BACKGROUND:Although several oesophageal squamous cell carcinoma (OSCC) studies have reported no definitive overall survival (OS) differences between neoadjuvant chemoradiotherapy (NACRT) and neoadjuvant chemotherapy (NAC), the higher pCR rate with NACRT has been viewed as a potential advantage. Beyond ongoing concerns about the validity of pCR as a surrogate endpoint, it remains uncertain whether survival differs between these modalities among patients with OSCC who achieve pCR. METHODS:An integrated analysis of individual patient data (IPD) from phase III trials evaluating perioperative therapies for resectable OSCC was conducted, emphasizing prognostic differences between NAC and NACRT, particularly among patients who achieved pCR. RESULTS:IPD from seven phase III RCTs across six countries included data for 1044 patients with OSCC (83.5% male; mean age of 62.3 years). Of these patients, 605 (58.0%) received NAC and 439 (42.0%) received NACRT, with R0 resection rates of 89.6% versus 84.7% and pCR rates of 6.9% versus 34.2% respectively. Among patients who achieved pCR (192 patients), 5-year OS was 97.5% in the NAC group and 70.4% in the NACRT group, while 5-year recurrence-free survival was 80.8% and 63.7% respectively. Multivariable analysis demonstrated a significant survival advantage for NAC among patients who achieved pCR. CONCLUSION:Among patients who achieved pCR, postoperative outcomes varied considerably by neoadjuvant treatment modality. The markedly favourable prognosis associated with pCR after NAC suggests that these patients may represent an optimal candidate cohort for future evaluation of surgery-avoidance and watch-and-wait strategies.

Minimally invasive surgery (MIS) has improved the management of colorectal cancer (CRC), offering reduced morbidity without compromising the oncological outcomes. However, its role in locally advanced colon cancer and its impact on the Textbook Outcome (TO)—a metric integrating key surgical success parameters— remain unclear. This retrospective study analyzed the data of 459 patients with T3/T4 colon cancer who underwent elective resection at Keio University Hospital between 2012 and 2020. TO was defined as R0 resection, ≥ 12 lymph nodes harvested, no severe complications, no unplanned stoma, and timely surgery. Multivariate regression was used to identify the factors influencing TO and overall survival (OS). TO was achieved in 59.0

Abstract Topic Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Background In the treatment of esophageal squamous cell carcinoma (ESCC), previous studies have shown comparable overall survival (OS) between neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT). While NACRT typically yields a higher pathological complete response (pCR) rate, the reliability of pCR as a surrogate marker for survival remains a subject of debate. Furthermore, it is not clear if survival outcomes differ between these two preoperative approaches specifically among patients who reach pCR. Methods This study performed an integrated individual patient data (IPD) analysis using data from phase III clinical trials focused on resectable ESCC. The primary objective was to compare the prognostic outcomes of NAC versus NACRT, with a particular emphasis on the subgroup of patients who achieved pCR. Results Data from 1,044 patients (83.5% male; mean age 62.3 years) were pooled from seven randomized controlled trials across six countries. Of these, 605 patients underwent NAC and 439 received NACRT. The pCR rates were 6.9% and 34.2%, respectively. Notably, among the 192 patients who achieved pCR, the NAC group demonstrated a 5-year OS of 97.5%, compared to 70.4% in the NACRT group. Similarly, 5-year recurrence-free survival was higher for NAC (80.8%) than for NACRT (63.7%). Multivariable models confirmed that NAC was associated with a significant survival benefit in the pCR population. Conclusion Postoperative prognosis differs significantly by the type of neoadjuvant therapy, even when pCR is achieved. The exceptionally high survival rates seen in patients reaching pCR after NAC suggest that this specific group may be the most suitable candidates for exploring "watch-and-wait" strategies or the omission of surgery in future clinical trials.

