Neoadjuvant Chemoradiotherapy Group Research Articles

Prognosis of patients with esophageal squamous cell carcinoma undergoing surgery versus no surgery after neoadjuvant chemoradiotherapy: a retrospective cohort study

Esophageal surgery is an invasive surgical method with high surgical risk, and seriously affects postoperative quality of life. This study compared the prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (Neo-CRT) plus surgery and Neo-CRT alone, in order to explore the necessity of continuing operation after Neo-CRT. We retrospectively analyzed 223 patients who received Neo-CRT in Taizhou Hospital Affiliated to Wenzhou Medical University from June 2007 to December 2014. According to the treatment, the patients were divided into Neo-CRT plus surgery group (operation group, n=185) and single Neo-CRT group (non-operation group, n=38). Patients in both groups were followed up for a long time until death or deadline. The overall survival (OS), adverse reactions, recurrence and death results of the two groups were evaluated. The risk factors of poor prognosis were analyzed. The two groups were comparable. The median follow-up time was 23.5 months in non-operation group and 112.9 months in operation group. The 1-year survival rate, 2-year survival rate and 5-year survival rate in non-operation group were 69.9%, 47.7% and 31.8%, respectively. The rates in operation group were 94.0%, 79.3% and 65.0%, respectively. The incidence of low hemoglobin was 73.7% (non-operation group) and 53.0% (operation group). The infection rates were 15.8% and 2.7%, respectively. There was no significant difference in the incidence of leukopenia, neutropenia and thrombocytopenia between the two groups. Multivariate analysis showed that recurrence and treatment were independent risk factors affecting the prognosis of patients. To sum up, no matter in terms of recurrence rate or OS rate, the prognosis of patients in the operation group was better than that in the non-operation group. Therefore, Neo-CRT combined with esophagectomy is recommended for locally advanced ESCC with acceptable surgical risk.

Preoperative Concurrent Chemoradiotherapy Versus Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: Phase II Randomized Study.

ObjectiveWe evaluated and compared the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) versus neoadjuvant chemotherapy (NACT) for locally advanced gastric cancer (LAGC) in a single-center randomized phase II trial.MethodsPatients with LAGC were enrolled and received either NACT or NACRT, followed by gastrectomy and adjuvant chemotherapy. The primary endpoint was an R0 resection rate.ResultsWe enrolled 75 patients: 75.7% (NACT, 28/37 patients) and 76.3% (NACRT, 29/38 patients) underwent surgery; R0 resection rates were 73.0% (27/37) and 73.7% (28/38), respectively. The NACRT group had significantly better major pathological response than the NACT group (37.9% vs 17.9%, p = 0.019). Between-group postoperative complications were not significantly different. The median follow-up was 59.6 months; 5-year overall survival (OS) rate was 50.1% (NACT) and 61.9% (NACRT); neither group reached the median OS; median progression-free survival was 37.3 and 63.4 months, respectively.ConclusionsS-1-based NACRT did not improve the R0 resection rate, although it presented better tumor regression with similar safety to NACT.Trial registrationClinicalTrial.gov NCT02301481

Adding Consolidation Capecitabine to Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Propensity-Matched Comparative Study.

AimTo determine whether adding consolidation capecitabine chemotherapy without lengthening the waiting period influences pathological complete response (pCR) and short-term outcome of locally advanced rectal cancer (LARC) receiving neoadjuvant chemoradiotherapy (NCRT).MethodTotally, 545 LARC who received NCRT and radical resection between 2010 and 2018 were enrolled. Short-term outcome and pCR rate were compared between patients with and without additional consolidation capecitabine. Logistic analysis was performed to identify predictors of pCR.ResultsAfter propensity score matching, 229 patients were matched in both NCRT and NCRT-Cape groups. Postoperative morbidity was comparable between groups except for operation time, which is lower in the NCRT group (213.2 ± 67.4 vs. 227.9 ± 70.5, p = 0.025). Two groups achieved similar pCR rates (21.8 vs. 22.7%, p = 1.000). Tumor size (OR = 0.439, p < 0.001), time interval between NCRT and surgery (OR = 1.241, p = 0.003), and post-NCRT carcinoembryonic antigen (OR = 0.880, p = 0.008) were significantly correlated with pCR in patients with LARC. A predictive nomogram was constructed with a C-index of 0.787 and 0.741 on internal and external validation.ConclusionAdding consolidation capecitabine chemotherapy without lengthening CRT-to-surgery interval in LARC patients after NCRT does not seem to impact pCR or short-term outcome. A predictive nomogram for pCR was successful, and it could support treatment decision-making.

Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial.

The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a statistically significant overall survival (OS) benefit. The long-term results are reported. In this multicenter, phase III trial, patients with resectable and borderline resectable pancreatic cancer were randomly assigned (1:1) to neoadjuvant chemoradiotherapy or upfront surgery in 16 Dutch centers. Neoadjuvant chemoradiotherapy consisted of three cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle. After restaging, patients underwent surgery followed by four cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by six cycles of adjuvant gemcitabine. The primary outcome was OS by intention-to-treat. No safety data were collected beyond the initial report of the trial. Between April 24, 2013, and July 25, 2017, 246 eligible patients were randomly assigned to neoadjuvant chemoradiotherapy (n = 119) and upfront surgery (n = 127). At a median follow-up of 59 months, the OS was better in the neoadjuvant chemoradiotherapy group than in the upfront surgery group (hazard ratio, 0.73; 95% CI, 0.56 to 0.96; P = .025). Although the difference in median survival was only 1.4 months (15.7 months v 14.3 months), the 5-year OS rate was 20.5% (95% CI, 14.2 to 29.8) with neoadjuvant chemoradiotherapy and 6.5% (95% CI, 3.1 to 13.7) with upfront surgery. The effect of neoadjuvant chemoradiotherapy was consistent across the prespecified subgroups, including resectable and borderline resectable pancreatic cancer. Neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine improves OS compared with upfront surgery and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer.

MFOLFOX4 with or without radiation in neoadjuvant treatment of locally advanced middle and low rectal cancer.

Neoadjuvant therapy can reduce the recurrence rate of locally advanced middle and low rectal cancer. Radiation therapy can not only bring benefits but also produce acute and late toxicity, which will affect the quality of life and organ function of patients; the application of neoadjuvant chemotherapy can avoid the toxicity of radiotherapy. To investigate the efficiency and side effects of preoperative modified FOLFOX4 (mFOLFOX4) chemotherapy with or without radiotherapy for locally advanced middle and low rectal cancer (LAMLRC). This study included 431 patients with LAMLRC receiving mFOLFOX4 chemotherapy independently or combined with radiotherapy before operation. The basic information, efficacy indicators, and adverse reactions of the two groups were recorded in detail. Side effects were evaluated using the Common Terminology Criteria for Adverse Events v. 3.0. Statistical analyses were conducted using SPSS (Statistical Package for Social Science, IBM SPSS Statistics, Version 22). Mann-Whitney test and Chi-square test were used for comparative analysis. Statistical significance was defined as P < 0.05. Of 128 patients who met the inclusion criteria, 52 received neoadjuvant chemotherapy (NCT), and 76 received neoadjuvant chemoradiotherapy (NCRT). The average operation time in the NCT group was 2.71 h, and that in the NCRT group was 3.35 h (P = 0.005). The pathological complete remission rates in the NCT and NCRT groups were 1.9% and 17.1%, respectively (P = 0.007). There was no significant difference in the T-stage decline rate and lymph node positive rate between the two groups. There were higher rates of leukopenia (32.7% vs. 57.9%; P < 0.05) and diarrhea (0% vs. 9.2%; P < 0.05) in the NCRT group. The 3-year overall survival rates in the NCT and NCRT groups were 80.3% and 82.8% (P = 0.715), respectively, and the respective 3-year disease-free survival rates were 68.8% and 70.5% (P = 0.966). NCT with mFOLFOX4 independently resulted in a lower pathological complete remission rate, with less toxicity and shorter operation time. NCT with mFOLFOX4 has certain clinical usefulness.

Vasculitis Associated with Preoperative Cheomoradiation Therapy for Pancreatic Cancer: A Preliminary Analysis

Introduction: Despite the widespread use of neoadjuvant chemotherapy (NAC) or neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer, little is known about its effects on vascular structures and surgical outcomes. In this study, we attempted to identify the primary loci of inflammation by conducting a pathological evaluation. Clinicopathological and transcriptome analysis were also performed to characterize vasculitis-associated changes. Methods: Patients who underwent preoperative NACRT between 2014 and 2019 were retrieved and specimens were subjected to pathologic evaluation and gene expression analysis. A total of 31 and 30 patients were included in the NACRT group and the NAC group, respectively. Results: All NACRT patients had preoperative SBRT of 30-33 Gy/5 fractions. Vascular inflammation or vasculitis (defined as vascular-associated myxoid change, vascular lymphocyte/macrophage infiltration) were more frequently observed in the RT group (38.7% vs 16.7%, p=0.067, HR: 3.2, CI 0.9-12.1). Within the NACRT group, subgroup analysis showed that longer “Duration from NAC to surgery” and “Postoperative complication > grade2” correlated with increased risk for vasculitis ([108.2 vs 85.0 days (median), p=0.017 ] and 66.7% vs 30%, p=0.027, HR: 5.3 CI 1.16-27.1], respectively). Gene set enrichment analysis(Subramanian et al. 2005) showed inflammation-related sets were up-regulated in the vasculitis group as defined by histopathologic features. Conclusion: Our preliminary analysis shows more vasculitis was observed in the NACRT group. RNAseq analysis suggested that the inflammatory pathway was up-regulated with histopathological evidence of vasculitis. The presence of vasculitis in the RT group correlated with postoperative complications. This suggests that vasculitis associated with NACRT might affect the surgical outcomes.

