Anal Preservation Rate Research Articles

First in human intraarterial delivery of tislelizumab for the treatment of pMMR locally advanced rectal cancer: A single-arm, open label, phase II clinical trial

BackgroundIntravenous immune checkpoint inhibitors (ICIs) have shown efficacy in treating locally advanced rectal cancer (LARC), but concerns about systemic toxicity persist. This study developed a unique approach termed chemo-immuno-embolization with transcatheter rectal arterial intervention (CIETAI), aiming to enhance the anti-tumor response while minimizing systemic toxicity. MethodThis is a prospective, single-arm, phase II clinical trial conducted in Daping hospital. Patients with previously untreated stage II/III LARC underwent preoperative CIETAI combined with PD-1 inhibitor tislelizumab plus oxaliplatin, followed by standard concomitant chemoradiotherapy (capecitabine and 50.4 Gy radiation). Intravenous tislelizumab was administered for an additional two cycles. ResultsBetween January 2023 and December 2023, a total of 38 patients were enrolled. As the primary endpoint, 17 (44.74 %) patients achieved pathological complete response (TRG0), with a major pathologic response (MPR) rate of 65.79 %. The anal preservation rate was 84.21 % (32/38), and importantly, 15 of 21 patients with low rectal cancer achieved organ preservation with functional maintenance. Eight patients experienced grade 3–4 adverse events (AEs). All immune-related AEs were grade 1–2, with the most common being endocrine toxicity (5/6, 83.33 %). No grade 5 AEs occurred. ConclusionThis study provides preliminary evidence supporting the safety and efficacy of intraarterial tislelizumab delivery in the neoadjuvant setting for LARC. These promising results encourage further exploration in larger cohorts to validate the clinical impact of this novel CIETAI strategy. Trial registrationClinicalTrials.gov Identifier: NCT05957016.

New opportunities and challenges of anal preservation strategies for rectal cancer in the era of immunotherapy

With the advancement of medical technology and concept, rectal cancer treatment methods continue to develop, further improving the efficacy of comprehensive treatment and quality of life for patients. Innovation in various anal preservation operations for low rectal cancer has continuously improved the rate of anal preservation, and the concept of the "watch and wait" strategy may become a new milestone in the treatment of rectal cancer. With the application of immunotherapy to all aspects of cancer treatment, it will certainly have a profound impact on the treatment of colorectal cancer, especially the anal preservation strategy. Combined with the new characteristics, advantages, and achievements of immunotherapy, more patients with rectal cancer can achieve the purpose of preserving the anus and organs through nonsurgical therapy, and obtain the same disease-free survival and overall survival while improving the quality of life. Currently, the study of sensitization immunotherapy for different types of bowel cancer is in the ascendancy, and the development of a better treatment plan is an urgent problem to be explored and solved.

A retrospective cohort study of neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitors in locally advanced rectal cancer

IntroductionThis study aimed to investigate the safety and efficacy of neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitors (ICIs) in patients with locally advanced rectal cancer (LARC). Patients diagnosed with LARC and treated with programmed cell death protein-1 (PD-1) inhibitors were recruited. MethodsFour different treatment strategies were employed in this study: plan A [long-course radiotherapy + PD-1 inhibitor/capecitabine + PD-1 inhibitor/XELOX+ total mesorectal excision (TME)], plan B (long-course radiotherapy + capecitabine + PD-1 inhibitor/XELOX + TME), plan C (short-course radiotherapy + PD-1 inhibitor/XELOX + TME), and plan D (PD-1 inhibitor/XELOX + short-course radiotherapy + TME). The basic information about patients, pathological indicators, adverse events, and efficacy indexes of treatment plans were analyzed. Results96.8 % of patients were mismatch repair proficient (pMMR) and only 2 patients belonged to mismatch repair deficient (dMMR). The 2 patients with dMMR showed a pathological complete response (pCR) rate of 100 %, while the pCR rate of pMMR patients was 43.3 %. The overall tumor descending rate reached 79 %, and the anus-retained rate was 88.7 % in all LARC patients. Plan A exhibited the highest pCR rate of 60 %, and plan C had the highest tumor descending rate and anal preservation rate. Radiation enteritis was the most common adverse event in LARC patients after neoadjuvant therapy, and its incidence was the highest in Plan A. ConclusionNeoadjuvant chemoradiotherapy combined with ICIs demonstrated favorable efficacy and safety in treating LARC patients.

