Local excision versus total mesorectal excision for rectal cancer patients with clinical complete or near-complete response after neoadjuvant chemoradiotherapy.

PURPOSE: Local excision is an effective approach for managing rectal cancer exhibiting substantial regression after neoadjuvant chemoradiotherapy. The purpose of this study is to compare the outcomes between local excision and total mesorectal excision in rectal cancer patients achieving clinical complete or near-complete response after neoadjuvant chemoradiotherapy. METHODS: This is a retrospective cohort study that includes a consecutive series of rectal cancer patients who responded well to neoadjuvant chemoradiotherapy followed by surgery. A total of 180 rectal cancer patients at a single institution during a 12-year period are included. The main outcomes include short-term outcomes, oncological outcomes, and functional outcomes between the two groups. RESULTS: A total of 180 patients were included in the study. Sixty-one (33.9%) received local excision and 119 (66.1%) received total mesorectal excision. The baseline characteristics were generally balanced between the two groups. The local excision group demonstrated a significantly shorter operative time, less blood loss, and shorter hospital stay (p < 0.001). 3-year overall survival rates were 97.5% (95% CI, 0.93-1.00) and 95.5% (95% CI, 0.91-1.00) between the two groups (p = 0.38). The local excision group exhibited significantly higher 3-year local recurrence rates 15.7% (95% CI, 0.74-0.97) vs 4.2% (95% CI, 0.92-1.00) (p = 0.017), yet lower 3-year distant metastasis rates 9.6% (95% CI, 0.82-1.00) vs 12.6% (95% CI, 0.81-0.94) (p = 0.33) and lower 3-year disease-free survival rates 76.8% (95% CI, 0.64-0.92) vs 84.7% (95% CI, 0.78-0.92) (p = 0.56) comparing with the total mesorectal excision group. The local excision group demonstrated significantly better functional outcomes compared with the total mesorectal excision group (p < 0.001). CONCLUSION: Patients who achieve either clinical complete or near-complete response after neoadjuvant chemoradiotherapy are suitable candidates for local excision. The local excision group demonstrated superior short-term and functional outcomes, and the oncological outcomes were not compromised.

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.

BACKGROUND: In 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. METHODS: This 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. RESULTS: After 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. CONCLUSIONS: Our 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.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for initially unresectable locally advanced colon cancer: short-term outcomes of an open-label, single-centre, randomised, controlled, phase 3 trial.

Background: Neoadjuvant chemotherapy (NACT) is commonly used to downstage the tumor in locally advanced colon cancer (LACC) and improve the R0 resection rate. Neoadjuvant chemoradiotherapy (NACRT) is the standard treatment for locally advanced rectal and esophageal cancers, but its benefits in LACC remain poorly understood. This study aimed to compare the effects and safety of NACRT and NACT on R0 resection and survival rates in initially unresectable LACC. Methods: This was an open-label, single-center, randomized, controlled trial conducted between May 11, 2019 and May 30, 2022. Forty-five patients with initially unresectable LACC were randomly allocated to the NACT (control, n = 20) or NACRT (research, n = 25) group. The NACT group received XELOX (oxaliplatin 100-130 mg/m2, qd, d1, every 3 weeks; and capecitabine 1000 mg/m2, bid, d1-d14, every 3 weeks) for 4 cycles. The NACRT group, in addition to chemotherapy, received daily irradiation (GTV 45-50 Gy/25 F; CTV 42.5-45 Gy/25 F). Surgery was scheduled 6-12 weeks after neoadjuvant treatment and adjuvant chemotherapy was administered if the patient developed resectable LACC. The primary endpoint was the 5-year overall survival (OS) rate. The secondary outcomes included the 3-year progression-free survival (PFS) and R0 resection rates. This study was registered with ClinicalTrials.gov (NCT03970694). Findings: In short-term outcome analysis, NACRT significantly improved the R0 resection rate (80% for NACRT vs. 20% for NACT, P < 0.001). The NACRT and NACT groups had a 3-year OS of 87.6% and 75% (P = 0.037) and a 3-year PFS of 76% and 45% (P = 0.049), respectively. The 5-year OS was not reached. In the NACRT group, no local or regional recurrence was observed in patients who underwent surgery during the follow-up period, compared to two patients in the NACT group. Both NACT and NACRT were well tolerated, with no significant differences in severe adverse events. The most commonly observed grade 3-4 AE was myelosuppression (39% for NACRT and 47% for NACT, P = 0.609). No grade 5 AEs were observed between the two groups. Interpretation: Adding radiation to NACT increased the R0 resection rate, prolonged the PFS, and potentially improved OS in selected patients with initially unresectable LACC. The trial findings indicate that this approach is safe, feasible, and may confer a survival benefit. Funding: This study was supported by grants from the National Natural Science Foundation of China (82373213 to Dr Gao, 82202952 to Dr Wang); and the Natural Science Foundation of Guangdong Province (2023A1515010290 to Dr Chang). Funding sources were not involved in the study design, data collection, analysis and interpretation, writing of the report, or decision to submit the article for publication.