BACKGROUND:Plasma fibrinogen (FNG) is a prognostic marker in esophageal squamous cell carcinoma (ESCC). However, its predictive value for immune checkpoint inhibitor (ICI) efficacy and the underlying mechanisms remain unclear. This study aimed to evaluate the clinical significance of plasma FNG levels in ICI-treated ESCC patients and investigate its association with tumor-associated neutrophils (TANs) and genomic alterations. METHODS:A retrospective, multicenter analysis of 167 ESCC patients treated with ICIs was performed. TANs were quantified via immunohistochemistry using CD11b and CD66b staining, and PD-L1 expression was assessed using the tumor proportion score (TPS). Whole-exome and RNA sequencing were conducted to analyze genomic and transcriptomic profiles. RESULTS:Elevated plasma FNG levels correlated with lower ICI response rates and decreased survival. In first-line treatment, chemo-ICI therapy demonstrated superior efficacy compared to dual-ICI therapy in high-FNG patients, while the reverse trend was observed in low-FNG patients. High-FNG tumors showed increased TAN infiltration, independent of PD-L1 expression. RNA sequencing revealed enrichment of neutrophil activation and extravasation pathways in high-FNG tumors. CONCLUSIONS:Elevated plasma FNG levels predict poor prognosis and reduced ICI efficacy in ESCC. They may be potential biomarkers for first-line ICI-based therapy and correlate with TAN infiltration. Further validation and mechanistic investigations are warranted.

345 Background: Most recurrences after curative surgery for esophageal cancer occur within two years. However, conventional recurrence-free survival (RFS), calculated from the time of surgery, does not accurately reflect the prognosis of patients who remain recurrence-free during this initial period. The aim of this study was to evaluate conditional RFS and recurrence timing to explore the potential for individualizing follow-up intervals. Methods: Individual patient data (IPD) analysis of phase III randomized controlled trials (RCTs) comparing perioperative treatments for resectable advanced esophageal and gastroesophageal junction cancer was conducted. Conditional RFS (i.e., the probability of recurrence-free surviving y additional years given that a patient has already recurrence-free survival for x years; [RFS y |RFS x ]) was performed. Results: IPD were available from 10 phase III RCTs (JCOG1109, JCOG9907, JCOG9204, FFCD9901, FFCD9102, SAKK75/08, CROSS, KOK, CMISG1701, NeoRes2), in addition to one phase II RCT (NeoRes), including 2,268 patients who underwent R0 resection (cStage IV, cT1N0 and cT4b excluded). Of these, 1,597 patients had squamous cell carcinoma (SCC), and 664 patients had adenocarcinoma. The 5-year RFS rate (RFS 5 |RFS 0 ) for patients with SCC was 47.9%; however, RFS 5 |RFS 1 , RFS 2 , RFS 3 , RFS 4 gradually increased to 63.0%, 72.5%, 78.2%, and 81.2%, respectively. At baseline (RFS 5 |RFS 0 ), patients with pN-positive disease or pM1 disease had substantially worse 5-year RFS than those with pN0 or pM0 disease. However, among patients who remained recurrence-free for 4 years after surgery (RFS 5 |RFS 4 ), the pattern was reversed, with the advanced groups showing better subsequent 5-year RFS. Among patients who experienced recurrence, those with pN-positive disease showed earlier recurrence patterns, with 58.8% recurring within one year and 81.7% within two years of randomization, compared to 42.8% and 69.9% in the pN0 group. These overall trends were also observed in patients with adenocarcinoma. Conclusions: Conditional RFS improved over time in patients with esophageal cancer, especially in those with advanced pTNM stage. Although patients with more advanced-stage disease are typically monitored more intensively after surgery, these findings suggest that similar follow-up intensity may be appropriate across all stages once a patient has remained recurrence-free for a certain postoperative period. Additionally, these findings may provide valuable insights for guiding survivorship care in patients who remain recurrence-free for several years, even if they were initially diagnosed with advanced disease.

