nCRT Group Research Articles

Comparison of pathologic response and survival outcomes between neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant immunochemotherapy (nICT) in patients with locally advanced esophageal squamous cell carcinoma: a propensity score-matched analysis

BackgroundIn locally advanced, operable esophageal squamous cell carcinoma (ESCC), neoadjuvant immunochemotherapy (nICT) has shown results that are somewhat comparable to those of standard neoadjuvant chemoradiotherapy (nCRT). The impact of these neoadjuvant treatments on survival outcomes, however, has yet to be elucidated.MethodsThis study included 489 patients with locally advanced ESCC who underwent surgery at Sichuan Cancer Hospital after receiving neoadjuvant treatment between June 2017 and September 2023. Patients were categorized into nCRT and nICT groups based on whether they received neoadjuvant treatment. To mitigate potential biases and balance covariates between the two cohorts, 1:2 propensity score matching (PSM) was conducted using a caliper width of 0.05.ResultsAfter PSM, the baseline characteristics of the 360 patients remained balanced between the two groups. The findings indicated a superior pathological response in the nCRT group, as evidenced by significantly greater rates of complete response (32.87% vs 14.58%, P < 0.001) and favorable tumor regression grade (TRG), as well as reduced ypT stages and less perineural and angioinvasion, despite comparable ypN stages. Despite the improvement in complete pathological response (pCR) in the nCRT group, the 3-year disease-free survival (DFS) and overall survival (OS) rates did not significantly differ between the groups (DFS: 58.32% vs 56.16%, P = 0.67; OS: 69.96% vs 71.99%, P = 0.99). Crucially, The nICT group showed a lower incidence of grade 3 and 4 adverse events in Leukopenia (2.8% vs 29%; P < 0.001) and Neutropenia (2.8% vs 24%; P < 0.001) during neoadjuvant treatment, comparing with nCRT group.ConclusionsOur preliminary findings suggest that nICT followed by surgery offers comparable survival rates to nCRT, despite being less effective in pathologic outcomes. Nonetheless, nICT is a safe and feasible strategy for locally advanced ESCC, warranting further exploration to understand its impact on long-term survival.

430. PROGNOSTIC PATTERNS OF LYMPH NODES WITH COMPLETE TREATMENT RESPONSE IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER NEOADJUVANT CHEMORADIOTHERAPY AND NEOADJUVANT CHEMOTHERAPY

Abstract Background The prognostic significance of lymph nodes with pathological complete treatment response (pcr-LN) has not been well investigated in esophageal squamous cell carcinoma (ESCC). We aimed to determine the prognostic impact of pcr-LNs in ESCC after either neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT). Methods 578 patients with ESCC from two medical facilities were analyzed retrospectively, with 303 patients receiving nCRT and 275 receiving nCT. Pcr-LNs were defined as LNs exhibiting regression changes, such as fibrosis, mucin lakes, keratinization, and giant cell responses but no evidence of living tumor cells. 5 LN status subgroups were identified based on the ypN category in 8th AJCC: ypN0/pcr-LN-, ypN0/pcr-LN+, ypN1, ypN2, and ypN3. The Kaplan-Meier approach was used to analyze the overall survival (OS), and subgroup findings were compared using the log-rank test. Multivariate analysis of OS was performed using a Cox proportional hazard model. Results 45 patients were classified into ypN0/pcr-LN+ (7.8%), 33 in the nCRT group, and 12 in the nCT group (p = 0.006). Compared to the nCRT group, the nCT group underwent a more thorough LN dissection (LN (mean (SD)): nCRT, 21.05 (8.77); nCT, 26.08 (11.66); p = 0.001). Survival analysis of OS showed the subgroup ypN0/pcr-LN+ had a significantly worse prognosis than ypN0/pcr-LN- in the nCRT group (p = 0.047), but no difference was seen in the nCT group. Multivariable analysis revealed that ypN0/pcr-LN+ patients in the nCRT group had a greater risk of mortality than ypN0/pcr-LN- patients (p = 0.0487). Conclusion The nCRT group had a more noticeable complete treatment response in LNs than the nCT group. However, in comparison to the nCT group, the nodal downstaging with radiotherapy in the nCRT group may not translate into improved outcomes. More aggressive systemic therapy might be required to improve the overall survival in esophageal cancer patients receiving neoadjuvant treatment.