The Role of Lateral Pelvic Lymph Node Dissection in Middle and Lower Rectal Cancer (Stage II or III): A Literature Review.

Lateral lymph node dissection and its inclusion in the treatment of rectal cancer is a controversial issue, with great differences, especially between Eastern and Western countries. Studies try to highlight the superiority of resection of these lymph nodes compared to simple mesorectal resection in terms of local recurrence of the disease, the overall survival of patients, and additional postoperative complications. In this study, the modern literature was reviewed, with the ultimate goal of clarifying the exact importance of lateral lymph node dissection, in terms of oncological outcome in patients with cancer of the middle and lower rectum, by studying the involvement of this lymph node dispersion in terms of local recurrence and overall survival of patients with rectal cancer. This review was carried out using electronic databases, including PubMed, Embase, and MEDLINE, with studies dating back to the last decade. Of the 31 studies that were eventually included in the final review, there is no statistically clear superiority and real benefit from lymph node resection beyond the lymph nodes of the mid-rectum. European guidelines are set against lateral lymph node dissection, except for lymph nodes that show suspicious features on preoperative imaging. In contrast, in Eastern countries, total mesorectal excision (TME) with extensive simultaneous resection of the lateral pelvic lymph nodes (LPLNs) is the protocol followed. Recent studies focus on the subcategory of patients with non-responsive to adjuvant therapy, lateral lymph nodes, in which the ultimate benefit of extensive lymph node dissection is explored. The decision to join the TME procedure for the removal of the LPLNs is a subject of intense research. There are no data on the criteria for determining these lymph nodes as an increased risk of metastatic outbreaks. Despite the great clinical and research interest worldwide nowadays, the resection of LPLNs remains a controversial issue of debate, with intense disagreements according to geographical area, while the existence of additional studies is necessary to come to final conclusions.

Prediction of pathological response and lymph node metastasis after neoadjuvant therapy in rectal cancer through tumor and mesorectal MRI radiomic features.

Establishing predictive models for the pathological response and lymph node metastasis in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) based on MRI radiomic features derived from the tumor and mesorectal compartment (MC). This study included 209 patients with LARC who underwent rectal MRI both before and after nCRT. The patients were divided into a training set (n = 146) and a test set (n = 63). Regions of interest (ROIs) for the tumor and MC were delineated on both pre- and post-nCRT MRI images. Radiomic features were extracted, and delta radiomic features were computed. The predictive endpoints were pathological complete response (pCR), pathological good response (pGR), and lymph node metastasis (LNM). Feature selection for various models involved sequentially removing features with a correlation coefficient > 0.9, and features with P-values ≥ 0.05 in univariate analysis, followed by LASSO regression on the remaining features. Logistic regression models were developed, and their performance was evaluated using the area under the receiver operating characteristic curve (AUC). Among the 209 LARC patients, the number of patients achieving pCR, pGR, and LNM were 44, 118, and 40, respectively. The optimal model for predicting each endpoint is the combined model that incorporates pre- and delta-radiomics features for both the tumor and MC. These models exhibited superior performance with AUC values of 0.874 (for pCR), 0.801 (for pGR), and 0.826 (for LNM), outperforming the MRI tumor regression grade (mrTRG) which yielded AUC values of 0.800, 0.715, and 0.603, respectively. The results demonstrate the potential utility of the tumor and MC radiomics features, in predicting treatment efficacy among LARC patients undergoing nCRT.

Outcomes of Watch-and-Wait Versus Abdominoperineal Resection in Lower Rectal Adenocarcinoma Post Neoadjuvant Therapy: An Iraqi Cohort Study.