Efficacy and Safety of Preoperative Transcatheter Rectal Arterial Chemoembolisation in Patients with Locally Advanced Rectal Cancer: Results from a Prospective, Phase II PCAR Trial

AimsThe PCAR study aimed to assess the efficacy and safety of preoperative transcatheter rectal arterial chemoembolisation (TRACE) in patients with locally advanced rectal cancer (LARC). Materials and methodsThis was a single-centre, prospective, phase II trial conducted in China. Eligible patients were adults aged 18 years and older with histologically confirmed stage II or III rectal carcinoma and an Eastern Cooperative Oncology Group performance status of 0–1. Patients received TRACE with oxaliplatin, followed by radiotherapy with a cumulative dose of 45 Gy (1.8 Gy/time/day, five times a week for 5 weeks) and received oral S1 capsules twice daily (7 days a week for 4 weeks). Patients underwent total mesorectal excision 4–8 weeks after the completion of chemoradiotherapy, followed by mFOLFOX6 or CAPOX regimens for 4–6 months. The hypothesis of this study was that adding TRACE to preoperative neoadjuvant chemoradiotherapy would improve tumour regression and prognosis. The primary end point was the pathological complete response rate; secondary end points included the major pathological response rate, anal preservation rate, 5-year disease-free survival (DFS), 5-year overall survival and treatment-related adverse events. ResultsIn total, 111 LARC patients received TRACE and subsequent scheduled treatment plans. The pathological complete response and major pathological response rates were 20.72% and 48.65%, respectively. The 5-year DFS and 5-year overall survival were 61.89% (95% confidence interval 51.45–74.45) and 74.80% (95% confidence interval 65.05–86.01), respectively. Grade 3–4 toxicities were reported in 29 patients (26.13%). The postoperative complication rate was 21.62%, without serious surgical complications. Multivariate Cox regression analysis showed that ypN stage (hazard ratio = 4.242, 95% confidence interval 2.101–8.564, P = 0.00017) and perineural invasion (hazard ratio = 2.319, 95% confidence interval 1.058–5.084, P = 0.0487) were independent risk factors associated with DFS, whereas ypN stage (hazard ratio = 3.164, 95% confidence interval 1.347–7.432, P = 0.0101), perineural invasion (hazard ratio = 4.118, 95% confidence interval 1.664–10.188, P = 0.0134) and serum carbohydrate antigen 199 (CA199; hazard ratio = 4.142, 95% confidence interval 1.290–13.306, P = 0.0344) were independent predictors for overall survival. ConclusionThe current study provides evidence that adding TRACE to neoadjuvant chemoradiotherapy can improve the pathological remission rate in LARC patients with acceptable toxicity. Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with LARC should be considered.

A Complete Pathological Response to Neoadjuvant Chemoradiotherapy in A Young Female with Local-Progressed Low Rectal Cancer Following ‘Wait-And-Watch’ Surveillance: A Case Report

Low rectal cancer is a common malignant tumor around the world, and the incidence rate is increasing over years. The abdominoperineal resection, known as the Miles procedure, combined with postoperative chemotherapy and radiotherapy are recommended for the low rectal cancer, that sacrifices the sphincter and can severely affect patient’s quality of life post-surgery. There is a young-onset tendency, and the young patients are more concerned about sphincter-preserving and life-quality post-surgery. With the advances in neoadjuvant therapy, the patient’s options without sacrificing sphincter are expanded. We hereby report a 31-year-old female patient with ultra-low rectal adenocarcinoma, 1.4 cm to the anus edge, was treated through Neoadjuvant chemoradiotherapy (nCRT), which combined CAPEOX chemotherapy and radiotherapy. The initial staging of the tumor was cT3N1M0, and the MRI indicated a threatened circumferential resection margin (CRM). After three cycles of treatment the tumor lesion was completely gone on MRI and colonoscopy, and a complete pathological response (cPR) was yielded then a ‘Wait-and-Watch’ surveillance was being pursued. We aim to advance further studies on the particular molecular and genetic mechanism for neoadjuvant therapy complete remission in young adult patients with low rectal cancer, so as to increase anal preservation rate in the population.

Revolutionizing sphincter preservation in ultra-low rectal cancer: exploring the potential of transanal endoscopic intersphincteric resection (taE-ISR): a propensity score-matched cohort study.