399. LYMPH NODE METASTATIC PATTERNS AND SENTINEL LYMPH NODES FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER DIFFERENT NEOADJUVANT REGIMENS

Abstract Background This study aimed to outline lymph node metastasis patterns in esophageal squamous cell carcinoma (ESCC) patients undergoing neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT), comparing regimens, assessing prognosis impact, and identifying potential sentinel lymph node stations for future individualized dissection. Methods Involving 578 ESCC patients undergoing nCRT (n=303) or nCT (n=275) followed by esophagectomy (2010-2022), we conducted propensity score matching, analyzing 171 pairs. Nodal metastasis patterns and station positivity associations with survival were assessed through univariate and multivariate models, adjusting for clinical factors. Results Among 171 nCRT patients, 36.8% had nodal metastases, 22.8% single-station, 8.2% two-station, and 5.8% ≥3-station occurrences. Specific station positivity correlated with poorer survival. The nCRT group had fewer nodal metastases (36.8% vs 50.3%), common sites being left gastric, right recurrent laryngeal nerve, and paraesophageal region. Increased nodal stations and positive nodes correlated with worse prognosis. In nCRT, mentioned areas were prognostic; in nCT, only left gastric nodal metastases were prognostic. Single and multi-station rates were similar, but nCT had more multi-station disease. For sentinel lymph nodes, positivity in left gastric, paraesophageal, right recurrent laryngeal nerve for nCRT, and subcarinal, left recurrent laryngeal nerve, paratracheal, left gastric, paraesophageal right recurrent laryngeal nerve for nCT, may indicate complex metastasis. Conclusions Over one-third of ESCC patients had post nCRT metastatic lymph nodes. Though nCRT reduced metastasis rates, survival outcomes didn't improve, emphasizing thorough lymph node dissection based on metastasis patterns.

604. REAL-WORLD MANAGEMENT AND OUTCOMES OF PATIENTS WITH NON METASTATIC ESOPHAGEAL SQUAMOUS CELL CARCINOMA IN THE FREGAT DATABASE

Abstract Background International guidelines for locally advanced esophageal squamous cell carcinoma (ESCC) recommend both neoadjuvant chemoradiotherapy (nCRT) followed by planned surgery (P-surg) or definitive chemoradiotherapy (dCRT) with salvage surgery (S-surg). However, the optimal treatment remains unknown, and the ongoing pragmatic NEEDS randomized trial is assessing the efficacy of an organ-preserving strategy after dCRT (Nilsson, Front Oncol 2022). Real-world data on the management of non-metastatic ESCC is limited. This study aims to describe the treatment strategies and prognosis of patients with non-metastatic ESCC in a real-world setting. Methods We conducted a retrospective cohort study of patient treated for non-metastatic ESCC between 2014 and 2022. Data were extracted from the FREGAT database. For the entire population, different treatment strategies were described. We compared patients who received nCRT with those who received dCRT under real-life conditions (“Real-life” population) and according to the NEEDS randomized trial criteria (“NEEDS-like” population). Five-year overall survival (OS) and relapse-free survival (RFS) were compared between nCRT and dCRT patients using a Cox proportional hazard model adjusting for major confounders. In operated patients, the impact of surgery on OS and RFS was assessed using a time-dependent Cox proportional hazard model. Postoperative outcomes were compared between P-surg and S-surg using Fisher’s exact test. Results From 971 patients diagnosed with non-metastatic ESCC, 867 (89.3%) received a curative treatment including dCRT (41.0%), nCRT (28.0%), primary esophagectomy (9.8%), neoadjuvant chemotherapy (3.4%), or endoscopic resection (1.0%). Fifty-nine patients (6,1%) received supportive care or chemotherapy alone. Forty-five patients (4.6%) died during or before treatment. In the “real-life” population (n=659), 269 patients received nCRT and 390 patients received dCRT. A total of 229 patients (93.5%) in nCRT group underwent P-surg and S-surg was performed in 44 patients (11.3%) in dCRT group. After adjustment, dCRT was associated with a significantly poorer 5-year OS and RFS (respectively HR=1.83, 95%CI 1.44-2.33; HR=1.98, 95%CI 1.57-2.49). A complete clinical response (cCR) was observed in 21.6% and 29.5% of the nCRT and dCRT groups, respectively. Among cCR undergoing resection, 35.8% had residual disease on pathological specimen. Time between CRT and surgery was 58 days (IQR44-72) vs. 109 days (IQR71-278) for P-surge and S-Surg respectively. The 90-day mortality, major morbidity (Clavien-Dindo III/IV) and pulmonary complication rates were similar in both groups, except for a higher risk of anastomotic leakage after S-surg (p=0.05). In the “NEEDS-like” population (n=598), findings were consistent and comparable to those observed in the “real-life” population. Conclusion Among non-mestastatic ESCC included in the FREGAT database, 10.6% had a non-curative approach or died prematurely. Most patients underwent dCRT, with S-surg rate of only 11.3%. Neoadjuvant CRT followed by P-surg was associated with the best outcome in terms of OS and RFS in both “rela life” and “Needs-like” populations. In operated patients, postoperative outcomes were similar after nCRT and dCRT, except for a higher incidence of anastomotic leakage after S-surg. This study highlighted the therapeutic strategies used and their results in real-life conditions for non-metastatic ESCC inside the FREGAT database. The treatment option of nCRT followed by P-surg appears to remain the optimal curative treatment regimen.

Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable esophageal squamous cell carcinoma: A pooled analysis of randomized clinical trials

BackgroundThe comparison of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) for locally advanced esophageal squamous cell carcinoma (ESCC) remains inconclusive, and the optimal regimen is still under investigation. MethodsProspective randomized clinical trials were systematically searched in electronic databases from inception to Oct 2023. A graphical reconstructive algorithm was employed to extract time-to-event outcomes from Kaplan-Meier curves presented in the original studies. Using reconstructed individual patient data, summary overall survival (OS) and disease progression-free survival (DFS) for nCRT versus nCT, primarily doublet chemotherapy were recalculated. Hazard Ratios (HRs) of OS and DFS reported were also pooled by the fixed-effects model. ResultsA total of 6 randomized clinical trials comprising 1162 patients were included in our analysis. In the individual patient data (IPD) pooled analysis, a significant OS benefit was found for nCRT in ESCC (HR=0.81, 95 %CI:0.67–0.98, p=0.029), compared with the treatment of nCT. The median overall survival time were 53 months (95 %CI:41.9–67.7 m) and 66 months(95 %CI:57.2-NA) respectively in the nCT and nCRT groups. Additionally, a significant improvement in PFS for nCRT compared to nCT in the IPD pooled analysis (HR=0.79,95 %CI:0.64–0.98; p=0.027). Consistent with above results, the pooled HRs of OS and DFS for nCRT versus nCT were 0.78 (95 % CI 0.65–0.92, p=0.004) and 0.79 (95 % CI: 0.65–0.97, p=0.02), respectively. Notably, no substantial heterogeneity across studies was observed. ConclusionsOur findings indicate that nCRT offers better survival outcomes for ESCC, at least when compared to neoadjuvant doublet chemotherapy.This evidence continues to support the clinical practice of employing nCRT in locally advanced resectable ESCC.

Esophagectomy after definitive chemoradiation in esophageal cancer: a safe therapeutic strategy.

The standard treatment regimen for esophageal cancer is chemoradiation followed by esophagectomy. However, the use of neoadjuvant chemoradiotherapy damages the surrounding tissue, which potentially increases the risk of postoperative complications, including anastomotic leakage. The impact of definitive chemoradiotherapy (dCRT, 50.4Gy radiotherapy) compared to the standard neoadjuvant scheme (nCRT, 41.4Gy radiotherapy) prior to surgery on the incidence of anastomotic leakage remains poorly understood. To study this, all patients who received dCRT between 2011 and 2021 followed by esophagectomy were included. For each patient, two patients who received nCRT were selected as matched controls. Outcomes included postoperative anastomotic leakage, pulmonary and other complications, anastomotic stenosis, pulmonary and other postoperative complications (Clavien Dindo Classification ≥1), and overall survival. One hundred and eight patients were included with a median follow-up of 28months. The time between neoadjuvant treatment and surgery was longer in the dCRT group compared to the nCRT group (65 vs. 48days, P < 0.001). Postoperatively, significantly more patients in the dCRT group suffered from anastomotic leakage (11% vs. 1%, P = 0.04) and anastomotic stenosis (42% vs. 17%, P < 0.01). No differences were found for other complications or overall survival between both groups. In conclusion, preoperative dCRT is associated with a higher risk of anastomotic leakage and stenosis. These complications, however, can be treated effectively. Therefore, esophagectomy after dCRT is considered to be an appropriate treatment strategy in a selected patient group.

Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis.

To compare the efficacy and safety of total neoadjuvant therapy (TNT) and neoadjuvant chemoradiotherapy (nCRT) in the treatment of middle and low locally advanced rectal cancer. Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates, surgical resection rates, tumor-free survival, and severe adverse events. To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options. A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese (CNKI, Wanfang, China Biomedical Literature Database) and English (PubMed, Embase) databases was performed. Two system assessors independently screened the studies according to the inclusion and exclusion criteria. Quality evaluation and data extraction were performed for the included literature. We used RevMan 5.3 software to perform a meta-analysis of the pathologic complete response (pCR) rate, T stage degradation rate, resection 0 (R0) rate, anal grade 3/4 acute toxicity rate, perioperative complications, overall survival (OS), and disease-free survival (DFS) in the TNT and nCRT groups. Finally, 14 studies were included, six of which were randomized controlled studies. A total of 3797 patients were included, including 1865 in the TNT group and 1932 in the nCRT group. The two sets of baseline data were comparable. The results of the meta-analysis showed that the pCR rate [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.30-1.90, P < 0.00001], T stage degradation rate (OR = 2.16, 95%CI: 1.63-2.57, P < 0.00001), and R0 resection rate (OR = 1.42, 95%CI: 1.09-1.85, P = 0.009) were significantly greater in the nCRT group than in the nCRT group. There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups. The 5-year OS [hazard ratio (HR) = 0.84, 95%CI: 0.69-1.02, P = 0.08] and DFS (HR = 0.94, 95%CI: 0.03-1.39, P = 0.74) of the TNT group were similar to those of the nCRT group. TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.