BACKGROUND: Rectal malignancy ranks among the most prevalent malignancies in humans. Neoadjuvant chemoradiotherapy (nCRT) is advocated as the standard treatment for locally advanced rectal cancer. In patients who achieve complete clinical response (cCR), successive surgical intervention may result in favorable immediate and long-lasting results; however, it may be associated with decreased quality of life. This study aims to evaluate the incidence of local recurrence in rectal adenocarcinoma between patients who underwent a watch-and-wait approach and those who underwent abdominoperineal resection following the achievement of a cCR after nCRT. METHODS: This is an analytic cohort study that included 68 patients and was conducted in Baghdad Teaching Hospital/Medical City, Baghdad. The data were collected from the 1st of April 2021 to the 1st of October 2023. All patients with stage II and III rectal adenocarcinoma who achieved cCR after receiving nCRT were included in the study. RESULTS: There was no statistically significant difference between the two study groups regarding non-regrowth disease-free survival (p-value = 0.708). Cox-regression multivariate analysis revealed that baseline T stage and serum carcinoembryonic antigen (CEA) were significantly associated with locoregional failure. CONCLUSION: The present study reveals that implementing the watch-and-wait strategy had the benefit of avoiding major surgery, stoma, and their complications without coming at the cost of reduced locoregional recurrence.

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

BACKGROUND: The 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. METHODS: Prospective 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. RESULTS: A 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. CONCLUSIONS: Our 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.

Predictive value of mono-exponential and multiple mathematical models in locally advanced rectal cancer response to neoadjuvant chemoradiotherapy.

PURPOSE: This prospective study aimed to assess the predictive value of mono-exponential and multiple mathematical diffusion-weighted imaging (DWI) models in determining the response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). METHODS: The study included 103 LARC patients scheduled for preoperative chemoradiotherapy between December 2021 and June 2023 Magnetic resonance imaging (MRI) scans were performed using a 3.0-T MR scanner, encompassing sagittal, axial, and oblique coronal T2-weighted images without fat saturation, along with DWI perpendicular to the rectum's long axis. Various DWI parameters, including apparent diffusion coefficient (ADC), stretched exponential model (SEM), continuous-time random-walk model (CTRW), and fractional-order calculus model (FROC), were measured. The pathologic complete response (pCR) rate and tumor downstaging (T-downstage) rate were determined. RESULTS: After nCRT, SEM-α, SEM-DDC, CTRW-α, CTRW-ß, CTRW-D, FROC-ß, and ADC values were significantly higher in the pCR group compared to the non-pCR group (all P < 0.05). SEM-DDC, CTRW-α, CTRW-D, FROC-ß, FROC-µ, and ADC values were significantly higher in the T-downstage group (ypT0-1) than in the non-T-downstage group (ypT2-4) (P < 0.05). The combination of CTRW (α + ß + D) exhibited the best diagnostic performance for assessing pCR after nCRT (AUC = 0.840, P < 0.001). Pre-nCRT CTRW (α + ß) demonstrated a predictive AUC of 0.652 (95%CI: 0.552-0.743), 90.3% sensitivity, and 43.1% specificity for pCR. Regarding T-downstage assessment after nCRT, the combination of CTRW (α + D) yielded the best diagnostic performance (AUC = 0.877, P = 0.048). CONCLUSION: In LARC patients, imaging markers derived from CTRW show promise in predicting tumor response before nCRT and assessing pCR after nCRT.

Oncologic Outcome of Patients With Pathologic T0 Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy.

BACKGROUND AND OBJECTIVE: To investigate the oncologic outcomes of patients with esophageal squamous cell carcinoma (ESCC) who have achieved a pathologic complete response (pCR) of the primary tumor (ypT0) after neoadjuvant chemoradiotherapy (NCRT). METHODS: Patients with thoracic ESCC who underwent scheduled NCRT followed by surgery at our hospital between January 2010 and December 2022 were retrospectively analyzed. Only patients with ypT0 disease were enrolled in this study. RESULTS: A total of 118 patients were ultimately enrolled in this study. Ninety-two patients achieved pCR in the primary tumor and lymph nodes (ypT0N0), while 26 patients had residual metastatic disease in 52 lymph nodes (ypT0N+). Forty-five of the 52 lymph nodes with residual tumors were abdominal lymph nodes. Positive lymph nodes were more often observed in patients with tumors located in the lower third of the esophagus. The 1-, 3-, and 5-year overall survival (OS) rates for the entire study group were 96.5%, 79.5%, and 77.1%, and the 1-, 3-, and 5-year disease-free survival (DFS) rates were 90.5%, 76.8%, and 69.0%, respectively. According to multivariate analyses, pN classification was an independent predictor of both OS and DFS (P < 0.05), while sex and cT classification were also found to be independent prognostic factors for DFS (P < 0.05). CONCLUSIONS: Residual nodal metastatic disease in patients with ypT0 ESCC after NCRT was more often found in the abdominal lymph nodes. pN classification was an independent predictor of both OS and DFS for ypT0 ESCC patients after NCRT.