Clinical outcome of patients after recurrent laryngeal nerve lymph node dissection for oesophageal squamous cell carcinoma.

OBJECTIVESRecurrent laryngeal nerve lymph node dissection (LND) has been incorporated into oesophagectomy for patients with oesophageal squamous cell carcinoma, but with uncertain oncological efficacy.METHODSThe data of patients with oesophageal squamous cell carcinoma, including who underwent upfront surgery (surgery group) and those who received neoadjuvant therapy followed by surgery (neoadjuvant chemoradiotherapy group), were retrospectively examined. The overall survival (OS) and disease-free survival (DFS) were compared between patients with and without recurrent laryngeal nerve LND.RESULTSAmong the 312 patients, no significant differences were found in 3-year OS and DFS between patients with and without recurrent laryngeal nerve LND in the entire cohort (OS: 57% vs 52%, P = 0.33; DFS: 47% vs 41%, P = 0.186), or the surgery group (n = 173, OS: 69% vs 58%, P = 0.43; DFS: 52% vs. 48%, P = 0.30) and the neoadjuvant chemoradiotherapy group (n = 139, OS: 44% vs 43%, P = 0.44; DFS: 39% vs 32%, P = 0.27). However, among patients with clinical positive recurrent laryngeal nerve lymph node involvement before treatment, there was significant OS and DFS differences between patients with and without recurrent laryngeal nerve LND (OS: 62% vs 33%, P = 0.029; DFS: 49% vs 26%, P = 0.031).CONCLUSIONSRecurrent laryngeal nerve LND is not a significant prognostic factor in patients with oesophageal squamous cell carcinoma; however, it is associated with better outcomes in patients with pre-treatment radiological evidence of recurrent laryngeal nerve lymph node involvement.

Impact of neoadjuvant chemoradiotherapy on the local recurrence and distant metastasis pattern of locally advanced rectal cancer: a propensity score-matched analysis.

Background:Previous studies have demonstrated different predominant sites of distant metastasis between patients with and without neoadjuvant chemoradiotherapy (NCRT). This study aimed to explore whether NCRT could influence the metastasis pattern of rectal cancer through a propensity score-matched analysis.Methods:In total, 1296 patients with NCRT or post-operative chemoradiotherapy (PCRT) were enrolled in this study between January 2008 and December 2015. Propensity score matching was used to correct for differences in baseline characteristics between the two groups. After propensity score matching, the metastasis pattern, including metastasis sites and timing, was compared and analyzed.Results:After propensity score matching, there were 408 patients in the PCRT group and 245 patients in the NCRT group. NCRT significantly reduced local recurrence (4.1% vs. 10.3%, P = 0.004), but not distant metastases (28.2% vs. 27.9%, P = 0.924) compared with PCRT. In both the NCRT and PCRT groups, the most common metastasis site was the lung, followed by the liver. The NCRT group developed local recurrence and distant metastases later than the PCRT group (median time: 29.2 [18.8, 52.0] months vs. 18.7 [13.3, 30.0] months, Z = –2.342, P = 0.019; and 21.2 [12.2, 33.8] vs. 16.4 [9.3, 27.9] months, Z = –1.765, P = 0.035, respectively). The distant metastases occurred mainly in the 2nd year after surgery in both the PCRT group (39/114, 34.2%) and NCRT group (21/69, 30.4%). However, 20.3% (14/69) of the distant metastases appeared in the 3rd year in the NCRT group, while this number was only 13.2% (15/114) in the PCRT group.Conclusions:The predominant site of distant metastases was the lung, followed by the liver, for both the NCRT group and PCRT group. NCRT did not influence the predominant site of distant metastases, but the NCRT group developed local recurrence and distant metastases later than the PCRT group. The follow-up strategy for patients with NCRT should be adjusted and a longer intensive follow-up is needed.

