Objective: Severe radiation-induced late rectal injury (sRLRI) directly affects the quality of life of patients with rectal cancer. Effective prediction of sRLRI before surgery may provide important information for the selection of surgical strategies and perioperative managements. The purpose of this study is to evaluate the feasibility of predicting sRLRI based on magnetic resonance imaging (MRI) features before and after radiotherapy for rectal cancer. Methods: This was a diagnostic study. Clinical and imaging data of 90 patients with rectal cancer receiving long-term radiotherapy from June 2013 to July 2018 in the Sixth Affiliated Hospital of Sun Yat-sen University were collected retrospectively. Case inclusion criteria: (1) rectal cancer was diagnosed by pathology and age of ≥ 18 years old; (2) patients received neoadjuvant chemoradiotherapy and anterior rectal resection; (3) follow up time ≥ 3 years; (4) patients had no history of other neoplasm. Exclusion criteria: (1) patients did not receive MRI examination in our hospital within 2 weeks before and/or 8 weeks after radiotherapy; (2) images were not good enough for evaluation; (3) medical records were incomplete; (4) patients had severe gastrointestinal diseases. According to the RTOG/EORTC classification criteria for radiation reactions, severe complications of grade 3-4 requiring surgical management were defined as sRLRI. T2WI and DWI images before and after radiotherapy were evaluated. The rectal wall thickness, bladder wall thickness, rectal sacral spacing and apparent diffusion coefficient (ADC) were measured. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the above indicators for sRLRI. Results: Among the 90 patients with rectal cancer, 34 (37.8%) developed sRLRI. Before radiotherapy, the median rectal wall thickness of sRLRI and non-sRLRI patients was 4.530 mm and 4.355 mm, respectively; the median bladder wall thickness was 3.962 mm and 3.868 mm, respectively; the median rectal sacral spacing was 15.557 mm and 12.433 mm, respectively; the median ADC value of rectal wall was 1.620 ×10(-3) mm(2)/s and 1.653 ×10(-3) mm(2)/s, respectively. There were no significant differences in above indicators between sRLRI and non-sRLRI patients (all P>0.05). After radiotherapy, compared with non-sRLRI patients, sRLRI patients had increased rectal wall thickness (median: 8.239 mm vs. 6.223 mm, Z=-3.512, P=0.001), rectal sacral spacing (median: 17.728 mm vs. 13.885 mm, Z=-2.247, P=0.025), and change of rectal wall thickness after radiotherapy (median: 98.106% vs. 49.584%, Z=-4.169, P<0.001). After radiotherapy, there were no significant differences in the bladder wall thickness and its change value, the ADC value of rectal wall and its change rate before and after radiotherapy between the two groups (all P>0.05). The area under the curve (AUC) of the change rates of rectal wall thickness after radiotherapy, rectal wall thickness and rectal sacral spacing after radiotherapy for predicting sRLRI was 0.763, 0.722 and 0.642, respectively, while the sensitivity was 85.3%, 70.6% and 76.5%, respectively, and the specificity was 64.3%, 71.4% and 57.1%, respectively. Conclusion: Based on MRI examinations, assessments of rectal wall thickness after radiotherapy, the change rate of rectal wall thickness after radiotherapy, and rectal sacral spacing after radiotherapy are helpful for evaluating the risk of sRLRI after radiotherapy for patients with rectal cancer.
