Neoadjuvant Chemoradiotherapy Group Research Articles

Comment on "Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial" by Mei et al.: Two Overtreatments Compared.

Mei et al. published in Annals of Surgery1 the initial results of the CONVERT trial, comparing neoadjuvant chemotherapy with CAPOX versus standard chemoradiation for rectal cancer with uninvolved mesorectal fascia. The design of the study, reported results and conclusions raise concerns. It seems that a vast majority of the cohort did experience an overtreatment, as their tumors could be adequately treated with surgery alone.2,3 The authors do not discuss these limitations, nor have they reported, whether surgery alone was one of the options given to patients during the consent process. It is not clear, what was the benefit of neoadjuvant treatment in patients with primary operable tumors. The price of this treatment is mentioned. Despite relatively young (median age of 60 years, age limit 75 years) and healthy cohort (ECOG performance status ≤1, adequate hematologic, liver, and renal function), 70.3% in the neoadjuvant chemotherapy group and 64.7% in the neoadjuvant chemoradiotherapy group experienced toxicities. The postoperative morbidity was 18.8% and 25.7%, respectively. Nearly 10% in both groups did not receive surgery at all, and 13% refused postoperative therapy. The authors describe the downstaging of the tumors, but without admitting that the reliability of comparison between MRI and pathological findings is low.4–6 Post-treatment functional impairment, frequency, and severity of low anterior syndrome are also not reported. A statistical comparison of 2 overtreatments does not make the treatment appropriate. All treatment modalities in rectal cancer: surgery, radiotherapy, and chemotherapy do have a significant risk of complication. The combination of these treatment options could possibly potentiate their risks and adverse effects; therefore, selecting the therapy course is a difficult and careful process. The goal is to find a minimal therapy sufficient for success, not a maximal therapy applicable to the patient.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy alone for patients with locally advanced rectal cancer: a propensity-score-matched analysis combined with SEER validation.

Neoadjuvant therapy followed by radical surgery is recommended for locally advanced rectal cancer (LARC). But radiotherapy can cause potential adverse effects. The therapeutic outcomes, postoperative survival and relapse rates between neoadjuvant chemotherapy (N-CT) and neoadjuvant chemoradiotherapy (N-CRT) patients have rarely been studied. From February 2012 to April 2015, patients with LARC who underwent N-CT or N-CRT followed by radical surgery at our center were included. Pathologic response, surgical outcomes, postoperative complications and survival outcomes (including overall survival [OS], disease-free survival [DFS], cancer-specific survival [CSS] and locoregional recurrence-free survival [LRFS]) were analyzed and compared. Concurrently, the Surveillance, Epidemiology, and End Results Program (SEER) database was used to compare OS in an external source. A total of 256 patients were input into the propensity score-matching (PSM) analysis, and 104 pairs remained after PSM. After PSM, the baseline data were well matched and there was a significantly lower tumor regression grade (TRG) (P < 0.001), more postoperative complications (P = 0.009) (especially anastomotic fistula, P = 0.003) and a longer median hospital stay (P = 0.049) in the N-CRT group than in the N-CT group. No significant difference was observed in OS (P = 0.737), DFS (P = 0.580), CSS (P = 0.920) or LRFS (P = 0.086) between the N-CRT group and the N-CT group. In the SEER database, patients who received N-CT had similar OS in both TNM II (P = 0.315) and TNM III stages (P = 0.090) as those who received N-CRT. N-CT conferred similar survival benefits but caused fewer complications than N-CRT. Thus, it could be an alternative treatment of LARC.

Influence of adverse effects of neoadjuvant chemoradiotherapy on the prognosis of patients with early-stage esophageal cancer (cT1b-cT2N0M0) based on the SEER database.

