• Advanced rectal cancer
• Complete pathologic response
• Complication
• Interval time
• Neoadjuvant therapy
• Surgery

• Humans
• Prospective Studies
• Rectal Neoplasms/pathology
• Rectum/surgery
• Disease-Free Survival
• Chemoradiotherapy
• Neoadjuvant Therapy
• Neoplasm Staging

• Interval
• Locally advanced rectal cancer
• Neoadjuvant chemoradiotherapy
• Waiting period

• Male
• Female
• Humans
• Middle Aged
• Neoadjuvant Therapy/methods
• Retrospective Studies
• Treatment Outcome
• Rectum
• Rectal Neoplasms/surgery
• Postoperative Complications/epidemiology
• Postoperative Complications/pathology
• Chemoradiotherapy
• Neoplasm Staging
• Neoplasm Recurrence, Local/pathology

• clinical trials
• neoadjuvant chemotherapy
• rectal cancer
• surgical oncology

• 5010-2018-04 5010 Clinical Research Foundation of Sun Yat-sen University

• Machine learning
• Neoadjuvant therapy
• Pathological complete response
• Radiomics
• Rectal cancer

• LTGY23H180017 Zhejiang Provincial Natural Science Foundation of China
• GF21H180051 Zhejiang Province Public Welfare Technology Application Research Project

• Delayed surgery
• Esophageal cancer
• Neoadjuvant chemoradiation

• pCR
• predictive model
• preoperative chemo-radiotherapy
• rectal cancer
• ultra-low rectal cancer

• Humans
• Carcinoembryonic Antigen
• Treatment Outcome
• Retrospective Studies
• Rectal Neoplasms/therapy
• Rectal Neoplasms/pathology
• Biomarkers, Tumor
• Chemoradiotherapy, Adjuvant
• Chemoradiotherapy
• Neoadjuvant Therapy
• Neoplasms, Second Primary
• Adenocarcinoma/therapy
• Adenocarcinoma/pathology

• Changhai Hospital Clinical Investigation Program
• Shenkang Center Innovation Research Program
• Youth Starup Fund

• Gastric cancer surgery
• Neoadjuvant chemotherapy
• Overall survival

• Aged
• Chemoradiotherapy, Adjuvant
• Disease-Free Survival
• Female
• Humans
• Italy
• Male
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Staging
• Rectal Neoplasms/mortality
• Rectal Neoplasms/pathology
• Rectal Neoplasms/surgery
• Rectal Neoplasms/therapy
• Retrospective Studies
• Time-to-Treatment

• colorectal
• neoadjuvant
• radiotherapy
• time interval

• Locally advanced rectal cancer (LARC)
• Meta-analysis
• Pathologic complete response (pCR)
• Total neoadjuvant therapy (TNT)

• Chemoradiotherapy
• Disease-Free Survival
• Humans
• Neoadjuvant Therapy
• Rectal Neoplasms/drug therapy
• Rectal Neoplasms/radiotherapy
• Rectum
• Treatment Outcome

In locally advanced rectal cancer, longer delay to surgery after neoadjuvant radiotherapy increases the likelihood of histopathological tumour response. Chronomodulated radiotherapy in rectal cancer has recently been reported as a factor increasing tumour response to neoadjuvant treatment in patients having earlier surgery, with patients receiving a larger proportion of afternoon treatments showing improved response. This paper aims to replicate this work by exploring the impact of these two temporal factors, independently and in combination, on histopathological tumour response in rectal cancer patients.

A retrospective review of all patients with rectal adenocarcinoma who received long course (≥24 fractions) neoadjuvant radiotherapy with or without chemotherapy at a tertiary referral centre was conducted. Delay to surgery and radiotherapy treatment time were correlated to clinicopathologic characteristics with a particular focus on tumour regression grade. A review of the literature and meta-analysis were also conducted to ascertain the impact of time to surgery from preoperative radiotherapy on tumour regression.

From a cohort of 367 patients, 197 patients met the inclusion criteria. Complete pathologic response (AJCC regression grade 0) was seen in 46 (23%) patients with a further 44 patients (22%) having at most small groups of residual cells (AJCC regression grade 1). Median time to surgery was 63 days, and no statistically significant difference was seen in tumour regression between patients having early or late surgery. There was a non-significant trend towards a larger proportion of morning treatments in patients with grade 0 or 1 regression (p = 0.077). There was no difference in tumour regression when composite groups of the two temporal variables were analysed. Visualisation of data from 39 reviewed papers (describing 27379 patients) demonstrated a plateau of response to neoadjuvant radiotherapy after approximately 60 days, and a meta-analysis found improved complete pathologic response in patients having later surgery.