Neoadjuvant versus Postoperative Chemoradiotherapy is Associated with Improved Survival for Patients with Resectable Gastric and Gastroesophageal Cancer

The optimal timing of chemoradiotherapy (CRT) for patients with localized gastric cancer remains unclear. This study aimed to compare the survival outcomes between neoadjuvant and postoperative CRT for patients with gastric and gastroesophageal junction (GEJ) cancer. This retrospective study analyzed 152 patients with gastric (42%) or GEJ (58%) adenocarcinoma who underwent definitive surgical resection and received either neoadjuvant or postoperative CRT between 2005 and 2017 at the authors' institution. The primary end point of the study was overall survival (OS). The median follow-up period was 37.5months. Neoadjuvant CRT was performed for 102patients (67%) and postoperative CRT for 50 patients (33%). The patients who received neoadjuvant CRT were more likely to be male and to have a GEJ tumor, positive lymph nodes, and a higher clinical stage. The median radiotherapy (RT) dose was 50.4Gy for neoadjuvant RT and 45.0Gy for postoperative RT (p<0.001). The neoadjuvant CRT group had a pathologic complete response (pCR) rate of 26% and a greater rate of R0 resection than the postoperative CRT group (95% vs. 76%; p=0.002). Neoadjuvant versus postoperative CRT was associated with a lower rate of any grade 3+ toxicity (10% vs. 54%; p<0.001). The multivariable analysis of OS showed lower hazards of death to be independently associated neoadjuvant versus postoperative CRT (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.36-0.91; p=0.020) and R0 resection (HR 0.50; 95% CI 0.27-0.90; p=0.021). Neoadjuvant CRT was associated with a longer OS, a higher rate of R0 resection, and a lower treatment-related toxicity than postoperative CRT. The findings suggest that neoadjuvant CRT is superior to postoperative CRT in the treatment of gastric and GEJ cancer.

Management of Clinically Involved Lateral Lymph Node Metastasis in Locally Advanced Rectal Cancer: A Radiation Dose Escalation Study.

BackgroundPatients with lateral lymph nodes (LLNs) metastasis are not effectively treated with neoadjuvant chemoradiotherapy. This study aimed to compare the efficacy of three neoadjuvant therapeutic regimens, namely, chemotherapy, chemoradiotherapy, and chemoradiotherapy with a dose boost of LLNs, and to identify the optimal approach for treating LLNs metastasis of locally advanced rectal cancer.MethodsA total of 202 patients with baseline LLNs metastasis (short axis ≥5 mm) and treated with neoadjuvant treatment, followed by radical surgery from 2011 to 2019, were enrolled. The short axis of the LLNs on baseline and restaging MRI were recorded. Survival outcomes were compared.ResultsIn the booster subgroup, shrinkage of LLNs was significantly greater than in the neoadjuvant chemotherapy and chemoradiotherapy subgroups (P <0.001), without increasing radiation related side effects (P = 0.121). For patients with baseline LLNs of short axis ≥5 mm in the booster subgroup, the response rate (short axis <5 mm on restaging MRI) was 72.9%, significantly higher than patients in the neoadjuvant chemotherapy subgroup (48.9%, P = 0.007) and higher than for patients in the neoadjuvant chemoradiotherapy group (65.0%), but there was no statistical difference (P = 0.411). The 3-year local recurrence and lateral local recurrence rates were both 2.3% in the dose booster group, which were lower than those of the other two subgroups (local recurrence: P <0.001; lateral local recurrence: P <0.001). The short axis of lateral lymph nodes (≥5 and <5 mm) on restaging MRI was an independent risk factor for prognosis (P <0.05).ConclusionRadiation dose boost is an effective way of increasing the response rate and decreasing recurrence rates. The restaging LLNs with short axis ≥5 mm is a predictor of poor prognosis.

Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma

The prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor after surgery. Neoadjuvant chemoradiotherapy (NCRT) has been shown to potentially improve survival. To compare the treatment efficacy of NCRT plus surgery with surgery alone for long-term survival among patients with locally advanced ESCC. The Neoadjuvant Chemoradiotherapy for Esophageal Cancer 5010 study was a multicenter open-label randomized phase 3 clinical trial that enrolled patients between June 1, 2007, and December 31, 2014. Follow-up ended on December 31, 2019. The study was conducted at 8 centers in China. A total of 451 patients aged 18 to 70 years with thoracic ESCC stage T1-4N1M0/T4N0M0 were enrolled and randomized. Data were analyzed from December 1, 2019, to June 30, 2020. Patients randomized to receive NCRT plus surgery (NCRT group) received preoperative chemotherapy (25 mg/m2 of vinorelbine on days 1 and 8 and 75 mg/m2 of cisplatin on day 1 or 25 mg/m2 of cisplatin on days 1 to 4) every 3 weeks for 2 cycles and concurrent radiotherapy (40.0 Gy, administered in 20 fractions of 2.0 Gy for 5 days per week) followed by surgery. Patients randomized to receive surgery alone (surgery group) underwent surgery after randomization. The primary end point was overall survival in the intention-to-treat population. The secondary end point was disease-free survival. A total of 451 patients (mean [SD] age, 56.5 [7.0] years; 367 men [81.4%]) were randomized to the NCRT (n = 224) and surgery (n = 227) groups and were eligible for the intention-to-treat analysis. By December 31, 2019, 224 deaths had occurred. The median follow-up was 53.5 months (interquartile range, 18.2-87.4 months). Patients receiving NCRT plus surgery had prolonged overall survival compared with those receiving surgery alone (hazard ratio, 0.74; 95% CI, 0.57-0.97; P = .03), with a 5-year survival rate of 59.9% (95% CI, 52.9%-66.1%) vs 49.1% (95% CI, 42.3%-55.6%), respectively. Patients in the NCRT group compared with the surgery group also had prolonged disease-free survival (hazard ratio, 0.60; 95% CI, 0.45-0.80; P < .001), with a 5-year survival rate of 63.6% (95% CI, 56.0%-70.2%) vs 43.0% (95% CI, 36.0%-49.7%), respectively. In this randomized clinical trial, treatment with NCRT plus surgery significantly improved long-term overall survival and disease-free survival and therefore may be considered a standard of care for patients with locally advanced ESCC. ClinicalTrials.gov Identifier: NCT01216527.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for the treatment of esophageal squamous cell carcinoma: a propensity score-matched study from the National Cancer Center in China.

The optimal mode of neoadjuvant treatment for esophageal squamous cell carcinoma (ESCC) has not been well characterized. Our study compared neoadjuvant chemotherapy (NCT) with neoadjuvant chemoradiotherapy (NCRT) for patients with ESCC. Data from ESCC patients receiving NCRT or NCT combined with esophagectomy between 2010 and 2018 from the National Cancer Center in China were retrospectively collected. Long-term survival, pathological response, and perioperative mortality and morbidity were compared between the NCRT and NCT groups. A Cox proportional hazards model and propensity score matching (PSM) were used to minimize bias due to potential confounding. Out of 327 eligible patients with ESCC in our study, 90 patients were identified in each group by PSM. The complete pathologic response (pCR) rate in the NCRT group was markedly higher than that in the NCT group (before PSM: 35.1% vs. 6.0%; after PSM: 38.9% vs. 5.6%; both P < 0.001). The rates of 30-day or 90-day mortality were comparable between the two groups, but the NCRT group had a longer postoperative hospital stay (P < 0.001 before PSM and P = 0.012 after PSM) and more postoperative complications (P < 0.001 before PSM and P = 0.014 after PSM), especially, anastomotic leaks (P = 0.001 before PSM and P = 0.013 after PSM). No significant differences in 5-year overall survival (OS) (P = 0.439) or 5-year relapse-free survival (RFS) (P = 0.611) were noted between unmatched groups, but the trend favored NCRT in the propensity score-matched group (77.3% vs. 61.3%; hazard ratio [HR] 1.57; 95% confidence interval [CI] 0.86-2.87; P = 0.141 for OS, and 77.8% vs. 60.5%; HR 1.72; 95% CI 0.95-3.11; P = 0.073 for RFS). Multivariate analysis showed that only ypT and ypN stages were independent predictors of OS before and after PSM (both P < 0.05). There was no difference in survival between the NCT and NCRT groups, although a trend favored NCRT related to the significantly higher pCR rates. Prospective head-to-head clinical trials to compare these two types of neoadjuvant therapies in ESCC are warranted.