Is postoperative adjuvant radiotherapy necessary for patients with esophageal cancer after neoadjuvant chemoradiotherapy? An analysis based on the SEER database.

OBJECTIVES: To evaluate the outcomes of adjuvant radiotherapy in patients with esophageal cancer (EC) who underwent esophagectomy following neoadjuvant chemoradiotherapy (NCRT). METHODS: The data of EC patients who received adjuvant therapy after NCRT between 2004 to 2019 was retrieved from the SEER database. The patients were split into the adjuvant radiotherapy with or without chemotherapy (RT±CT) and the adjuvant chemotherapy (CT) groups. The process of propensity score matching (PSM) was employed. RESULTS: Following PSM, 157 patients in total were recruited in each treatment group. There were no significant variations in either overall survival (OS) or cancer-specific survival (CSS) between the RT±CT and CT groups (median OS: 28 months versus. 51 months, p=0.063; median CSS: 31 months versus. 52 months, p=0.16). Within the CT group, patients with ypI/II or cI/II tumor stage, positive lymph node ratio (LNR) ≤0.1, and tumor size ≥50 mm (p<0.05) had higher OS compared to the RT±CT groups. Among patients with cT3-4 tumors in N-stage downstaging group, the OS and CSS were significantly greater for those underwent RT±CT as opposed to the CT group (5-year OS:56.6% versus 19.4%, p=0.042; 5-year CSS:67.9% versus. 19.4%, p=0.023). Multivariate Cox regression analysis identified the tumor histology grade as an independent prognostic factor of OS and CSS. CONCLUSION: Radiotherapy-based adjuvant therapy does not significantly improve the prognosis of EC patients after NCRT, although it may provide a survival benefit for patients with cT3-4 tumors in N-stage downstaging.

Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.

Factors associated with pathological complete remission after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a real-world clinical setting.

Objective: This study aims to identify factors associated with achieving a pathological complete remission (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT). Methods: We conducted a cohort analysis of 171 LARC patients who underwent curative resection post-nCRT at the First Affiliated Hospital of Guangxi Medical University between January 2015 and December 2021. The data encompassed clinical and pathological information. Univariate and binary logistic regression multivariate analyses were employed to examine the factors influencing pCR achievement after nCRT. Kappa value tests were utilized to compare clinical staging after nCRT with postoperative pathological staging. Results: Postoperative histopathology revealed that of the 171 patients, 40 (23.4%) achieved TRG 0 grade (pCR group), while 131 (76.6%) did not achieve pCR, comprising 36 TRG1, 42 TRG2, and 53 TRG3 cases. Univariate analysis indicated that younger age (p=0.008), reduced tumor occupation of intestinal circumference (p =0.008), specific pathological types (p=0.011), and lower pre-nCRT CEA levels (p=0.003) correlated with pCR attainment. Multivariate analysis identified these factors as independent predictors of pCR: younger age (OR=0.946, p=0.004), smaller tumor occupation of intestinal circumference (OR=2.809, p=0.046), non-mucinous adenocarcinoma pathological type (OR=10.405, p=0.029), and lower pre-nCRT serum CEA levels (OR=2.463, p=0.031). Clinical re-staging post-nCRT compared to postoperative pathological staging showed inconsistent MRI T staging (Kappa=0.012, p=0.718, consistency rate: 35.1%) and marginally consistent MRI N staging (Kappa=0.205, p=0.001, consistency rate: 59.6%). Conclusion: LARC patients with younger age, presenting with smaller tumor circumferences in the intestinal lumen, lower pre-nCRT serum CEA levels, and non-mucinous adenocarcinoma are more likely to achieve pCR after nCRT. The study highlights the need for improved accuracy in clinical re-staging assessments after nCRT in LARC.

