Concurrent Chemoradiotherapy In Patients Research Articles

Oncological outcomes of robotic-assisted total mesorectal excision after neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer

AimsThis study analyzed the oncological outcomes of robotic-assisted total mesorectal excision (TME) in patients with rectal cancer after neoadjuvant concurrent chemoradiotherapy (CCRT). MethodsWe enrolled 109 consecutive patients with stage II–III rectal cancer who underwent robotic-assisted TME after neoadjuvant CCRT at one hospital between July 2013 and June 2018. ResultsAll 109 patients underwent preoperative CCRT. Of them, 37 (33.9%) achieved a pathologic complete response, and 29 (26.6%) experienced relapse, with local recurrence in 9 (8.3%) and distant metastasis in 20 (18.3%). R0 resection was performed in 104 (95.7%) patients; however, 7 (6.7%) of them developed local recurrence and 17 (16.3%) developed distant metastasis. Over a median follow-up of 42 months, the 3-year disease-free survival and overall survival rates were 73.4% and 87.2%, respectively. ConclusionsRobotic-assisted TME after neoadjuvant CCRT is safe and effective for treating patients with stage II–III rectal cancer in one institution with acceptable short-term oncological outcomes. It may be a therapeutic alternative to salvage surgery for T4 tumors invading adjacent organs, such as the bladder, prostate, and uterus.

Updated applications of Ultrasound in Uterine Cervical Cancer.

Cervical cancer is a common gynecologic malignancy worldwide. It is the fourth for both incidence and mortality. For cervical cancer, imaging and pathology assessments are incorporated in the revised 2018 Federation of Gynecology and Obstetrics (FIGO) staging system. Uses of imaging techniques for the pre-treatment work-up of cervical cancer have been increasing. Among imaging techniques for the evaluation of cervical cancer, ultrasound is cheaper, faster and widely available than other imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI). Advanced technique in ultrasound, such as three-dimension (3D) ultrasound and color Doppler, have improved the clinical application of ultrasound in cervical cancer. Ultrasound may provide highly accurate information on detecting tumor presence and evaluating local tumor extent if performed by ultrasound-trained gynecologists; the experience of readers is also critical for correct pretreatment staging and assessment of response to treatment. Sonographic images could be useful to predict response of neoadjuvant chemotherapy, radiotherapy, chemotherapy and concurrent chemoradiotherapy in patients with cervical cancer. This review article attempted to present the most updated specific applications of ultrasound in cervical cancer.

Paclitaxel and Carboplatin Versus Cisplatin and 5-Fluorouracil in Concurrent Chemoradiotherapy in Patients With Esophageal Cancer.

Cisplatin with 5-fluouracil (Cis/5Fu) and paclitaxel with carboplatin (Pac/Car) are common regimens used in concurrent chemoradiotherapy (CCRT) for patients with locally advanced esophageal cancer (EC). Here, we aimed to compare the survival outcomes and treatment-related toxicities between these regimens in neoadjuvant CCRT in patients with locally advanced EC. One hundred and thirty-six patients with locally advanced EC (98% squamous cell carcinoma) were prospectively recruited between 2016 and 2017 in a non-randomized manner. Patients were categorized into two groups according to the chemotherapeutic agents administered (Pac/Car group, n=87; Cis/5Fu group, n=47) in CCRT to compare the survival outcome and severe adverse event (sAE) incidence. Forty-two patients (85.7%) and 80 patients (91.4%) in the Cis/5Fu and Pac/Car groups completed pre-planned CCRT (p=0.26), respectively. The Cis/5Fu group presented a higher incidence of non-hematological sAE than the Pac/Car group (69.45% vs. 51.7%, p=0.049). Patients in the Pac/Car group showed a higher rate of surgical resection than those in the Cis/5Fu group (49.4% vs. 22.4%, p<0.001). After a median follow-up duration of 22.0 months (range=1.9-31.8), the 2-year survival rate was 56.9% for patients in the Pac/Car group and 28.7% for the Cis/5Fu group. The hazard ratio (HR) of overall survival was 0.45 (95%CI=0.28-0.72, p=0.001) in the comparison between the groups. Overall, neoadjuvant CCRT with Pac/Car is associated with a better survival outcome, higher surgical resection rate, and better safety profiles than Cis/5Fu in patients with locally advanced EC.

