus surgery group (nICT group) and a surgery-only group (S group). Primary endpoints were the two-year overall survival (OS) and disease-free survival (DFS) rates. Secondary endpoints were the safety and efficacy of neoadjuvant immunochemotherapy for patients with locally advanced esophageal cancer, and compared the surgery and postoperative outcomes between the two groups. A total of 47 patients in the nICT group and 73 patients in the S group were included for further analysis, the stage of the nICT group was more advanced than that of the S group. In the group nICT, 8 patients (17%) achieved the complete pathological response (pCR), 29 patients (61.7%) achieved major pathological response (MPR), including 6 patients (12.8%) with a primary tumor achieving pCR but had residual tumor cells in the lymph nodes (pT0N+), and the treatment-related AES was manageable. The surgery and postoperative outcomes were comparable in both groups. The two-year OS and DFS rates for the nICT group were 91.5% and 85.5% respectively, while those for the S group were 71.2% and 68.5%, and Kaplan-Meier survival analysis and log-rank test revealed significant differences in DFS and OS between the two groups. Patients who achieved MPR in the nICT group showed better DFS and OS, while the Three-cycle subgroup did not exhibit any survival benefit compared to the Two-cycle subgroup. Neoadjuvant sintilimab combined with chemotherapy has promising efficacy and safety in the treatment of locally advanced resectable ESCC. The treatment modality has the potential to become a standard therapy for locally advanced resectable ESCC.

Cai H ，Chen L ，Huang J ，Ma H ，Zhang S ，Zhong K ，Yang D ，Sun J ，Liu H ，Song R ... -  《Frontiers in Immunology》

Adjuvant immunotherapy after neoadjuvant immunochemotherapy and esophagectomy for esophageal squamous cell carcinoma: a real-world study.

The role of immunotherapy in the adjuvant setting seems promising in recent years. As per the findings of the CheckMate 577 trial, patients with esophageal cancer (EC) who had neoadjuvant chemoradiation with residual pathologic disease should be considered adjuvant immunotherapy (AIT). However, it is unknown if individuals with esophageal squamous cell carcinoma (ESCC) who have received neoadjuvant immunochemotherapy (NICT) followed by radical surgery also require AIT. A retrospective analysis was performed on the data from patients who underwent NICT and radical surgery for ESCC between 2019 and 2020. To compare disease-free survival (DFS) and overall survival (OS), Kaplan-Meier survival curves were produced. To determine the parameters linked to DFS and OS, a Cox model using hazard ratios (HRs) was completed. Among the 292 eligible patients, 215 cases with a mean age of 63.3 ± 6.8 years, including 190 (88.4%) men and 25 (11.6%) women, were finally recruited. The percentage of R0 resection was 98.3%. After NICT, 65 (30.2%) patients achieved pathological complete response. AIT was given to 78 (36.3%) patients following radical resection. For all patients, the 3-year DFS and OS were 62.3% and 74.0%, respectively. In terms of 3-year DFS (61.5% vs. 62.8%, P=0.984) or OS (76.9% vs. 72.3%, P=0.384), no statistically significant difference was found between patients with and without AIT. AIT significantly improved survival in patients with ypT+N+ (DFS: 23.9% vs. 38.5%, P=0.036; OS: 37.0% vs. 61.5%, P=0.010), but not in those with ypT0N0 or ypT+N0. It was found that AIT was related to both DFS (HR: 0.297; P<0.001) and OS (HR: 0.321; P=0.001) in patients with ypT+N+. In ypT+N+ ESCC patients, AIT after NICT followed by radical surgery reduces the recurrence and death, thereby improving the DFS and OS. Randomized controlled trials ought to be conducted to further assess the results of this retrospective investigation.

Feng J ，Wang L ，Yang X ，Chen Q ... -  《Frontiers in Immunology》

Perioperative tislelizumab with four cycles of neoadjuvant chemotherapy for resectable locally advanced esophageal squamous cell carcinoma: a phase 2 study.