With the optimization of neoadjuvant treatment regimens, the indications for intersphincteric resection (ISR) have expanded. However, limitations such as unclear surgical field, impaired anal function, and failure of anal preservation still exist. Transanal total mesorectal excision can complement the drawbacks of ISR. Therefore, this study combined these two techniques and proposed transanal endoscopic intersphincteric resection (taE-ISR), aiming to explore the value of this novel technique in anal preservation for ultra-low rectal cancer. Four high-volume centres were involved. After 1:1 propensity score-matching, patients with ultra-low rectal cancer underwent taE-ISR ( n =90) or ISR ( n =90) were included. Baseline characteristics, perioperative outcomes, pathological results, and follow-up were compared between the two groups. A nomogram model was established to assess the potential risks of anal preservation. The incidence of adjacent organ injury (0.0% vs. 5.6%, P =0.059), positive distal resection margin (1.1% vs. 8.9%, P =0.034), and incomplete specimen (2.2% vs. 13.3%, P =0.012) were lower in taE-ISR group. Moreover, the anal preservation rate was significantly higher in taE-ISR group (97.8% vs. 82.2%, P =0.001). Patients in the taE-ISR group showed a better disease-free survival ( P =0.044) and lower cumulative recurrence ( P =0.022) compared to the ISR group. Surgery procedure, tumour distance, and adjacent organ injury were factors influencing anal preservation in patients with ultra-low rectal cancer. taE-ISR technique was safe, feasible, and improved surgical quality, anal preservation rate and survival outcomes in ultra-low rectal cancer patients. It held significant clinical value and showed promising application prospects for anal preservation.

Capecitabine, Oxaliplatin, and Irinotecan (XELOXIRI) as Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

Purpose: This study describes the efficacy and safety of irinotecan and oxaliplatin in combination with capecitabine (XELOXIRI) as a neoadjuvant chemotherapy (NAC) regimen for patients with locally advanced rectal cancer (LARC). Methods: From January 2019 through December 2022, 68 LARC patients treated with XELOXIRI were enrolled in the study. XELOXIRI is administered in a three-week cycle consisting of oxaliplatin 70-110 mg/m2 IV for >120 min on day 1; irinotecan 120-160 mg/m2 IV for 90 min on day 1; and capecitabine 700-1100 mg/m2 orally twice daily for 14 days followed by 7 days off. Sixteen cases were treated with combined radiotherapy, including 8 with long-course radiotherapy and 8 with short-course radiotherapy. The efficacy was evaluated based on pelvic MRI (including TNM stage, CRM, and EMVI status), tumor downstaging rate (to ypT0-2N0M0), pCR rate, R0 resection rate, DFS, and OS, and the safety was assessed according to the incidence of adverse events. Results: Sixty-six people had surgery; the R0 resection rate was 100%, and the rate of anal preservation was 97%. The tumor downstaging rate (to ypT0-2N0M0) in the entire group was 53.0%, and the pCR rate was 12.1%. In the XELOXIRI alone group (N = 47), the tumor downstaging rate was 55.3%, and the pCR rate was 12.8%. In the group receiving radiotherapy (N = 16), the tumor downstaging rate was 56.3%, and the pCR rate was 12.5%. In the whole group, the 3-year DFS was 89.0%, and the 3-year survival rate was 98.5%. The 3-year DFS of the XELOXIRI and XELOXIRI + RT groups was 89.9% and 87.2%, respectively. The most frequent grade 3–4 preoperative toxic reactions were neutropenia (8.8%), diarrhea (4.4%), and anemia (2.9%). All adverse events were tolerable. Conclusions: Neoadjuvant chemotherapy with XELOXIRI appears to be feasible and efficacious for patients with LARC. Although neoadjuvant XELOXIRI alone did not yield our expected pCR rate as NAC for LARC, tumor downstaging, R0 resection, sphincter preservation, local recurrence rate, 3-year DFS, OS, and safety were all satisfactory.

The clinical efficacy and safety of neoadjuvant chemoradiation therapy with immunotherapy for the organ preservation of ultra low rectal cancer: A single arm and open label exploratory study.

