BACKGROUND:Many patients with cancer benefit little from immune checkpoint blockade (ICB), a major obstacle to immunotherapy for decades. Finding alternative immune checkpoints that control CD8+ T-cell exhaustion is urgent if we are to improve the efficacy of immunotherapies, particularly in microsatellite stable (MSS) colorectal cancer (CRC) that is resistant to ICB. METHODS:Spatial proximity is essential for suppressive ligand-receptor signaling. Here, we mapped the spatial tumor microenvironment of patients with MSS CRC at single-cell resolution and analyzed the cells interacting with exhausted CD8+ T cells to identify immune checkpoint ligand-receptor pairs. To investigate the function of this previously unrecognized immune checkpoint, we performed validation studies spanning cellular experiments, mouse models, and clinical patient samples. RESULTS:We found that a subset of MSS CRC exhibits substantial CD8+ T-cell infiltration, but their function is suppressed. We identified CLEC2B (ligand)-KLRB1 (receptor) as a novel inhibiting ligand-receptor pair for CD8+ T cells. KLRB1 acts as an immune checkpoint receptor, increasing CD8+ T-cell exhaustion and facilitating immune escape in various human cancers. Binding of CLEC2B to KLRB1 initiates immunosuppressive signaling in CD8+ T cells. Clinically, CLEC2B-KLRB1 expression correlates positively with cancer progression and poor response to ICB, demonstrating that KLRB1+ CD8+ T cells are a key marker of the poorly responsive ICB subtype. Furthermore, blocking CLEC2B-KLRB1 signaling with antibodies enhances the antitumor function of CD8+ T cells, providing a potential immunotherapy target for ICB non-responders. CONCLUSIONS:Our study revealed CLEC2B-KLRB1 as a previously unrecognized immune checkpoint axis that drives T-cell exhaustion specifically in ICB poor responsive MSS CRC. Blockade of KLRB1 with a therapeutic antibody reinvigorated CD8+ T-cell antitumor immunity, positioning this axis as a promising target for enhancing immunotherapy efficiency in malignancies, including CRC and other ICB-resistant cancers.
Explosive tumor growth is characterized by rapid tumor growth in a short time period. Currently, there is no precise scientific definition for the condition, which is often accompanied with a poor clinical prognosis. Herein, we presented a study of a young patient with colon cancer who experienced explosive tumor growth. A clinical multidisciplinary team (MDT) collaborated with bioinformaticians to provide precise treatment and elucidate the biological mechanisms underpinning this growth. A 28-year-old male patient diagnosed with colon cancer experienced explosive tumor growth. Peripheral bloods (PB) during immunotherapy were collected for immune cytokine analyses and flow cytometry assays on immune cell subsets. To further examine the underlying mechanisms of this explosive-growth, we conducted whole exome sequencing (WES) and RNA-sequencing (RNA-seq) of samples taken at different time points. The patient was diagnosed with Lynch syndrome. We implemented an immunotherapy and performed PB immune cytokine assays before, during, and after this therapy. Our observations suggested that immunotherapy may remodel interferon-gamma (IFN-γ) signaling and enhance T cell-mediated immune responses. By exploring explosive tumor growth mechanisms, we observed that tumors had significantly less insertion and deletion (INDEL) mutations and INDEL-derived neoantigens. Additionally, they had deficient antigen presentation functions as characterized by decreased IFN-γ signaling activity. Neoantigen loss and decreased IFN-γ signaling activity contributed to explosive tumor growth in this patient. Recovered IFN-γ signaling may lead to effective immunotherapy outcomes.