Accuracy of High Resolution Multidetector Computed Tomography in the Local Staging of Rectal Cancer

Abstract Background Magnetic resonance imaging (MRI) is the gold standard for local staging of rectal cancer. Advanced computed tomography (CT) machines are now capable of high-resolution images of rectal cancer and utilized for CT perfusion. The possibility of local staging of rectal cancer by CT needs to be explored. Purpose The aim of the study is to evaluate accuracy of high-resolution CT for local rectal cancer staging. Methods A high-resolution CT was performed for local staging of rectal cancer in our study group of 93 patients, where 64 underwent primary surgery and 29 underwent surgery post neoadjuvant chemoradiotherapy (NACRT). Results In differentiating stages T2-and-less than T2 from T3–T4 rectal cancer, accuracy, sensitivity, specificity, and kappa score in overall patients were 91%, 87%, 94%, and 0.8; in primary surgery group were 89%, 76%, 94%, and 0.7; in NACRT group were 97%, 100%, 94%, and 0.9; in low rectal group were 94%, 89%, 97%, and 0.82, respectively. Conclusion High resolution CT is an accurate tool for local staging of rectal cancer.

P10: LYMPH NODE YIELD IS NOT A RELIABLE PROGNOSTIC MARKER IN ANTERIOR RESECTION AND ABDOMINOPERINEAL RESECTION FOLLOWING NEOADJUVANT THERAPY FOR RECTAL CANCER

Abstract Introduction International guidelines recommend a minimum lymph node yield (LNY) of ≥12 for oncological resection in colorectal cancer (CRC). Neoadjuvant chemoradiotherapy (NACRT) decreases LNY, which questions its ability to provide accurate prognostic information. The consensus of this significance remains undetermined. This study aimed to investigate the significance of LNY on recurrence and survival following anterior resection and abdominoperineal resection with or without NACRT for rectal cancer. Method Prospectively collected data on patients diagnosed with rectal cancer in a tertiary referral centre was interrogated retrospectively. Patients were divided into primary surgery and NACRT groups. Univariable analysis was performed using Fisher's exact test, t-test, and x2 test, while multivariable analysis utilised a multiple regression model. Disease recurrence and survival was analysed with logrank test for Kaplan-Meier curves. Result 148 patients were included [56.1% (n=83) receiving NACRT]. The median LNY of the primary surgery group was 14 [interquartile range (IQR) 11-19] and for the NACRT group was 12 (IQR 8-14) (p &amp;lt;0.001). Disease recurrence was similar in both primary surgery and NACRT groups. There was a significant decrease in overall mortality in NACRT patients (p = 0.03), but there was no significant difference observed in recurrence or mortality amongst LNYs of &amp;lt;8, 8-11, and ≥12. Conclusion LNY less than 12 was not a negative prognostic indicator following NACRT and surgery for rectal cancer. Take-home message A lymph node yield of less than 12 is not a negative prognostic indicator in rectal cancer patients who receive neoadjuvant chemotherapy.

Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: A Systematic Review and Metaanalysis of Oncological and Operative Outcomes.

Total neoadjuvant therapy in rectal cancer refers to the administration of chemoradiotherapy plus chemotherapy before surgery. Recent studies have shown improved pathological complete response and disease-free survival with this approach. However, survival benefits remain unproven. Our objective is to present a metaanalysis of oncological outcomes of total neoadjuvant therapy in locally advanced rectal cancer. A comprehensive search was performed on PubMed, Medline, and Google Scholars. Studies comparing total neoadjuvant therapy with standardneoadjuvant chemoradiotherapy were included. Data extracted from the individual studies were pooled and a metaanalysis performed. The outcomes of interest are the rate of complete pathological response, nodal response, resection margin, anal preservation, anastomotic leak, local recurrence, distant recurrence, disease-free survival, and overall survival. There were 15 comparative studies with 2437 patients in the neoadjuvant chemoradiotherapy group and 2284 in the total neoadjuvant therapy group. The pooled complete pathological response was 22.3% in the total neoadjuvant therapy group, compared with 14.2% in the standard neoadjuvant chemoradiotherapy group (p<0.001). Even though there was no difference in local recurrence rate, there was a significantly lower rate of distant recurrence (OR 0.81, p=0.02), and better 3-year disease-free survival (70.6% vs. 65.3%, respectively, p<0.001) and overall survival (84.9% vs. 82.3%, respectively, p=0.006), favoring the total neoadjuvant therapy group. Due to significant heterogeneity in the study protocols, there remains uncertainty on the ideal chemotherapy/radiotherapy sequence. This study provides supporting evidence on the favorable immediate and intermediate oncological outcomes with the use of total neoadjuvant therapy for locally advanced rectal cancer.