Adolescent ; Chemoradiotherapy ; Diffusion Magnetic Resonance Imaging ; Humans ; Magnetic Resonance Imaging ; Neoadjuvant Therapy ; Quality of Life ; Rectal Neoplasms/radiotherapy* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To explore the efficacy of radiotherapy combined with surgery for locally advanced rectal mucinous adenocarcinoma. METHODS: Clinical data of patients with locally advanced rectal mucinous adenocarcinoma (T3-4 and/or N+) diagnosed by postoperative pathology from 1992 to 2013 were retrieved from the US Surveillance, Epidemiology, and End Results (SEER) database. Patients with local excision only, tumor biopsy or combined organ excision and incomplete follow-up information were excluded. All the enrolled patients were divided into three groups according to different treatments, including surgery alone (SA) group, preoperative radiotherapy combined with surgery (RT+S) group and surgery combined with postoperative radiotherapy (S+RT) group. The extracted data included basic data of patients and tumor, treatment status, and follow-up results. The χ² test was used to compare the count data. Kaplan-Meier method was used to draw the survival curve and calculate the survival rate. The survival was analyzed and compared by Log-rank test. The R language 2.8.1 was used to match the patients as 1:1 pairing through the propensity score matching (PSM). The matching variables included gender, age at diagnosis, year at diagnosis, ethnicity, degree of tissue differentiation, TNM stage, depth of invasion, making the baseline data of subgroups comparable. The Cox proportional hazard model was used for multivariate analysis of prognostic factors. RESULTS: A total of 2 149 patients with locally advanced rectal mucinous adenocarcinoma were enrolled in the study, including 1 255 males (58.4%) and 894 females (41.6%). There were 706 patients (32.9%) in the SA group, 772 patients (35.9%) in the RT+S group and 671 patients (31.2%) in the S+RT group. In SA, RT+S and S+RT groups, the median overall survival time was 39, 85, and 74 months respectively; the 5-year overall survival (OS) rate was 38.7%, 56.5%, and 55.2% respectively; the median cancer-specific survival (CSS) time was 86, 127, and 111 months respectively, and the 5-year CSS rate was 53.7%, 62.2% and 60.7% respectively. In comparison among the 3 groups, the 5-year OS rate and CSS rate in the SA group were significantly lower than those in the RT+S group and S+RT group (all P<0.001); the 5-year OS rate and CSS rate between RT+S group and S+RT group were not significantly different (P=0.166 and 0.392,respectively). After the baseline data of subgroups were corrected through PSM, the 5-year OS rate and CSS rate in the SA group (n=375) were significantly lower than those in the RT+S group (n=375)(OS:40.1% vs. 54.5%, P<0.001; CSS:54.3% vs. 63.3%, P=0.023). The 5-year OS rate and CSS rate in the SA group (n=403) were also lower than those in the S+RT group (n=403) (OS:37.4% vs. 54.7%,P<0.001;CSS:51.6% vs. 61.0%,P=0.031). The 5-year OS rate and CSS rate between RT+S group (n=363) and S+RT group (n=363) were not significantly different (OS:51.7% vs. 55.5%, P=0.789; CSS:57.7% vs. 60.5%, P=0.484). Cox multivariate analysis showed that radiotherapy (HR=0.845, 95%CI: 0.790 to 0.903, P=0.001) was an independent prognostic factor for OS of locally advanced rectal mucinous adenocarcinoma; radiotherapy (HR=0.907, 95% CI: 0.835 to 0.985, P=0.021) was also an independent prognostic factor affecting CSS in patients with locally advanced rectal mucinous adenocarcinoma. CONCLUSION As compared with surgery alone, surgery combined with preoperative or postoperative radiotherapy is beneficial to the long-term survival of patients with locally advanced rectal mucinous adenocarcinoma.