Hsa-miR-483-5p/mRNA network that regulates chemotherapy resistance in locally advanced rectal cancer identified through plasma exosome transcriptomics.

BACKGROUND: Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy (nCRT) for rectal cancer. However, the underlying mechanisms remain elusive. AIM: To detect the differential expression profiles of plasma exosomal microRNAs (miRNAs) in poor and good responders and explore the potential mechanisms of chemoresistance. METHODS: In this study, the profiles of plasma exosomal miRNAs were compared in two dimensions according to treatment responses (poor/good responders) and treatment courses (pre/post-nCRT) using RNA sequencing. RESULTS: Exosome hsa-miR-483-5p was up-regulated in good responders post-nCRT. Bioinformatics analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways, such as the MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, Toll-like receptor signaling pathway, VEGF signaling pathway, and mTOR signaling pathway. Further analysis indicated that MAPK3, RAX2, and RNF165 were associated with inferior recurrence-free survival in patients with rectal cancer, and the profiles of MAPK3, TSPYL5, and ZNF417 were correlated with tumor stage. In addition, the expression profiles of MAPK3, RNF165, and ZNF417 were negatively correlated with inhibitory concentration 50 values. Accordingly, an hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 network was constructed. CONCLUSION: This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs. However, further research is required within the framework of our established miRNA-mRNA network.

The addition of pembrolizumab to neoadjuvant chemoradiotherapy did not increase the risk of developing postoperative anastomotic leakage for ESCC: an analysis from a prospective cohort.

BACKGROUND: To compare the difference of postoperative anastomotic leakage (AL) rate between neoadjuvant chemoradiotherapy (NCRT) with pembrolizumab and NCRT group, and investigate the risk factors of developing AL for locally advanced esophageal squamous cell cancer (ESCC). MATERIALS AND METHODS: The GF was contoured on the pretreatment planning computed tomography and dosimetric parameters were retrospectively calculated. Univariate and multivariate logistic regression analysis was performed to determine the independent risk predictors for the entire cohort. A nomogram risk prediction model for postoperative AL was established. RESULTS: A total of 160 ESCC patients were included for analysis. Of them, 112 were treated with NCRT with pembrolizumab and 44 patients with NCRT. Seventeen (10.6%) patients experienced postoperative AL with a rate of 10.7% (12/112) in NCRT with pembrolizumab and 11.4% (5/44) in NCRT group. For the entire cohort, mean, D50, Dmax, V5, V10 and V20 GF dose were statistically higher in those with AL (all p < 0.05). Multivariate logistic regression analysis indicated that tumor length (p = 0.012), volume of GF (p = 0.003) and mean dose of GF (p = 0.007) were independently predictors for postoperative AL. Using receiver operating characteristics analysis, the mean dose limit on the GF was defined as 14 Gy. CONCLUSION: Based on our prospective database, no significant difference of developing AL were observed between NCRT with pembrolizumab and NCRT group. We established an individualized nomograms based on mean GF dose combined with clinical indicators to predict AL in the early postoperative period.

Comparison of the treatment outcomes of different neoadjuvant chemoradiotherapy regimens for resectable locally advanced esophageal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by radical esophagectomy is the standard treatment for locally advanced esophageal squamous cell cancer (LA-ESCC). However, various nCRT regimens have been used, and their comparative efficacy and safety remain unclear. METHODS: Patients with histologically confirmed LA-ESCC who underwent nCRT followed by radical esophagectomy between January 2016 and February 2022 were enrolled in this study. Of note, 3 different nCRT regimens were retrospectively compared: conventional radiotherapy (RT) + cisplatin/5-fluorouracil (FP) (Conv-FP), hypofractionated RT + FP (Hypo-FP), and regimens from the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial (CROSS). The overall survival (OS), pathologic complete response (pCR), toxicity, and treatment compliance rates were analyzed. RESULTS: Among the 600 patients, 225 received Conv-FP, 255 received Hypo-FP, and 120 received the CROSS regimen. The OS rates at 1 year were 78.7%, 83.9%, and 88.1% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P < .001). The pCR rates were 30.6%, 33.9%, and 35.0%, respectively (P = .653). The overall incidence of grade 3 toxicities was 10.2%. Hematologic and nonhematologic toxicities of grade ≥ 3 were observed in 8.4% and 11.4%, 0% and 7.6%, and 5.5% and 0.8% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P = .002 and P = .030). Weight loss of > 5% was observed in 44.0%, 51.4%, and 32.5% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P < .001). In the multivariate analysis, clinical T stage (P = .004), N stage (P = .012), FP chemotherapy regimen (P = .013), surgical resection (P < .001), hematologic toxicity (P = .001), and weight loss (P = .004) were significantly associated with poor OS. CONCLUSION: The choice of nCRT regimen did not significantly affect the pCR rates in patients with LA-ESCC. However, the CROSS regimen demonstrated better OS and lower toxicity, suggesting that it may be the optimal treatment option among the groups.