Background Induction chemotherapy combined with neoadjuvant chemoradiotherapy has been recommended for patients with high-risk, locally advanced rectal cancer. However, the benefit of more intensive total neoadjuvant treatment (TNT) is unknown. This study aimed to assess the safety and efficacy of induction chemotherapy combined with chemoradiotherapy and consolidation chemotherapy for magnetic resonance imaging-stratified high-risk rectal cancer. Methods This was a single-center, single-arm, prospective Phase II trial in Peking University Cancer Hospital (Beijing, China). Patients received three cycles of induction oxaliplatin and capecitabine (CapeOX) followed by chemoradiotherapy and two cycles of consolidation CapeOX. The primary end point was adverse event rate and the second primary end points were 3-year disease-free survival rate, completion of TNT, and pathological downstaging rate. Results Between August 2017 and August 2018, 68 rectal cancer patients with at least one high risk factor (cT3c/3d/T4a/T4b, cN2, mesorectal fascia involvement, or extramural venous invasion involvement) were enrolled. The overall compliance of receiving the entire treatment was 88.2% (60/68). All 68 patients received induction chemotherapy, 65 received chemoradiotherapy, and 61 received consolidation chemotherapy. The Grade 3-4 adverse event rate was 30.8% (21/68). Nine patients achieved clinical complete response and then watch and wait. Five patients (7.4%) developed distant metastasis during TNT and received palliative chemotherapy. Fifty patients underwent surgical resection. The complete response rate was 27.9%. After a median follow-up of 49.2 months, the overall 3-year disease-free survival rate was 69.7%. Conclusions For patients with high-risk rectal cancer, this TNT regimen can achieve favorable survival and complete response rates but with high toxicity. However, it is necessary to pay attention to the possibility of distant metastasis during the long treatment period.
Approximately 10% of stage I colorectal cancer (CRC) patients experience unfavorable clinical outcomes after surgery. However, little is known about the subset of stage I patients who are predisposed to high risk of recurrence or death. Previous evidence was limited by small sample sizes and lack of validation. We aimed to identify early indicators and develop a risk stratification model to inform prognosis of stage I patients by employing two large prospective cohorts. Prognostic factors for stage II tumors, including T stage, number of nodes examined, preoperative carcinoma embryonic antigen (CEA), lymphovascular invasion, perineural invasion (PNI), and tumor grade were investigated in the discovery cohort, and significant findings were further validated in the other cohort. We adopted disease-free survival (DFS) as the primary outcome for maximum statistical power and recurrence rate and overall survival (OS) as secondary outcomes. Hazard ratios (HRs) were estimated from Cox proportional hazard models, which were subsequently utilized to develop a multivariable model to predict DFS. Predictive performance was assessed in relation to discrimination, calibration and net benefit. A total of 728 and 413 patients were included for discovery and validation. Overall, 6.7% and 4.1% of the patients developed recurrences during follow-up. We identified consistent significant effects of PNI and higher preoperative CEA on inferior DFS in both the discovery (PNI: HR = 4.26, 95% CI: 1.70–10.67, p = 0.002; CEA: HR = 1.46, 95% CI: 1.13–1.87, p = 0.003) and the validation analysis (PNI: HR = 3.31, 95% CI: 1.01–10.89, p = 0.049; CEA: HR = 1.58, 95% CI: 1.10–2.28, p = 0.014). They were also significantly associated with recurrence rate. Age at diagnosis was a prominent determinant of OS. A prediction model on DFS using Age at diagnosis, CEA, PNI, and number of LYmph nodes examined (ACEPLY) showed significant discriminative performance (C-index: 0.69, 95% CI:0.60–0.77) in the external validation cohort. Decision curve analysis demonstrated added clinical benefit of applying the model for risk stratification. PNI and preoperative CEA are useful indicators for inferior survival outcomes of stage I CRC. Identification of stage I patients at high risk of recurrence is feasible using the ACEPLY model, although the predictive performance is yet to be improved.