e15603 Background: Neoadjuvant chemoradiotherapy (nCRT) not only could bring tumor downsizing and downstaging but also could achieve clinical complete response (cCR) or pathological complete response (pCR). Although immunotherapy benefits MSI-H/dMMR rectal cancer patients, little response is observed in MSS/pMMR patients. Several clinical trials including VOLTAGE trial demonstrated that a combination of PD-1 inhibitor and nCRT could result in a promising pathological response even in MSS/pMMR patients. But the elucidation regarding organ preservation after treatment is lacking. Watch and Wait (W&W) is an effective strategy in rectal cancer patients showing cCR after nCRT to preserve organs. This study was designed to explore the efficacy, safety, and organ preservation rate of a combination of nCRT and PD-1 inhibitor(sintilimab) in MSS/pMMR patients with ultra-low rectal cancers. Methods: This was a single-arm, phase II trial. Patients with ultra-low rectal cancer that was confirmed as MSS/pMMR T1-3aN0-1M0 and received 50 Gy (25×2 Gy) chemoradiotherapy and 2 cycles of sintilimab, followed by 6 cycles of capecitabine or CAPOX regimen plus 2 cycles of sintilimab as consolidation therapy. Patients with cCR were managed using the W&W strategy, patients with ncCR were given local excision. The primary outcome was cCR rate and secondary outcomes were anal preservation rate, organ preservation rate, tumor regression grade (TRG), and safety profile. Results: From 2021 January to 2021 December, a total of 23 patients were enrolled. The median age was 55 y (range; 38 to 75). Male patients were 61%. cT2 was 56.5% (13/23), cT3 was 43.5% (10/23), cN0 was 69.6% (16/23), and cN1 was 30.4% (7/23). All patients completed 50Gy chemoradiotherapy. Nineteen patients received 4 cycles of sintilimab treatment, 3 patients received 3 cycles of sintilimab, and 1 patient received 1 cycle of sintilimab. cCR was 43.5% (10/23), ncCR was 26.1% (6/23), and cPR was 30.4% (7/23). The anal preservation rate was not assessed in 1 patient due to cerebral ischemic stroke. The anal preservation rate was 95.5% (21/22), rectal preservation rate was 59.1% (13/22). Ten patients underwent surgery. Among them, two patients achieved pCR, and the major pathologic response rate (TRG0-1) was 60.0% (6/10). The overall CR(cCR+pCR) rate was 52.2% (12/23). Grade 3/4 treatment-related adverse events occurred in 17.4% (4/23) of patients. No unexpected adverse events or deaths were observed. Conclusions: Given the favorable tolerability and encouraging cCR rate, nCRT plus sintilimab could be a feasible and safe option for patients with pMMR/MSS, ultra-low rectal cancer who have a strong desire to preserve the anus. Based on these results, a prospective, randomized, controlled, multicenter, phase III study is currently in progress (NCT05215379). Clinical trial information: ChiCTR2100042785.

Does a long interval between neoadjuvant chemoradiotherapy and surgery benefit the clinical outcomes of locally advanced rectal cancer? A systematic review and meta analyses.

The study aims to systematically evaluate the clinical efficacy after 8weeks (long interval, LI) between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer. The PubMed database, EMBASE database, and the Cochrane Library (deadline: September 25, 2021) were searched to select clinical studies that compared two intervals between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer: after 8weeks (long interval, LI) and within 8weeks (short interval, SI). The included studies were screened and evaluated according to the inclusion and exclusion criteria, and meta-analysis was performed by RevMan 5.3 software. Eighteen studies were included, with 9070 cases in the LI group and 14,207 cases in the SI group. The analysis results showed that the pathologic complete response (PCR) rate in the LI group was higher than that in the SI group (P < 0.00001). There was no significant difference in the R0 resection rate (P = 0.85), anal preservation rate (P = 0.89), morbidity rate (P = 0.60), anastomotic leakage rate (P = 0.06), operation time (P = 0.58), local recurrence rate (P = 0.56), distant metastasis rate (P = 0.32), or overall survival (OS) rate (P = 0.17) between the two groups. A longer interval between neoadjuvant chemoradiotherapy and surgery can improve the PCR rate; however, it has no significant impact on the clinical efficacy or long-term prognosis. Due to some limitations in the number and quality of the studies, these findings still need to be further verified by multicenter, large-sample high-quality RCTs in the future.

The efficacy and safety of different radiotherapy doses in neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

This study aimed to evaluate efficacy and adverse effects of different radiotherapy (RT) doses in neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Fifty-nine patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy in hospital between January 2015 and May 2017 were enrolled in retrospective analysis. The patients were divided into the 56-Gy group and the 50-Gy group. The concurrent chemotherapy regimen was based on capecitabine. All patients received one cycle of oxaliplatin combined with capecitabine induction chemotherapy. All patients completed neoadjuvant chemoradiotherapy and received radical surgery. Of the patients in this study, 29 patients and 30 patients received a radiation dose of 56- and 50-Gy, respectively. All clinical characteristics were matched between the two groups. All patients received surgery 6 to 8 weeks after completing RT. The therapeutical effective rate in the 56-Gy group was 93.10% (27/29), compared with 66.67% in the 50-Gy group (20/30); the difference between the two groups was statistically significant (χ2=6.36, P=0.01). The pathological complete remission (pCR) rate in the 56-Gy group (37.93%, 11/29) was statistically significantly higher than that in the 50-Gy group (13.33%, 4/30) (χ2=4.71, P=0.030). The anal preservation rate in the 56-Gy group (65.5%, 19/29) was statistically significantly higher than that in the 50-Gy group (33.33%, 10/30) (χ2=6.11, P=0.01). The 56-Gy group had a local recurrence rate of 0% (0/29) and a distant metastasis rate of 10.34% (3/29), while the 50-Gy group had a local recurrence rate of 6.67% (2/30) and a distant metastasis rate of 16.67% (5/30); no significant difference existed between the two groups (χ2=2.00, 0.50, P=0.16, 0.48). The incidence of adverse reactions (gastrointestinal reactions, bone marrow suppression, and perianal skin reactions) in the 56-Gy group was not significantly different from that in the 50-Gy group (P>0.05). Increasing the radiation dose can significantly improve the anal preservation and pCR rates of patients with locally advanced rectal cancer, thus improving their life quality. Moreover, it does not increase the rates of recurrence or adverse reactions. Our findings have certain clinical significance, but further prospective study is needed.