Investigation of neoadjuvant therapy for borderline resectable pancreatic cancer

Aim: Although there are a few reports on the efficacy of neoadjuvant therapy (NAT) as a treatment for borderline resectable pancreatic carcinoma (BRPC), the topic remains controversial. Therefore, we conducted a retrospective study to analyze the long-term outcome. Method: Fifty-one patients who underwent neoadjuvant chemotherapy (NAC) or neoadjuvant chemoradiotherapy (NACRT) for BRPC at our hospital, between April 2003 and September 2019 were recruited in this study. Result: Altogether, 51 patients were diagnosed with BRPC based on the General Rules for the Study of Pancreatic Cancer (7th edition), of which, 15 had NAC, and 36 underwent NACRT. In total, 33 patients underwent resection of the pancreas (10 from NAC group (66.7%) and 23 from NACRT group (63.9%)), and 32 had radical surgery (9 from NAC group (60.0%) and 23 from NACRT group (63.9%)). R0 resection rate was 50% (16/32), and there was no significant difference between the NAC and NACRT groups (44.4% vs. 52.2%, P = 0.16). OS (21.0 months vs. 36.1 months, P = 0.974) and RFS (20.0 months vs. 24.0 months, P = 0.266) showed no significant differences between the NAC and NACRT groups. As revealed by the pathological findings, the percentage of patients with positive dissected peripancreatic tissue margin was significantly lower for the NACRT group than that of the NAC group (66.7% vs. 26.1%, P = 0.033). Conclusion: Although no significant difference was observed regarding long-term prognosis between the NAC and the NACRT groups, the results indicate the effectiveness of radiotherapy in local tumor control of BRPC.

Clinical characteristics of rectal cancer patients with neoadjuvant chemoradiotherapy: a nationwide population-based cohort study in South Korea.

PurposeNeoadjuvant chemoradiotherapy has been accepted as a standard treatment for stage II–III rectal cancer. This study aimed to evaluate the clinical characteristics of patients who underwent neoadjuvant chemoradiotherapy for rectal cancer and effects on overall survival (OS) of neoadjuvant chemoradiotherapy in South Korea.MethodsPatients who underwent curative resection for rectal cancer from 2014 to 2016 were retrospectively reviewed from the database of the National Quality Assessment program in South Korea. Patients were categorized into the upfront surgery group and neoadjuvant chemoradiotherapy group. We evaluated factors associated with the administration of neoadjuvant chemoradiotherapy and its effects on OS. Inverse probability of treatment weighting was performed to account for baseline differences between subgroups.ResultsA total of 6,141 patients were categorized into the upfront surgery group (n = 4,237) and neoadjuvant chemoradiotherapy group (n = 1,904). The neoadjuvant chemoradiotherapy was more frequently administered to male, midrectal cancer, and younger patients. In the neoadjuvant chemoradiotherapy group, old age, underweight, and pathologic stage were significant risk factors of OS, and male sex, the level of tumor and clinical stages were not associated with OS. After adjustment, the OS of the neoadjuvant chemoradiotherapy group followed the OS of the upfront surgery group of the same pathologic stage.ConclusionMale sex and the level of tumor were not related to the OS of rectal cancer patients with neoadjuvant chemoradiotherapy. The OS of patients who underwent neoadjuvant chemoradiotherapy was decided by their pathologic stages regardless of clinical stages.

Comparison with Short- and Long-term Neoadjuvant Chemoradiotherapy for Resectable and Borderline Resectable Pancreatic Adenocarcinoma

Introduction: The indications of preoperative treatment for resectable (R) borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) are still obscure, and the protocol has not yet been standardized. Method: The patients were divided into R, BR with venous involvement (BR-V) according to the 2019 NCCN guidelines. Between September 2009 and May 2016, short neoadjuvant chemoradiotherapy (NACRT) (3Gy x 10fr.+S-1) in 2 weeks was given to patients with R(n=33), BR-V(n=19). Subsequently, since June 2016, long NACRT (2Gy x 25fr.+S-1) in 5 weeks was given to patients with R(n=51) and BR-V(n=14) PDAC. Results: There was no significant difference in adverse event rate and completion rate of NACRT protocol between short and long NACRT. The reduction rates of CA19-9 level and SUV max were both significantly higher in patients with long NACRT than those with short NACRT (64%vs30%:P=0.009 and 51%vs23%:P< 0.0001, respectively). There was no significant difference in operation time, R0 reduction rate, Evans grade, and induction and completion rates of postoperative adjuvant chemotherapy between the two groups. However, resection rate was significantly lower in long NACRT group (96% vs 85%, P=0.041) because distant metastasis was more frequently detected before surgery. There was no significant difference in OS and RFS between R patients with short and long NACRT (P=0.871 and P=0.743, respectively). In contrast, BR-V patients with long NACRT had significantly better OS and RFS than those with short NACRT (P=0.004 and P=0.022, respectively). Conclusions: There was no significant difference between short and long NACRT in R-PDAC. Long NACRT might be more effective against BR-V PDAC.