BackgroundIn patients with locally advanced T4 esophageal cancer, surgery is typically considered if curative resection appears feasible after chemotherapy or chemoradiotherapy. Many institutions do not perform surgery in cases with persistent T4 diseases, while some challenge combined organ resection to achieve curative resection. However, this approach may be inappropriate for patients at high risk of developing early postoperative distant metastases.MethodsWe retrospectively analyzed 445 patients with esophageal squamous cell carcinoma who were unable to undergo curative esophagectomy due to cancer invasion into surrounding organs. Survival outcomes, progression patterns, and predictive factors for distant progression as the initial site of failure were evaluated.ResultsDuring follow-up, 242 patients (54.8%) developed distant metastases as the initial site of progression. Multivariable analysis revealed pN2-3 (hazard ratio [HR] 2.14; 95% confidence interval [95% CI] 1.45-3.17), pM1 (HR 2.11; 95% CI 1.22-3.64), and preoperative chemotherapy (HR 1.52; 95% CI 1.09-2.11) as significant predictors of distant progression. The 2-year distant progression rates were 76.3% (95% CI 67.2%-82.9%) for pN2-3, 78.3% (95% CI 55.5%-88.4%) for pM1, and 46.3% (95% CI 32.5%-57.3%) for pN0.ConclusionsIn patients with T4 esophageal cancer and extensive lymph node metastasis, the decision to perform combined organ resection should be made with caution. Conversely, T4 patients without lymph node metastasis may benefit from extended surgery with combined organ resection.

BACKGROUND:Most recurrences after curative surgery for esophageal cancer occur within 2 years. Conventional recurrence-free survival (RFS), calculated from the time of surgery, may underestimate prognosis for patients who remain recurrence-free during the early postoperative years. This study aimed to evaluate conditional RFS and recurrence timing to inform individualized follow-up strategies. METHODS:An individual patient data (IPD) analysis was conducted using randomized controlled trials (RCTs) comparing perioperative treatments for resectable esophageal or gastroesophageal junction cancer. Conditional RFS, defined as the probability of remaining recurrence-free for an additional y years given x years already survived without recurrence (RFSy|RFSx), was estimated. RESULTS:IPD from 10 phase III and 1 phase II RCTs were analyzed (n = 2268 patients with R0 resection). In squamous cell carcinoma (SCC), RFS5|RFS0 was 47.9%, which increased to 63.0%, 72.5%, 78.2%, and 81.2% at RFS5|RFS1-4. Among patients who recurred, 58.8% of pN-positive cases recurred within 1 year and 81.7% within 2 years, compared with 42.8% and 69.9% in pN0. At baseline (RFS5|RFS0), patients with pN-positive disease or pM1 disease had worse 5-year RFS than those with pN0 or pM0 disease. However, among patients who remained recurrence-free for 4 years after surgery (RFS5|RFS4), the pattern was reversed, with advanced groups showing better subsequent 5-year RFS. Similar trends were observed in adenocarcinoma. CONCLUSIONS:Conditional RFS improves over time, particularly in advanced-stage esophageal cancer. Although advanced cases are typically monitored more intensively, findings suggest comparable follow-up intensity may be appropriate once patients remain recurrence-free for a certain postoperative period.

OBJECTIVE:To validate the utility of recurrence prediction value (RPV) in identifying patients with UICC stage II colon cancer who would benefit from adjuvant chemotherapy (AC). SUMMARY BACKGROUND DATA:The benefits of AC in Stage II colon cancer remain insufficient. METHODS:We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer who had undergone surgery. RPV was developed based on the weighting of each high-risk factor. Data from multi-institutional databases in Japan, the United States, and Jordan were used (cohort 1). In addition, nationwide data were obtained from Denmark (Cohort 2). The primary endpoint was recurrence-free survival (RFS). RESULTS:According to the RPV, a low score was found in 750 (70.2%) patients and high scores in 318 (29.8%) patients in cohort 1. The corresponding numbers were 1031 (70.4%) and 433 (29.6%) patients in cohort 2, respectively. The five-year RFS rates were significantly higher in the group of patients who received AC than in the group who did not in the RPV high sub-group of cohort1 (76.2% vs. 55.6%, P <0.001) and in cohort2 (65.6% vs. 49.8%, P=0.001). Multivariate analyses revealed that AC was an independent prognostic factor for RFS only in the RPV high sub-group of both cohort 1 (hazard ratio (HR) 0.48; 95% confidence interval (CI) 0.29-0.81; P=0.005) and cohort2 (HR 0.69; 95% CI 0.48-0.99; P=0.043). CONCLUSIONS:This global study validates a readily available clinical data-based algorithm for predicting recurrence in Stage II colon cancer, identifying patients across diverse populations who benefit significantly from AC.