Optimization of treatment strategies based on preoperative imaging features and local recurrence areas for locally advanced lower rectal cancer after lateral pelvic lymph node dissection.

Local recurrence (LR) is the main cause of treatment failure in locally advanced lower rectal cancer (LALRC). This study evaluated the preoperative risk factors for LR in patients with LALRC to improve the therapeutic strategies. LALRC patients who underwent total mesorectal excision (TME) with lateral pelvic lymph node (LPN) dissection (LPND) from January 2012 to December 2019 were reviewed. The log-rank test was used to assess local recurrence-free survival (LRFS), and multivariate Cox regression was used to identify the prognostic risk factors for LRFS. Follow-up imaging data were used to classify LR according to the location. Overall, 376 patients were enrolled, and 8.8% (n=33) of these patients developed LR after surgery. Multivariate analysis identified positive clinical circumferential resection margin (cCRM) as an independent prognostic factor for LRFS (HR: 4.94; 95% CI, 1.75-13.94; P=0.003). The most common sites for LR were the pelvic plexus and internal iliac area (PIA) (54.5%), followed by the central pelvic area (CPA) (39.4%) and obturator area (OA) (6.1%). Following a subgroup analysis, LR in the OA was not associated with positive cCRM. Patients treated with upfront surgery (n=35, 14.1%) had a lower cCRM positive rate when compared with patients treated with neoadjuvant chemoradiotherapy (nCRT) (n=12, 23.5%). However, the LR rate in the nCRT group was still lower (n=28, 36.4%) than that in the upfront surgery group (n=35, 14.%). Among patients with positive cCRM, the LR rate in patients with nCRT remained low (n=3, 10.7%). Positive cCRM is an independent risk factor for LR after TME plus LPND in LALRC patients. LPND is effective and adequate for local control within the OA regardless of cCRM status. However, for LALRC patients with positive cCRM, nCRT should be considered before LPND to further reduce LR in the PIA and CPA.

Multimodal Therapy Versus Primary Surgery for Gastric and Gastroesophageal Junction Diffuse Type Carcinoma, with a Focus on Signet Ring Cell Carcinoma: A Nationwide Study.

Diffuse type adenocarcinoma and, more specifically, signet ring cell carcinoma (SRCC) of the stomach and gastroesophageal junction (GEJ) have a poor prognosis and the value of neoadjuvant chemo(radio)therapy (nCRT) is unclear. All patients who underwent surgery for diffuse type gastric and GEJ carcinoma between 2004 and 2015 were retrospectively included from the Netherlands Cancer Registry. The primary outcome was overall survival after surgery. Kaplan-Meier curves were plotted. Furthermore, multivariable Poisson and Cox regressions were performed, correcting for confounders. To comply with the Cox regression proportional hazard assumption, gastric cancer survival was split into two groups, i.e. <90 days and >90 days, postoperatively by adding an interaction variable. Analyses included 2046 patients with diffuse type cancer: 1728 gastric cancers (50% SRCC) and 318 GEJ cancers (39% SRCC). In the gastric cancer group, 49% received neoadjuvant chemotherapy (nCT) and 51% received primary surgery (PS). All-cause mortality within 90 days postoperatively was lower after nCT (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.20-0.44; p<0.001). Also after 90 days, mortality was lower in the nCT group (HR for the interaction variable 2.84, 95% CI 1.87-4.30, p<0.001; total HR 0.29*2.84=0.84). In the GEJ group, 38% received nCT, 22% received nCRT, and 39% received PS. All-cause mortality was lower after nCT (HR 0.63, 95% CI 0.43-0.93; p=0.020) compared with PS. The nCRT group was removed from the Cox regression analysis since the Kaplan-Meier curves of nCRT and PS intersected. The results for gastric and GEJ carcinomas were similar between the SRCC and non-SRCC subgroups. For gastric and GEJ diffuse type cancer, including SRCC, nCT was associated with increased survival.

OGC P60 Impact of deprivation on treatment of oesophageal squamous cell carcinoma across a regional cancer network