CTSE Overexpression Is an Adverse Prognostic Factor for Survival among Rectal Cancer Patients Receiving CCRT.

The introduction of preoperative concurrent chemoradiotherapy (CCRT) increases the rate of anal preservation and allows tumor downstaging for clinical stage T3/T4 or node-positive rectal cancer patients. However, there is no precise predictive tool to verify the presence of residual tumor apart from surgical resection. The gastrointestinal (GI) tract not only digests nutrients but also coordinates immune responses. As the outermost layer of the GI tract, mucus plays a key role in mediating the interaction between the digestive and immune systems, and aberrant mucus mesh formation may cause chemoresistance by impeding drug delivery. However, the correlations among digestion-related genes, mucin synthesis, and chemoresistance remain poorly understood. In the present study, we evaluated genes related to digestion (GO: 0007586) and identified cathepsin E (CTSE), which is involved in immune regulation, as the most significantly upregulated gene associated with CCRT resistance in rectal cancer in a public transcriptome dataset (GSE35452). We recovered 172 records of rectal cancer patients receiving CCRT followed by surgical resection from our biobank and evaluated the expression level of CTSE using immunohistochemistry. The results revealed that tumors with CTSE overexpression were significantly correlated with pre-CCRT and post-CCRT positive nodal status (both p < 0.001), advanced pre-CCRT and post-CCRT tumor status (p < 0.001 and p = 0.002), perineural invasion (p = 0.023), vascular invasion (p < 0.001), and a lesser degree of tumor regression (p = 0.003). At the univariate level, CTSE overexpression was an adverse prognostic factor for all three endpoints: disease-specific survival (DSS), metastasis-free survival (MeFS) (both p < 0.0001), and local recurrence-free survival (LRFS) (p = 0.0001). At the multivariate level, CTSE overexpression remained an independent prognostic factor for poor DSS, MeFS (both p = 0.005), and LRFS (p = 0.019). Through bioinformatics analysis, we speculated that CTSE overexpression may confer CCRT resistance by forming a defensive mucous barrier. Taken together, these results suggest that CTSE overexpression is related to CCRT resistance and inferior survival in rectal cancer patients, highlighting the potential predictive and prognostic value of CTSE expression.

Radical resection versus local excision for low rectal gastrointestinal stromal tumor: A multicenter propensity score-matched analysis

BackgroundThe surgical approaches and resection extent for rectal gastrointestinal stromal tumors (GISTs) are controversial due to the low incidence of this disease. A multicenter retrospective cohort study was conducted to compare the postoperative and oncologic outcomes of local excision (LE) and radical resection (RR) in patients with low rectal GIST. Patients and methodsThe medical records of rectal GIST patients from 11 large-scale medical centers in China (January 2000-December 2019) were reviewed. All patients were divided into either the LE group or the RR group. Propensity score matching (PSM) was conducted to reduce confounders. ResultsA total of 280 patients with low rectal GIST were enrolled. After PSM, 144 patients were included (72 in each group). The LE group showed a higher anal preservation rate (100.0% vs. 76.4%, P < 0.001), shorter operation time (77.1 ± 68.4 min vs. 159.1 ± 83.6 min, P < 0.001), fewer complications (8.3% vs. 22.2%, P = 0.021) and shorter postoperative hospital stay (4.9 ± 4.1 d vs. 10.7 ± 8.1 d, P < 0.001) than the RR group. There was no significant difference in recurrence-free survival (RFS) between the RR and LE groups among patients with tumors ≤2 cm (P = 0.220), and the RR group had a superior RFS than the LE group in patients with tumors >2 cm (P = 0.046). ConclusionsLE resulted in improved postoperative outcomes and comparable oncological safety with a low rectal GIST of ≤2 cm. However, for patients with a low rectal GIST of >2 cm, RR might be a more appropriate option with better RFS.

Safety and efficacy of endoscopic submucosal dissection for metachronous early cancer or precancerous lesions emerging at the anastomotic site after curative surgical resection of colorectal cancer.