Although combinations of immune-checkpoint inhibitors (ICI) with chemotherapy have been approved for esophageal squamous cell carcinoma (ESCC), it remains unclear whether immunochemotherapy (ICT) offers advantages over the simple addition of individual monotherapies. This study aimed to investigate whether ICT exhibits a synergistic effect in patients with advanced ESCC. Reconstructed individual patient data of 3330 patients were electronically extracted from the Kaplan–Meier (KM) curves of eight randomized-controlled trials (ATTRACTION-3, CheckMate648, KEYNOTE-181, KEYNOTE-590, RATIONALE-302, RATIONALE-306, ESCORT, and ESCORT-1st). The observed progression-free survival (PFS) curve of each constituent monotherapies was used to estimate simulated PFS curves expected under a model of independent drug action. If the observed curve demonstrated significantly better PFS than the simulated curve, the combination of ICI and chemotherapy may have a synergistic effect, implying a superior outcome compared to simply adding the component monotherapy. The 1-year, 2-year, and median PFS of the observed and simulated KM curves were 26.3

BACKGROUND:Overall survival (OS) is the standard endpoint for oncological treatment efficacy, but requires long follow-up. The aim of this study was to evaluate pCR as a surrogate for OS in oesophageal cancer. METHODS:An integrated analysis of individual patient data (IPD) from phase III trials comparing perioperative therapies for resectable oesophageal and gastro-oesophageal junction cancer was conducted. Individual-level surrogacy between pCR and OS was assessed using Kendall's rank correlation coefficient (τ). A τ of 0.8 was considered a threshold for a good surrogate. As no method estimating τ between an ordinal endpoint and OS has been reported, a new method was proposed using the inverse-probability-of-censoring weighted estimator adjusted for tied data. RESULTS:Of 22 eligible trials, 10 provided IPD for 1641 patients, including 624 who received neoadjuvant chemotherapy (NAC; 45 (7.2%) achieved pCR) and 1017 who received neoadjuvant chemoradiotherapy (NACRT; 299 (29.4%) achieved pCR). In the NAC subgroup, patients with pCR had an HR for OS of 0.12 (95% c.i. 0.05 to 0.33), the C-index was 0.54 (95% c.i. 0.52 to 0.56), and τ was 0.256. In the NACRT subgroup, the HR was 0.57 (95% c.i. 0.47 to 0.70), the C-index was 0.56 (95% c.i. 0.54 to 0.58), and τ was 0.174. Hypothetical data suggested that achieving strong surrogacy (τ of 0.8) required an HR of 0.09 (95% c.i. 0.07 to 0.11). CONCLUSION:Although pCR was correlated with OS, no evidence of individual-level surrogacy with OS was demonstrated, making it inappropriate to consider pCR as a surrogate endpoint for OS in resectable oesophageal cancer.

405 Background: Combinations of immune checkpoint inhibitors (ICI) and chemotherapy (CT) have been approved for gastric cancer. However, there is a hypothesis that this combination may blunt antitumor immune responses because most chemotherapeutic agents also target lymphocytes. The primary objective was to investigate that the ICI and CT does not interfere each other’s therapeutic effects in advanced gastric cancer (GC) or gastroesophageal junction cancer (GEJC) patients. Methods: The reconstructed individual patient data was electronically extracted from the Kaplan-Meier curve of phase III randomized controlled trials (RCTs). The observed PFS curve of each constituent monotherapies was used to estimate simulated PFS curves expected under a model of independent drug action. If the observed curve demonstrated significantly better PFS than simulated curve, the combination of ICI and CT may have a synergistic effect, implying a superior outcome compared to simply adding the component monotherapy. Results: The study included 2,538 unresectable advanced, recurrent, or metastatic GC or GEJC patients from three RCTs comparing pembrolizumab (KEYNOTE-061, KEYNOTE-062 and KEYNOTE-859). In patients with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or greater, the 1-year and median PFS of the observed and simulated curves were 28.0% vs. 27.9%, and 6.89 months vs. 6.88 months, respectively. One sample log-rank test showed no significant differences between the observed and simulated curves (p = 0.107). In the subgroups with PD-L1 CPS ≥10 or <1, the 1-year PFS of the observed and simulated curves was 34.7% vs 32.8%, and 28.5% vs 26.8%. Conclusions: The observed PFS of ICT involving pembrolizumab was comparable to the simulated PFS estimated from the data for each monotherapy regardless of the magnitude of PD-L1 CPS. Although it was not clear whether potential synergies existed for ICT, these findings at least suggest that the benefits of ICI and CT are not interfering each other, thereby providing theoretical support for the efficacy of ICT in patients with advanced GC or GEJC.