To analyze the prognostic impact of neoadjuvant chemoradiotherapy (NCRT) on early-stage (cT1b-cT2N0M0) esophageal cancer (ESCA) and construct a prognostic nomogram for these patients. We extracted the clinical data about patients diagnosed with early-stage esophageal cancer from the 2004-2015 period of the Surveillance, Epidemiology, and End Results (SEER) database. We applied the independent risk factors affecting the prognosis of patients with early-stage esophageal cancer obtained after screening by univariate and multifactorial COX regression analyses to establish the nomogram and performed model calibration using bootstrapping resamples. The optimal cut-off point for continuous variables is determined by applying X-tile software. After balancing the confounding factors by propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) method, Kaplan-Meier(K-M) curve, and log-rank test were applied to evaluate the prognostic impact of NCRT on early-stage ESCA patients. Among patients who met the inclusion criteria, patients in the NCRT plus esophagectomy (ES) group had a poorer prognosis for overall survival (OS) and esophageal cancer-specific survival (ECSS) than patients in the ES alone group (p < 0.05), especially in patients who survived longer than 1 year. After PSM, patients in the NCRT + ES group had poorer ECSS than patients in the ES alone group, especially after 6 months, while OS was not significantly different between the two groups. IPTW analysis showed that, prior to 6 months patients in the NCRT + ES group had a better prognosis than patients in the ES group, regardless of OS or ECSS, whereas after 6 months, patients in the NCRT + ES group had a poorer prognosis. Based on multivariate COX analysis, we established a prognostic nomogram which showed areas under the ROC curve (AUC) for 3-, 5-, and 10-year OS 0.707, 0.712, and 0.706, respectively, with the calibration curves showing that the nomogram was well calibrated. Patients with early-stage ESCA (cT1b-cT2) did not benefit from NCRT, and we established a prognostic nomogram to provide clinical decision aid for the treatment of patients with early-stage ESCA.

Risk factors for and longitudinal course of male sexual dysfunction after robotic rectal cancer surgery.

The aim of this work was to investigate the risk factors associated with the incidence of sexual dysfunction in patients who underwent robot-assisted surgery with several treatment options, such as neoadjuvant chemoradiotherapy and lateral lymph node dissection, and clarify the longitudinal course of erectile function in risk groups. A total of 203 male patients who underwent robot-assisted total mesorectal excision for rectal cancer between 2013 and 2019 were included. The risk factors for erectile and ejaculatory dysfunction as well as the longitudinal course of erectile function were retrospectively investigated in all cohorts and several risk groups, including those who underwent neoadjuvant chemoradiotherapy, lateral lymph node dissection and adjuvant chemotherapy. Erectile dysfunction was assessed using the International Index of Erectile Function and ejaculatory dysfunction was assessed using original questions. The survey was performed preoperatively and at 3, 6 and 12 months postoperatively. Erectile and ejaculatory dysfunction occurred in 46.8% and 15.7% of the patients, respectively. Multivariate analysis showed that neoadjuvant chemoradiotherapy was an independent risk factor for erectile dysfunction. Erectile function recovered longitudinally to the preoperative level overall, as well as in lateral lymph node dissection and postoperative adjuvant chemotherapy subgroups; however, recovery was poor in the neoadjuvant chemoradiotherapy group, even at 12 months postoperatively. Neoadjuvant chemoradiotherapy was found to be a risk factor for erectile dysfunction after robot-assisted surgery for rectal cancer. Erectile function recovered postoperatively in patients undergoing lateral lymph node dissection; however, those receiving neoadjuvant chemoradiotherapy showed poor recovery, even at 12 months postoperatively.

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.