Objective:To explore the clinical efficacy of radical resection for lung metastasis from colorectal cancer and the prognostic factors.Methods:The retrospective cohort study was conducted. The clinicopathological data of 63 colorectal cancer patients with lung metastasis who were admitted to Peking University Cancer Hospital from January 2004 to December 2015 were collected. There were 35 males and 28 females, aged (57±12)years. Patients underwent radical resection for primary lesion and lung metastasis from colorectal cancer. Observation indicators: (1) diagnosis and treatment; (2) follow-up and survival; (3) prognostic factors analysis. Follow-up was conducte by outpatient examination and telephone interview to detect the survival of patients after operation up to December 2018. Measurement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. Log-rank test was used for univariate analysis and COX proportional hazard model was used for multivariate analysis. Results:(1) Diagnosis and treatment: of 63 patients with lung metastasis from colorectal cancer, 6 had synchronous lung metastasis and 57 had metachronous lung metastasis. Eighteen cases of suspected lung metastasis were initially detected by chest X-ray, and further confirmed by computed tomography (CT). Forty-five cases of suspected lung metastasis were initially detected by chest CT. All the 63 patients underwent radical resection for primary and metastatic lesions. Two of 22 cases undergoing mediastinal lymph nodes dissection were detected one positive lymph node, respectively. All patients recovered well after operation, without severe complications. There were 57 of 63 patients receiving more than 6 months of postoperative adjuvant chemotherapy and targeted therapy based on fluorouracils. (2) Follow-up and survival: 63 patients were followed up for 8-143 months, with a median follow-up time of 58 months. During the follow-up, 19 of 63 patients died, 24 patients had secondary recurrence with a 5-year recurrence rate of 38.1%(24/63) and a recurrence interval of 18 months(range, 3-58 months). Of 24 patients with secondary recurrence, 19 had lung metastasis, 3 had brain metastasis, 2 had bone metastasis, 2 had liver metastasis; some patients had multiple metastases. Of 24 patients with secondary recurrence, 5 underwent reoperation and 19 underwent chemotherapy and radiochemotherapy. The 5-year overall survival rate of 63 patients was 62.7%. (3) Prognostic factors analysis: results of univariate analysis showed that location of primary lesion, the number of lung metastases and carcinoembryonic antigen (CEA) level before resection of lung metastasis were related factors for prognosis of patients with lung metastasis from colorectal cancer ( χ2=4.162, 7.175, 6.725, P<0.05). Results of multivariate analysis showed that the number of lung metastases and CEA level before resection of lung metastasis were independent influencing factors for prognosis of patients with lung metastasis from colorectal cancer ( hazard ratio=2.725, 2.778, 95% confidence interval as 1.051-7.064, 1.072-7.021, P<0.05). Conclusions:Radical resection for lung metastasis from colorectal cancer is safe and feasible. The number of lung metastases and CEA level before resection for lung metastasis are independent influencing factors for prognosis of patients with lung metastasis from colorectal cancer.
BACKGROUND: Prognostic and pathologic risk factors typically guide clinicians and patients in their choice of surveillance or adjuvant chemotherapy when managing high-risk stage II colon cancer. However, variations in treatment and outcomes in patients with stage II colon cancer remain. OBJECTIVE: This study aimed to assess the survival benefits of treatments concordant with suggested therapeutic options from Watson for Oncology, a clinical decision support system. DESIGN: This is a retrospective observational study of concordance between actual treatment and Watson for Oncology therapeutic options. SETTING: This study was conducted at a top-tier cancer center in China. PATIENTS: Postoperative treatment data were retrieved from the electronic health records of 306 patients with high-risk stage II colon adenocarcinoma. MAIN OUTCOME MEASURES: The primary outcomes measured were the treatment patterns plus 3- and 5-year overall and disease-free survival for concordant and nonconcordant cases. RESULTS: Overall concordance was 90%. Most nonconcordant care resulted from adjuvant chemotherapy use (rather than surveillance) in patients with high-level microsatellite instability and >= 70 years old. No difference in overall survival (p= 0.56) or disease-free survival (p= 0.19) was observed between concordance groups. Patients receiving adjuvant chemotherapy had significantly higher 5-year overall survival than those undergoing surveillance (94% vs 84%,p= 0.01). LIMITATIONS: This study was limited by the use of retrospective cases drawn from patients presenting for surgery, the lack of complete follow-up data for 58% of patients who could not be included in the analysis, and a survival analysis that assumes no unmeasured correlation between survival and censoring. CONCLUSIONS: Watson for Oncology produced therapeutic options highly concordant with human decisions at a top-tier cancer center in China. Treatment patterns suggest that Watson for Oncology may be able to guide clinicians to minimize overtreatment of patients with high-risk stage II colon cancer with chemotherapy. Survival analyses suggest the need for further investigation to specifically assess the association between surveillance, single-agent and multiagent chemotherapy, and survival outcomes in this population.
Objective: To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer. Methods: A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR). Results: Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE. Conclusion: Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.