BACKGROUND:We occasionally experience incomplete resection of esophageal cancer due to the surrounding organ invasion. The efficacy of additional treatment in these cases is unknown. METHODS:We studied 445 patients with esophageal squamous cell carcinoma who were unable to undergo curative esophagectomy due to cancer invasion to the surrounding organs at 45 esophageal centers in Japan. Survival outcomes were compared based on the additional treatment modalities. RESULTS:Postoperatively, 175 (40.0%) received no additional treatment, while 59 (13.5%), 153 (35.0%), and 50 (11.4%) received additional chemotherapy, chemoradiotherapy, or radiotherapy, respectively. The three-year disease progression and overall survival rates were 90.6% (95% confidence interval 87.2-93.1%) and 15.4% (95% confidence interval 12.2-19.3%), respectively. Multivariable analysis revealed that chemotherapy, chemoradiotherapy, and radiotherapy were all independently associated with reduced disease progression (hazard ratios [95% confidence intervals]: 0.57 [0.40-0.81], 0.52 [0.39-0.69], and 0.48 [0.33-0.72], respectively). Meanwhile, additional treatment with chemotherapeutic agents (chemotherapy and chemoradiotherapy) was independently associated with better overall survival (hazard ratios [95% confidence intervals]: 0.51 [0.35-0.73] and 0.59 [0.44-0.79], respectively); however, radiotherapy alone had a limited impact (hazard ratio [95% confidence interval]: 0.74 [0.50-1.10]). CONCLUSIONS:Any additional treatment could suppress disease progression after incomplete resection, but radiotherapy alone has a limited effect. Additional systemic chemotherapeutics may increase patient survival.

PURPOSE:Although immune checkpoint inhibitors (ICIs) and chemotherapy combinations have been approved for the treatment of gastric and gastroesophageal junction cancer (GC/GEJC), whether immunochemotherapy (ICT) offers advantages over the simple addition of individual monotherapies remains unclear. This study aimed to investigate whether ICT has a synergistic effect in patients with advanced GC/GEJC. MATERIALS AND METHODS:Reconstructed individual patient data were electronically extracted from the Kaplan-Meier curves of 3 randomized controlled trials comparing pembrolizumab (KEYNOTE-061, KEYNOTE-062, and KEYNOTE-859). The observed progression-free survival (PFS) curve for each monotherapy was used to estimate the simulated PFS curve expected under an independent drug action model. If the observed curve demonstrated significantly better PFS than the simulated curve, combined ICI and chemotherapy was determined to have a synergistic effect, implying a superior outcome compared to adding-component monotherapy. RESULTS:In patients with programmed cell death ligand 1 combined positive scores of ≥1 (n=2,194), the 1-year and median PFS of the observed and simulated curves were 28.0% vs. 27.9% and 6.89 months vs. 6.88 months, respectively. The one-sample log-rank test revealed no significant differences between the observed and simulated curves (P=0.107). CONCLUSIONS:The observed PFS with ICT was comparable to the predicted PFS based on the data for each monotherapy. Our findings do not provide direct evidence of synergistic effects, but they suggest that combining ICI and chemotherapy does not compromise efficacy. These results may support the continued clinical use of ICT in patients with advanced GC/GEJC.