Definitive Chemoradiotherapy versus Trimodality Therapy for Locally Advanced Esophageal Adenocarcinoma: A Multi-Institutional Retrospective Cohort Study.

The optimal management of patients with locally advanced esophageal adenocarcinoma is unclear. Neoadjuvant chemoradiotherapy followed by esophagectomy (trimodality therapy) is supported as a standard of care, but definitive chemoradiotherapy is frequently given in practice to patients who may have been surgical candidates. This multi-institutional retrospective cohort study compared the outcomes of consecutive patients diagnosed with stage II to IVA esophageal adenocarcinoma between 2004 and 2018 who planned to undergo trimodality therapy or definitive chemoradiotherapy. A total of 493 patients were included, of whom 435 intended to undergo trimodality therapy and 56 intended to undergo definitive chemoradiotherapy. After a median follow-up of 7.3 years, trimodality therapy was associated with a lower risk of locoregional failure (5-year risk, 30.5% vs. 61.3%; HR, 0.39; 95% CI, 0.24-0.62; p<0.001) but not distant metastases (5-year risk, 58.2% vs. 53.9%; HR, 1.21; 95% CI, 0.77-1.91; p=0.40). There were no differences in overall survival (HR, 0.78; 95% CI, 0.56-1.09; p=0.14) or cancer-specific survival (HR, 0.83; 95% CI, 0.57-1.21; p=0.33). Findings were consistent on propensity score-matched sensitivity analyses. In conclusion, trimodality therapy was associated with a lower risk of locoregional failure, but this did not translate into a significantly lower risk of distant failure or improved survival. Further studies are required to accurately estimate the trade-offs between the two treatment strategies.

Effects of nutritional interventions on cancer patients receiving neoadjuvant chemoradiotherapy: a meta-analysis of randomized controlled trials.

BACKGROUND: Malnutrition commonly occurs in cancer patients, impacting their quality of life and survival duration. The objective of this meta-analysis and systematic review is to assess the effects of nutritional interventions on patients undergoing neoadjuvant chemoradiotherapy. METHODS: A comprehensive search was conducted in PubMed, Embase, and the Cochrane Library databases to obtain randomized controlled trials of nutritional interventions in patients with neoadjuvant chemoradiotherapy. Outcomes assessed included toxicity reactions to neoadjuvant therapy, levels of inflammation-related markers, nutritional status, and relevant clinical outcomes. The relative risk (RR) or weighted mean difference (WMD) and 95% confidence interval (CI) were used as effect sizes. RESULTS: A total of 16 studies were included, involving 954 patients. Nutritional intervention significantly reduced the incidence of vomiting (RR = 0.37, 95%CI: 0.21-0.67, P = 0.001) and mucositis (RR = 0.82, 95%CI: 0.67-1.00, P = 0.046) in patients with neoadjuvant chemoradiotherapy. For the nutritional status of cancer patients, nutritional intervention significantly increased the proportion of well-nourished patients (RR = 12.74, 95%CI: 4.43-36.69, P < 0.001). In addition, nutritional intervention also reduced the length of hospital stay in neoadjuvant chemoradiotherapy patients after surgery (WMD = - 0.82, 95%CI: - 1.61- - 0.02, P = 0.043). However, there was no improvement in nausea (P = 0.534), diarrhea (P = 0.068), febrile neutropenia (P = 0.551), levels of albumin (P = 0.211), prealbumin (P = 0.063), C-reactive protein (P = 0.430), clinical remission (P = 0.148), or postoperative complications (P = 0.098). CONCLUSION: Nutritional intervention can reduce the toxicity of neoadjuvant chemoradiotherapy (vomiting and mucositis), improve the nutritional status of patients, and shorten the length of postoperative hospital stay. Well-designed and high-quality studies are necessary to confirm the effect of nutritional interventions on cancer patients, with a specific focus on reaching nutritional goals and providing the right nutrients.