There was no observed benefit of chronomodulated radiotherapy in our cohort of rectal cancer patients. Review of the literature and meta-analysis confirms the benefit of delayed surgery, with a plateau in complete response rates at approximately 60-days between completion of radiotherapy and surgery. In our cohort, time to surgery for the majority of our patients lay along this plateau and this may be a more dominant factor in determining response to neoadjuvant therapy, obscuring any effects of chronomodulation on tumour response. We would recommend surgery be performed between 8 and 11 weeks after completion of neoadjuvant radiotherapy in patients with locally advanced rectal cancer.

• Adult
• Aged
• Aged, 80 and over
• Female
• Humans
• Logistic Models
• Male
• Middle Aged
• Neoadjuvant Therapy/adverse effects
• Neoplasm Staging
• Proportional Hazards Models
• Rectal Neoplasms/pathology
• Rectal Neoplasms/radiotherapy
• Rectal Neoplasms/surgery
• Time Factors

• Apoptosis
• CRT
• Pathological response
• Tumor regression grade

An accurate assessment of potential pathologic complete response(pCR) following neoadjuvant chemoradiotherapy(NCRT) is important for the appropriate treatment of rectal cancer. However, the factors that predict the response to neoadjuvant chemoradiotherapy have not been well defined. Therefore, this study analyzed the predictive factors on the development of pCR after neoadjuvant chemoradiation for rectal cancer.

From January 2008 to January 2018, a total of 432 consecutive patients from a single institution patients who underwent a long-course neoadjuvant chemoradiotherapy were reviewed in this study. The clinicopathological features were analyzed to identify predictive factors for pathologic complete response in rectal cancer after neoadjuvant chemoradiation.

The rate of pathologic complete response in rectal cancer after neoadjuvant chemoradiation was 20.8%, patients were divided into the pCR and non-pCR groups. The two groups were well balanced in terms of age, gender, body mass index, ASA score, tumor stage, tumor differentiation, tumor location, surgical procedure, chemotherapy regimen and radiation dose. The multivariate analysis revealed that a pretreatment carcinoembryonic antigen (CEA) level of ≤5 ng/mL and an interval of ≥8 weeks between the completion of chemoradiation and surgical resection were independent risk factors of an increased rate of pCR.

Pretreatment carcinoembryonic antigen (CEA) level of ≤5 ng/mL and an interval of ≥8 weeks between the completion of chemoradiation and surgical resection are predictive factors for pathologic complete response in rectal cancer after neoadjuvant chemoradiation. Using these predictive factors, we can predict the prognosis of patients and develop adaptive treatment strategies. A wait-and-see policy might be possible in highly selective cases.

• CEA
• Interval
• Pathologic complete response
• neoadjuvant chemoradiotherapy
• rectal cancer

• Locally advanced rectal cancer
• Neoadjuvant chemoradiotherapy
• Postoperative complications
• Recurrence-free survival
• Time interval

• Chemoradiotherapy
• China/epidemiology
• Disease-Free Survival
• Humans
• Neoadjuvant Therapy
• Neoplasm Recurrence, Local/pathology
• Neoplasm Staging
• Rectal Neoplasms/pathology
• Retrospective Studies
• Treatment Outcome

• (No. 2012-649) National Clinical Key Specialty Construction Project (General Surgery) of China
• (81902378) National Natural Science Foundation of China
• (2017-1-39) Young Scientist Foundation of Fujian Provincial Commission of Health and Family Planning
• (2017Y9038, 2017Y9103, 2019Y9101) Joint Funds for the Innovation of Science and Technology, Fujian province
• (2020J011030) Natural Science Foundation of Fujian Province
• (B20062DS) Medical Science Research Foundation of Beijing Medical and Health Foundation

• Gastric cancer
• NAT-surgery interval time
• lesion assessment
• neoadjuvant therapy
• regimens

• Neoadjuvant radio-chemiotherapy
• Rectal cancer
• Surgical interval
• pCR

• Adolescent
• Chemoradiotherapy
• Humans
• Neoadjuvant Therapy
• Neoplasm Recurrence, Local/pathology
• Neoplasm Staging
• Randomized Controlled Trials as Topic
• Rectal Neoplasms/pathology
• Treatment Outcome

