Underwent R0 Resection Research Articles

Short-course radiation(SCRT) followed by 6 cycles of cadonilimab plus mFOLFOX6 as neoadjuvant therapy for patients with locally advanced rectal cancer (LARC): A multicenter, single arm, phase II trial (NeoCaCRT).

LBA210 Background: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) is recommended for mismatch repair-proficient (pMMR) or microsatellite stability(MSS) LARC. Recent studies have shown that anti-PD-1/PD-L1 in combination with CRT can improve pathological complete response (pCR) compared to CRT in the neoadjuvant setting. This trial aims to investigate the efficacy and safety of SCRT followed by cadonilimab, a first-in-class anti-PD-1/CTLA-4 bispecific antibody, plus mFOLFOX6 in patients (pts) with LARC. Methods: Eligible pts aged 18-79 years with pMMR/MSS, nonmetastatic, stage cT3-4N0 or cT1-4N1-2 rectal adenocarcinoma located below the peritoneal reflection were enrolled and given SCRT (25Gy/5F) followed by 6 cycles of cadonilimab (6mg/kg, q2w) plus mFOLFOX6. The primary endpoint was pCR. Secondary endpoints included clinical complete response (cCR), major pathological response (MPR), disease-free survival (DFS), overall survival (OS), safety and quality of life. The exploratory endpoint explored potential biomarkers related to response. Results: From April 2023 to May 2024, 27 pts were enrolled and received at least 1 dose of treatment. As of data cutoff date of October 20, 2024,median follow-up was 9.7 months (IQR 5.4–18·8)，and all pts received study treatment, and 24/27(88.9%) underwent R0 resections (one delayed surgery due to chemotherapy-related pneumonia, while the other two were assessed unresectable). The primary endpoint was met with a pCR of 37%(10/27)(95% CI, 19.4%–57.6%) and MPR of 55.6%. A cCR of 22.2%(6/27) was observed, and among them, 83.3%(5/6) still received local excisions. The T downstaging was observed in 59.3%(16/27) while N downstaging in 66.7%(18/27). Grade 3–5 adverse events occurred in 5 (18.5%) of 27 pts; the most common were diarrhea (ten [37%]),nausea (ten [37%]) and fatigue (ten [37%]), and neutropenia (seven [26%]). Drug-related serious adverse events occurred in eight (30%) of 27 patients. No new safety signal was identified. Conclusions: In pts with pMMR/MSS LARC, neoadjuvant SCRT with cadonilimab plus mFOLFOX6 resulted in promising pCR rates with intolerable toxicities. Follow up continues. These data deserve further investigations in a phase III randomized trial. Clinical trial information: NCT05792735 .

Impact of combined resection of pancreas on long-term survival in patients with gastric cancer.

359 Background: In patients with advanced gastric cancer invading adjacent organs, extended multivisceral resection is required to achieve R0 resection. However, the survival benefit of combined resection of pancreas remains controversial. We investigated the safety and efficacy of combined pancreatic resection in gastric cancer. Methods: This study included 64 patients who underwent gastrectomy with pancreatectomy (pancreaticoduodenectomy (PD) or distal pancreatectomy with splenectomy (PS)) for primary gastric cancer with invasion to the pancreas by primary tumor or lymph node metastasis and invasion to the duodenum. Patients who underwent R2 resection were excluded. Short- and long-term outcomes were assessed. Results: PD was performed in 18 patients (28.1%) and PS in 46 patients (71.9%). Macroscopic invasion to the pancreas by primary tumor was observed in 47 patients (73.4%), by lymph node in 13 patients (20.3%), and the invasion to the duodenum by primary lesion was in 4 patients (6.3%). Pathologically, pancreatic invasion was confirmed in 27 out of 47 patients (57.4%). Postoperative intra-abdominal infectious complications (PIIC) of Clavien-Dindo (CD) Grade III or higher were observed in 33 patients (51.6%). The most common postoperative complication was pancreatic fistula, which was observed in 31 patients (48.4%). There was no mortality within 30 days after surgery. Univariate analysis revealed that invasion the duodenum was highly associated with PIIC (p=0.038). Twelve patients (18%) resulted in R1 resection due to positive peritoneal cytology in 11 patients and positive surgical margin in one patient. The 5-year overall survival (OS) rate was 42.9%, which was 53.6% in R0 resection and 0% in R1 resection. Multivariate analysis revealed R1 resection was an independent prognostic factor for OS (HR:5.315, p<0.001). The 5-year recurrence-free survival (RFS) rate was 44.5%. The 5-year RFS rate was significantly worse in patients with PIIC (28.7%) than in patients without it (58.7%). Multivariate analysis revealed that PIIC was an independent prognostic factor for RFS (HR:2.345, p=0.036). Conclusions: Pancreatic resection for gastric cancer is considered safe and effective when R0 resection is possible. However, surgeon should pay particular attention to avoid the postoperative complications.