Relationships between postoperative recurrences and standardized uptake value on 18F-fluorodeoxyglucose-positron emission tomography in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma who underwent curative pancreatic resection after neoadjuvant chemoradiotherapy.

BACKGROUND: This study aimed to examine postoperative recurrence after curative pancreatic resection following neoadjuvant chemoradiotherapy (NACRT) in patients with resectable (R-) and borderline resectable (BR-) pancreatic ductal adenocarcinoma (PDAC), focusing on its relationship with the standardized uptake value (SUV) on 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). METHOD: The postoperative initial recurrence patterns were examined in patients with R- and BR-PDAC who underwent NACRT followed by curative pancreatic resection. Data collected from three prospective clinical trials were retrospectively analysed. RESULTS: After a median follow-up of 29 months, 91 (60 %) of 151 patients experienced postoperative recurrence. The median recurrence-free survival (RFS) for all patients was 18 months. The sites of first recurrence were lung-only in 24 (26 %) patients, liver-only in 23 (25 %), local-only in 11 (12 %), peritoneum-only in 10 (11 %), other single site in 5 (5 %), and multiple sites in 19 (21 %) patients. Multivariate analysis identified the maximum standardized uptake value (SUVmax) on FDG-PET at diagnoses ≥5.40 (hazard ratio [HR], 1.62; 95 % confidence interval [CI], 1.01-2.61; p = 0.045) and node-positive pathology (HR, 2.01; 95 % CI, 1.32-3.08; p = 0.001) as significant predictors of RFS. Furthermore, the SUVmax at initial diagnosis and after NACRT correlated with liver metastasis. CONCLUSION: R- and BR-PDACs with high SUV on FDG-PET at diagnosis are risk factors for postoperative recurrence. Among patients who undergo surgery after NACRT, those with a high SUVmax at diagnosis or post-NACRT require careful attention for postoperative liver recurrence.

Characterization and proteomic analysis of plasma-derived small extracellular vesicles in locally advanced rectal cancer patients.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) stands as a pivotal therapeutic approach for locally advanced rectal cancer (LARC), yet the absence of a reliable biomarker to forecast its efficacy remains a challenge. Thus, this study aimed to assess whether the proteomic compositions of small extracellular vesicles (sEVs) might offer predictive insights into nCRT response among patients with LARC, while also delving into the proteomic alterations within sEVs post nCRT. METHODS: Plasma samples were obtained from LARC patients both pre- and post-nCRT. Plasma-derived sEVs were isolated utilizing the TIO2-based method, followed by LC-MS/MS-based proteomic analysis. Subsequently, pathway enrichment analysis was performed to the Differentially Expressed Proteins (DEPs). Additionally, ROC curves were generated to evaluate the predictive potential of sEV proteins in determining nCRT response. Public databases were interrogated to identify sEV protein-associated genes that are correlated with the response to nCRT in LARC. RESULTS: A total of 16 patients were enrolled. Among them, 8 patients achieved a pathological complete response (good responders, GR), while the remaining 8 did not achieve a complete response (poor responders, PR). Our analysis of pretreatment plasma-derived sEVs revealed 67 significantly up-regulated DEPs and 9 significantly down-regulated DEPs. Notably, PROC (AUC: 0.922), F7 (AUC: 0.953) and AZU1 (AUC: 0.906) demonstrated high AUC values and significant differences (P value < 0.05) in discriminating between GR and PR patients. Furthermore, a signature consisting of 5 sEV protein-associated genes (S100A6, ENO1, MIF, PRDX6 and MYL6) was capable of predicting the response to nCRT, yielding an AUC of 0.621(95% CI: 0.454-0.788). Besides, this 5-sEV protein-associated gene signature enabled stratification of patients into low- and high-risk group, with the low-risk group demonstrating a longer overall survival in the testing set (P = 0.048). Moreover, our investigation identified 11 significantly up-regulated DEPs and 31 significantly down-regulated DEPs when comparing pre- and post-nCRT proteomic profiles. GO analysis unveiled enrichment in the regulation of phospholipase A2 activity. CONCLUSIONS: Differential expression of sEV proteins distinguishes between GR and PR patients and holds promise as predictive markers for nCRT response and prognosis in patients with LARC. Furthermore, our findings highlight substantial alterations in sEV protein composition following nCRT.