The application of neoadjuvant immunotherapy in the treatment of esophageal cancer needs further exploration. This study aimed to investigate the safety and effectiveness of tislelizumab, an anti-PD-1 antibody, combined with chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (LA-ESCC). In this phase II study, patients with clinical stages of II-IVA (T3-T4 and/or node positive) potentially resectable LA-ESCC were enrolled. Patients received neoadjuvant tislelizumab and chemotherapy every 3 weeks for 4 cycles before surgery and adjuvant tislelizumab for 9 months. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included R0 resection, disease free survival (DFS), adverse events (AE), and biomarkers for predicting efficacy. The study included 30 patients. 25 patients completed neoadjuvant chemoimmunotherapy and underwent surgery, 96% with R0 resection. The pCR and MPR rate was 44% and 52%. The 6-month and 1-year DFS rate was 100% and 75.3%. 43.3% patients experienced severe (grade 3-4) treatment-related adverse events (TRAEs) and 5 patients developed severe immune-related adverse events (irAEs). Further exploration found that a group of peripheral lymphocyte subsets increased significantly after 2 cycles of neoadjuvant therapy in patients who achieved pCR, suggesting the importance of dynamic monitoring of circulating lymphocyte. The combination of perioperative tislelizumab and neoadjuvant chemotherapy has achieved an encouraging pCR rate and demonstrated a manageable safety profile in patients with potentially resectable ESCC. https://www.chictr.org.cn/, identifier ChiCTR2100043772.

Zhou N ，Hua Y ，Ge Y ，Wang Q ，Wang C ，He J ，Zhao L ，Yu S ，Yan J ，Zhao L ，Li L ，Bai C ... -  《Frontiers in Immunology》

Impact of residual disease as a prognostic factor for survival in women with advanced epithelial ovarian cancer after primary surgery.

Ovarian cancer is the seventh most common cancer among women and a leading cause of death from gynaecological malignancies. Epithelial ovarian cancer is the most common type, accounting for around 90% of all ovarian cancers. This specific type of ovarian cancer starts in the surface layer covering the ovary or lining of the fallopian tube. Surgery is performed either before chemotherapy (upfront or primary debulking surgery (PDS)) or in the middle of a course of treatment with chemotherapy (neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS)), with the aim of removing all visible tumour and achieving no macroscopic residual disease (NMRD). The aim of this review is to investigate the prognostic impact of size of residual disease nodules (RD) in women who received upfront or interval cytoreductive surgery for advanced (stage III and IV) epithelial ovarian cancer (EOC). To assess the prognostic impact of residual disease after primary surgery on survival outcomes for advanced (stage III and IV) epithelial ovarian cancer. In separate analyses, primary surgery included both upfront primary debulking surgery (PDS) followed by adjuvant chemotherapy and neoadjuvant chemotherapy followed by interval debulking surgery (IDS). Each residual disease threshold is considered as a separate prognostic factor. We searched CENTRAL (2021, Issue 8), MEDLINE via Ovid (to 30 August 2021) and Embase via Ovid (to 30 August 2021). We included survival data from studies of at least 100 women with advanced EOC after primary surgery. Residual disease was assessed as a prognostic factor in multivariate prognostic models. We excluded studies that reported fewer than 100 women, women with concurrent malignancies or studies that only reported unadjusted results. Women were included into two distinct groups: those who received PDS followed by platinum-based chemotherapy and those who received IDS, analysed separately. We included studies that reported all RD thresholds after surgery, but the main thresholds of interest were microscopic RD (labelled NMRD), RD 0.1 cm to 1 cm (small-volume residual disease (SVRD)) and RD > 1 cm (large-volume residual disease (LVRD)). Two review authors independently abstracted data and assessed risk of bias. Where possible, we synthesised the data in meta-analysis. To assess the adequacy of adjustment factors used in multivariate Cox models, we used the 'adjustment for other prognostic factors' and 'statistical analysis and reporting' domains of the quality in prognosis studies (QUIPS) tool. We also made judgements about the certainty of the evidence for each outcome in the main comparisons, using GRADE. We examined differences between FIGO stages III and IV for different thresholds of RD after primary surgery. We considered factors such as age, grade, length of follow-up, type and experience of surgeon, and type of surgery in the interpretation of any heterogeneity. We also performed sensitivity analyses that distinguished between studies that included NMRD in RD categories of < 1 cm and those that did not. This was applicable to comparisons involving RD < 1 cm with the exception of RD < 1 cm versus NMRD. We evaluated women undergoing PDS and IDS in separate analyses. We found 46 studies reporting multivariate prognostic analyses, including RD as a prognostic factor, which met our inclusion criteria: 22,376 women who underwent PDS and 3697 who underwent IDS, all with varying levels of RD. While we identified a range of different RD thresholds, we mainly report on comparisons that are the focus of a key area of clinical uncertainty (involving NMRD, SVRD and LVRD). The comparison involving any visible disease (RD > 0 cm) and NMRD was also important. SVRD versus NMRD in a PDS setting In PDS studies, most showed an increased risk of death in all RD groups when those with macroscopic RD (MRD) were compared to NMRD. Women who had SVRD after PDS had more than twice the risk of death compared to women with NMRD (hazard ratio (HR) 2.03, 95% confidence interval (CI) 1.80 to 2.29; I2 = 50%; 17 studies; 9404 participants; moderate-certainty). The analysis of progression-free survival found that women who had SVRD after PDS had nearly twice the risk of death compared to women with NMRD (HR 1.88, 95% CI 1.63 to 2.16; I2 = 63%; 10 studies; 6596 participants; moderate-certainty). LVRD versus SVRD in a PDS setting When we compared LVRD versus SVRD following surgery, the estimates were attenuated compared to NMRD comparisons. All analyses showed an overall survival benefit in women who had RD < 1 cm after surgery (HR 1.22, 95% CI 1.13 to 1.32; I2 = 0%; 5 studies; 6000 participants; moderate-certainty). The results were robust to analyses of progression-free survival. SVRD and LVRD versus NMRD in an IDS setting The one study that defined the categories as NMRD, SVRD and LVRD showed that women who had SVRD and LVRD after IDS had more than twice the risk of death compared to women who had NMRD (HR 2.09, 95% CI 1.20 to 3.66; 310 participants; I2 = 56%, and HR 2.23, 95% CI 1.49 to 3.34; 343 participants; I2 = 35%; very low-certainty, for SVRD versus NMRD and LVRD versus NMRD, respectively). LVRD versus SVRD + NMRD in an IDS setting Meta-analysis found that women who had LVRD had a greater risk of death and disease progression compared to women who had either SVRD or NMRD (HR 1.60, 95% CI 1.21 to 2.11; 6 studies; 1572 participants; I2 = 58% for overall survival and HR 1.76, 95% CI 1.23 to 2.52; 1145 participants; I2 = 60% for progression-free survival; very low-certainty). However, this result is biased as in all but one study it was not possible to distinguish NMRD within the < 1 cm thresholds. Only one study separated NMRD from SVRD; all others included NMRD in the SVRD group, which may create bias when comparing with LVRD, making interpretation challenging. MRD versus NMRD in an IDS setting Women who had any amount of MRD after IDS had more than twice the risk of death compared to women with NMRD (HR 2.11, 95% CI 1.35 to 3.29, I2 = 81%; 906 participants; very low-certainty). In a PDS setting, there is moderate-certainty evidence that the amount of RD after primary surgery is a prognostic factor for overall and progression-free survival in women with advanced ovarian cancer. We separated our analysis into three distinct categories for the survival outcome including NMRD, SVRD and LVRD. After IDS, there may be only two categories required, although this is based on very low-certainty evidence, as all but one study included NMRD in the SVRD category. The one study that separated NMRD from SVRD showed no improved survival outcome in the SVRD category, compared to LVRD. Further low-certainty evidence also supported restricting to two categories, where women who had any amount of MRD after IDS had a significantly greater risk of death compared to women with NMRD. Therefore, the evidence presented in this review cannot conclude that using three categories applies in an IDS setting (very low-certainty evidence), as was supported for PDS (which has convincing moderate-certainty evidence).