BackgroundThe incidence of metachronous early cancer or precancerous lesions (MECPL) emerging at the anastomotic site (AS) after curative surgical resection of colorectal cancer (CRC) is so low that few study have been conducted to explore the clinical characteristics, diagnosis and treatment of these lesions. Endoscopic submucosal dissection (ESD) is technically difficult for these lesions because of the presence of severe fibrosis and AS. The aim of this study was to explore the safety and efficacy of ESD for MECPL emerging at the AS after curative surgical resection of CRC.MethodsThe data used in the analysis were retrospectively collected from CICAMS in Beijing China between January 2013 and May 2019 and from all the patients who underwent ESD for MECPL emerging at the AS after curative surgical resection of CRC. The rates of en bloc resection (ER), complete resection (CR), curative resection (CuR) and incidence of complications were analyzed by SPSS software.ResultsA total of 11 patients were included. The rates of ER, CR and CuR were 63.6%, 54.5% and 54.5%, respectively. No additional surgery was performed, and no recurrences were found. Bleeding occurred in only one case and there was no perforation after the operation.ConclusionsOverall, ESD is safe and effective in the treatment of MECPL emerging at the AS after curative surgical resection of CRC. Especially for patients with anastomotic recurrence close to anal margin, this method can avoid the risks of reoperation and improve the rate of anal preservation.

544P - Feasibility of robot-assisted surgery in elderly patients with rectal cancer

BackgroundAlthough surgical resection is the main treatment for rectal cancer, the optimal surgical protocol for elderly patients with rectal cancer remains controversial. Robot-assisted surgery has the following advantages: smaller wounds, less blood loss, quicker recovery, early recovery, and high rate of anal preservation. This study evaluated the feasibility of robot-assisted surgery in elderly patients with rectal cancer. MethodsThis retrospective study enrolled 125 patients aged 28–93 years diagnosed with stage I–III rectal cancer who underwent robot-assisted surgery between May 2013 and April 2018 in a single institution. ResultsIn total, 125 patients with rectal cancer, including 100 nonelderly (aged <70 years) and 25 elderly (aged ≥70 years) patients, who underwent robot-assisted surgery were recruited. Between the patient groups, the incidence of overall postoperative complications and postoperative length of hospital stay did not differ significantly (p=0.930 and 0.095, respectively). No surgical related deaths were noted. The disease-free and overall survival did not differ significantly between the 2 groups (p=0.610 and 0.298, respectively). ConclusionsRobot-assisted surgery for rectal cancer is an appropriate approach that is well tolerated in elderly patients, with similar results as for the non-elderly patients. Oncological outcomes, including postoperative complications and survival, did not depend on patient age. Thus, in elderly patients, robot-assisted surgery is a safe and feasible surgical modality for treating operable rectal cancer and leads to age-independent postoperative outcomes. Legal entity responsible for the studyWei-Chih Su. FundingKaohsiung Medical University Hospital. DisclosureAll authors have declared no conflicts of interest.

87O - mFOLFOXIRI versus mFOLFOX6 as neoadjuvant chemotherapy in locally advanced rectal cancer: A propensity score analysis from two prospective trials

Background: Neoadjuvant chemoradiotherapy (CRT) is the standard of treatment for locally advanced rectal cancer, but it delays administration of systemic chemotherapy, leading to high incidence of distant metastases. To enhance systemic chemotherapy and avoid the damage of radiation, full dose of neoadjuvant chemotherapy regimens with mFOLFOXIRI or mFOLFOX6 were both under investigation. Here, we aimed to compare the efficacy of preoperative chemotherapy with mFOLFOXIRI versus mFOLFOX6 in locally advanced rectal cancer. Methods: Prospectively maintained databases of patients from two clinical trials (NCT01211210 and NCT02217020) underwent preoperative treatment for locally advanced rectal cancer in a single center were included. Those had received mFOLFOXIRI or mFOLFOX6 chemotherapy alone preoperatively was selected for this study, including 90 patients with mFOLFOXIRI and 119 patients with mFOLFOX6. All patients had undergone total mesorectal excision. A comparative analysis was performed after the implementation of propensity score matching on the 2 main cohorts (mFOLFOXIRI and mFOLFOX6). Results: A total of 209 patients were enrolled in the study. After propensity score matching, 180 patients were selected. 90 patients were comparable in the two groups. Higher pathologic complete response rate was observed in mFOLFOXIRI group than that of mFOLFOX6 group (16.7% vs. 5.6%, p = 0.03). However, the tumor downstaging rate was comparable in this two group (41.1% vs. 37.8%, P = 0.76). The anal preservation rate was similar between the two groups (87.8% vs. 89.2%). But higher incidence of grade 3/4neutropenia (42.2% vs. 10%, P < 0.001) was shown in mFOLFOXIRI alone group than that of mFOLFOX6 group. Conclusions: Preoperative mFOLFOXIRI alone showed higher pCR rate than that of mFOLFOX6. The tumor downstaging rate was comparable between the two regimens. But the adverse events were more common in mFOLFOXIRI group. The intensive regimen might only fit for some highly selected patients. Whether the intensive regimen would improve the survival is unknown. Further follow-up is needed. Clinical trial identification: NCT01211210 and NCT02217020. Legal entity responsible for the study: Yanhong Deng. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Short- and Long-term Outcomes of Laparoscopic Total Mesenteric Excision for Neuroendocrine Tumors of the Rectum.