Pathologic responses and surgical outcomes after neoadjuvant immunochemotherapy versus neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Currently, the role of immunotherapy in neoadjuvant setting for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is gradually attracting attention. Few studies compared the efficacy of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT). Our study aimed to compare treatment response and postoperative complications after NICT followed by surgery with that after conventional NCRT in patients with locally advanced ESCC. Of 468 patients with locally advanced ESCC, 154 received conventional NCRT, whereas 314 received NICT. Treatment response, postoperative complications and mortality between two groups were compared. Pathological response of primary tumor was evaluated using the Mandard tumor regression grade (TRG) scoring system. Pathological complete response (pCR) of metastatic lymph nodes (LNs) was defined as no viable tumor cell within all resected metastatic LNs. According to regression directionality, tumor regression pattern was summarized into four categories: type I, regression toward the lumen; type II, regression toward the invasive front; type III, concentric regression; and type IV, scattered regression. Inverse probability propensity score weighting was performed to minimize the influence of confounding factors. After adjusting for baseline characteristics, the R0 resection rates (90.9% vs. 89.0%, P=0.302) and pCR (ypT0N0) rates (29.8% vs. 34.0%, P=0.167) were comparable between two groups. Patients receiving NCRT showed lower TRG score (P<0.001) and higher major pathological response (MPR) rate (64.7% vs. 53.6%, P=0.001) compared to those receiving NICT. However, NICT brought a higher pCR rate of metastatic LNs than conventional NCRT (53.9% vs. 37.1%, P<0.001). The rates of type I/II/III/IV regression patterns were 44.6%, 6.8%, 11.4% and 37.1% in the NICT group, 16.9%, 8.2%, 18.3% and 56.6% in the NCRT group, indicating a significant difference (P<0.001). Moreover, there were no significant differences in the incidence of total postoperative complications (35.8% vs. 39.9%, P=0.189) and 30-d mortality (0.0% vs. 1.1%, P=0.062). For patients with locally advanced ESCC, NICT showed a R0 resection rate and pCR (ypT0N0) rate comparable to conventional NCRT, without increased incidence of postoperative complications and mortality. Notablely, NICT followed by surgery might bring a promising treatment response of metastatic LNs.

Neoadjuvant Chemoradiotherapy Significantly Improved R0 Resection Rate in Unresectable Locally Advanced Colon Cancer: The Initial Analysis from the Randomized Controlled Phase 3 Trial

<h3>Purpose/Objective(s)</h3> Neoadjuvant chemotherapy (NACT) is often used for tumor downstaging in locally advanced colon cancer (LACC) and improves the R0 resection rate. Based on previous findings, we hypothesized that neoadjuvant chemoradiotherapy (NACRT) might bring a higher R0 resection rate and survival benefit to patients with unresectable LACC. Our perspective study aimed at comparing NACRT versus NACT for unresectable LACC to confirm our hypothesis. <h3>Materials/Methods</h3> We performed the world's first randomized controlled phase 3 trial on NACRT for LACC at our institution. Eligible patients had newly diagnosed unresectable LACC. We randomly allocated patients open-label to the NACT group (control group) or the NACRT group (research group). Chemotherapy regimen was XELOX (oxaliplatin 100-130mg/m2, iv drip, d1, every 3 weeks; capecitabine 1,000mg/m2, bid, d1-d14, every 3 weeks). Patients allocated radiotherapy received a daily irradiation schedule (GTV:50Gy/25F/5W, CTV:45Gy/25F/5W). Surgery scheduled 6–8 weeks after radiotherapy and adjuvant chemotherapy were given if patients transformed into resectable LACC. <h3>Results</h3> Between July 2019 and July 2021, 49 patients with unresectable LACC underwent randomization and 45 patients (4 excluded) were analyzed for efficacy finally. There were 23, 6, 8, 7 and 1 patients with primary tumor location at sigmoid colon, descending colon, transverse colon, ascending colon and ileocecus. The median follow-up time was 20.7 months. Allocated groups were balanced, with 25 patients receiving NACRT and 20 patients receiving NACT. Twenty-one (84%) patients in the NACRT group transformed to resectable LACC after planned neoadjuvant treatment and received surgery while there were only 5 (20%) patients in the NACT group. Compared to NACT, the use of NACRT improved the R0 resection rate (80% vs 20%) significantly. The 2-year progression-free survival is 72.2% in the NACRT group and 37.4% in the NACT group (p=0·029). The 2-year overall survival is 95.5% in the NACRT group and 73.1% in the NACT group (p=0·035). No increasing toxicities and postsurgical complications were observed from the NACRT group compared with the NACT group. The trial is terminated since the R0 resection rate and survival between the two groups had shown a significant difference. Also, the patients' MMR/MSI status was not considered at the beginning of the study design. <h3>Conclusion</h3> Based on neoadjuvant chemotherapy, the addition of radiotherapy provided a higher R0 resection rate, longer progression-free survival and even might improve overall survival for patients with unresectable LACC. We concluded that this approach is safe, feasible and might associate with a better survival benefit. We are designing new clinical studies to further demonstrate the value of NACRT in LACC. This trial is registered with ClinicalTrials.gov, number NCT03970694.