Adenocarcinoma, Mucinous ; pathology ; radiotherapy ; surgery ; therapy ; Female ; Humans ; Male ; Neoplasm Staging ; Proctectomy ; Prognosis ; Radiotherapy, Adjuvant ; Rectal Neoplasms ; pathology ; radiotherapy ; surgery ; therapy ; Retrospective Studies ; SEER Program ; Survival Analysis ; Treatment Outcome

PURPOSE: This study aimed to identify prognostic factors for locoregional recurrence (LRR) in pT3N0 rectal cancer patients who were treated with surgery alone and had negative resection margin including circumferential resection margin (CRM) for optimal indication of adjuvant radiotherapy. MATERIALS AND METHODS: We reviewed patients with pT3N0 rectal cancer who were treated via upfront surgery and had no other adjuvant treatment from January 2003 to December 2012. In total, 122 patients who had negative resection margin including negative CRM were included in the analysis. RESULTS: The median follow-up period after surgery was 60 months (range, 3 to 161 months). During this time, 6 patients (4.9%) experienced LRR at the anastomotic site (4 patients), and regional lymphatic area (2 patients). The estimated 5-year rates of overall survival, recurrence-free survival, and LRR-free survival were 96.7%, 84.6%, and 94.0%, respectively. Multivariate analysis showed that level of tumor ≤5 cm was a significant prognostic factor for LRR-free survival (LRRFS) (p = 0.04; hazard ratio = 7.08; 95% confidence interval, 1.06–47.30). Patients with level of tumor ≤5 cm had an estimated 5-year LRRFS of 66.8%, which was much higher than 2.3% in patients with level of tumor >5 cm. There was no significant factor for recurrence-free survival or overall survival. CONCLUSION: In T3N0 rectal cancer, adjuvant chemoradiotherapy should be recommended in patients with level of tumor ≤5 cm for better local control. However, in patients with pT3N0 disease, negative resection margin, and level of tumor >5 cm, adjuvant chemoradiotherapy should be carefully suggested.
Chemoradiotherapy, Adjuvant ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Radiotherapy, Adjuvant ; Rectal Neoplasms ; Recurrence ; Risk Factors

PURPOSE: The aim of this study was to assess oncological outcomes of postoperative radiotherapy plus chemotherapy (CRT) versus chemotherapy alone (CTx) in stage II or III upper rectal cancer patients who underwent curative surgery. METHODS: We retrospectively reviewed 263 consecutive patients with pathologic stage II or III upper rectal cancer who underwent primary curative resection with postoperative CRT or CTx from January 2008 to December 2014 at Chonnam National University Hwasun Hospital. Multivariate and propensity score matching analyses were used to reduce selection bias. RESULTS: Median follow-up was 48.1 months for the entire cohort and 53.5 months for the matched cohort. In subgroup analysis of the propensity score matched cohort, the 3-year local recurrence-free survival was 94.1% (95% confidence interval [CI], 87.8%–100%) in the CRT group and 90.1% (95% CI, 82.8%–97.9%) in the CTx group (P = 0.370). No significant difference in disease-free survival was observed according to treatment type. On multivariate analysis, circumferential resection margin involvement (hazard ratio [HR], 2.386; 95% CI, 1.190–7.599; P = 0.032), N stage (HR, 6.262; 95% CI, 1.843–21.278, P = 0.003), and T stage (HR, 5.896, 95% CI, 1.298–6.780, P = 0.021) were identified as independent risk factors for local recurrence of tumors of the upper rectum. CONCLUSION: Omission of radiotherapy in an adjuvant treatment setting may not jeopardize oncologic outcomes in stages II and III upper rectal cancer.
Chemoradiotherapy ; Cohort Studies ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Jeollanam-do ; Multivariate Analysis ; Propensity Score ; Radiotherapy ; Rectal Neoplasms ; Rectum ; Recurrence ; Retrospective Studies ; Risk Factors ; Selection Bias

PURPOSE: Rectovaginal fistula (RVF) after low anterior resection for rectal cancer is a type of anastomotic leakage. The aim of this study was to find out the difference of leakage, according to RVF presence or absence and to identify the optimal strategy for RVF. METHODS: All female patients who underwent low anterior resection with colorectal anastomosis or coloanal anastomosis (n = 950) were retrospectively analyzed. Patients' demographics and perioperative outcomes were analyzed between the RVF group and leakage without the RVF (nRVF) group. We performed 4 types of procedures—primary repair, diverting stoma, redo coloanal anastomosis (RCA), and conservative procedure—to treat RVF, and calculated the success rates of each type of procedure. RESULTS: The leakage occurred in 47 patients (4.9%). Among them, 18 patients (1.9%) underwent an RVF and 29 (3.0%) underwent nRVF. The RVF group received more perioperative radiotherapy (27.8% vs. 3.4%, P < 0.015) and occurred late onset after surgery (181.3 ± 176.4 days vs. 23.2 ± 53.6 days, P < 0.001) more than did the nRVF group. In multivariate analysis for the risk factor of the RVF group, the RVF group was statistically associated with less than 5 cm of anastomosis more than was the no-leakage group. A total of 35 procedures were performed in 18 patients with RVF for treatment. RCA showed satisfactory success rates (85.7%, n = 6) and, primary repair (transanal or transvaginal) showed acceptable success rate (33.3%, n = 8). CONCLUSION: After low anterior resection for rectal cancer, RVF was strongly correlated with a lower level of primary tumor location. Among the patients who underwent leakages, receipt of perioperative radiotherapy was significantly high in the RVF group than that of the nRVF group. Additionally, this study suggests that RCA might be considered another successful treatment strategy for RVF.