Phase 2 Study of Nimotuzumab in Combination With Concurrent Chemoradiotherapy in Patients With Locally Advanced Non–Small-Cell Lung Cancer

BackgroundWe evaluated the tolerability and efficacy of nimotuzumab, a humanized IgG1 monoclonal anti–epidermal growth factor receptor antibody, with concurrent chemoradiotherapy in patients with unresectable locally advanced non–small-cell lung cancer. Patients and MethodsIn this multicenter, single-arm, open-label, phase 2 trial conducted in Japan (JapicCTI-090825), patients received thoracic radiotherapy (60 Gy, 2 Gy per fraction, 6 weeks) and four 4-week cycles of chemotherapy (day 1, cisplatin 80 mg/m2; days 1 and 8, vinorelbine 20 mg/m2). Nimotuzumab 200 mg was administrated weekly for 16 weeks. The primary endpoint was treatment completion rate, defined as the percentage of patients completing 60 Gy of radiotherapy within 8 weeks, 2 cycles of chemotherapy, and at least 75% of the required nimotuzumab dose during the initial 2-cycle concurrent chemoradiotherapy period. ResultsOf 40 patients enrolled, 39 received the study treatment, which was well tolerated, with a completion rate of 87.2%. Thirty-eight patients completed 60 Gy of radiotherapy within 8 weeks. Infusion reaction, grade 3 or higher rash, grade 3 or higher radiation pneumonitis, or grade 4 or higher nonhematologic toxicity were not observed. The objective response rate was 69.2%. The median progression-free survival (PFS) and 5-year PFS rate were 508 days and 29.0%, respectively. The 5-year PFS rate in patients with non–squamous cell carcinoma (n = 23) was 13.7% and in patients with squamous cell carcinoma (n = 16) was 50.0%. The 5-year overall survival rate was 58.4%. ConclusionAddition of nimotuzumab to the concurrent chemoradiotherapy regimen was well tolerated and showed potential for treating patients with locally advanced non–small-cell lung cancer, particularly squamous cell carcinoma.

Preoperative concurrent chemoradiotherapy MRI characteristics favouring pathologic complete response in patients with rectal cancer: Usefulness of MR T2-stage as an ancillary finding for predicting pathologic complete response.

This study sought to assess preoperative concurrent chemoradiotherapy (CRT) magnetic resonance imaging (MRI)-based findings according to a structured MRI report template for primary staging of rectal cancer, and to evaluate the prognostic relevance of the pre-CRT MRI-based findings in patients with rectal cancer after CRT. We retrospectively evaluated pre- and post-CRT MRI data of patients with pathologically proven rectal adenocarcinoma, between January 2008 and October 2019. Image interpretation was performed independently by two radiologists and each reviewer assessed the cancer characteristics on MRI, based on the structured MRI report for primary staging. MRI-based findings associated with pathologic complete tumour regression grade (TRG) after CRT were analysed by univariate and multivariate analysis. Significant factors from pre-CRT MRI were weighted to score mrTRG in post-CRT MRI. On univariate analysis, MR T-stage, tumour infiltration, mesorectal fascia involvement, extramural vascular invasion and serum carcinoembryonic antigen level correlated significantly with pathologic complete response (pCR). Multivariate analysis identified that only MR T-stage was independently associated with pCR (odds ratio, 3.89, 95% confidence interval, 1.18-12.84; P=0.0278). Adding MRI-based T2-stage as an ancillary finding to mrTRG statistically significantly improved the sensitivity as compared to using only mrTRG for considering a CR. T2_mrTRG was significantly different in terms of the time to tumour progression between the CR and non-CR group. The MR T2-stage was independently associated with pCR after CRT in patients with rectal cancer and was helpful as ancillary predictive factor, adding to mrTRG for prediction of pCR.

196TiP Perioperative sintilimab in combination with concurrent chemoradiotherapy for patients with locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma

196TiP Perioperative sintilimab in combination with concurrent chemoradiotherapy for patients with locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma

Neoadjuvant Versus Definitive Concurrent Chemoradiotherapy In Stage III Esophageal Cancer Patients