Bryant A ，Hiu S ，Kunonga PT ，Gajjar K ，Craig D ，Vale L ，Winter-Roach BA ，Elattar A ，Naik R ... -  《Cochrane Database of Systematic Reviews》

The short-term efficacy and safety of neoadjuvant Sintilimab combined with chemotherapy for resectable gastroesophageal junction adenocarcinoma.

To explore whether neoadjuvant Sintilimab is suitable for patients with gastroesophageal junction (GEJ) adenocarcinoma, we designed this study to evaluate the short-term efficacy and safety of neoadjuvant Sintilimab in combination with chemotherapy for resectable GEJ adenocarcinoma. We retrospectively collected data on patients with GEJ adenocarcinoma who underwent surgery after receiving neoadjuvant immunotherapy combined with chemotherapy at Jining First People's Hospital between October 2020 and October 2023. The primary endpoint was complete pathological response (pCR) rate; secondary endpoints: major pathological response (MPR) rate, neoadjuvant therapy-related adverse events (AES), the safety of surgery, Postoperative Complications, and overall survival (OS). 24 eligible patients were enrolled in the study and achieved a pCR rate of 16.7%. The treatment-related AES was manageable. The median time interval between the end of neoadjuvant therapy and surgery was 35 days (28-81 days), R0 resection rate was 100%. The most common postoperative complications in the study were pneumonia (n = 11, 45.8%). Median follow-up was 13.5(interquartile range: 8.00, 25.50) months, Kaplan-Meier survival analysis showed median OS was not reached. It was safe and effective for resectable GEJ adenocarcinoma to undergo neoadjuvant Sintilimab combined with chemotherapy followed by surgery, and long-term efficacy needs to be confirmed by further follow-up.

Chen L ，Zhang S ，Ma H ，Zhong K ，Yang D ，Sun J ，Liu H ，Song R ，Cai H ... -  《-》