Prognostic factors for gastric cancer patients with positive peritoneal cytology who underwent upfront surgery.

400 Background: Positive peritoneal cytology (CY1) is classified as Stage IV disease, the standard treatment for which is systemic chemotherapy. However, CY1 is often diagnosed after surgery in patients for whom staging laparoscopy is not indicated. In addition, the treatment strategy for patients with CY1 diagnosed during surgery is controversial. The Japanese guidelines recommend upfront surgery followed by adjuvant chemotherapy for patients diagnosed with CY1 during surgery. To identify patients with CY1 who are most likely to benefit from upfront surgery, we investigated prognostic factors in patients with CY1 who underwent upfront surgery. Methods: A total of 169 gastric cancer patients diagnosed as P0CY1 during or after surgery who underwent R1 resection other than positive resection margins were included. The diagnosis of CY1 was obtained by staging laparoscopy or during laparotomy in 69 patients and after surgery in 87 patients. Fourteen patients were initially diagnosed as CY0 by staging laparoscopy but were rediagnosed as CY1 after surgery. The clinicopathological factors of overall survival (OS) and progression-free survival (PFS) were investigated. Prognostic factors were identified using Cox regression models. Results: The median patient age was 72 years, and there were 108 males. The histological type was undifferentiated type in all of 102 patients. The macroscopic types were 0 in 10) patients 1 in 3, 2 in 27 3 in 84 and 4 in 45). cT grades and cN grades were cT1 in 3, cT2 in 7, cT3 in 12, cT4 in 147, cN0 in 65cN1 in 30), cN2 in 46 and cN3 in 28. The median OS and PFS were 25.1 months and 14.6 months, with 5-year OS rate and PFS rate of 30% and 23%, respectively. A multivariate analysis for OS identified macroscopic type 0-2, Charlson Comorbidity Index<3, and adjuvant chemotherapy as independent prognostic factors. Similarly, macroscopic type 0-2, tumor size <80 mm, and adjuvant chemotherapy were identified as independent prognostic factors for PFS. In a subgroup analysis of patients who received adjuvant chemotherapy, macroscopic type 0-2 was the only independent prognostic factor for PFS. The 5-year PFS rate in patients with macroscopic type 0-2 was 42%. Conclusions: Patients with macroscopic type 0-2 who are suitable for adjuvant chemotherapy may have benefit from upfront surgery, even if peritoneal cytology is positive.

Adjuvant radiation therapy is not associated with a survival benefit after R0 resection in non-metastatic adrenocortical carcinoma.

The benefit of adjuvant radiation therapy (RT) in adrenocortical carcinoma (ACC) is not well characterized for those who undergo initial R0 surgical resection. Patients in the NCDB who underwent R0 resection were placed into two cohorts - those who underwent adjuvant RT and those who did not. 388 patients were identified with 51 receiving RT. No difference was observed between Kaplan-Meier survival estimates of the two cohorts (p​=​0.54). After adjusting for age, sex, co-morbidity index, race, receipt of chemotherapy, tumor size, grade, stage, and nodal stage, RT was not associated with improved OS. However, tumor size ≥6​cm (HR 1.54, [1.03-2.32], p​=​0.04), high tumor-grade (HR 3.46, [1.83-6.55], p​<​0.001), and N1-stage (HR 2.30, [1.06-4.94], p​=​0.03) were associated with worse OS, without benefit of RT on subgroup analysis of these factors. Treatment with adjuvant RT in patients with ACC who underwent R0 resection was not associated with an OS benefit.

Conversion Therapy for Stage IV Gastric Cancer: Report From the Expert Consensus Meeting at KINGCA WEEK 2024.