The treatment for locally advanced esophageal cancer remains unclear. We compared the clinical outcomes between neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery and definitive CCRT in patients with clinical stage III esophageal cancer from Asians population using a national cancer registry database. Eligible patients diagnosed from 2010 to 2015 were collected from the Taiwan Cancer Registry. To balance observable potential confounders, we constructed a 1:1 propensity score-matched cohort (surgery: CCRT = 1:1). We compared the overall survival for 5 years. Our study population included 1988 patients, 944 in the surgery group and 944 in the CCRT group. The histological type of the patients contained 97.2% squamous cell carcinoma and 1.6% adenocarcinoma. The 3-year-survival rate between surgery and CCRT group was 43% and 19%, respectively. The 5-year-survival rate between surgery and CCRT group were 33% and 13%, respectively (P value <0.0001). The hazard ratio of mortality was 0.452 [95% confidence interval 0.405∼0.505] when surgery was compared to CCRT. Based on the analysis of the database, neoadjuvant CCRT followed by surgery was associated with improved overall survival for stage III esophageal cancer compared to definitive CCRT.

Correlation between Nutritional Status and Toxicity of Concurrent Chemoradiotherapy in Patients with Rectal Cancer

Correlation between Nutritional Status and Toxicity of Concurrent Chemoradiotherapy in Patients with Rectal Cancer

Complete Pathological Response Rates and Outcome of Two Cycles Neoadjuvant Chemotherapy Followed by Long Course Concurrent Chemoradiotherapy in Patients of Locally Advanced Carcinoma Rectum

Complete Pathological Response Rates and Outcome of Two Cycles Neoadjuvant Chemotherapy Followed by Long Course Concurrent Chemoradiotherapy in Patients of Locally Advanced Carcinoma Rectum

Hypo-Fractionated Radiotherapy Boost And Concurrent Chemo-Radiotherapy For Patients With Muscle-Invasive Bladder Cancer (MIBC): A Preliminary Report Of The Prospective Phase II Study

The primary endpoint was to assess the bladder preservation and the toxicity of bladder. This report presented the acute toxicity profile of this tri-modality treatment (TMT) for patients with MIBC. A total of 38 consecutive patients with cT2-4a bladder cancer underwent TURBT as complete as possible, which was visibly complete in 10 cases. They received hypo-fractionated radiotherapy (RT) to tumor or tumor bed in bladder followed by conventional fractionated RT to pelvis and total bladder, and concurrent infusion Gemcitabine 100 mg/m2 per week. During hypo-fractionated RT, intravesical installation of isovolumetric saline through urinary catheter ensured adequate bladder filling. Patients were reevaluated by the means of cystoscopy and pelvic CT or MRI at 1 month and then every 3 months. Toxicities were assessed using RTOG acute and late gastrointestinal (GI), genitourinary (GU) toxicity criteria. The median age was 72 (35-89). The median follow-up for the entire group was 9 (1-37) months. The two-year overall survival (OS) and cancer specific survival (CSS) was 75% and 90% for all patients, 80% and 100% for N0M0 patients. None patients received salvage cystectomy due to muscle-invasive recurrence in bladder. During radiotherapy, 1 patient (2.6%) complained of Grade 3 GI toxicity, 5 patients (13.2%) complained of Grade 2 GI toxicity. 1 patient (2.6%) reported Grade 3 GU toxicity, 8 patients (21.0%) complained of Grade 2 GU toxicity. 3 patients (20%) complained of urinary moderate pain after radiotherapy and recovered to mild after one month. 1 patient (2.6%) complained of small bladder (<150ml) after 6 months follow-up. None of patients reported urinary incontinence. This combined hypo-fractionated radiation/chemotherapy regimen with TURBT appears to be a well-tolerable and effective treatment strategy for MIBC patients who are not candidates for cystectomy or who wish to avoid cystectomy, and this tri-modality treatment warrants further investigation.

Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concurrent Chemoradiotherapy in Patients With Stage IIA-IIIA Cervical Carcinoma

Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concurrent Chemoradiotherapy in Patients With Stage IIA-IIIA Cervical Carcinoma

Concurrent Chemoradiotherapy Increases the Levels of Soluble Immune Checkpoint Proteins in Patients with Locally Advanced Cervical Cancer