To our knowledge, no studies to date have assessed the short- and long-term outcomes of laparoscopic total mesenteric excision in patients with neuroendocrine tumors of the rectum. The purpose of this study was to investigate the short- and long-term outcomes of patients who underwent laparoscopic rectal resection plus total mesenteric excision for rectal neuroendocrine tumors at our institution. This was a single center, retrospective study. The study was conducted at a tertiary care facility. Eight-two patients with neuroendocrine tumors who underwent rectal resection with total mesenteric excision, 77 laparoscopically, between June 2005 and August 2015 were included. Laparoscopic rectal resection and total mesenteric excision were the study interventions. Demographic characteristics and surgical and postoperative outcomes were measured. Median tumor size was 8.8 mm (range, 3.0-35.0 mm); 63.6% of tumors were located in the lower rectum, with the median distance from the tumor to the anal verge being 50.0 mm (range, 20.0-130.0 mm). Anal preservation was achieved in all of the patients. Anastomotic leakage occurred in 5 patients (6.5%), but there were no deaths. Seventy-one patients (92.2%) had tumor invasion confined to the submucosa. Lymph node metastasis was present in 29 patients (37.7%), including 26 (33.8%) with perirectal and 5 (6.5%) with lateral lymph node metastasis. The median follow-up period in 59 patients was 42 months (range, 11-113 months), and the 3-year overall survival rate was 97.8%. The study was limited by its single-center, retrospective analysis. Laparoscopic rectal resection with total mesenteric excision is safe in patients with rectal neuroendocrine tumors, with good short- and long-term outcomes. Because rectal neuroendocrine tumors are smaller and show superficial invasion, the rate of anal preservation may be high.

Comparison of safety and rate of postoperative complications between laparoscopic and open radical resection for mid or low rectal cancer following neoadjuvant chemoradiotherapy

Objective To investigate the safety and rate of postoperative complications between laparoscopic and open radical resection for mid or low rectal cancer following neoadjuvant chemoradiotherapy. Methods 112 patients with middle and low rectal cancer admitted to our department were randomly divided into observation group and control group, with 56 cases in each group. All patients were treated with neoadjuvant chemoradiotherapy. The patients in the observation group were given laparoscopic surgery (LS), and those in the control group received traditional open surgery (OS). The tumor treatment conditions (the distal and proximal cut-off lengths of tumor resection specimens, the positive rate of circumferential and distal resection margins, the rate of anal preservation and the short-term complications after surgery) of the two groups were observed and compared. Results The rate of anal preservation and the distal cut-off length in the LS group were significantly increased as compared with those in the OS group (P<0.05). The overall incidence of postoperative complications in LS group and OS group was 5.35% (3/56) and 33.92% (19/56) respectively, with the difference being statistically significant (P<0.01). Conclusion Compared to the patients with advanced rectal cancer which had received neoadjuvant chemoradiation therapy, LS is better than OS in the safety and effect. Key words: Laparoscopic surgery; Rectal cancer; Neoadjuvant chemoradiation

Outcomes of neoadjuvant chemoradiotherapy in Japanese locally advanced rectal carcinoma patients.

BackgroundWe investigated the efficacy and prognosis of neoadjuvant chemoradiotherapy (NACRT) for Japanese locally advanced rectal carcinoma patients.MethodsFifty-seven patients diagnosed with cT3-4 or any cT/cN+ disease using enhanced computed tomography or magnetic resonance imaging from 2002 to 2014 were enrolled. The male/female ratio was 42/15, and the median age was 67 years. Ra/Rb/Rb-P/P was expressed by 6/35/14/2 patients. Histological tumor types were tub1/tub2/por/muc in 22/30/4/1 patients. For NACRT, radiotherapy doses were 40–50.4 Gy chemotherapy consisted of 5′-DFUR, capecitabine, or S1.ResultsAll 57 patients received curative surgical treatment. The anal preservation rate was 65.0 %. The ypStage of 0/I/II/IIIa/IIIb was 7/10/25/11/4 cases. The histological antitumor effect (HATE) was ≥grade (G) 2 and G3 in 31 (54.4 %) and 7 (12.3 %) cases, respectively. Postoperative complications occurred in 17 patients and exceeded GIII (Clavien–Dindo classification) in four patients. Recurrence was observed in 19 patients; the primary local recurrence rate was 5.3 %. The 3-year relapse-free survival (RFS) and overall survival (OS) rates were 64.8 and 95.5 %, respectively; the 5-year RFS and OS rates were 60.2 and 61.0 %, respectively. In multivariate analysis, ypN+ was a high-risk factor for distant organ recurrence. As predictive factors regarding the efficacy of NACRT, a neutrophil concentration <70 % and a neutrophil/lymphocyte ratio <3.0 in peripheral blood prior to treatment indicated that NACRT would be significantly more effective.ConclusionsNACRT was effective in reducing local recurrence but did not suppress distant organ recurrence in Japanese locally advanced rectal carcinoma patients. A further investigation of an extension of the NACRT regimen is required.