Conversion therapy is a treatment strategy that shifts from palliative systemic therapy to curative surgical treatment for primary and/or metastatic stage IV gastric cancer (GC). To address its clinical statements, the Korean Gastric Cancer Association aims to present a consensus on conversion therapy among experts attending KINGCA WEEK 2024. The KINGCA Scientific Committee and Development Working Group for Korean Practice Guidelines prepared preformulated topics and 9 clinical statements for conversion therapy. The Delphi method was applied to a panel of 17 experts for consensus and opinions. The final comments were announced after the statement presentation and discussed during the consensus meeting session of KINGCA WEEK 2024. Most experts agreed that conversion therapy provides a survival benefit for selected patients who respond to systemic therapy and undergo R0 resection (88.3%). Patients with limited metastases were considered good candidates (94.2%). The optimal timing was based on the response to systemic therapy (70.6%). The regimen was recommended to be individualized (100%) and the duration to be at least 6 months (88.3%). A minimally invasive approach (82.3%) and D2 lymph node dissection (82.4%) were considered for surgery. However, resection for metastases with a complete clinical response after systemic therapy was not advocated (41.2%). All experts agreed on the need for large-scale randomized-controlled trials for further evidence (100%). Recent advancements in treatment may facilitate radical surgery for patients with stage IV GC. Further evidence is warranted to establish the safety and efficacy of conversion therapy.

IINS Vs CALLY Index: A Battle of Prognostic Value in NSCLC Patients Following Surgery.

This research sought to assess the predictive potential of the inflammation-immunity-nutrition score (IINS) and the high-sensitivity C-reactive protein-albumin-lymphocyte (CALLY) index in individuals with NSCLC post-surgery. The study enrolled 506 patients with NSCLC undergoing R0 resection at the First Affiliated Hospital of Xi'an Jiaotong University. The training cohort was analyzed utilizing X-tile software to identify the ideal threshold values for categorizing high-sensitivity C-reactive protein, albumin, lymphocyte count, and the CALLY index. The predictive significance of the IINS and CALLY index was evaluated through Kaplan-Meier survival curves and univariate and multivariate Cox regression analyses. Predictive capabilities of the IINS and CALLY index were compared utilizing receiver operating characteristic (ROC) curve analysis, time-dependent ROC curve analysis, and decision curve analysis (DCA). Internal validation was performed in the validation cohort and all data from both the training and validation cohorts using Kaplan-Meier curves and DCA. Patients with lower IINS exhibited prolonged overall survival (OS), whereas those with lower CALLY had shorter OS. Multivariate analysis identified N stage, NSE, and IINS as independent prognostic factors for individuals with NSCLC. ROC analysis revealed that IINS provided superior prognostic performance to CALLY and other traditional indicators (CAR, PLR, and NLR). Time-dependent ROC analyses and DCA further confirmed the superior prognostic value of IINS over the CALLY index at 1, 2, and 3 years. This study reveals that both the IINS and CALLY index are effective in forecasting the prognosis of individuals with NSCLC following surgery, with the IINS demonstrating superior prognostic efficacy to the CALLY index.

Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings.

Neoadjuvant chemoimmunotherapy has achieved overall survival (OS) benefit for patients with resectable non-small cell lung cancer (NSCLC). Here, we present outcomes after 3 years of follow-up from the first reported study of neoadjuvant atezolizumab+chemotherapy. This open-label, multicenter single-arm investigator-initiated phase II study conducted at three US hospitals tested up to four cycles of atezolizumab, carboplatin, and nab-paclitaxel prior to surgery. Major pathological response (MPR, primary endpoint) was previously reported; here, we report 3-year disease-free survival (DFS), OS, and clinical characteristics of patients developing brain metastases (BM) with integrated data from tumor genomics, gene expression, and quantitative immunofluorescent measurement of immune markers. Of 30 enrolled patients, 29 were taken to the operating room. 26 underwent R0 resection, with 17 experiencing MPR (10 pCR). With a median follow-up of 39.5 months, the median OS was 55.8 months, and the median DFS was 34.5 months. Landmark OS at 36 months was 77%. Among 14 patients with recurrent disease, 6 patients had BM. Patients whose tumors had mutations in STK11 and KEAP1 did not have a significantly higher incidence of BM. Reduced copy number of STK11 and KEAP1, both residing on chromosome 19p, was observed in ~1/3 of tumors. Reduced CN of STK11 was significantly associated with worse pathological response and incidence of BM. Consistent with recent phase III studies, 3-year OS data with neoadjuvant atezolizumab+chemotherapy was associated with prolonged PFS and OS. Establishing associations between STK11 and KEAP1 genomic alterations and key clinical outcomes in early-stage NSCLC requires further study.