Concurrent chemoradiotherapy (CCRT) could influence systematic immunity in cancer patients, but its impact on soluble immune checkpoint molecules remain largely unknown. Here, we investigated the dynamic alterations of 16 soluble immune checkpoint molecules in locally advanced cervical cancer (LACC) patients treated with CCRT. Sixty LACC patients treated with CCRT were prospectively enrolled and patients’ blood was collected before, during, and at the end of CCRT. Sixteen soluble immune checkpoint molecules were tested by Luminex platform. Tumor response was evaluated based on RECIST 1.1 guidelines at one month after CCRT. One-way analysis of variance with Bonferroni's post-test or paired t tests were used to evaluate the change of the levels of soluble immune checkpoint molecules. Forty-five (75%) patients experienced complete response (CR), 12 (20%) patients experienced partial response (PR), and 3 (5%) patients experienced stable disease after CCRT. Levels of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) increased both during and at the end of CCRT (P = .015 and .003, respectively), while inducible T-cell costimulator (ICOS), B7-2, glucocorticoid-induced tumor necrosis factor receptor ligand (GITRL) increased at the end of CCRT (P = .032, .048, and .050, respectively). The other soluble immune checkpoint molecules including CD40 showed no significant change throughout CCRT (all P >0.05). Interestingly, we found that these changes were more significant in patients with CR than patients with PR/SD. Specifically, for patients with CR, levels of TIM-3 were significantly elevated both during and at the end of CCRT (P = .008 and < .001, respectively), while ICOS, B7-2, GITRL were significantly elevated at the end of CCRT (P = .023, .039, and .042, respectively). Meanwhile, CD40 was significantly elevated at the end of CCRT in patients with CR (P = .040). However, patients with PR/SD, no soluble immune checkpoint molecules were significantly changed (all P > 0.05). Our study reveals that CCRT could induce the elevation of the levels of soluble TIM-3, ICOS, B7-2, and GITRL in the blood of patients with LACC. This phenomenon was more obvious in patients with good response to CCRT.

Neoadjuvant chemotherapy followed by radical surgery versus concurrent chemoradiotherapy in patients with FIGO stage IIB cervical cancer

Objective: The aim of this study was to compare the long-term survival of patients with FIGO stage IIB cervical cancer treated with neoadjuvant chemotherapy followed by radical hysterectomy (NACT + RS) with the survival of those treated with concurrent chemoradiotherapy (CCRT).

The Safety and Efficacy of Apatinib Treatment in Addition to Concurrent Chemoradiotherapy in Patients with Nonoperative Locally Advanced Esophageal Squamous Cell Carcinoma.

BackgroundEsophageal cancer is a common gastrointestinal malignancy in China. We evaluated the efficacy and safety of adding Apatinib to concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.Material/MethodsIn this single-center retrospective study, we compared short-term efficacy, long-term efficacy, and adverse events between patients who received Apatinib and concurrent chemoradiotherapy (Apatinib group), and those who received only concurrent chemoradiotherapy (CCRT group).ResultsSixty-five patients with stage II and III esophageal squamous cell carcinoma were enrolled (31 in the Apatinib group, 34 in the CCRT group). After treatment, the therapy response rate (the sum of the complete and partial remission rates) was significantly higher in the Apatinib group than in the CCRT group (P=0.045); the complete remission rate was particularly higher in the Apatinib group. Median progression-free survival in the Apatinib group (12 months) was higher than that of the CCRT group (7 months), and the 1- and 2-year progression-free survival rates were significantly higher in the Apatinib group than in the CCRT group (47.0% vs. 30.3% and 20.2% vs. 12.1%, respectively; P=0.040). The main adverse effects of Apatinib treatment were elevated blood pressure, proteinuria, hand-foot syndrome, fatigue, and oral mucositis, all of which were level 1–2. Cox multivariate regression analysis indicated T stage and short-term efficacy were independent prognostic factors for overall and progression-free survival.ConclusionsFor patients with locally advanced esophageal squamous cell carcinoma, combining Apatinib with concurrent chemoradiotherapy can improve patient survival and significantly prolong progression-free survival, with tolerable adverse reactions.

Cost-utilityanalysis of adjuvant chemotherapy after concurrent chemoradiation in patients with locally advanced cervical cancer.