• Advanced rectal cancer
• Complication
• Disease-free survival
• Interval time
• Neoadjuvant therapy
• Pathologic complete response
• Sphincter preservation
• Surgery

• Chemoradiotherapy/adverse effects
• China
• Disease-Free Survival
• Humans
• Neoadjuvant Therapy/adverse effects
• Neoplasm Staging
• Rectal Neoplasms/pathology
• Rectal Neoplasms/therapy
• Retrospective Studies
• Treatment Outcome

• Neoadjuvant radiation therapy
• Outcomes
• Sarcoma

• Interval
• Long course
• Radiotherapy
• Rectal cancer

• Aged
• Aged, 80 and over
• Chemoradiotherapy, Adjuvant
• Combined Modality Therapy
• Female
• Humans
• Male
• Middle Aged
• Multivariate Analysis
• Neoadjuvant Therapy
• Rectal Neoplasms/pathology
• Rectal Neoplasms/surgery
• Rectal Neoplasms/therapy
• Remission Induction
• Safety
• Time Factors
• Time-to-Treatment
• Treatment Outcome

The purpose of this study is to evaluate the short-term clinical and oncological outcome of prolonging operation interval to 11 weeks after the end of radiotherapy for locally advanced middle and low rectal cancer.

A total of 123 patients with stage II/III (cT3/T4 or N+) low and middle rectal cancer who had undergone operation after neoadjuvant chemoradiotherapy were selected. According to the interval time between the last radiotherapy and operation, they were assigned to a short-interval group (SG, <11 weeks, n=66) and long-interval group (LG, ≥11 weeks, n=57). The relations among interval time and short-term clinical outcome and oncological outcome were analyzed.

The analysis found that basic information, clinical characteristics, and preoperative treatment between the two groups had no significant difference. There were no differences in operation time, estimated intraoperative blood loss and postoperative complications. The rate of sphincter preservation in the low and middle rectum was 66.7% in the short-interval group and 59.7% in the long-interval group (P=0.42). The incidence of anastomotic leak in the long-interval group was higher than that in the short-interval group (P=0.08). There was no significant difference in the recovery time of intestinal function and median duration of hospitalization between the two groups. The pathological complete remission rate was 17.07%. Multivariate analysis showed interval time had no influence on pathological complete remission. There was no significant difference in 3-year overall survival and 3-year disease-free survival between the two groups. The risk of recurrence and metastasis in patients with positive lymph nodes was higher than those with negative lymph nodes (P<0.05), HR=4.812 (95% CI 2.4–9.648).

Prolonging the interval time of operation to 11 weeks after neoadjuvant chemoradiotherapy for middle and low rectal cancer does not improve the pathologic complete remission, morbidity, and mortality. There was no significant effect on oncologic outcome after prolonging the operation interval. Therefore, it is safe to prolong the interval of operation to 11 weeks.

• clinical outcome
• neoadjuvant chemoradiotherapy
• oncological outcome
• pathological complete remission
• rectal cancer

• IMRT
• preoperative radiotherapy
• rectal cancer
• surgery
• three-dimensional conformal radiotherapy

• National Natural Science Foundation of China

Preoperative chemoradiotherapy is the recommended standard of care for patients with local advanced rectal cancer. However, it remains unclear, whether a prolonged time interval to surgery results in an increased perioperative morbidity, reduced TME quality or better pathological response. Aim of this study was to determine the time interval for best pathological response and perioperative outcome compared to current recommended interval of 6 to 8 weeks.

This is a retrospective analysis of the German StuDoQ|Rectalcarcinoma registry. Patients were grouped for the time intervals of “less than 6 weeks”, “6 to 8 weeks”, “8 to 10 weeks” and “more than 10 weeks”. Primary endpoint was pathological response, secondary endpoint TME quality and complications according to Clavien-Dindo classification.

Due to our inclusion criteria (preoperative chemoradiation, surgery in curative intention, M0), 1.809 of 9.560 patients were suitable for analysis. We observed a trend for increased rates of pathological complete response (pCR: ypT0ypN0) and pathological good response (pGR: ypT0-1ypN0) for groups with a prolonged time interval which was not significant. Ultimately, it led to a steady state of pCR (16.5%) and pGR (22.6%) in “8 to 10” and “more than 10” weeks. We were not able to observe any differences between the subgroups in perioperative morbidity, proportion of rectal extirpation (for cancer of the lower third) or difference in TME quality.