Abstract Background Oesophageal cancer accounts for 8000 deaths per year in the United Kingdom, and 400,000 deaths globally. There are two main histological subtypes: oesophageal squamous cell carcinoma (OSCC) and oesophageal adenocarcinoma (OAC), with the former accounting for 90% of cases. Oesophageal cancer, particularly OSCC displays a strong correlation with deprivation, with females and males in the most deprived quintile having a corresponding 43% and 50% higher incidence rate compared to the least deprived. This study aims to look at whether deprivation across a regional network also affects treatment choice offered to patients, primarily definitive chemoradiotherapy versus neoadjuvant chemoradiotherapy. Methods A total of 76 patients diagnosed with oesophageal squamous cell carcinoma were identified from the regional cancer network database from 2016 to 2019. Patients were ranked into 10 deprivation quintiles using the English indices of deprivation 2019 (IoD2019). Patients were subdivided into two groups based on treatment modality, definitive chemoradiotherapy (dCRT) or neoadjuvant chemoradiotherapy with a plan for surgery (nCRT). Statistical analysis was performed using R-statistical software with logistical regression and T-tests performed. Results A total of 76 patients were included in the final data set with 52 patients receiving dCRT and 24 receiving nCRT. Deprivation was associated with a statistically significant impact on treatment choice, with patients in higher deprivation quintiles more likely to be offered nCRT (logOR 0.40, 95%CI 0.11-0.75) p-value 0.013. Other important factors were gender, with male patients more likely to be offered dCRT (LogOR -1.8, 95%CI -3.7- -0.30) p-value 0.030. Important cofounders were cancer staging and gender with the dCRT group having a higher number of stage 4 cancers and males compared to the nCRT group. Conclusions In conclusion, deprivation had a statistically significant impact on treatment modality of OSCC, with patients in higher deprivation quintiles more likely to be offered nCRT. However, there are important confounders to take into consideration, particularly cancer staging and gender which may explain the results.

Comparison of Pathologic Response and Survival Outcomes between Neoadjuvant Immunochemotherapy (nICT) and Neoadjuvant Chemoradiotherapy (nCRT) in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Analysis

The neoadjuvant immunochemotherapy (nICT) is a novel treatment, which is likely to be safer for locally advanced, surgically resectable Esophageal squamous cell carcinoma (ESCC) that comparing with the traditional neoadjuvant therapy. However, the efficacy of nICT was controversial and the survival benefit remain unknown. This study included 313 patients with locally advanced ESCC who underwent surgery following neoadjuvant therapy at Sichuan Cancer Hospital from June 2017 and September 2021. The patients were divided into nICT group and neoadjuvant chemoradiotherapy (nCRT) group according to the neoadjuvant strategy. A 1:2 propensity score matching (PSM) was used to balance potential bias across several covariates between two groups with a caliper 0.05. Among the 146 patients after PSM, the baseline factors were comparable between two groups. Compared with the nCRT group, the nICT group shown a lower pathologic complete response(pCR) rate (11.54% vs 35.11%; P = 0.0039) and lymph nodes uninvolved rate (ypN0: 44.23% vs 62.77%; P = 0.0154), but a higher perineural invasion (32.69% vs 12.77%; P = 0.0075) and angioinvasion rate (40.38% vs 10.64%; P = 0.0001). However, the 2-year OS and DFS rates were similar between the nICT group and the nCRT group in overall study cohort, and these data were confirmed in the matched samples (2-year OS, 78.2% vs 77.2% [p = 0.95]; DFS, 56.9% vs 58.0% [p = 0.69]). Our preliminary findings indicate that, for individuals with locally advanced ESCC, nICT followed by surgery appears to be less effective in pathologic outcomes, while having a comparable survival rate to nRCT. These results imply a complicated and possibly multifaceted link between the kind of neoadjuvant therapy, the pathologic outcomes, and the final survival.

Enhanced antitumour immunity following neoadjuvant chemoradiotherapy mediates a favourable prognosis in women with resected pancreatic cancer

BackgroundThis study investigates sex disparities in clinical outcomes and tumour immune profiles in patients with pancreatic ductal adenocarcinoma (PDAC) who underwent upfront resection or resection preceded by gemcitabine-based neoadjuvant chemoradiotherapy...

Neoadjuvant chemoradiation therapy combined with immunotherapy for microsatellite stable ultra-low rectal cancer (CHOICE II): study protocol of a multicentre prospective randomised clinical trial

IntroductionNeoadjuvant chemoradiotherapy (nCRT) could bring tumour shrinking and downstaging and increase the probability of organ preservation for patients with low rectal cancer. But for ultra-low rectal cancer, there is little...

Postoperative recurrence in locally advanced rectal cancer: how does neoadjuvant treatment affect recurrence pattern?