Background Heterogeneity with respect to recurrence and survival in high-risk stage II colon cancer patients still exists, and further classification is urgently required. This study aimed to ascertain the prognostic value of DNA ploidy, stroma-tumour fraction and nucleotyping in the prognosis of high-risk stage II colon cancer. Methods A total of 188 high-risk stage II colon cancer patients received radical surgery in Peking University Cancer Hospital, from 2009 to 2015. Status of mismatch repair proteins in tumours was analysed using immunohistochemistry. DNA ploidy, stroma-tumour fraction and nucleotyping were estimated by automated digital imaging systems. Results Nucleotyping and DNA ploidy were significant prognostic factors, while stroma-tumour fraction were not significantly prognostic in the univariate analysis. In the multivariable model, the dominant contributory factor of disease-free survival was chromatin heterogeneous vs. chromatin homogeneous [HR 3.309 (95% CI: 1.668–6.564), P = 0.001]. Conclusions Our study indicates that nucleotyping is an independent prognostic factor in high-risk stage II colon cancer. Therefore, it may help subdivide patients into different subgroups and give them different strategies for follow-up and treatment in the future.
Background: Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This multicentre randomised controlled trial (RCT) aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. Methods: This superiority phase III trial was undertaken at 17 hospitals in 9 provinces of China. Patients with adenocarcinoma located between the cecum and the right third of the transverse colon, without evidence of distant metastases, were randomly assigned (in a 1:1 ratio) to receive either CME or D2 dissection during laparoscopic right colectomy. Morbidity and mortality in the first 30 days after surgery were compared between the two groups using a modified intention-to-treat (mITT) analysis. Findings: A total of 1072 patients were enrolled between January 11, 2016, and December 26, 2019. Of these patients, 995 (495 CME patients, 500 D2 patients) were included in the mITT analysis. The 30-day postoperative morbidity rate was 19·6% in the CME group vs. 21·8% in the D2 group (difference, -2·2% [95%CI, -0·07, - 0·03]; P = 0·34); no deaths occurred in either group. The CME procedures harvested significantly more lymph nodes (26·0 vs 23·0, difference, 3·4 [95%CI, 2·0, 4·9]; P<0·001), and larger mesentery areas (116·4 cm2 vs 107·8 cm2; difference, 8·4 [95%CI, 3·3, 13·5]; P = 0·001), but took longer time (163·0 minutes vs 150·5 minutes, difference 11·6 [95%CI, 5·7, 17·5]; P = 0·0002), and slight more blood loss (50 mL vs 50 mL, difference 5·4 [95%CI, -2·6, 13·4]; P = 0·049) than D2 dissections. Interpretation: When performed by experienced surgeons, CME during laparoscopic right hemicolectomy does not increase risk for intra/postoperative complications.Trial Registration: This study was registered with ClinicalTrials.gov (No.NCT02619942.)Funding Statement: This trial was sponsored by the Capital Characteristic Clinical Project of Beijing Municipal Science & Technology Commission (Z161100000516014) and the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (2019XK320003).Declaration of Interests: We declare that we have no conflicts of interest.Ethics Approval Statement: The study protocol and all amendments were approved by the Ethics Committee of Peking Union Medical College Hospital. Approval of the local ethics committee at each centre was also obtained before starting the study. All patients provided written informed consent.
BACKGROUND Malignant bowel obstruction (MBO) is a common event for end-stage gastrointestinal cancer patients. Previous studies had demonstrated manifestations and clinical management of MBO with mixed malignancies. There still lack reports of the surgical treatment of MBO. AIM To analyze the short-term outcomes and prognosis of palliative surgery for MBO caused by gastrointestinal cancer. METHODS A retrospective chart review of 61 patients received palliative surgery between January 2016 to October 2018 was performed, of which 31 patients underwent massive debulking surgery (MDS) and 30 underwent ostomy/by-pass surgery (OBS). The 60-d symptom palliation rate, 30-d morbidity and mortality, and overall survival rates were compared between the two groups. RESULTS The overall symptom palliation rate was 75.4% (46/61); patients in the MDS group had significantly higher symptom palliation rate than OBS group (90% vs 61.2%, P = 0.016). Patients with colorectal cancer who were in the MDS group showed significantly higher symptom improvement rates compared to the OBS group (overall, 76.4%; MDS, 61.5%; OBS, 92%; P = 0.019). However, patients with gastric cancer did not show a significant difference in symptom palliation rate between the MDS and OBS groups (OBS, 60%; MDS, 80%; P = 1.0). The median survival time in the MDS group was significantly longer than in the OBS group (10.9 mo vs 5.3 mo, P = 0.05). CONCLUSION For patients with MBO caused by peritoneal metastatic colorectal cancer, MDS can improve symptom palliation rates and prolong survival, without increasing mortality and morbidity rates.
