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Background： The effectiveness of neoadjuvant chemoradiotherapy （NCRT） treatment for patients with esophageal carcinoma （EC） remains controversial. The aim of this study was to compare the effect of NCRT followed by surgery （NCRTS） with surgery alone （SA） for EC. Methods： The PubMed, EMBASE, and the Cochrane Library databases were electronically searched up to August 2015 for all the published studies that investigated EC patients receiving either NCRTS or SA, and the reference lists were also manually examined for the eligible studies. The risk ratio （RR） with 95% confidence intervals （CI s） as effective size was determined to assess the 1-, 3-, 5-year survival rates （SRs）, postoperative morbidity, and postoperative mortality. Heterogeneity was determined using the Q-test. The Begg＇s test and Egger＇s test were used for assessing any potential publication bias. Results： Of 1120 identified studies, 16 eligible studies were included in this analysis （involving 2549 patients）. Overall, the pooled results suggested that NCRTS was associated with significantly improved 1-year （RR： 1.07, 95% CI： 1.02–1.13）, 3-year （RR： 1.26, 95% CI： 1.14–1.39）, and 5-year （RR： 1.36, 95% CI： 1.18–1.56） SRs. However, the results also indicated that NCRTS had no or little effect on postoperative morbidity （RR： 0.93, 95% CI： 0.82–1.05） and postoperative mortality （RR： 1.17, 95% CI： 0.56–2.44）. Conclusions： Compared with SA, NCRTS can increase 1-, 3-, and 5-year SRs in patients with EC.

Despite advancements in diagnosis and therapy, relapse of rectal cancer after clinical complete remission (cCR) remains a frequent event. The key factors influencing the treatment strategy for the management of patients achieving cCR following neoadjuvant chemoradiotherapy (Neo-CRT) remain to be identified. We present the case of a 64-year-old man with rectal cancer. The patient was initially admitted to the hospital in September 2011 with a 3-month history of change in his stools. Following his re-hospitalization in November 2011, a biopsy specimen of the neoplasm suggested the presence of rectal adenocarcinoma; laboratory investigations also revealed elevated levels of carcinoembryonic antigens (CEA; carbohydrate antigen 199) in the serum. Subsequently, the patient received Neo-CRT, as well as symptomatic and supportive treatment. The level of serum CEA returned to normal, without signs of swollen lymph nodes in the pelvic cavity. The patient was diagnosed with rectal cancer based on the elevated level of serum CEA, colonoscopy, and contrast-enhanced magnetic resonance imaging. He relapsed 4 months after cCR following Neo-CRT and underwent laparoscopic Miles' surgery in April 2013. The relapse may have been mainly attributed to residual tumor cells. This case report and literature review may contribute to the clinical recognition of treatment for patients with rectal cancer achieving cCR following Neo-CRT.

Background Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4–6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6–8 weeks after CRE-I. CRE-II will include 18F–FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care.

Several studies have explored the effectiveness of PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy (nCRT) in the treatment of locally advanced rectal cancer(LARC), particularly in microsatellite stable(MSS) or mismatch repair proficient(pMMR) LARC patients. We undertook a single-arm systematic review to comprehensively evaluate the advantages and potential risks associated with the use of PD-1/PD-L1 inhibitors in conjunction with nCRT for patients diagnosed with locally advanced rectal cancer. The PubMed, Embase, Cochrane Library, ClinicalTrials.gov, ASCO and ESMO were searched for related studies. The main outcomes were pathologic complete response (pCR), major pathological response (MPR), anal preservation, and adverse effects (AEs). Fourteen articles including 533 locally advanced rectal cancer (LARC) patients were analyzed. The pooled pCR, MPR, and anal preservation rates were 36%, 66% and 86%. Grade ≥3 adverse events occurred in 20%. Subgroup analysis showed that; dMMR/MSI-H had a pooled pCR (100%) and MPR (100%), pMMR/MSS had a pooled pCR (38%) and MPR (60%); the short-course radiotherapy and long-course radiotherapy had pooled pCR rates of 51% and 30%, respectively. The rates of pCR for the concurrent and sequential immuno-chemoradiotherapy subgroups at 30% and 40%, mirroring pCR rates for the PD-L1 and PD-1 inhibitor subgroups were 32% and 40%, respectively. In cases of locally advanced rectal cancer, PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy have shown promising response rates and acceptable toxicity profiles. PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy hence has a positive outcome even in MSS LARC patients. https://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42023465380.