Total gastrectomy (TG) remains the standard surgical approach for proximal gastric and gastroesophageal junction (P/GEJ) cancers. However, experts increasingly perform proximal gastrectomy (PG) with anti-reflux reconstruction. The benefits of minimally invasive PG (MIPG) over minimally invasive TG (MITG), particularly regarding postoperative quality of life (QoL), remain unclear. We conducted a transpacific, multicenter, nonrandomized, prospective cohort study to compare symptom burden outcomes (symptom occurrence, symptom severity, and daily functioning) between MIPG and MITG in patients with P/GEJ cancers. Symptom burden data was collected using the MD Anderson Symptom Inventory (MDASI-GI +). Among 71 patients with P/GEJ cancers enrolled from 2022 through 2024, 64 underwent either MITG (n = 26, 41

BACKGROUND:Liver resection for colorectal liver metastases (CRLM) with concurrent extrahepatic disease (EHD) has demonstrated potential benefits for long-term prognosis; however, its effectiveness remains controversial. Additionally, the prognostic impact of different EHD sites is not well elucidated. This study aimed to assess the significance of liver resection in patients with CRLM with concurrent EHD and evaluate how different EHD sites influence prognosis. METHODS:A nationwide multicenter database was used for a retrospective analysis of patients diagnosed during two periods: 2005-2007 and 2013-2015. EHD was classified into the following five subgroups: lung, peritoneum, lymph nodes, local, and others. The inverse probability of treatment weighting (IPTW) method was applied to minimize selection bias. Kaplan-Meier survival curves and Cox proportional hazards models were used to compare the overall survival (OS) between the different treatment groups and EHD subgroups. RESULTS:Among 3787 patients, 874 (23.1%) underwent liver resection. Following IPTW adjustment, the hepatectomy (HT) group demonstrated significantly better OS than the non-hepatectomy (non-HT) group (5-year hazard ratio, 0.322; 95% confidence interval, 0.273-0.379; P < 0.001). Analysis by the EHD site subgroup demonstrated that liver resection was associated with a better prognosis across all sites. However, the prognostic impact differed by EHD site, with peritoneal metastasis associated with poorer outcomes in both the HT (5-year OS rates, 30.1% vs. 45.0%) and non-HT (5-year OS rates, 4.4% vs. 8.6%) groups. CONCLUSIONS:Regardless of the EHD site, liver resection was associated with a significantly better OS in patients with CRLM with concurrent EHD. The prognostic impact varies across EHD sites, underscoring the significance of considering differential prognostic risks when selecting treatment strategies.

4068 Background: Overall survival (OS) is regarded as the gold standard efficacy endpoint but requires long follow-up. This study aimed to determine the validity of recurrence-free survival (RFS) as a surrogate endpoint for OS in resectable esophageal cancer. Methods: A systematic review of phase III randomized controlled trials (RCTs) comparing perioperative treatments for resectable advanced esophageal and gastroesophageal junction cancer was conducted. Individual patient data (IPD) were requested from all included trials. Surrogacy between RFS and OS was assessed at the individual level using the Kendall rank correlation coefficient ( τ ) and at the trial level using the coefficient of determination ( R² ) from a meta-regression model. A τ of 0.8 and an R² of 0.65 were considered thresholds indicative of a good surrogate endpoint. Results: Twenty-two eligible trials were identified by the systematic review, and IPD were available from 10 RCTs (JCOG1109, JCOG9907, JCOG9204, FFCD9901, FFCD9102, SAKK75/08, CROSS, KOK, NeoRes2 and CMISG1701), including 2,145 patients who underwent R0 resection (cStage IV, cT1N0 and cT4b excluded). Of these, 1563 patients had squamous cell carcinoma, and 575 patients had adenocarcinoma. The 5-year OS and RFS rates were 53.2% and 46.2%, respectively, with a median OS of 6.2 years and a median RFS of 3.6 years. For individual-level surrogacy, Kendall’s τ was 0.823 (95% CI: 0.807–0.839). Subgroup analysis based on treatment modality revealed τ values of 0.830 (95% CI: 0.800–0.861) for patients receiving neoadjuvant chemotherapy (NAC; n = 586), 0.827 (95% CI: 0.803–0.850) for those receiving neoadjuvant chemoradiotherapy (NACRT; n = 982), 0.770 (95% CI: 0.713–0.828) for the surgery-alone group (n = 320), and 0.861 (95% CI: 0.824–0.898) for the adjuvant chemotherapy group (n = 257). Trial-level surrogacy analysis across all 22 trials demonstrated an R 2 of 0.735 (95% CI: 0.512–0.939). The surrogate threshold effect was 0.929, indicating the minimum RFS treatment effect required to predict a nonzero effect on OS. Conclusions: This study demonstrated strong individual-level and trial-level surrogacy between RFS and OS in surgically resectable esophageal cancer across all perioperative treatment modalities. These findings hold promise for expediting the development of novel perioperative treatment by shortening the follow-up of clinical trials on esophageal cancer.