Comparison of Efficacy and Safety of Taxanes Plus Platinum and Fluorouracil Plus Platinum in the First-Line Treatment of Esophageal Cancer: A Systematic Review and Meta-Analysis.

Fluoropyrimidine plus platinum (FP) and taxanes plus platinum (TP) are standard treatments for esophageal cancer (EC). This systematic review and meta-analysis aim to explore the difference in the therapeutic effect and toxicity of FP and TP regimens in EC patients. PubMed, Embase, and Cochrane were fully searched and analyzed to find relevant articles on EC patients treated with FP and TP regimens up to 22 March 2022. Thirty-one studies, with a total of 3432 participants, were included in this review. The primary outcomes showed that the prognosis and therapeutic efficacy of TP groups were better than those of FP groups for the EC patients treated with definitive chemoradiotherapy treatment (3-year OS: RR: 1.25, 95% CI: 1.08–1.44, p = 0.003; 3-year PFS: RR: 1.43, 95% CI: 1.17–1.75, p = 0.0006; ORR: RR: 1.17, 95% CI: 1.06–1.29, p = 0.001). However, TP therapy was significantly correlated with a higher incidence of leukopenia and thrombocytopenia (p < 0.05). In the preoperative neoadjuvant chemoradiotherapy group, these two groups had a similar survival time (p > 0.05). The FP regimen corresponded to a higher incidence of thrombocytopenia, while the TP regimen was associated with an increased incidence of febrile leukopenia (p < 0.05). Therefore, TP regimens could generate both superior clinical response and survival benefits when compared with FP regimens in EC patients undergoing definitive chemoradiotherapy.

A Comparison Between Neoadjuvant Chemotherapy and Neoadjuvant Chemoradiotherapy in Treating Esophageal Carcinoma: A Study at a Tertiary Care Cancer Center in Suburban India.

Background and objectiveEsophageal carcinoma remains a disease associated with high mortality rates among patients even after receiving treatment. Management with surgery alone offers a five-year survival of only 20%. Hence adjuvant and neoadjuvant therapies were instituted to treat this condition along with surgery. Neoadjuvant chemoradiotherapy (NACRT) followed by surgery is currently the standard of care. Neoadjuvant chemotherapy (NACT) is also recommended by some authors as a method of adequate care. There is a scarcity of studies in the literature comparing NACRT with NACT. In light of this, we employed the criteria of pathological response as a primary endpoint to compare the effectiveness of NACT and NACRT in treating esophageal carcinoma.Materials and methodsA total of 50 patients with esophageal cancer having Eastern Cooperative Oncology Group (ECOG) scores 0-2 with cancer stages cT2-T4a, cN0-N1, and cM0 were enrolled. The patients were further classified into two groups of 25 each. While one group received chemotherapy using inj. paclitaxel and carboplatin (NACT group), the other was managed with inj paclitaxel and carboplatin as well as 42 Gy of fractionated irradiation (NACRT group). Six weeks after the last dose of radiation or three weeks after chemotherapy, they were evaluated and offered transthoracic esophagectomy (TTE).ResultsSquamous cell carcinoma was found in 39 (78%) cases and 11 (22%) cases had adenocarcinoma. Pathologically complete or near-complete responses were seen in 42% of patients in the NACRT group and 22% in the NACT group.ConclusionWhile NACT and NACRT are both effective therapies for esophageal cancers, NACRT offers better tumor regression compared to NACT. Given the higher rates of complete or near-complete response in the NACRT group, NACRT is likely to offer higher overall survival rates than NACT.