Anastomotic Leak ; Colectomy ; Demography ; Female ; Humans ; Multivariate Analysis ; Radiotherapy ; Rectal Neoplasms ; Rectovaginal Fistula ; Retrospective Studies ; Risk Factors

PURPOSE: Dysbiosis of gut microbiota has been reported to participate in the pathogenesis of colorectal cancer, but changes in microbiota due to radiotherapy have not been studied. In this study, we tried to elucidate the changes in the microbiome in rectal cancer after chemoradiotherapy using RNA sequencing analysis.MATERIALS AND METHODS: We included 11 pairs of human rectal cancer tissues before and after irradiation between August 2016 and December 2017 and performed RNA sequencing analysis. Mapped reads to human reference genomes were used for pair-wise transcriptome comparisons, and unmapped (non-human) reads were then mapped to bacterial marker genes using PathSeq.RESULTS: At microbiome level, interindividual variability of mucosal microbiota was greater than the change in microbial composition during radiotherapy. This indicates that rapid homeostatic recovery of the mucosal microbial composition takes place short after radiotherapy. At single microbe level, Prevotella and Fusobacterium, which were identified as important causative microbes of the initiation and progression of rectal cancer were decreased by radiotherapy. Moreover, changes in Prevotella were associated with changes in the human transcriptome of rectal cancer. We also found that there was a gene cluster that increased and decreased in association with changes in microbial composition by chemoradiation.CONCLUSION: This study revealed changes in tumor-associated microbial community by irradiation in rectal cancer. These findings can be used to develop a new treatment strategy of neoadjuvant therapy for locally advanced rectal cancer by overcoming radio-resistance or facilitating radio-sensitivity.
Chemoradiotherapy ; Colorectal Neoplasms ; Dysbiosis ; Fusobacterium ; Gastrointestinal Microbiome ; Genes, vif ; Genome ; Humans ; Microbiota ; Neoadjuvant Therapy ; Prevotella ; Radiotherapy ; Rectal Neoplasms ; Sequence Analysis, RNA ; Transcriptome

OBJECTIVE: To compare the application among intensity-modulated radiotherapy (IMRT), three-dimensional conformal radiotherapy(3D-CRT) and conventional radiotherapy (CRT) for locally advanced middle-low rectal cancer. METHODS: From January 2015 to December 2016, 93 locally advanced middle-low rectal cancer patients with clinical stage cT3N+M0 or cT4N0/+M0 who underwent preoperative concurrent chemoradiotherapy at Department of Colorectal Surgery, the Third Affiliated Hospital of Kunming Medical University and had complete data were enrolled in this retrospective cohort study. Patients were divided into IMRT group (17 cases), 3D-CRT group (28 cases) and CRT group (48 cases) according to different radiotherapy methods. The frequency and dose of CRT were 1 time/day, 5 times/week, for a total of 5 weeks, with a single dose of 2.0 Gy, the total dose was 50 Gy. Frequency and dose of 3D-CRT and IMRT were 1 time/day, 5 times/week, for a total of 23 to 28 times, with a single dose of 1.8 to 2.0 Gy, and a total dose of 45.0 to 50.4 Gy. The chemotherapy regimen was performed with capecitabine tablets at a dose of 825 mg/m twice a day for 5 days every week, at the same time during radiotherapy. The efficacy, chemotherapy adverse reactions and immune function of the three groups were compared. RESULTS: There was no significant difference in the baseline data among the three groups (all P>0.05). The proportion of patients receiving permanent ostomy in the IMRT group and the 3D-CRT group was 29.4%(5/17) and 32.1%(9/28) respectively, which was lower than 58.3%(28/48) in CRT group, and the difference was statistically significant (χ²=7.982, P=0.030), while this proportion was not significantly different between IMRT