BackgroundThe treatment strategy for locally advanced rectal cancer (LARC) has recently expanded from total mesorectal excision to additional neoadjuvant chemoradiotherapy (nCRT) and/or systemic chemotherapy (NAC). Data on disease recurrence after each treatment strategy are limited.MethodsClinical stage II to III rectal cancer patients who underwent curative surgery between July 2005 and February 2021 were analyzed. The cumulative incidence and site of first recurrence were assessed. The median follow-up duration was 4.6 years.ResultsAmong the 332 patients, we performed nCRT and NAC in 15.4% (N=51) and 14.8% (N=49), respectively. The overall recurrence rate was 23.5% (N=78). Although several differences in tumor stage or location were observed, there was no significant difference in the rate among the surgery alone (N=54, 23.3%), nCRT (N=11, 21.6%), and NAC (N=13, 26.5%) groups. In this cohort, the local recurrence rate (18.4%) was higher than the rate of distant metastasis in the NAC group (14.3%). All patients with recurrence in the nCRT group had distant metastases (N=11: one patient had distant and local recurrences simultaneously). For pathological stage 0-I, the recurrence rate was higher in the nCRT and NAC groups than in the surgery-alone group (nCRT, 10.0%; NAC, 15.4%; and surgery-alone, 2.0%). Curative-intent resection of distant-only recurrences significantly improved patients’ overall survival (hazard ratio [95% confidence interval], 0.34 [0.14–0.84]), which was consistent even when stratified according to neoadjuvant treatment. Regardless of neoadjuvant treatment, >80% of recurrences occurred in the first 2.2 years, and 98.7% within 5 years after surgery.ConclusionRegardless of neoadjuvant treatment, detecting distant metastases with intensive surveillance, particularly in the first 2 years after surgery, is important. Also, even if neoadjuvant treatment can downstage LARC to pathological stage 0-I, careful follow-up is needed.

Preoperative chemoradiation-induced hematological toxicity and related vertebral dosimetry evaluations in patients with locally advanced gastric cancer: data from a phase III clinical trial

BackgroundTo explore the hematological toxicity (HT) induced by neoadjuvant chemoradiotherapy (nCRT) compared with neoadjuvant chemotherapy (nCT) and to identify the appropriate vertebral body (VB) dosimetric parameters for predicting HT in patients with locally advanced gastric cancer (GC).MethodsIn the phase III study, 302 patients with GC from an ongoing multi-center randomized clinical trial (NCT 01815853) were included. Patients from two major centers were grouped into training and external validation cohorts. The nCT group received three cycles of XELOX chemotherapy, while the nCRT received the same dose-reduced chemotherapy plus 45 Gy radiotherapy. The complete blood counts at baseline, during neoadjuvant treatment, and in the preoperative period were compared between the nCT and nCRT groups. The VB was retrospectively contoured and the dose-volume parameters were extracted in the nCRT group. Patients’ clinical characteristics, VB dosimetric parameters, and HTs were statistically analyzed. Instances of HT were graded according to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). The receiver operating characteristic (ROC) curves were generated to identify the optimal cut-off points for dosimetric variables and verify the prediction efficiency of the dosimetric index in both training and external validation cohorts.ResultsIn the training cohort, 27.4% Grade 3 + HTs were noted in the nCRT group and 16.2% in the nCT group (P = 0.042). A similar result was exhibited in the validation cohort, with 35.0% Grade 3 + HTs in the nCRT group and 13.2% in the nCT group (P = 0.025). The multivariate analysis of the training cohort revealed that V5 was associated with Grade 3 + leukopenia (P = 0.000), Grade 3 + thrombocytopenia (P = 0.001), and Grade 3 + total HTs (P = 0.042). The Spearman correlation analysis identified a significant correlation of V5 with the white blood cell nadir (P = 0.0001) and platelet nadir (P = 0.0002). The ROC curve identified the optimal cut-off points for V5 and showed that V5 < 88.75% could indicate a decreased risk of Grade 3 + leukopenia, thrombocytopenia, and total HTs in the training as well as the external validation cohorts.ConclusionsCompared with nCT, nCRT could increase the risk of Grade 3 + HT in patients with locally advanced GC. Dose constraints of V5 < 88.75% in irradiated VB could reduce the incidence of Grade 3 + HT.

Identification of patients with locally advanced rectal cancer eligible for neoadjuvant chemotherapy alone: Results of a retrospective study.

Neoadjuvant chemotherapy (nCT) appears in a few clinical studies as an alternative to neoadjuvant chemoradiation (nCRT) in selected patients with locally advanced rectal cancer (LARC). We aimed to compare the clinical outcomes of nCT with or without nCRT in patients with LARC and to identify patients who may be suitable for nCT alone. A total of 155 patients with LARC who received neoadjuvant treatment (NT) were retrospectively analysed from January 2016 to June 2021. The patients were divided into two groups: nCRT (n = 101) and nCT (n = 54). More patients with locally advanced disease (cT4, cN+ and magnetic resonance imaging-detected mesorectal fascia [mrMRF] positive [+]) were found in the nCRT group. Patients in the nCRT group received a dose of 50 Gy/25 Fx irradiation with concurrent capecitabine, and the median number of nCT cycles was two. In the nCT group, the median number of cycles was four. The median follow-up duration was 30 months. The pathologic complete response (pCR) rate in the nCRT group was significantly higher than that in the nCT group (17.5% vs. 5.6%, p = 0.047). A significant difference was observed in the locoregional recurrence rate (LRR); 6.9% in the nCRT group and 16.7% in the nCT group (p = 0.011). Among patients with initial mrMRF (+) status, the LRR in the nCRT group was significantly lower than that in the nCT group (6.1% vs. 20%, p = 0.007), but not in patients with initial mrMRF negative (-) (10.5% in each group, p = 0.647). Compared with the nCT group, a lower LRR was observed in patients in the nCRT group with initial mrMRF (+) converted to mrMRF (-) after NT (5.3% vs. 23%, p = 0.009). No significant difference was observed between the two groups regarding acute toxicity and overall and progression-free survivals. Multivariate analysis showed that nCRT and ypN stage were independent prognostic factors for the development of LRR. Patients with initial mrMRF (-) may be suitable for nCT alone. However, patients with initial mrMRF (+) converted to mrMRF (-) after nCT are still at high risk of LRR, and radiotherapy is recommended. Prospective studies are required to confirm these findings.