Circular RNAs (circRNAs) are an emerging class of non-coding RNAs, identified to participate in multiple malignancies. Nevertheless, the clinical significance, biological function, and regulatory mechanisms of circRNAs in colon cancer (CC) remain largely unclear. In this study, the circRNA expression profile in CC and matched normal tissues was analyzed using circRNA microarrays. A novel circRNA, circCTNNA1, was significantly upregulated in CC, and its level was associated with advanced tumor–node–metastasis stage and poor prognosis of patients with CC. Functional experiments, including Cell Counting Kit-8, colony formation, 5‐ethynyl‐2′‐deoxyuridine, transwell, wound healing, flow cytometric analysis, and in vivo tumorigenesis assay were then performed to investigate the oncogenic role of circCTNNA1. The results revealed that circCTNNA1 promoted CC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, RNA pull-down, RNA immunoprecipitation, dual-luciferase reporter assays, and fluorescent in situ hybridization were performed to unveil that circCTNNA1 can serve as a competing endogenous RNA of miR-149-5p to counteract the suppressive effect of miR-149-5p on downstream target Forkhead Box M1 (FOXM1). In summary, our study demonstrated that circCTNNA1 facilitated CC proliferation and invasion via the circCTNNA1/miR-149-5p/FOXM1 axis, and it might function as a novel diagnostic or therapeutic target for patients with CC.
Objective: To understand the perceptions, attitudes and treatment selection of Chinese surgeons on the "watch and wait" strategy for rectal cancer patients after achieving a clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT). Methods: A cross-sectional survey was used in this study. Selection of subjects: (1) Domestic public grade III A (provincial and prefecture-level) oncology hospitals or general hospitals possessing the radiotherapy department and the diagnosis and treatment qualifications for colorectal cancer. (2) Surgeons of deputy chief physician or above. Using the "Questionnaire Star" online survey platform to create a questionnaire about cognition, attitude and treatment choice of the "watch and wait" strategy after cCR following nCRT for rectal cancer. The questionnaire contained 32 questions, such as the basic information of doctor, the current status of rectal cancer surgery, the management of pathological complete remission (ypCR) after nCRT for rectal cancer, the selection of examination items for diagnosis of cCR, the selection of suitable people undergoing "watch and wait" approach, the nCRT mode for promotion of cCR, the choice of evaluation time point, the willingness to perform "watch and wait" approach and the treatment choice, and the risk and monitoring of "watch and wait" approach. A total of 116 questionnaires were sent to the respondents via WeChat between January 31 and February 19, 2019. Statistical analysis was performed using Fisher's exact test for categorical variables. Results: Forty-eight hospitals including 116 surgeons meeting criteria were enrolled, of whom 77 surgeons filled the questionnaire with a response rate of 66.4%. "Watch and wait" strategy was carried out in 76.6% (59/77) of surgeons. Seventy surgeons (90.9%) were aware of the ypCR rate of rectal cancer after preoperative nCRT and 49 surgeons (63.6%) knew the 3-year disease-free survival of patients with ypCR in their own hospitals. Fifty-five surgeons (71.4%) believed that patients with ypCR undergoing radical surgery met the treatment criteria and were not over-treated. Three most necessary examinations in diagnosing cCR were colonoscopy (96.1%, 74/77), digital rectal examination (DRE) (90.9%,70/77) and DWI-MRI (83.1%, 64/77). Responders preferred to consider a "watch and wait" strategy for patients with baseline characteristics as