and 3D-CRT group(χ²=0.037, P=0.848). The pathologic complete response(pCR) rate was 23.7%(22/93) in the whole study, and the pCR rate was 39.3%(11/28) in the 3D-CRT group, which was higher than that of CRT group and IMRT group [12.5%(6/48) and 29.4%(5/17)], and the difference was statistically significant (χ²=7.407, P=0.025), while there was no significant difference in pCR rate between CRT group and IMRT group (χ²=2.554, P=0.110). There was no adverse reaction of grade 3 or above in all three groups. No significant difference in the incidence of bone marrow suppression, abnormal liver and kidney function markers, digestive tract reaction or radiation dermatitis was found(all P>0.05). After receiving concurrent chemoradiotherapy, the proportion of CD3/CD4 cells in the IMRT group and the CRT group decreased compared with that before treatment(23.1±9.3 vs. 31.1±10.9, 27.4±10.7 vs. 33.6±7.2, respectively); the proportion of CD3/CD8 cells was up-regulated (36.1±15.2 vs. 24.8±10.9, 30.9±14.4 vs. 24.0±8.3,respectively), and the differences were statistically significant (both P<0.05), while the above indexes before and after treatment were not significantly different in the 3D-CRT group(all P>0.05). After treatment, the proportion of CD4/CD8 cells in IMRT group decreased (0.8±0.6 vs. 1.6±1.0, t=3.838, P=0.003), while this proportion was not significantly different in CRT group and 3D-CRT group(all P>0.05). CONCLUSIONS IMRT and 3D-CRT can reduce the rate of permanent stoma. 3D-CRT can increase pCR rate. No obvious advantage is shown in IMRT as compared with 3D-CRT in the short-term efficacy. On the contrary, an immunosuppressive status may occur. Therefore, 3D-CRT is recommended as the best preoperative treatment strategy for patients with locally advanced middle-low rectal cancer, especially for those with immunosuppression status.
Humans ; Radiotherapy ; methods ; standards ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Conformal ; standards ; Radiotherapy, Intensity-Modulated ; standards ; Rectal Neoplasms ; radiotherapy ; Retrospective Studies

PURPOSE: This study aimed to assess complications and outcomes of a new approach, that is, combining short course radiotherapy (SRT), concurrent and consolidative chemotherapies, and delayed surgery. MATERIALS AND METHODS: In this single arm phase II prospective clinical trial, patients with T3-4 or N+ M0 rectal adenocarcinoma were enrolled. Patients who received induction chemotherapy or previous pelvic radiotherapy were excluded. Study protocol consisted of three-dimensional conformal SRT (25 Gy in 5 fractions in 1 week) with concurrent and consolidation chemotherapies including capecitabine and oxaliplatin. Total mesorectal excision was done at least 8 weeks after the last fraction of radiotherapy. Primary outcome was complete pathologic response and secondary outcomes were treatment related complications. RESULTS: Thirty-three patients completed the planned preoperative chemoradiation and 26 of them underwent surgery (24 low anterior resection and 2 abdominoperineal resection). Acute proctitis grades 2 and 3 were seen in 11 (33.3%) and 7 (21.2%) patients, respectively. There were no grades 3 and 4 subacute hematologic and non-hematologic (genitourinary and peripheral neuropathy) toxicities and perioperative morbidities such as anastomose leakage. Grade 2 or higher late toxicities were observed among 29.6% of the patients. Complete pathologic response was achieved in 8 (30.8%) patients who underwent surgery. The 3-year overall survival and local control rates were 65% and 94%, respectively. CONCLUSION: This study showed that SRT combined with concurrent and consolidation chemotherapies followed by delayed surgery is not only feasible and tolerable without significant toxicity but also, associated with promising complete pathologic response rates.