Perioperative outcomes of neoadjuvant immunotherapy plus chemotherapy and neoadjuvant chemoradiotherapy in the treatment of locally advanced esophageal squamous cell carcinoma: a retrospective comparative cohort study.

Neoadjuvant chemoradiotherapy (nCRT) is recommended as the preferred treatment for locally advanced esophageal squamous cell carcinoma. Recent studies have shown that immune checkpoint inhibitors are beneficial in treating advanced esophageal cancer. Therefore, a growing number of clinical centers are conducting trials of neoadjuvant immunotherapy or neoadjuvant immunotherapy plus chemotherapy (nICT) in patients with locally advanced resectable esophageal cancer. Immunocheckpoint inhibitors are expected to play a role in neoadjuvant therapy for esophageal cancer. However, there were few studies comparing nICT with nCRT. This study compared the efficacy and safety of nICT with that of nCRT administered prior to esophagectomy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). The study included patients with locally advanced resectable ESCC who were scheduled to receive neoadjuvant therapy at Gaozhou People's Hospital from January 1, 2019, to September 1, 2022. The enrolled patients were divided into 2 groups (nCRT or nICT) according to their neoadjuvant therapy regimen. The 2 groups were compared for their baseline data, the incidence of adverse events during neoadjuvant therapy, the clinical evaluation after neoadjuvant therapy, perioperative indicators, and the incidence of postoperative complications and postoperative pathological remission. A total of 44 patients were enrolled; 23 in the nCRT group and 21 in the nICT group. There were no significant differences between the 2 groups in the baseline data. In the nCRT group, leukopenia occurred more often than in the nICT group, and hemoglobin-decreasing events were rarer (P=0.03<0.05). A significantly higher proportion of patients in the nICT group experienced erythema following neoadjuvant therapy compared to the nCRT group (23.81% vs. 0%; P=0.01<0.05). Neoadjuvant therapy showed no significant difference between the 2 groups for adverse event rates, surgery-related indicators, postoperative pathological remission rates, and postoperative complications. nICT was a safe and feasible treatment for locally advanced ESCC and it may be a potential new treatment modality.

Perioperative outcomes of neoadjuvant chemotherapy plus camrelizumab compared with chemotherapy alone and chemoradiotherapy for locally advanced esophageal squamous cell cancer.

Neoadjuvant chemoimmunotherapy (nCIT) is becoming a new therapeutic frontier for resectable esophageal squamous cell carcinoma (ESCC); however, crucial details and technical know-how regarding surgical techniques and the perioperative challenges following nCIT remain poorly understood. The study investigated and compared the advantages and disadvantages of esophagectomy following nCIT with neoadjuvant chemotherapy (nCT) and chemoradiotherapy (nCRT). We retrospectively analyzed data of patients initially diagnosed with resectable ESCC at clinical stage T2-4N+ and received neoadjuvant therapy followed by esophagectomy at the Hunan Cancer Hospital between October 2014 and February 2021. Patients were divided into three groups according to neoadjuvant treatment: (i) nCIT; (ii) nCT; and (iii) nCRT. There were 34 patients in the nCIT group, 97 in the nCT group, and 31 in the nCRT group. Compared with nCT, nCIT followed by esophagectomy achieved higher pathological complete response (pCR; 29.0% versus 4.1%, p<0.001) and major pathological response (MPR; 52.9% versus 16.5%, p<0.001) rates, more resected lymph nodes during surgery (25.06 ± 7.62 versus 20.64 ± 9.68, p=0.009), less intraoperative blood loss (200.00 ± 73.86 versus 266.49 ± 176.29 mL, p=0.035), and comparable results in other perioperative parameters. Compared with nCRT, nCIT achieved similar pCR (29.0% versus 25.8%) and MPR (52.9% versus 51.6%, p=0.862) rates, with significantly more lymph nodes resected during surgery (25.06 ± 7.62 versus 16.94 ± 7.24, p<0.001), shorter operation time (267.79 ± 50.67 versus 306.32 ± 79.92min, p=0.022), less intraoperative blood loss (200.00 ± 73.86 versus 264.53 ± 139.76 mL, p=0.022), and fewer ICU admissions after surgery (29.4% versus 80.6%, p<0.001). Regarding perioperative adverse events and complications, no significant statistical differences were detected between the nCIT and the nCT or nCRT groups. The 3-year overall survival rate after nCIT was 73.3%, slightly higher than 46.1% after nCT and 39.7% after nCRT, with no statistically significant differences (p=0.883). This clinical analysis showed that nCIT is safe and feasible, with satisfactory pCR and MPR rates. Esophagectomy following nCIT has several perioperative advantages over nCT and nCRT, with comparable perioperative morbidity and mortality. The long-term survival benefits after nCIT still requires further investigation.