Introduction A precise preoperative tumor monitoring method that reflects tumor burden during neoadjuvant treatment is required to guide individualized perioperative treatment strategies for esophageal squamous cell carcinoma (ESCC). This study examined the clinical significance of preoperative circulating tumor DNA (ctDNA) in the plasma of patients undergoing neoadjuvant chemotherapy (NAC) followed by esophagectomy. Materials and methods Plasma samples were collected longitudinally for ctDNA analysis as well as genomic DNA from primary lesions from patients with histologically confirmed ESCC who received neoadjuvant chemotherapy (NAC) followed by subtotal esophagectomy. Next-generation sequencing was used to identify mutations in both the plasma and primary tumors. We evaluated the relationship between ctDNA alterations and recurrence in patients with locally advanced ESCC. Results Pretreatment samples from 25 patients (100 %) showed the same mutations in both ctDNA and primary tumors; therefore, they were classified as ctDNA-positive before treatment. In the cohort of 25 patients analyzed, those who tested positive for ctDNA after NAC had a significantly higher risk of recurrence; the 36-month recurrence-free survival rates were 92 % for ctDNA-negative patients and 8 % for ctDNA-positive patients (p < 0.001). Conclusions Preoperative ctDNA status may be a promising prognostic biomarker that can be assessed before surgery in patients with ESCC who received NAC. Expanded cohort validation will allow for more personalized multidisciplinary treatment approaches for ESCC tailored to ctDNA analysis.