Elderly patients with locally advanced esophageal adenocarcinoma (EAC) have a poor prognosis. The purpose of this study was to identify prognostic factors and construct a risk stratification for assessing the prognosis of elderly (≥ 70 years old) EAC patients who receiving neoadjuvant chemoradiotherapy (NCRT) and esophagectomy. A total of 688 patients with non-metastatic locally advanced EAC who underwent NCRT and esophagectomy were selected from the Surveillance Epidemiology and End Results (SEER) database. Multivariable Cox analysis was used to identify prognostic factors of overall survival (OS). Restricted Cubic Splines (RCS) was used to examine the linear relationship between the number of lymph node dissection (LND) and OS. RCS showed a linear relationship between LND and OS (P = 0.690). As the number of LND increased, the risk of death decreased. Multivariable analysis demonstrated that LND > 23, grade III/IV, and regional node positive were independent prognostic factors. Subgroup analysis indicated that enlarged lymph node dissection (LND > 23) did not improve OS in patients with grade I/II or T1-2 stage, whereas enlarged lymph node dissection significantly improved OS in patients with grade III/IV or T3-4 stage. Furthermore, we constructed a novel risk score based on LND, grade, and regional node status, which stratified patients into low-, medium-, and high-risk groups. Patients in the high-risk group (risk score = 3) had a worse prognosis. Enlarged lymph node dissection (LND > 23) improved OS in patients with grade III/IV or T3-4 stage. Moreover, a novel risk score was constructed, which facilitated risk stratification and postoperative surveillance in elderly EAC patients.

For locally advanced (T3-4/N+M0) rectal cancer (LARC), neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment. It was demonstrated to decrease the local recurrence rate and increase the tumor response grade. However, the distant metastasis remains an unresolved issue. And the demand for anus preservation and better quality of life increases in recent years. Radiotherapy and immunotherapy can be supplement to each other and the combination of the two treatments has a good theoretical basis. Recently, multiple clinical trials are ongoing in terms of the combination of nCRT and immunotherapy in LARC. It was reported that these trials achieved promising short-term efficacy in both MSI-H and MSS rectal cancers, which could further improve the rate of clinical complete response (cCR) and pathological complete response (pCR), so that increase the possibility of ‘Watch and Wait (W&W)’ approach. However, the cCR and pCR is not always consistent, which occurs more frequent when nCRT is combined with immunotherapy. Thus, the efficacy evaluation after neoadjuvant therapy is an important issue for patient selection of W&W approach. Evaluating the cCR accurately needs the combination of multiple traditional examinations, new detective methods, such as PET-CT, ctDNA-MRD and various omics studies. And finding accurate biomarkers can help guide the risk stratification and treatment decisions. And large-scale clinical trials need to be performed in the future to demonstrate the surprising efficacy and to explore the long-term prognosis.

BackgroundCurrently, 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.MethodsOf 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.ResultsAfter 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).ConclusionFor 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.

PurposeThe 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.MethodsData 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.ResultsOut 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).ConclusionThere 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.

Background The Surgery As Needed for Oesophageal cancer (SANO) trial compares active surveillance with standard oesophagectomy for patients with a clinically complete response (cCR) to neoadjuvant chemoradiotherapy. The last patient with a clinically complete response is expected to be included in May 2021. The purpose of this update is to present all amendments to the SANO trial protocol as approved by the Institutional Research Board (IRB) before accrual is completed. Design The SANO trial protocol has been published ( https://doi.org/10.1186/s12885-018-4034-1 ). In this ongoing, phase-III, non-inferiority, stepped-wedge, cluster randomised controlled trial, patients with cCR (i.e. after neoadjuvant chemoradiotherapy no evidence of residual disease in two consecutive clinical response evaluations [CREs]) undergo either active surveillance or standard oesophagectomy. In the active surveillance arm, CREs are repeated every 3 months in the first year, every 4 months in the second year, every 6 months in the third year, and yearly in the fourth and fifth year. In this arm, oesophagectomy is offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant metastases. The primary endpoint is overall survival. Update Amendments to the study design involve the first cluster in the stepped-wedge design being partially randomised as well and continued accrual of patients at baseline until the predetermined number of patients with cCR is reached. Eligibility criteria have been amended, stating that patients who underwent endoscopic treatment prior to neoadjuvant chemoradiotherapy cannot be included and that patients who have highly suspected residual tumour without histological proof can be included. Amendments to the study procedures include that patients proceed to the second CRE if at the first CRE the outcome of the pathological assessment is uncertain and that patients with a non-passable stenosis at endoscopy are not considered cCR. The sample size was recalculated following new insights on response rates (34% instead of 50%) and survival (expected 2-year overall survival of 75% calculated from the moment of reaching cCR instead of 3-year overall survival of 67% calculated from diagnosis). This reduced the number of required patients with cCR from 264 to 224, but increased the required inclusions from 480 to approximately 740 patients at baseline. Conclusion Substantial amendments were made prior to closure of enrolment of the SANO trial. These amendments do not affect the outcomes of the trial compared to the original protocol. The first results are expected late 2023. If active surveillance plus surgery as needed after neoadjuvant chemoradiotherapy for oesophageal cancer leads to non-inferior overall survival compared to standard oesophagectomy, active surveillance can be implemented as a standard of care.