Application of short-course radiotherapy with total neoadjuvant therapy in the treatment of middle and low rectal cancer

Objective: To compare the efficacy and safety of short-course radiotherapy with total neoadjuvant therapy (SCRT-TNT) and neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced middle and low rectal cancer. Methods: A retrospective cohort study was carried out. A of 126 patients with locally advanced middle and low rectal cancer who were treated in the Department of Gastrointestinal Cancer Surgery of Fujian Cancer Hospital from September 2016 to March 2020 were enrolled, including 73 males and 53 females, with a mean age of (56.5±9.8) (23-77) years. Based on neoadjuvant regimen (nCRT treatment was performed before December 2018 and SCRT-TNT treatment was carried out after January 2019), patients were divided into nCRT group (n=68) and SCRT-TNT group (n=58). There were no statistically significant differences in age, sex, distance from tumor to anal verge, Eastern Cooperative Oncology Group (ECOG) performance status and clinical TNM stage between the two groups (all P>0.05). Patients in both groups received pelvic intensity-modulated radiotherapy (IMRT). The radiotherapy dose of nCRT group was 50Gy/25 times/5 weeks. Patients in nCRT group received oral capecitabine chemotherapy during radiotherapy and underwent surgery 6-8 weeks after chemoradiation. However, patients in SCRT-TNT group received CapeOX regimen (oxaliplatin+capecitabine) for 2 cycles of induction chemotherapy, followed by short-course radiotherapy (25Gy/5 times/5 days), then underwent a radical surgery two weeks after completion of consolidation chemotherapy (4 cycles). The adverse reactions, perioperative safety and efficacy of neoadjuvant therapy were compared and analyzed between the two groups. Results: Both groups completed neoadjuvant therapy as planned. Patients in nCRT group and SCRT-TNT group had similar incidence of adverse reactions to radiotherapy and chemotherapy, however, there were no statistically significant differences in the incidence of surgical complications, operation time, intraoperative blood loss and postoperative length of hospital stay (all P>0.05). A total of 119 patients underwent total mesenterectomy (TME), including 64 patients in the nCRT group and 55 patients in the SCRT-TNT group, all with R0 resection. The pathological complete response (pCR) rate was 10.9% (7/64) in the nCRT group and 25.5% (14/55) in the SCRT-TNT group, respectively, with a statistically significant difference (P=0.038). Two years after surgery, there was no statistically significant difference in local recurrence rate and overall survival rate between the two groups (both P>0.05). However, the clinical metastasis rate of SCRT-TNT group was significantly lower than that of nCRT group (20.3% vs 9.1%), with a statistically significant difference (P<0. 05). Conclusion: SCRT-TNT do not increase the adverse reactions of radio chemotherapy and perioperative risks in the treatment of locally advanced middle and low rectal cancer, and the tumor regression effect is good, which is worthy of clinical promotion.

Impact of Lymph Node Dissection on Survival After Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: From the Results of NEOCRTEC5010, a Randomized Multicenter Study.

To clarify whether systemic LND influences the safety of surgery and the survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (nCRT). Prognostic impact of systemic lymphadenectomy during surgery after nCRT for ESCC is still uncertain and requires clarification. This is a secondary analysis of NEOCRTEC5010 trial which compared nCRT followed by surgery versus surgery alone for locally advanced ESCC. Relationship between number of LND and perioperative, recurrence, and survival outcomes were analyzed in the nCRT group. Three-year overall survival was significantly better in the nCRT group than the S group (75.2% vs 61.5%; P = 0.011). In the nCRT group, greater number of LND was associated with significantly better overall survival (hazard ratio, 0.358; P < 0.001) and disease-free survival (hazard ratio, 0.415; P = 0.001), but without any negative impact on postoperative complications. Less LND (<20 vs ≥20) was significantly associated with increased local recurrence (18.8% vs 5.2%, P = 0.004) and total recurrence rates (41.2% vs 25.8%, P = 0.027). Compared to patients with persistent nodal disease, significantly better survival was seen in patients with complete response and with LND ≥20, but not in those with LND <20. Systemic LND does not increase surgical risks after nCRT in ESCC patients. And it is associated with better survival and local diseasecontrol. Therefore, systemic lymphadenectomy should still be considered as an integrated part of surgery after nCRT for ESCC.