BACKGROUND:Extended colectomy is considered a standard treatment for neoplasia associated with ulcerative colitis, but there is limited supporting evidence, particularly from large-scale studies. OBJECTIVE:This study aimed to assess the prognostic benefits of extended colectomy in patients with neoplasia associated with ulcerative colitis using a nationwide database. DESIGN:Multicenter retrospective study. SETTINGS:Forty-three institutions in Japan participated in this study. PATIENTS:The medical records of patients with ulcerative colitis and diagnosed intestinal neoplasia between 1983 and 2020 at 43 institutions were analyzed. MAIN OUTCOME MEASURES:Five-year overall survival and disease-free survival were assessed on the basis of different surgical procedures, with a subgroup analysis comparing neoplasia associated with ulcerative colitis to sporadic cancer. RESULTS:Among 879 patients, 801 were diagnosed with neoplasia associated with ulcerative colitis and 78 with sporadic cancer. The 5-year disease-free survival for total proctocolectomy and subtotal colectomy were similar (87.8% and 83.9%), and both were superior to segmental colectomy (72.0%). When comparing neoplasia associated with ulcerative colitis to sporadic cancer, extended colectomy (total proctocolectomy and subtotal colectomy) showed significantly better outcomes for neoplasia associated with ulcerative colitis, whereas no significant difference was observed for sporadic cancer. Multivariable analysis revealed a significantly better prognosis for extended colectomy compared to segmental colectomy in neoplasia associated with patients with ulcerative colitis, both in overall survival and disease-free survival ( p < 0.001). LIMITATION:Nonrandomized retrospective study design. CONCLUSIONS:This nationwide cohort study supports extended colectomy as the criterion standard for neoplasia associated with ulcerative colitis management and underscores the importance of accurate diagnosis to distinguish between neoplasia associated with ulcerative colitis and sporadic cancer for optimal treatment decisions. See Video Abstract. DIFERENCIA EN EL BENEFICIO PRONSTICO ENTRE LA COLECTOMA EXTENDIDA Y SEGMENTARIA PARA PACIENTES CON NEOPLASIA ASOCIADA A COLITIS ULCERATIVA UN ESTUDIO MULTICNTRICO A NIVEL NACIONAL:ANTECEDENTES:La colectomía extendida se considera el tratamiento estándar para la neoplasia asociada con la colitis ulcerativa, pero hay evidencia de respaldo limitada, particularmente de estudios a gran escala.OBJETIVO:Este estudio tuvo como objetivo evaluar los beneficios pronósticos de la colectomía extendida en pacientes con neoplasia asociada con colitis ulcerativa utilizando una base de datos nacional.DISEÑO:Estudio retrospectivo multicéntrico.ESCENARIO:Cuarenta y tres instituciones en Japón participaron en este estudio.PACIENTES:Se analizaron pacientes con colitis ulcerativa diagnosticados con neoplasia intestinal entre 1983 y 2020 en 43 instituciones.PRINCIPALES MEDIDAS DE RESULTADOS:Se evaluaron la supervivencia general a cinco años y la supervivencia libre de enfermedad en función de diferentes procedimientos quirúrgicos, con un análisis de subgrupos que comparaba la neoplasia asociada con colitis ulcerativa con el cáncer esporádico.RESULTADOS:Entre 879 pacientes, 801 fueron diagnosticados con neoplasia asociada con colitis ulcerativa y 78 con cáncer esporádico. La supervivencia libre de enfermedad a 5 años para la proctocolectomía total y la colectomía subtotal fue similar (87,8% y 83,9%), ambas superiores a la colectomía segmentaria (72,0%). Al comparar la neoplasia asociada a la colitis ulcerativa con el cáncer esporádico, la colectomía extendida (proctocolectomía total y colectomía subtotal) mostró resultados significativamente mejores para la neoplasia asociada a la colitis ulcerativa, mientras que no se observó una diferencia significativa para el cáncer esporádico. El análisis multivariable reveló un pronóstico significativamente mejor para la colectomía extendida en comparación con la colectomía segmentaria en pacientes con neoplasia asociada a la colitis ulcerativa, tanto en la supervivencia general como en la supervivencia libre de enfermedad (p < 0,001).LIMITACIÓN:Diseño de estudio retrospectivo no aleatorizado.CONCLUSIÓN:Este estudio de cohorte a nivel nacional respalda la colectomía extendida como el estándar de oro para el manejo de la neoplasia asociada a la colitis ulcerativa y subraya la importancia de un diagnóstico preciso para distinguir entre la neoplasia asociada a la colitis ulcerativa y el cáncer esporádico para tomar decisiones óptimas de tratamiento. (Traducción- Dr. Francisco M. Abarca-Rendon ).

OBJECTIVE:This study evaluated recurrence-free survival (RFS) as a surrogate endpoint for overall survival (OS) in esophageal cancer. BACKGROUND:OS is regarded as the gold-standard efficacy endpoint of oncological treatments but requires long follow-up. METHODS:An integrated analysis of individual patient data (IPD) from phase III trials comparing perioperative therapies for resectable esophageal and gastroesophageal junction cancer was conducted. Surrogacy between RFS and OS was assessed at the individual level using the Kendall rank correlation coefficient (τ) and at the trial level using the coefficient of determination (R²). A τ of 0.8 and an R² of 0.65 were considered thresholds for a good surrogate. RESULTS:Twenty-two eligible trials were identified, and IPD were available from 10 randomized trials, including 2,145 patients who underwent R0 resection. The 5-year OS and RFS rates were 53.2% and 46.2%, with median OS of 6.2 and RFS of 3.6 years. For individual-level surrogacy, Kendall's τ was 0.823 (95% confidence interval [CI]: 0.807-0.839). Subgroup analysis by treatment modality revealed τ values of 0.830 (95% CI: 0.800-0.861) for neoadjuvant chemotherapy (NAC; n=586), and 0.827 (95% CI: 0.803-0.850) for neoadjuvant chemoradiotherapy (NACRT; n=982). Trial-level surrogacy analysis across all 22 trials demonstrated an R2 of 0.735 (95% CI: 0.512-0.939). The surrogate threshold effect was 0.929. CONCLUSIONS:This study demonstrated strong individual- and trial-level surrogacy between RFS and OS in resectable esophageal cancer across all perioperative treatments. These findings may accelerate perioperative treatment development by shortening follow-up in esophageal cancer trials.