mrN0 (77.9%, 60/77), mrT2 (68.8%, 53/77) and well-differentiated adenocarcinoma (68.8%, 53/77). Sixty-six surgeons (85.7%) believed that long-term chemoradiotherapy (LCRT) with combination or without combination of induction and/or consolidation of the CapeOX regimen (capecitabine + oxaliplatin) should be the first choice as a neoadjuvant therapy to achieve cCR. Forty-one surgeons (53.2%) believed that a reasonable interval of judging cCR after nCRT should be ≥ 8 weeks. Forty-four surgeons (57.1%) routinely, or in most cases, informed patient the possibility of cCR and proposed to "watch and wait" strategy in the initial diagnosis of patients with non-metastatic rectal cancer. Thirteen surgeons (16.9%) would take the "watch and wait" strategy as the first choice after the patient having cCR. Fifty-two surgeons (67.5%) would be affected by the surgical method, that was to say, "watch and wait" approach would only be recommended to those patients who would achieve cCR and could not preserve the anus or underwent difficult anus-preservation surgery. Sixteen surgeons (20.8%) demonstrated that "watch and wait" strategy would not be recommended to patients with cCR regardless of whether the surgical procedure involved anal sphincter. Eleven surgeons (14.3%) believed that the main risk of "watch and wait" approach came from distant metastasis rather than local recurrence or regrowth. Twenty-nine of surgeons (37.7%) did not understand the difference between "local recurrence" and "local regrowth" during the period of "watch and wait". Twenty-six surgeons (33.8%) thought that the monitoring interval for the first 3 years of "watch and wait" strategy was 3 months, and the follow-up monitoring interval could be 6 months to 5 years. Surgeons from cancer specialist hospitals had higher approval rate, notification rate, and referral rate of "watch and wait" strategy than those from general hospitals. Thirty-one surgeons (42.5%) considered that the difficulty and concern of carrying out "watch and wait" approach in the future was the disease progress leading to medical disputes. Twenty-six surgeons (35.6%) demonstrated that their concern was lack of uniform evaluation standard for cCR. Conclusions: Chinese surgeons seem to have inadequate knowledge of non-operative management for rectal cancer patients achieving cCR after nCRT and show relatively conservative attitudes toward the strategy. Chinese consensus needs to be formed to guide the non-operative management in selected patients. Chinese Watch & Wait Database (CWWD) is also needed to establish and provide more evidence for the use of alternative procedure after a cCR following nCRT.
目的 探讨中低位直肠癌新辅助放化疗后行经肛门局部切除的有效性和安全性.方法 回顾性分析2011年3月至2016年6月北京大学肿瘤医院胃肠肿瘤中心诊治的行新辅助放化疗并接受经肛门局部切除的19例中低位直肠癌病人的临床资料.主要的研究终点为:无病生存(disease free survival)、术后短期(1个月)并发症;次要研究终点为:术后1年的生活质量和肛门功能.结果 肿瘤直径为1.0(0.3~3.0)cm.8例(42.1%)肿瘤位于前壁,6例(31.6%)位于后壁,3例(15.8%)位于左侧壁,2例(10.5%)位于右侧壁;肿瘤距肛缘中位距离为4.0(1.5~12.0)cm;术后病理学检查示,ypT0 12例(63.2%),ypT1 3例(15.8%),ypT24例(21.1%).放化疗结束距手术的时间间隔为4.3(2.0~36.0)个月.局部切除手术时间为50(20~137)min,术中出血量为10(0~50)mL,术后住院时间为4(1~5)d.随访30(2~62)个月,1例局部复发,3例出现远处转移(1例腹盆腔和2例肺转移),肿瘤复发率为21.1%(4/19).局部切除病例肛门功能评分术前和术后差异无统计学意义(P>0.05),而TME病例肛门功能评分术前和术后差异有统计学意义(P<0.05).局部切除病例术后生活质量(EORTC QLQ-C30)和肛门功能(Wexner)评分低于同期TME手术组(P<0.01).结论 中低位直肠癌新辅助放化疗后,ycT0~2N0病例行经肛门局部切除是一种安全可行的治疗选择,可获得较好的肛门功能保留和生活质量.
目的:了解多学科协作(multidisciplinary team,MDT)模式下直肠癌术后肺转移治疗决策现状和结局,为加强医疗质量管理、完善MDT模式提供依据.方法:回顾性收集2007年7月至2015年2月北京大学肿瘤医院680例接受术前新辅助治疗联合根治术的直肠癌患者临床资料,调查术后发生肺转移的患者在MDT模式下的治疗决策、执行情况和生存结局.结果:研究纳入85例术后肺转移患者,68例采用MDT模式治疗,其中28例建议行局部根治,40例建议行姑息治疗;决策总执行率为89.7%(61/68),未执行者均选择进一步保守治疗.局部根治的患者在直肠原发灶术后首次发生复发/转移后的3年复发/转移后生存率(survival after recurrence,SAR)高于姑息治疗患者(84.8%vs.37.6%,P<0.001).结论:在MDT模式运行良好的情况下,直肠癌根治术后肺转移的治疗决策执行率较高,部分患者在该模式下有机会获得根治且预后良好;引入"患者参与"和"社会支持"将有助于构建全新MDT模式和提高医疗质量管理水平.