A prolonged time interval between neoadjuvant chemoradiation can be performed, as the rate of pCR seems to be increased without influencing perioperative morbidity.

• Radiochemotherapy
• Rectal cancer
• Surgery
• Time interval

• Colorectal cancer
• Gastric cancer
• Pancreatic cancer
• Time to surgery

Response to preoperative chemoradiation (PRTCT) for rectal cancer predicts the long-term outcome.

Tertiary care hospital.

The aim is to study the factors affecting the response to chemoradiation.

Retrospective.

Twenty-three patients of rectal cancer undergoing PRTCT followed by surgery and adjuvant chemotherapy were followed up for 20–56 months. Postoperative response, tumor downstaging and nodal downstaging were correlated with the disease status.

Tumor downstaging was seen in 11 (50%) and nodal downstaging in 12 (63.15%) patients. Nodal downstaging was statistically significant with P = 0.004. Pathological complete response (PCR) was seen in one patient and partial response (PR) in 17 patients. Thirteen (72.2% of patients) were alive and disease free and the negative nodal status correlated with long-term control with P = 0.04.

Most patients of rectal cancer show PR to PRTCT, and the benefit is more for node-positive patients. Nodal PCR is associated with a higher chance of long-term disease control.

• Downstaging
• long-term outcome
• preoperative radiation
• rectal cancer

• Magnetic resonance imaging
• Medical audit
• Rectal cancer
• Template-reporting

The time interval between CRT and surgery in rectal cancer patients is still the subject of debate. The aim of this study was to first evaluate the nationwide use of restaging magnetic resonance imaging (MRI) and its impact on timing of surgery, and, second, to evaluate the impact of timing of surgery after chemoradiotherapy (CRT) on short- and long-term outcomes.

Patients were selected from a collaborative rectal cancer research project including 71 Dutch centres, and were subdivided into two groups according to time interval from the start of preoperative CRT to surgery (< 14 and ≥ 14 weeks).

From 2095 registered patients, 475 patients received preoperative CRT. MRI restaging was performed in 79.4% of patients, with a median CRT–MRI interval of 10 weeks (interquartile range [IQR] 8–11) and a median MRI–surgery interval of 4 weeks (IQR 2–5). The CRT–surgery interval groups consisted of 224 (< 14 weeks) and 251 patients (≥ 14 weeks), and the long-interval group included a higher proportion of cT4 stage and multivisceral resection patients. Pathological complete response rate (n = 34 [15.2%] vs. n = 47 [18.7%], p = 0.305) and CRM involvement (9.7% vs. 15.9%, p = 0.145) did not significantly differ. Thirty-day surgical complications were similar (20.1% vs. 23.1%, p = 0.943), however no significant differences were found for local and distant recurrence rates, disease-free survival, and overall survival.

These real-life data, reflecting routine daily practice in The Netherlands, showed substantial variability in the use and timing of restaging MRI after preoperative CRT for rectal cancer, as well as time interval to surgery. Surgery before or after 14 weeks from the start of CRT resulted in similar short- and long-term outcomes.

The online version of this article (10.1245/s10434-018-07097-7) contains supplementary material, which is available to authorized users.

• clinical stage
• pathologic stage
• prognosis
• rectal cancer
• survival

• interval
• neoadjuvant chemoradiotherapy
• rectal cancer
• surgery
• survival

• Chemoradiotherapy
• Consolidation chemotherapy
• Disease free survival
• Pathologic complete response
• Rectal cancer

• Adenocarcinoma/mortality
• Adenocarcinoma/pathology
• Adenocarcinoma/therapy
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Chemoradiotherapy/methods
• Chemoradiotherapy/standards
• Chemotherapy, Adjuvant/methods
• Chemotherapy, Adjuvant/standards
• Consolidation Chemotherapy/methods
• Consolidation Chemotherapy/standards
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Neoadjuvant Therapy/methods
• Neoadjuvant Therapy/standards
• Neoplasm Staging
• Practice Guidelines as Topic
• Randomized Controlled Trials as Topic
• Rectal Neoplasms/mortality
• Rectal Neoplasms/pathology
• Rectal Neoplasms/therapy
• Rectum/pathology
• Rectum/surgery
• Republic of Korea
• Treatment Outcome
• Young Adult

• Preoperative chemotherapy
• Rectal Cancer

To evaluate whether the neoadjuvant chemotherapy (NACT)-surgery interval time significantly impacts the pathological complete response (pCR) rate and long-term survival.