Combining the Albumin-to-fibrinogen ratio and pathologic factors predicts survival in surgically treated patients with esophageal squamous cell carcinoma

Abstract Objectives The primary objectives of this research were to examine the prognostic significance of the albumin-to-fibrinogen ratio (AFR) in patients who have undergone surgery for esophageal squamous cell carcinoma (ESCC) and to develop an easily implementable predictive model with clinical utility. Methods The present study retrospectively analyzed the clinical data of 414 patients who underwent R0 resection after being diagnosed with stage I–III ESCC. The prognostic value of AFR was evaluated using Kaplan-Meier survival curves and COX proportional risk regression modeling, and the effectiveness of AFR compared with other inflammatory markers was evaluated. Additionally, a nomogram prediction model was developed, and its accuracy was evaluated using the receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and calibration curves. Results AFR was significantly correlated with tumor length, T-stage, N-stage, pathological stage, and vascular infiltration (p&lt;0.05 for all). The multivariate analysis results demonstrated that AFR was an independent prognostic factor that affected patient outcomes, whereas other inflammatory and nutritional biomarkers did not. Furthermore, the overall C-index of the nomogram risk prediction model was 0.737 (95 %-CI: 0.700–0.776). The calibration curves showed that the 3- and 5-year overall survival (OS) probabilities predicted by the nomogram were consistent with actual observations. Moreover, the DCA and ROC curves showed that our model had better clinical utility. Conclusions Preoperative AFR, a clinical indicator based on inflammation and nutrition, plays a clear role in the predictions of patient prognosis. The prognostic prediction model incorporating pathological factors and AFR demonstrates simplicity, efficacy, and exceptional accuracy.

The First Report on Liver Resection Using the Novel Japanese hinotori™ Surgical Robot System: First Case Series Report of 10 Cases.

Background: In Japan, the hinotori™ surgical robot system (Medicaroid Corporation, Kobe, Japan) was approved for gastrointestinal surgeries in October 2022. This report details our initial experience performing liver resection using the hinotori™ system. Methods: Ten patients, who were assessed as cases that would benefit from the robot-assisted procedure, underwent liver resections using the hinotori™ system at Fujita Health University, Okazaki Medical Center, between August 2023 and October 2024. The backgrounds (patient, tumor, and liver function conditions, along with types of liver resections and previous surgical procedures) and short-term outcomes (operation time, blood loss, postoperative complications, open conversion, length of hospital stay, and mortality) of the cases were evaluated. Results: Eight cases of partial liver resection, one extended left medial sectionectomy, and one left hemi-hepatectomy were performed. Six cases of hepatocellular carcinomas, three cases of liver metastases, and one case of hepatolithiasis were included. There were seven male and three female patients with a median age of 70 years. Three physical status class III and seven class II patients were included. The median body mass index was 24. Five patients had previous upper abdominal surgical histories and five patients had liver cirrhosis. The median operation time was 419.5 min, and the median intraoperative blood loss was 276 mL. An open conversion in one hepatocellular carcinoma case was carried out due to bleeding from collateral vessels in the round ligament. The median length of hospital stay was 7.5 days. A grade IIIa complication (delayed bile leakage) was developed in one case. All patients with tumors underwent R0 resection. There were no cases of mortality. Conclusions: Liver resection using the hinotori™ system was feasibly performed. This study reports the first global use of the hinotori™ system for liver resection.

Phase I study of neoadjuvant chemoradiotherapy with S-1 for clinically resectable type 4 or large type 3 gastric cancer in elderly patients aged 75years and older (OGSG1303).

Purpose The prognosis for type 4 and large type 3 gastric cancer (GC) is extremely poor, especially in elderly patients (≥ 75years). To improve the prognosis of these types of GC, we performed a phase I study to determine the recommended dose (RD) of S-1 combined with neoadjuvant radiotherapy. Methods Patients with clinically resectable type 4 and large type 3 GC were enrolled to successive cohorts in a conventional 3 + 3 design. Three dose levels were designed, as follows: level 0: S-1 60mg/m2/day on Days 1-14; level 1: S-1 80mg/m2/day on Days 1 -14; level 2: S-1 80mg/m2/day on Days 1-14 and Days 22-35. The starting dose was level 1. Radiotherapy was delivered at a total dose of 40Gy in fractions for 4weeks. Results Ten patients were enrolled from July 2014 to August 2018. Six patients were registered at level 1, and one patient developed a dose limiting toxicity as gastric stenosis (grade 3). Two of four patients enrolled at level 2 developed dose limiting toxicity (inability to receive S-1 for hematological reasons). Therefore, the RD was determined as level 1. All patients underwent the protocol surgery; one patient underwent R1 resection because of positive peritoneal washing cytology. There were no treatment-related deaths, and the pathological response rate was 80%. The 5-year overall- and progression-free survival rates were both 60.0%. Conclusion The RD was determined as level 1. A phase II trial using the RD should be initiated.