Postoperative pancreatic fistulas decrease the survival of pancreatic cancer patients treated with surgery after neoadjuvant chemoradiotherapy: A retrospective analysis

Background and objectivesA postoperative pancreatic fistula (POPF) is a critical complication after surgery for pancreatic cancer. Whether a POPF affects the long-term prognosis of pancreatic cancer cases remains controversial. This study aimed to clarify the effect of a POPF on the long-term prognosis of pancreatic cancer patients, especially after neoadjuvant chemoradiotherapy (NACRT). MethodsPatients who underwent curative pancreatectomy for pancreatic cancer between January 2012 and June 2019 at Kyoto University Hospital were retrospectively investigated. A fistula ≥ Grade B was considered a POPF. ResultsDuring the study period, 148 patients underwent upfront surgery (Upfront group), and 52 patients underwent surgery after NACRT (NACRT group). A POPF developed in 16% of patients in the Upfront group and 13% in the NACRT group (p = 0.824). In the Upfront group, development of a POPF did not have a significant effect on recurrence-free survival (p = 0.766) or overall survival (p = 0.863). However, in the NACRT group, development of a POPF significantly decreased recurrence-free survival (HR 5.856, p = 0.002) and overall survival (HR 7.097, p = 0.020) on multivariate analysis. ConclusionsThe development of a POPF decreases the survival of pancreatic cancer patients treated by surgery after NACRT.

Neoadjuvant versus Postoperative Chemoradiotherapy in Gastric Cancer

The optimal timing of chemoradiotherapy (CRT) in patients with gastric cancer remains unclear. We sought to compare the survival outcomes between neoadjuvant CRT (NCRT) vs. postoperative CRT (postCRT) in patients with gastric cancer. We hypothesized that NCRT would be associated with better survival compared to postCRT. We retrospectively reviewed patients with gastroesophageal junction (GEJ) or gastric adenocarcinoma who underwent surgical resection and NCRT or postCRT between 2005-2017 at a single institution. Clinical parameters such as sex, age, performance status, histology, stage, surgical outcomes, chemotherapy (CTX), and radiotherapy (RT) regimen were analyzed. CRT-related toxicity was graded according to CTCAE v5.0. The primary endpoint was overall survival (OS), assessed from the time of diagnosis. Survival analysis was conducted using Cox proportional hazards regression and Kaplan Meier estimates. We identified 152 patients, and median follow-up was 37.5 months. Median age was 63. 77% were male. 93% had an ECOG <2. Tumor location was gastroesophageal junction (GEJ) in 58% and gastric in 42%. Clinical stage was mostly II (44%) or III (44%). 102 (67%) patients underwent NCRT while 50 (33%) underwent postCRT. Patients who received NCRT were more likely to be male (83% vs. 64%; p = 0.013) and have a GEJ tumor (76% vs. 22%, p<0.001), greater number of involved lymph nodes (median 1 vs. 0; p = 0.005), and higher clinical stage (p = 0.002). Median RT dose was 50.4 Gy for neoadjuvant RT and 45.0 Gy for postoperative RT (p<0.001). Concurrent CTX was carboplatin/taxol (47%), cisplatin/fluorouracil (FU; 17%), or FOLFOX (folinic acid/FU/oxaliplatin; 14%) in the neoadjuvant setting and single-agent with FU (86%) in the postoperative setting (p<0.001). The NCRT group had a pathologic complete response (pCR) rate of 26% and had greater rate of R0 resection compared to the postCRT group (95% vs. 76%; p = 0.002). NCRT vs. postCRT was associated with a lower rate of any Grade 3 or higher toxicity (10% vs. 54%; p<0.001). Only 1% had treatment break(s) in the NCRT setting vs. 10% in the postCRT setting (p = 0.015). On multivariable analysis of OS, NCRT vs. postCRT (HR = 0.57 [95% CI 0.36-0.91]; p = 0.020) and R0 resection (HR = 0.50 [95% CI 0.27-0.90]; p = 0.021) were independently associated with lower hazards of death. The estimated 5-year OS was 67% (95% CI 0.55-0.76) in the NCRT group vs. 40% (95% CI 0.26-0.54) in the postCRT group (log-rank p = 0.003). NCRT was associated with a higher rate of R0 resection and longer OS with a lower toxicity compared to postCRT. Our findings suggest NCRT is superior to postCRT and support randomized trials to establish the optimal timing of CRT in gastric cancer.