One hundred and seventy-six patients with gastric cancer undergoing NACT and a planned gastrectomy at the Chinese PLA General Hospital were selected from January 2011 to January 2017. Univariate and multivariable analyses were used to investigate the impact of NACT-surgery interval time (< 4 wk, 4-6 wk, and > 6 wk) on pCR rate and overall survival (OS).

The NACT-surgery interval time and clinician T stage were independent predictors of pCR. The interval time > 6 wk was associated with a 74% higher odds of pCR as compared with an interval time of 4-6 wk (P = 0.044), while the odds ratio (OR) of clinical T₃vs clinical T₄ stage for pCR was 2.90 (95%CI: 1.04-8.01, P = 0.041). In Cox regression analysis of long-term survival, post-neoadjuvant therapy pathological N (ypN) stage significantly impacted OS (N₀vs N₃: HR = 0.16, 95%CI: 0.37-0.70, P = 0.015; N₁vs N₃: HR = 0.14, 95%CI: 0.02-0.81, P = 0.029) and disease-free survival (DFS) (N₀vs N₃: HR = 0.11, 95%CI: 0.24-0.52, P = 0.005; N₁vs N₃: HR = 0.17, 95%CI: 0.02-0.71, P = 0.020). The surgical procedure also had a positive impact on OS and DFS. The hazard ratio of distal gastrectomy vs total gastrectomy was 0.12 (95%CI: 0.33-0.42, P = 0.001) for OS, and 0.13 (95%CI: 0.36-0.44, P = 0.001) for DFS.

The NACT-surgery interval time is associated with pCR but has no impact on survival, and an interval time > 6 wk has a relatively high odds of pCR.

• Gastric cancer
• Timing of surgery
• Neoadjuvant chemotherapy

• Adult
• Aged
• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents/adverse effects
• Chemotherapy, Adjuvant
• Chi-Square Distribution
• China
• Disease Progression
• Disease-Free Survival
• Female
• Gastrectomy/adverse effects
• Gastrectomy/mortality
• Hospitals, General
• Humans
• Kaplan-Meier Estimate
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Neoadjuvant Therapy/adverse effects
• Neoadjuvant Therapy/mortality
• Neoplasm Staging
• Odds Ratio
• Proportional Hazards Models
• Retrospective Studies
• Risk Factors
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/mortality
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery
• Time Factors
• Time-to-Treatment
• Treatment Outcome
• Young Adult

Novel effective chemopreventive agents against cancer are required to improve current therapeutic rates. The aim of the present study was to investigate the anti-carcinogenesis effect of AntiGan, an extract obtained from the European conger eel, Conger conger, in vitro (human tumor cell lines) and in vivo (murine model of colitis) models. The potential apoptogenic activity after 24 h of incubation with 10, 25 and 50 µl/ml AntiGan was reported using growth inhibition and apoptosis activity assays. In vivo studies were performed in mice by inducing colitis with oral administration of 2% dextran sulphate sodium (DSS) for 5 weeks. Apoptosis was observed in HL-60, Hs 313.T, SW-480, Caco-2 and HT-29 cell lines. The highest level of growth inhibition was observed in Caco-2 (66, 75.8 and 88.1%), HT-29 (56, 73 and 87.6%) and SW-480 (38.5, 61.6, 78.6%) for AntiGan doses of 10, 25 and 50 µl/ml, respectively, compared to untreated cells, while the results of the expression of genes associated with apoptosis indicated a downregulation of B-cell lymphoma 2 (Bcl-2) in all cell lines studied. In vivo, morphopathological alterations in the colon were analyzed by immunohistochemical and staining methods. Tumoral markers, including β-catenin, cyclooxygenase 2 and Bcl-2 were expressed in cryptal cells of the dysplastic colonic mucosa, whereas the levels of interferon-γ expression were also increased when no treatment was applied. In the experimental murine model, the optimal concentration of AntiGan for an effective dose-response was 10% in diet. These results suggested that AntiGan displays a powerful anti-inflammatory effect in DSS-induced colitis, acting as a chemopreventive agent against colon carcinogenesis, most likely due to its apoptogenic peptides that contribute to the induction of apoptosis.

• biotherapy
• cancer
• chemoprevention
• cyto-protection
• inflammation

• Colorectal cancer
• Improvement of prognosis
• Neoadjuvant chemoradiotherapy
• Therapeutic management