Development and Validation of the Predictive and Prognostic ChemoResist Signature in Resected Pancreatic Ductal Adenocarcinoma: Multicenter Study.

To develop and validate a signature to precisely predict prognosis in pancreatic ductal adenocarcinoma (PDAC) undergoing resection and adjuvant chemotherapy. PDAC is largely heterogeneous, and responds discrepantly to treatment. 551 consecutive patients with PDAC from 3 tertiary centers were initially enrolled. Genetic events of the four most commonly mutated genes in PDAC and expressions of 12 PI3K/AKT/mTOR pathway markers were examined. A 9-feature signature for prediction of chemotherapy benefits was constructed in the training cohort using the LASSO Cox regression model, and validated in 2 independent cohorts. Utilizing the LASSO model, a predictive and prognostic signature, named ChemoResist, was established based on KRAS SNV, PTEN and mTOR expressions, and six clinicopathologic features. Significant differences in survival were observed between high- and low-ChemoResist patients receiving chemotherapy in both the training (median OS, 17 vs. 42 months, P<0.001; median DFS, 10 vs. 23 months, P<0.001) and validation cohorts (median OS, 18 vs. 35 months, P=0.034; median DFS, 11 vs. 20 months, P=0.028). The ChemoResist classifier also significantly differentiated patient survival in the whole patients regardless of chemotherapy. Multivariable-adjusted analysis substantiated the ChemoResist signature as an independent predictive and prognostic factor. For predicting 2-year OS, the ChemoResist classifier had significantly higher AUC than TNM stage (0.788 vs. 0.636, P<0.001), other clinicopathologic characteristics (0.505-0.668), and single molecular markers (0.507-0.591) in the training cohort. Furthermore, patients with low ChemoResist score exhibited a more favorable response to adjuvant chemotherapy compared to those with high ChemoResist score (HR for OS: training, 0.22 vs. 0.57; validation, 0.26 vs. 0.50; HR for DFS: training, 0.35 vs. 0.54; validation, 0.18 vs. 0.59). The ChemoResist signature was further validated in the total cohort undergoing R0 resection. The ChemoResist signature could precisely predict survival in PDAC undergoing resection and chemotherapy, and its predictive value surpassed TNM stage and other clinicopathologic factors. Moreover, the ChemoResist classifier could assist with identifying patients who would more likely benefit from adjuvant chemotherapy.

Outcomes of Intraoperative Radiotherapy for Locally Advanced Adenocarcinoma of the Esophagogastric Junction After Neoadjuvant Therapy: A Single-Arm, Phase 1 Trial Fromthe Chinese National Cancer Center.

The role of intraoperative radiotherapy (IORT) for adenocarcinoma of the esophagogastric junction (AEG) remains uncertain. Therefore, a prospective phase 1 trial was conducted to assess the safety and feasibility of IORT for locally advanced AEG. The study enrolled patients with AEG at stages II-IVA from January 2019 to September 2019. Eligible patients received esophagectomy and a single fraction of electron beam radiotherapy. The primary endpoint of the study was a safety profile for IORT. Additionally, survival outcomes and the locoregional recurrence rate (LRR) were compared between the non-IORT and IORT cohorts using propensity score-matching. For 15 (93.8 %) of the 16 patients in the study, R0 resection was successfully achieved, with only one patient undergoing R1 resection. A total postoperative complication morbidity rate of 43.8 % (7/16) was observed, with major complications (Clavien-Dindo classification ≥3) in 12.5 % of the cases (2/16). Total treatment-related adverse events were reported for seven patients (43.8 %, 7/16). After matching, a lower LRR was observed in the IORT group than in the non-IORT group (0 % [0/12] vs 33.3 % [4/12]; p = 0.028). However, the two groups did not differ significantly in 3-year progression-free survival (PFS: IORT [50.9 %] vs non-IORT [53.4 %]; p = 0.93) or 3-year overall survival (OS: IORT [58.3 %] vs IORT [72.9 %]; p = 0.23). The current study demonstrated favorable feasibility and safety of IORT for locally advanced AEG. Although IORT is beneficial for improving local control, it may not prolong PFS or OS for patients with locally advanced AEG. A phase 2 trial is warranted for further validation of these outcomes.