Adenocarcinoma ; Antineoplastic Combined Chemotherapy Protocols ; Arm ; Capecitabine ; Combined Modality Therapy ; Consolidation Chemotherapy ; Drug Therapy ; Humans ; Induction Chemotherapy ; Iran ; Proctitis ; Prospective Studies ; Radiotherapy ; Radiotherapy, Conformal ; Rectal Neoplasms

PURPOSE: Traditionally, three-dimensional conformal radiation therapy (3D-CRT) is used for neoadjuvant chemoradiation in locally advanced rectal cancer. Intensity-modulated radiation therapy (IMRT) was later developed for more conformal dose distribution, with the potential for reduced toxicity across many disease sites. We sought to use the National Cancer Database (NCDB) to examine trends and predictors for IMRT use in rectal cancer. MATERIALS AND METHODS: We queried the NCDB from 2004 to 2015 for patients with rectal adenocarcinoma treated with neoadjuvant concurrent chemoradiation to standard doses followed by surgical resection. Odds ratios were used to determine predictors of IMRT use. Univariable and multivariable Cox regressions were used to determine potential predictors of overall survival (OS). Propensity matching was used to account for any indication bias. RESULTS: Among 21,490 eligible patients, 3,131 were treated with IMRT. IMRT use increased from 1% in 2004 to 22% in 2014. Predictors for IMRT use included increased N stage, higher comorbidity score, more recent year, treatment at an academic facility, increased income, and higher educational level. On propensity-adjusted, multivariable analysis, male gender, increased distance to facility, higher comorbidity score, IMRT technique, government insurance, African-American race, and non-metro location were predictive of worse OS. Of note, the complete response rate at time of surgery was 28% with non-IMRT and 21% with IMRT. CONCLUSION: IMRT use has steadily increased in the treatment of rectal cancer, but still remains only a fraction of overall treatment technique, more often reserved for higher disease burden.
Adenocarcinoma ; Bias (Epidemiology) ; Comorbidity ; Continental Population Groups ; Humans ; Insurance ; Male ; Odds Ratio ; Radiotherapy ; Radiotherapy, Intensity-Modulated ; Rectal Neoplasms

For patients at risk of premature ovarian failure with cancer treatment, it is an important option to re-implant the ovarian tissue (OT) after cryopreservation to preserve endocrine function and fertility. With this technique, about 30% of pregnancy success rate and about 90 live births have been reported to date. However, there has been no case report of successful in vitro fertilization (IVF) and embryo transfer (ET) with oocytes collected from transplanted cryopreserved OT in Korea. We report a 30-year old woman with rectal cancer who underwent IVF and ET after cryopreserved OT thawing and re-implantation. She has been diagnosed with stage IIIC rectal cancer after surgery, and right ovary was removed and cryopreserved between cycles of chemotherapy. After completion of chemotherapy and radiotherapy, the patient underwent orthotopic transplantation of cryopreserved OTs. Three months after transplantation, the serum follicle-stimulating hormone level decreased from 91.11 mIU/mL to 43.69 mIU/mL. Thereafter, the patient underwent 11 ovarian stimulation cycles, and in 7 cycles, follicle growth was observed at the OT graft site. In one of these cycles, the oocyte was successfully retrieved and one embryo was transplanted after IVF. The patient was not pregnant, but the cryopreservation of OT can save the fertility after anticancer chemotherapy.
Cryopreservation ; Drug Therapy ; Embryo Transfer* ; Embryonic Structures* ; Female ; Fertility ; Fertility Preservation ; Fertilization in Vitro* ; Follicle Stimulating Hormone ; Humans ; In Vitro Techniques* ; Korea ; Live Birth ; Oocytes ; Ovary ; Ovulation Induction ; Pregnancy ; Primary Ovarian Insufficiency ; Radiotherapy ; Rectal Neoplasms ; Transplantation ; Transplants