Preoperative radiotherapy combined with simultaneous chemotherapy with capecitabine plus oxaliplatin versus surgery alone: A single-centered, phase II study in patients with mid/low rectal cancer.

609 Background: Though total mesorectal excision (TME) has proved to effectively decrease local recurrence rate of mid/low rectal cancer, the efficacy of preoperative radiotherapy in Asian patients remains unclear. The present study aimed to compare the efficacy of TME alone versus TME after preoperative radiotherapy and simultaneous chemotherapy with capecitabine plus oxaliplatin in Chinese patients with stage II and III mid/low rectal adenocarcinoma. Methods: Patients (n=192) aged between 18 and 70 years enrolled from March 23, 2008 to August 2, 2012 were randomly divided into two groups. Group A (n=97) received preoperative radiotherapy and simultaneous chemotherapy [46-50 GY/23-25 with oxaliplatin 100 mg/m2 (D1) and capecitabine 1,000 mg/m2 (bid, D1-15), repeated since D22], which was followed by TME; while patients in group B (n=95) underwent TME alone. While disease free survival (DFS) was the primary endpoint; the following were evaluated as secondary endpoints: pathological response rate, pathologic complete response (PCR) rate, anal preservation rate, local recurrence rate, distant metastasis rate, acute toxic effects, and late toxic effects. Results: Excluding the drop outs, 90 and 94 patients were analyzed in group A and B, respectively. The median follow-up time was 29 (range: 0 to 59) months. PCR was achieved for 32 patients (35.6%). The median survival time and overall survival (OS) rate in group A were 24 months and 92.5% (95% CI: 88.3-96.7), respectively; while the same were 34 months and 88.7% (95% CI: 84.8-92.6) in group B. The median DFS time was 22 and 31 months in group A and B, respectively; and the overall DFS was 86.1% (95% CI: 81.6-90.6%) and 80.6% (95% CI: 74.8-85.4%) in both groups. No significant differences were observed between groups in OS rate (p=0.323), overall DFS, (p=0.612), and anal preservation rate (p=0.849). Conclusions: Preoperative radiotherapy combined with chemotherapy of capecitabine plus oxaliplatin could result in higher PCR rate. However, studies with long follow up and large sample are recommended to demonstrate the efficacy of this treatment strategy over TME alone. Clinical trial information: ChiCTR-TRC-00000122.

Preoperative chemoradiotherapy as neoadjuvant therapy for 35 patients with locally advanced lower rectal carcinoma

To explore the effect of combined preoperative chemotherapy with radiotherapy on locally advanced lower rectal carcinoma. Thirty- five patients with locally advanced lower rectal carcinoma were received a new regimen of combined preoperative chemotherapy with radiotherapy. Routine fr action of radiation was given with total dose of 46 Gy,2 Gy per fraction,five ti mes a week. Patients received oxaliplatin 130 mg/m(2) (infusion) on day 1, plus leu novorin 200 mg/m(2) and 5- FU 500 mg/m(2)(intravenous bolus) from day 1 to day 3 eve ry 3 weeks for total two cycles before irradiation. Operation was performed 4 to 6 weeks later after neoadjuvant therapy. After neoadjuvant therapy,all patients underwent surgical resection with complete pathologic response in 7 patients,average tumor size decrease of in 34.4%, tumor stage decrease in 65.7% o f patients and nodal- negative change rate of 55.6%. Radical resection was per formed in 34 patients,in whom 18 patients received abdominoperineal resection(AP R) and 16 patients received sphincter- preserving surgery with 45.7% of anal preservation rate. One patient received palliative resection. No local recurrence occurred in all patients who received radical resection,but two cases had liver metastasis. Combined preoperative chemotherapy with radiotherapy is a better neoadjuvant therapy for lower advanced rectal cancer,which can decrease tumor stage,improve resectability and anal sphincter preservation rate,therefore ,this new neoadjuvant therapy with tolerable toxicity will has a promising application in the clinical setting.