Neoadjuvant immunotherapy plus chemotherapy in high altitude natives with resectable esophageal squamous cell carcinoma in Tibet

Neoadjuvant therapy followed by surgery has been proved to improve the survival of patients with ESCC, and neoadjuvant chemoradiotherapy (nCRT) is the standard of care in most areas of the world. However, multimodality therapy including radiation therapy is actually limited in the current treatment of esophageal cancer in Tibet. The role of neoadjuvant immunotherapy in resectable esophageal cancer has been assessed in multiple phase II clinical trials, but there's lack of evidence of applying neoadjuvant immunotherapy plus chemotherapy in Tibetan residents. Patients with previously treatment-naïve, resectable ESCC were included in this study. The preoperative treatment regimen included Tislelizumab, nab-paclitaxel and carboplatin. Surgery was planned for every patient who completed neoadjuvant treatment. Surgical approaches and extent of esophageal resection was chosen depended on tumor location. 23 patients with resectable ESCC were included from January 2022 to May 2024 in this study. Among all patients, 5 (21.7%) had thyroid nodules or dysfunction. 19 of 23 (82.6%) patients finished 2-3 cycles of treatment. 19 (82.6%) patients experienced treatment-related adverse events (TRAEs), with 11 (47.8%) patients experiencing grade 3-4 TRAEs. Thyroid toxicity of grade 1-2 was observed in 12 (52.2%) patients. The objective response rate (ORR) was 69.6%, and the disease control rate (DCR) was 100%.。14 (60.9%) of 23 patients underwent surgery. All patients underwent R0 resection. The pCR rate was 21.4%. The median follow-up was 22.4 months. During the follow-up period, there were no recurrences, but 3 patients died due to non-tumor-related causes. Esophagectomy following neoadjuvant immunotherapy plus chemotherapy appears to be safe and feasible in high altitude natives with resectable esophageal squamous cell carcinoma in Tibet.

The impact of positive resection margin in perihilar cholangiocarcinoma, ductal margin vs radial margin.

Resection margin status is the important prognostic factor in resected perihilar cholangiocarcinoma (pCCA). Although the impact of ductal margin (DM) was reported in many studies, the influence of radial margin (RM) is unclear. This study aims to investigate the effect of positive RM on survival. Patients with pCCA underwent curative resection between 2013 and 2018 were retrospectively reviewed. Resection margin status was divided into negative resection margin (R0) and positive resection margin (R1); positive RM alone (RM+) and positive DM with or without positive RM (DM+). Of the 167 pCCA patients, 62 (37.1%) had R1 margin. Among 62 R1 patients; 17 (27.4%) had positive DM alone, 20 (32.3%) had positive RM alone and 25 (40.3%) had both positive DM and RM. The R1 patients had a significantly greater number of lymph node metastasis (LNM) and advanced tumor staging than R0 patients, however there was no difference between the RM + and DM + patients. The median survival time of patients with RM + was significantly poorer than R0 patients (13.8 vs. 24.5 months; p < 0.001, respectively) and similar to the DM + patients (9.1 months, p = 0.556). However, in patients with LNM, those who underwent R0 resection had no statistically significant difference in survival outcomes compared to those with R1 resection. Positive resection margin remains the important prognostic factor, and positive RM is common in these patients. Positive RM also had a comparable effect on survival as positive DM. As a result, in pCCA, surgical resection should target both RM and DM.

Short term efficacy and safety of PD-1 inhibitor and apatinib plus S-1 and oxaliplatin as neoadjuvant chemotherapy for patients with locally advanced gastric cancer.