This study aimed to compare the cost utility of concurrent chemoradiation (CCRT) to CCRT followed by adjuvant chemotherapy (CCRT/ACT) in locally advanced cervical cancer (LACC) using provider and societal viewpoints. Data from our trial which was a multi-centre study evaluating the efficacy of ACT compared to CCRT/ACT were entered into a decision tree model. The data included clinical probability, direct medical and non-medical costs, and utility obtained from the patients. The total cost, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were estimated for a time horizon of 3years. All costs and outcomes were discounted at 3% annually. The cost of CCRT and CCRT/ACT was approximately 3,058 and 6,896 USD and 4,309 and 7,480 USD from provider and from societal viewpoints, respectively. The QALYs for CCRT and CCRT/ACT were 2.31480 and 2.32045, respectively. The ICER was 569,575 USD per QALY. For stage III-IVA LACC, the ICER was 28,050 USD per QALY. In the sensitivity analysis, the cost of ACT was the most significant influential parameter on the ICER. The ICER would be 0.26-fold lower if the cost of ACT was reduced by 25%. At the current ceiling threshold of 5,000 USD/QALY, CCRT had a 100% probability of being the best option. In the Thai context, CCRT is more cost effective than CCRT/ACT for stage IIB-IVA LACC. CCRT/ACT may be considered only for stage III-IVA LACC because it has a lower ICER than other types of LACC.

1431P Study on the safety and efficacy of apatinib combined with concurrent chemoradiotherapy in the treatment of non-operative oesophageal cancer

Apatinib is a small molecule inhibitor of vascular endothelial growth factor receptor 2. In vitro experiments have shown that it can inhibit proliferation, promote apoptosis, and induce cell cycle redistribution of oesophageal cancer cells, and also had potential radiation sensitization effects. Therefore, we aimed to evaluate the efficacy and safety of apatinib combined with concurrent chemoradiotherapy in patients with non-operative oesophageal cancer. Patients with oesophageal cancer who were not operated on in our centre from May 2016 to April 2019 were analysed retrospectively. They were divided into two groups: apatinib combined with concurrent chemoradiotherapy (experimental group, EG) and concurrent chemoradiotherapy (control group, CG). Patients were followed until April 30, 2020 or until death. The differences in tumour response, progression free survival (PFS), overall survival (OS) and adverse events (AEs) between these two groups were observed and compared. 65 patients were enrolled, 31 in EG, 34 in CG. There was no significant difference in sex, age, KPS score, tumour location and type, TNM stage, radiotherapy and chemotherapy dose between the two groups (P>0.05). The complete and partial response rates of the EG were 22.6% and 61.3%, respectively, while those of the CG were 2.9% and 70.6%, respectively (Χ2=6.099, P=0.045). The mOS, 1y- and 3y-OS rates of the EG and the CG were 20 months, 71%, 24.1% and 16 months, 61.8%, 12.4%, respectively (Χ2=0.788, P=0.375). The mPFS and 1y-PFS of the EG and the CG were 12 months, 47% and 7 months, 30.3% (Χ2=4.225, P=0.040). The main AEs in the EG were hypertension (48.4%), grade 2-3 radioactive pneumonia (42.0%), grade 2-3 radiation esophagitis (96.8%), grade 2-3 myelosuppression (74.2%), albuminuria (9.6%), fatigue (16.1%). The incidence of grade 2-3 radiation pneumonia in the EG was significantly lower than that in the CG (42.0% vs. 73.6%, Χ2=7.955, P=0.006). Apatinib combined with concurrent chemoradiotherapy could significantly improve the short-term efficacy and PFS of patients with non-operative oesophageal cancer in a safe and effective way.

866P Neoadjuvant chemotherapy followed by radical surgery versus concurrent chemoradiotherapy in patients with stage IIA-IIIA cervical carcinoma

The optimal therapy strategy for locally advanced cervical cancer is uncertain, and whether neoadjuvant chemotherapy followed by radical surgery (NACT+RS) could replace the standard concurrent chemoradiation (CCRT) is controversial. We retrospectively evaluated clinical outcomes and adverse effects of patients treated in two different ways and tried to figure out this question.

Predictive value and changes of miR-34a after concurrent chemoradiotherapy and its association with cognitive function in patients with nasopharyngeal carcinoma.

This study explored the changes and predictive value of miR-34a in nasopharyngeal carcinoma (NPC) after concurrent chemoradiotherapy (CCRT), and its association with cognitive function. Fifty NPC patients admitted to Shunde Hospital, and another fifty healthy individuals were assigned into treated group and control group, respectively. Patients in the treated group received 3 courses of CCRT. The relative expression of miR-34a in the two groups was detected, and the cognitive function of patients was assessed. Diagnostic and predictive values of miR-34a in advanced NPC were analyzed. The expression of miR-34a in the control group was significantly higher than that in the treated group (t=13.364, P<0.001), with an area under the curve (AUC) of 0.979. The expression of miR-34a was significantly upregulated after treatment (t=4.559, P<0.001). After treatment, there were 32 complete remission (CR) patients and 18 partial remission (PR) patients. According to efficacy, CR patients were classified as significant group and PR patients as general group. The expression of miR-34a in the significant group was higher than that in the general group before treatment (t=4.704, P<0.001), with an AUC of 0.852. The Montreal Cognitive Assessment (MoCA) score was significantly decreased after treatment (t=13.042, P<0.001). The expression of miR-34a was positively correlated with the MoCA score after treatment, that is, MoCA score gradually increased with the upregulation of miR-34a expression (r=0.379, P=0.006). There is a positive correlation between miR-34a and cognitive function of patients. Moreover, the expression of miR-34a can be used as a potential predictor of the efficacy of CCRT in patients with NPC.