The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts’ clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.
e15670 Background: Overall survival (OS) and disease free survival (DFS) advantage conferred on patients with stage II colon cancer remains unproven and controversial. In addition, optimal adjuvant chemotherapy regimen for stage II disease remains debatable. The FOLFOX regimen was superior to short-term FU/LV in the MOSAIC trial, however, OS and DFS benefit was limited to stage III disease. An investigative analysis showed an absolute difference in 5-year DFS that favored FOLFOX in stage II patients with high-risk tumors, but it was not statistically significant. The SEER study showed no difference in median 5-years OS between patients in chemotherapy group and the surveillance group (56.1% vs 56.7%). The promise of precision medicine and cognitive technology tools such as IBM Watson for Oncology (WFO) may be beneficial for facilitating personalized treatment choices based on evidence and survival outcomes. Methods: This study leveraged WFO for treatment evidence comparison. We measured survival outcomes and prognostic factors for 229 patients with Stage II colon who received resection between 2006-2015. Five-year OS and DFS was examined using the Kaplan Meier survival analysis, and comparison of OS and DFS curve was performed by log rank test. Results: The 3-year OS, 5-year OS, 3-year DFS and 5-year DFS, were 92.1, 88.5, 87.2, and 83.0%, respectively. Patients that received chemotherapy had significantly higher 5-year OS than those received surveillance (94.9% vs 84.1%, p = 0.03). OS and DFS was significantly shorter in patients with 2 or more risk factors (log rank test, p = 0.01 and 0.02 respectively). Conclusions: Study showed overall superior OS and DFS compared to patients in real world studies including trials in WFO curated literature. Limitations of this study included use of retrospective cases, inadequate number of cases with 2 or more prognostic factors and uneven clinicopathological features for the analysis. Performance status and co-morbidities were not assessed, which may influence survival outcomes. Nonetheless this study was important for assessing survival outcomes in Chinese patients with Stage II colon cancer. This suggests need for further clinical trials targeting this group.
e18582 Background: Studies have demonstrated the benefits of adjuvant chemotherapy in patients with stage III colon cancer. However, benefits of adjuvant chemotherapy for patients with Stage II disease are less certain. Various factors, including clinicopathologic, and MSI phenotypes, are typically used to guide care, but treatment in high-risk patients remain variable. Clinical decision support (CDS) technologies armed with machine learning continue to demonstrate potential to transform standard of care, decrease treatment disparities and improve patient quality of cancer care. Methods: A cross-sectional retrospective concordance study was conducted to assess recommendations provided by IBM Watson for Oncology (WFO), a CDS system, and a multidisciplinary tumor board (MDT) decision for treatment of Stage II colon cancer. 229 patients seen at Beijing Cancer Hospital were used in the analysis. Clinical and pathological features associated with worse prognosis and defined as high risk by the MDT, included T4 primary, high-grade, poorly differentiated histology (grade 3/4 excluding MSI-H), lymphovascular invasion, bowel obstruction or perforation, perineural invasion, and inadequately sampled lymph nodes. Subgroup concordance analyses of clinicopathologic features were conducted to examine the groups that might derive some benefit from the use of WFO where evidence was limited. Results: Overall concordance was 89.1% (204/229) with high-risk subgroup results ranging from 87.5% (p = 0.68) in T4 primary to 92.7% (p = 0.02) in poorly differentiated histology. Concordance in MSI subgroup was highly significant, MSI-H 71.4% vs MSI-L 94.5% (p = 0.0). Concordance with actual treatment decisions for tumor grade was statistically significant (p = 0.02). Reasons for non-concordance included different age threshold for oxaliplatin in elderly patients and preference for capecitabine for MSI-H. Conclusions: WFO generated treatment recommendation for Stage II colon cancer can potentially augment the clinical decision-making process within MDT. Future studies are needed to assess benefits for integrating local treatment and evidence for use outside of MDT settings.