Surgical resection is the cornerstone of treatment for locally advanced gastric cancer (LAGC). Hence, downstaging of the tumor with neoadjuvant therapy is critical for R0 resection and prolongs the overall survival. Data from related studies are lacking, and the literature is scarce. Therefore, a single arm-study was performed on PD-1 inhibitor and apatinib plus S-1 and oxaliplatin as neoadjuvant chemotherapy for patients with LAGC. The findings are expected to serve as a reference for neoadjuvant therapy for LAGC. We assessed 130 LAGC patients using PD-1 inhibitor, apatinib plus S-1, and oxaliplatin as neoadjuvant chemotherapy from January 2021 to October 2022. A total of 104 patients received gastric transcatheter chemoembolization (GTC). The primary endpoint was the rate of clinical complete response, pathological complete response, and safety, while the secondary endpoints were the R0 resection rate and objective response rate of the disease and the disease control rate. A total of 130 patients completed the clinical assessment, of which 6 patients (4.6%) achieved clinical complete response, 87 patients (66.9%) achieved partial response, 30 patients (23.0%) achieved stable disease, and 7 patients (5.5%) experienced progressive disease. The overall response rate was 71.5% (93/130), and the disease control rate was 94.5% (123/130). A remarkable downstaging effect was observed in this study. Downstaging of the T stage and N stage was achieved in 71.5% and 80% of the patients, respectively, which translated into a high R0 resection rate. The findings revealed that 125 patients underwent R0 resection, and the R0 resection rate was 96.1%. According to the observed results, 21.6% of the patients achieved pathological complete response after neoadjuvant chemotherapy. Gastric transcatheter chemoembolization in the first cycle of neoadjuvant therapy was beneficial for tumor regression (P < .001). All adverse events were relieved and disappeared after symptomatic treatment, and no grade 4 adverse events were noted. PD-1 inhibitor and apatinib plus S-1 and oxaliplatin are safe and effective as neoadjuvant treatment of LAGC. Gastric transcatheter chemoembolization is useful for tumor regression during neoadjuvant therapy.

Multidisciplinary Approach to Perihilar and Intrahepatic Cholangiocarcinoma: A Single-Center Experience.

Treatment of perihilar cholangiocarcinoma (PHCC) and intrahepatic cholangiocarcinoma (IHCC) is a challenging issue. We aimed to investigate the clinical characteristics of both tumors and the outcome of our treatment policy. We retrospectively analyzed data of 117 patients who were diagnosed with PHCC or IHCC between January 2007 and September 2023. Postoperative outcomes and the effects of prognostic factors on overall survival (OS) were investigated. Surgical resection was performed on 47 patients (PHCC, n = 33 and IHCC, n = 14). Preoperative biliary drainage was applied in 32 of 33 cases with PHCC and 2 of 14 cases with IHCC. The mortality rate was 8.5% (n = 4). The complication rate was 68.1%. The R0 resection rate was 73% in PHCC. The mean OS time of PHCC cases that underwent R0 resection was 26.5 ± 24.8 months. The mean OS time of patients who underwent resection for IHCC was 28.7 ± 35.5 months. The OS was poorly affected by high CA19-9 levels (≥37 U/mL) (P = .005), the presence of lymphovascular invasion (P = .049), positive surgical margins after resection (P < .001), and the development of postoperative acute renal failure (P = .078). The OS of patients receiving adjuvant chemotherapy was significantly longer (P = .071). CA19-9 levels of more than 37 U/mL (P = .027) and positive surgical margin (P < .001) were independent factors for poor OS. Surgical resection is the mainstay of multidisciplinary treatment for PHCC and IHCC. In advanced stages of IHCC, the combination of loco-regional therapies and repeat surgery, along with the enhanced efficacy of systemic chemotherapy, plays a significant role in a patient's survival.

Staging Paradox and recurrence pattern among stage IIB, IIC, and IIIA Colon cancers: a retrospective cohort study

PurposeThe survival rates of patients with stage IIB and IIC colon cancer are paradoxically inferior to that of patients with stage IIIA colon cancer. This study aimed to examine the oncological outcomes and investigate the factors that could affect the staging paradox among stage IIB, IIC, and IIIA colon cancers based on a 9-year cancer database.MethodsPatients with stage IIB (pT4aN0M0), IIC (pT4bN0M0), or IIIA (pT1-2N1M0) colon cancer were retrospectively selected from a prospectively maintained medical database from January 2011 to December 2019. Factors that might influence the staging paradox, including radicality, harvested lymph nodes, and chemotherapy administration, were examined.ResultsA total of 282 patients (stage IIB, n = 59; stage IIC, n = 46; and stage IIIA, n = 177) were enrolled. Patients with stage IIB/C cancer demonstrated higher carcinoembryonic antigen levels, larger tumor size, more frequent tumor obstruction, and higher locoregional recurrence than those with stage IIIA cancer. With respect to 10-year locoregional recurrence-free survival and cancer-specific survival, patients with stage IIB and IIC cancers had significantly lower survival rates than did those with stage IIIA cancer (73.7% vs. 66.3% vs. 91.2%, P = 0.0003; 5.4% vs. 10.9% vs. 11.2%, P = 0.0023). The staging paradox persisted in patients who underwent R0 resection, had harvested lymph nodes ≥ 12, and received chemotherapy, as confirmed by multivariate regression analysis.ConclusionsBased on the inferior oncological outcomes and higher locoregional recurrence rate, this study highlighted the need for intensified cytotoxic chemotherapy specific to this recurrence pattern for patients with stage IIB/C colon cancer.