Usefulness of Restaging Pelvis Magnetic Resonance Imaging After Neoadjuvant Concurrent Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer

IntroductionIn patients with locally advanced rectal cancer, restaging pelvis magnetic resonance imaging (MRI) after neoadjuvant concurrent chemoradiotherapy is recommended despite its limited accuracy in predicting pathologic T (ypT) and N (ypN) stage. Neoadjuvant rectal (NAR) score is a novel short-term surrogate endpoint for disease-free survival (DFS) and overall survival (OS). We tested the agreement between restaging MRI T (yT) and N (yN) with ypT and ypN stages, respectively, and explored the prognostic significance of restaging MRI NAR (mNAR) score. Patients and MethodsBetween 2014 and 2018, 43 patients with locally advanced rectal cancer completed neoadjuvant concurrent chemoradiotherapy, had a restaging MRI, and underwent surgery. Weighted kappa was used to test the agreement between yT and yN with ypT and ypN, respectively. A kappa value of less than 0.5 was deemed unacceptable. Paired t test was used to compare NAR and mNAR mean scores. Survival was estimated by Kaplan-Meier curves. ResultsRestaging MRI could not predict ypT stage (slight agreement, κ = 0.111) or ypN stage (fair agreement, κ = 0.278). The mean mNAR score was higher than the mean NAR score (20 vs. 16, P = .0079). The median DFS for patients with low-intermediate NAR and high NAR was not reached vs. 30 months (P = .0063). The median OS for patients with low-intermediate NAR and high NAR was not reached vs. 40 months (P = .0056). There was a trend for longer DFS and OS in patients with low-intermediate mNAR scores (not reached in both groups, P = .058) compared to patients with high mNAR scores (not reached in both groups, P = .15). ConclusionRestaging MRI could not predict ypT and ypN stage. The mean mNAR score was higher than the mean NAR score. There was a trend for longer DFS and OS in patients with low-intermediate mNAR scores compared to patients with high mNAR scores.

BMI1-KLF4 axis deficiency improves responses to neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer

PurposeNeoadjuvant concurrent chemoradiotherapy (CCRT) is a gold standard treatment for patients with stage II/III rectal cancer. B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) is a member of the polycomb group of proteins that are involved in regulating gene expression. High levels of BMI1 have been demonstrated to contribute to the malignant phenotypes of several cancers; however, its relevance in rectal cancer treated with CCRT is largely unknown. Methods and materialsWe used two patient cohorts to address the clinical relevance of BMI1 in human cancers. In addition, HT-29 and HCT-116 cells were chosen as our in vitro models to verify the role of BMI1 in cell response to ionizing radiation. Stemness-related proteins were analyzed by western blotting and cell survival was determined using clonogenic assays. ResultsBMI1 overexpression was found to significantly correlate with advanced pre-treatment nodal status (N1-N2; p < 0.001), post-treatment tumor stage (T1-T2; p = 0.015), inferior tumor regression grade (p = 0.001), and also an independent prognosis factor in 172 rectal cancer patients receiving CCRT. Serial cell-based functional examination indicated that BMI1 deficiency sensitized cells to radiation treatment by modulating the gene expression of Kruppel-like factor 4 (KLF4) and enhanced radiosensitivity in microsatellite stable (MSS) colorectal cancers. Overexpression of KLF4 partially overcame BMI1-deficiency-mediated γ-H2AX expression after ionizing radiation exposure. Consistent with in vitro data, an analysis of an additional 30 rectal cancer tissue specimens revealed a positive correlation between BMI1 and KLF4 (p = 0.02). ConclusionHigher levels of BMI1 are associated with poor therapeutic response and adverse outcomes in rectal cancer patients receiving CCRT.