Objective To explore the applying values of comprehensive nursing intervention in perioperative period of rectal cancer patients underwent Dixon.Methods From February 2012 to January 2016,86 patients with rectal cancer in Peking University Cancer Hospital were selected and divided into observation group and control group by envelope method,with 43 cases in each group.All patients were treated with Dixon,and the control group was treated with the perioperative routine nursing,while the observation group was treated with comprehensive nursing care based on the control group.The prognosis and nursing satisfaction of the two groups were recorded.Results The exhaust time,defecation time and postoperative hospital stay in the observation group were significantly less than that those in the control group (P < 0.05).At discharge,the nursing satisfaction of the observation group was significantly higher than that of the control group (P < 0.05).One month after operation,occurrence of complications in the observation group was significantly lower than that of the control group (P < 0.05).Conclusion The comprehensive nursing intervention can be conducive to the rehabilitation of patients,reduce the incidence of complications,and improve nursing satisfaction of patients,which is applied in perioperative nursing in patients with rectal cancer underwent Dixon.
目前, 结直肠癌的辅助化疗多采用基于氟尿嘧啶药物的化疗方案. 肿瘤TNM分期是最常用也是最有效的预后指标, 也为术后是否需要辅助化疗提供了直接的参考依据.NSABP C-07试验表明, 与单纯氟尿嘧啶药物化疗方案相比,在5-氟尿嘧啶-甲酰四氢叶酸(5-FU/LV)方案基础上增加奥沙利铂, 可以显著延长Ⅱ期和Ⅲ期结肠癌患者的无病生存时间(disease-free survival,DFS)[1-2]. 然而,TNM分期相同的患者对化疗的反应性并不相同, 并非所有的患者都能从化疗中获益[3].因此,需要在传统TNM分期基础之上增加新的危险评估手段或探索新的预后标志物.
OBJECTIVE:To investigate the effect of adjuvant chemotherapy on the prognosis of stage II( colon cancer patients with high risk factors.METHODS:Clinicopathological and follow-up data of stage II( colon cancer patients undergoing radical surgery from January 2001 to March 2012 at Gastrointestinal Cancer Center of Peking University Cancer Hospital were retrospectively analyzed. The effect of adjuvant chemotherapy (within postoperative 2 month, fluorine uracil as main drugs) on the prognosis of high-risk patients was analyzed. High risk factors were defined as having at least one of the following factors: (1) tumor stage T4; (2) poor differentiation; (3) with vascular cancer embolus; (4) number of harvested lymph node less than 12; (5) complicated with obstruction or perforation.RESULTS:A total of 497 patients with stage II( colon cancer were included in this study, of whom 258 cases(51.9%) had high risk factors, including stage T4 tumor in 80 cases(16.1%), poor differentiation in 80 cases (16.1%), cancer embolus in 37 cases (7.4%), lymph node harvested number less than 12 in 88 cases (17.7%), and obstruction or perforation in 85 cases (17.1%). Among 497 patients, number of cases with 1 to 4 high risk factors was 170 (34.2%), 68 (13.7%), 16 (3.2%) and 4 (0.8%), respectively. The last follow-up time was December 2016. The 5-year overall survival rate of all the 497 patients was 81.7%. The 5-year overall survival rate of 239 patients without high risk factors was 87.0%. The 5-year survival rate in patients with 1 to 4 risk factors was 81.9%, 73.7%, 66.7% and 25.0%, respectively (P=0.001). There was no significant difference in 5-year survival rate between 103 patients with adjuvant chemotherapy and 394 patients without adjuvant chemotherapy (79.6% vs. 82.8%, P=0.814). In patients with high risk factors, 80(31.0%) received adjuvant chemotherapy. There was no significant difference of 5-year survival rate between 80 patients with adjuvant chemotherapy and 178 patients without adjuvant chemotherapy (81.4% vs. 74.7%, P=0.147). Multivariate analysis showed that preoperative CEA level, T4 stage, lymph node harvested number, and tumor differentiation were the independent prognostic factors of patients with stage II( colon cancer (all P<0.05).CONCLUSIONS:The proportion of patients with at least one risk factor is quite high in stage II( colon cancer cases. Adjuvant chemotherapy can not prolong the overall survival time of high risk patients.