DAXX is associated with early recurrence of pancreatic neuroendocrine tumors after R0 resection

IntroductionATRX, DAXX, MEN1, and PTEN mutations are proposed drivers of pancreatic neuroendocrine tumor tumorigenesis and independent prognostic factors for metastasis and mortality. However, their implications after R0 resection remain debated. Thus, we sought to identify genomic signatures of pancreatic neuroendocrine tumor disease-specific mortality and recurrence after surgery for curative intent. MethodsPancreatic neuroendocrine tumor patients who underwent whole exome sequencing with available survival data were identified using cBioPortal. Clinicopathologic variables, genomics, and outcomes were analyzed. ResultsSeventy patients who underwent R0 resection were identified. Forty-five of 70 patients were disease free at last follow-up, whereas 25 of 70 patients had disease-specific mortality or recurrent disease and therefore were categorized as part of the recurrent cohort. There were no significant differences in age (P = .245), sex (P = .201), or median follow-up (38.9 vs 33.7 months, P = .122) between groups. Clinicopathologically, the recurrent cohort had significantly greater tumor size (median 5.0 cm vs 3.2 cm, P = .012) and were more likely to have vascular invasion (88% vs 40%, P = .000), positive lymph nodes (68.0% vs 35.6%, P = .013), and metastatic disease (44% vs 4.4%, P < .000). For both cohorts, most tumors were well or moderately differentiated. Tumor mutation burden was greater in the recurrent cohort (median 0.77 vs 0.43 mutations/Mb, P = .004). DAXX mutations were more frequent in the recurrent cohort (36% vs 11%, P = .026) and in those with vascular invasion (51% vs 92%, P = .010). ConclusionOur analysis demonstrated the prognostic significance of DAXX mutations after curative-intent surgery. Future studies investigating DAXX mutations as a biomarker for aggressive features to guide treatment are warranted.

Identifying genomic signatures of recurrence in adrenocortical carcinoma after R0 resection

BackgroundAdrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited treatment options. Although there have been recent advancements revealing genomic drivers of these tumors, it remains unclear which genomic signatures are associated with recurrence, particularly following R0 resection. MethodsAdrenocortical carcinoma patients treated with adrenalectomy in the Cancer Genome Atlas with recurrence data were identified using cBioPortal. Clinicopathologic variables, genomics, treatment patterns, and outcomes were retrospectively analyzed. ResultsAmong 92 adrenocortical carcinoma patients, 84 had recurrence data, with 52% experiencing tumor recurrence. Age and sex were not significantly different between recurrent and nonrecurrent groups. Nonrecurrent patients had a significantly longer overall survival (54 months vs 35 months, P = .0036). Adjuvant radiation was administered similarly in both groups (25.0% vs 16.2%, P = .4164). There were no differences in capsular or venous invasion or median tumor size. Sixty-two patients had R0 resection and 40.3% (n = 25/62) recurred. Multivariate logistic regression in this cohort, when controlling for vascular invasion, venous invasion, and capsular invasion, revealed that the WNT (odds ratio 4.43 [1.09–18.0], P = .034), PI3K (odds ratio 7.80 [1.33–45.65], P = .023), and cell cycle (odds ratio 6.81 [1.43–32.30], P = .016) pathways were significantly associated with recurrence. Median time to recurrence was 7.9 months; early recurrence (<7.9 months) was associated with MYC pathway alterations (40.9% vs 9.1%, P = .0339). ConclusionThis study identified genomic signatures in the PI3K, WNT, and cell cycle pathways associated with adrenocortical carcinoma recurrence, including in those who underwent R0 resection. Investigations regarding the utility of these signatures as a prognostic tool to dictate adjuvant therapies or targeted treatment are warranted.

Dendritic cells pulsed with multifunctional Wilms’ tumor 1 (WT1) peptides combined with multiagent chemotherapy modulate the tumor microenvironment and enable conversion surgery in pancreatic cancer

BackgroundWe aimed to develop a chemoimmunotherapy regimen consisting of a novel Wilms’ tumor 1 (WT1) peptide-pulsed dendritic cell (WT1-DC) vaccine and multiagent chemotherapy and to investigate the safety, clinical outcomes,...