Impact of total neoadjuvant therapy consisting of consolidation chemotherapy on locally advanced rectal cancer survival.

The objective was to compare disease-free survival (DFS) and distant metastasis in patients with neoadjuvant chemoradiotherapy (NCRT) and total neoadjuvant therapy (TNT) for locally advanced rectal cancer. Patients with cT3-4N0M0 or cTxN1-2M0 rectal cancer were included in this retrospective study. Patients who received NCRT (radiotherapy with concurrent capecitabine) or TNT (radiotherapy with two concurrent cycles of capecitabine and oxaliplatin (CAPOX) followed by another two cycles of CAPOX) during January 2011 and November 2016 at Beijing Chaoyang Hospital, Capital Medical University were included. All patients had received radical surgery. Adverse events, pathological response and survival outcomes in the two groups were compared. One hundred eighty-two patients were enrolled, 120 in the TNT and 62 in the NCRT groups. No significant between-group differences in neoadjuvant therapy-associated adverse events or surgical complications were found. TNT achieved a higher pathological complete response (pCR) rate (25.8%) compared with NCRT (12.9%, P = 0.044). Patients in the TNT group had a higher 3-year DFS rate (82.8% versus 75.7%, P = 0.041) and lower distant metastasis rate (19.2% versus 33.1%, P = 0.049) than those in the NCRT group. Multivariate analysis showed that NCRT was an independent risk factor for DFS (95%CI 2.023-13.415, P = 0.001) and distant metastasis (95% CI 2.149-20.082, P = 0.001). With similar adverse events and a higher pCR rate when compared with NCRT, TNT might be considered as a safe and effective therapeutic strategy to improve prognosis in patients with locally advanced rectal cancer.

The comparisons of neoadjuvant chemoimmunotherapy versus chemoradiotherapy for oesophageal squamous cancer.

The aim of this study was to evaluate the short-term outcomes of neoadjuvant chemoimmunotherapy (NACI) followed by oesophagectomy for locally advanced oesophageal squamous carcinoma. Patients receiving NACI or chemoradiotherapy between September 2019 and September 2021 were identified. The primary outcomes were tumour response and survival. Secondary outcomes were toxic effects and postoperative complications. The propensity score matching for enrolled patients was performed. Data of 149 patients with clinical stage II-IV oesophageal squamous cancer, including 55 receiving NACI and 94 receiving neoadjuvant chemoradiotherapy (NACR), were analysed after propensity score matching. With regard to tumour response score, 24 (43.6%) and 59 (62.8%) patients were scored 0/1 in the NACI and NACR groups, respectively (P = 0.023). Of note, 17 (30.9%) patients in the NACI group achieved pathological complete response (CR) (ypT0N0), while 48 (51.1%) patients in NACR group achieved pathological CR (P = 0.026). NACR was associated with the higher risk of postoperative pneumonia (P = 0.034) and less lymph nodes and stations dissected (P ≤ 0.001). The 1-year cumulative overall survival rate was 94.5% and 86.2% in the NACI and NACR groups, respectively (P = 0.170). We found that NACI compared with NACR was associated with lower pneumonia rate and was safe and feasible for locally advanced oesophageal squamous cancer. However, the tumour regression score and the pathological CR rate of patients treated with neoadjuvant immunotherapy were lower than those of patients treated with NACR. The short-term follow-up results were comparable between 2 treatment modalities.

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.

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.