1文献来源Le D T,Kim T W,Van Cutsem E,et al.PhaseⅡopen⁃label study of pembrolizumab in treatment⁃refractory,microsatellite instability⁃high/mismatch repair⁃deficient metastatic colorectal cancer:KEYNOTE⁃164[J].J Clin ...1文献来源Le D T,Kim T W,Van Cutsem E,et al.PhaseⅡopen⁃label study of pembrolizumab in treatment⁃refractory,microsatellite instability⁃high/mismatch repair⁃deficient metastatic colorectal cancer:KEYNOTE⁃164[J].J Clin Oncol,2019,38(1):11-19.2证据水平2a。3背景•微卫星高度不稳定性(microsatellite instability high,MSI⁃H)或错配修复功能缺陷(mismatch repair⁃deficient,dMMR)结直肠癌患者的预后比微卫星稳定(microsatellite stability,MSS)结直肠癌患者的预后差。展开更多
Brain metastasis in colorectal cancer is a rare occurrence with poor prognosis and limited treatment options.This case report presents a unique and previously unreported case of brain metastasis in a patient with dMMR...Brain metastasis in colorectal cancer is a rare occurrence with poor prognosis and limited treatment options.This case report presents a unique and previously unreported case of brain metastasis in a patient with dMMR(DNA mismatch repair-deficient)colorectal cancer.The patient,a 70-year-old male,initially presented with abdominal pain and was diagnosed with moderately differentiated adenocarcinoma of the right colon.Following surgical resection and adjuvant chemotherapy,the patient developed cognitive decline and was found to have a metastatic lesion in the left temporal lobe.Immunohistochemical analysis revealed MSH2 positivity and MSH6,MLH1,and PMS2 negativity,indicating dMMR status.Further genetic testing showed wild-type Kras,Nras,and Braf,and high tumor mutational burden(TMB).The patient was subsequently treated with pembrolizumab immunotherapy,resulting in a significant improvement of symptoms and a reduction in the size of brain metastasis.This case highlights the rarity and challenging management of brain metastasis in colorectal cancer,particularly in the context of dMMR tumors.The successful use of immunotherapy in this case provides valuable insights into the potential efficacy of immune-based treatments for dMMR colorectal cancer with brain metastasis,underscoring the need for further research in this field.展开更多
1文献来源Chalabi M,Fanchi L F,Dijkstra K K,et al.Neoadjuvant immunotherapy leads to pathological responses in MMR⁃proficient and MMR⁃deficient early⁃stage colon cancers[J].Nat Med,2020,26(4):566-576.2证据水平1b。3背景...1文献来源Chalabi M,Fanchi L F,Dijkstra K K,et al.Neoadjuvant immunotherapy leads to pathological responses in MMR⁃proficient and MMR⁃deficient early⁃stage colon cancers[J].Nat Med,2020,26(4):566-576.2证据水平1b。3背景•程序性死亡受体⁃1(programmed cell death 1,PD⁃1)和细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte⁃associated antigen⁃4,CTLA⁃4)抑制剂的治疗方案对错配修复功能缺陷(mismatch repair⁃deficient,dMMR)的晚期结直肠癌非常有效,但在错配修复功能完整(proficient mismatch repair,pMMR)的晚期结直肠癌患者中疗效不佳。展开更多
BACKGROUND Programmed death protein(PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient(dMMR)/microsatellite instability-high(MSI-H)gastrointestinal malig...BACKGROUND Programmed death protein(PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient(dMMR)/microsatellite instability-high(MSI-H)gastrointestinal malignancies such gastric and colorectal cancer.However,the data on preoperative immunotherapy are limited.AIM To evaluate the short-term efficacy and toxicity of preoperative PD-1 blockade immunotherapy.METHODS In this retrospective study,we enrolled 36 patients with dMMR/MSI-H gastrointestinal malignancies.All the patients received PD-1 blockade with or without chemotherapy of CapOx regime preoperatively.PD1 blockade 200 mg was given intravenously over 30 min on day 1 of each 21-d cycle.RESULTS Three patients with locally advanced gastric cancer achieved pathological complete response(pCR).Three patients with locally advanced duodenal carcinoma achieved clinical complete response(cCR),followed by watch and wait.Eight of 16 patients with locally advanced colon cancer achieved pCR.All four patients with liver metastasis from colon cancer reached CR,including three with pCR and one with cCR.pCR was achieved in two of five patients with nonliver metastatic colorectal cancer.CR was achieved in four of five patients with low rectal cancer,including three with cCR and one with pCR.cCR was achieved in seven of 36 cases,among which,six were selected for watch and wait strategy.No cCR was observed in gastric or colon cancer.CONCLUSION Preoperative PD-1 blockade immunotherapy in dMMR/MSI-H gastrointestinal malignancies can achieve a high CR,especially in patients with duodenal or low rectal cancer,and can achieve high organ function protection.展开更多
Colon cancer is a leading cause of cancer-related mortality worldwide,with surgical resection followed by adjuvant chemotherapy being the traditional standard for localized disease.However,the emergence of neoadjuvant...Colon cancer is a leading cause of cancer-related mortality worldwide,with surgical resection followed by adjuvant chemotherapy being the traditional standard for localized disease.However,the emergence of neoadjuvant therapies has introduced new possibilities for improving outcomes in locally advanced colon cancer(LACC).Neoadjuvant chemotherapy has demonstrated promising results in tumor downstaging,improved resectability,and reduced recurrence rates,as highlighted in trials like FOxTROT(Fluoropyrimidine oxaliplatin and targeted receptor pre-operative therapy),OPTICAL(A phase III study to evaluate the 3-year disease-free survival in patients with locally advanced colon cancer receiving either perioperative or postoperative chemotherapy with FOLFOX or CAPOX regimens),and NeoCol(Neoadjuvant chemotherapy versus standard treatment in patients with locally advanced colon cancer).For deficient mismatch repair(dMMR)tumors,neoadjuvant immunotherapy,exemplified by the NICHE(Neoadjuvant immune checkpoint inhibition and novel IO combinations in early-stage colon cancer)trial,has shown good pathologic response rates.Despite these advancements,challenges such as disease progression during treatment,staging inaccuracies,and chemotherapy-related toxicities underscore the need for precise patient selection and monitoring.Immunotherapy offers significant potential for dMMR tumors,potentially leading to non-surgical management strategies,while neoadjuvant chemotherapy presents a viable option for MMR-proficient(pMMR)patients,improving long-term outcomes in select populations.As the landscape of LACC management evolves,this review emphasizes the importance of personalized treatment strategies informed by biomarkers such as MMR status to maximize therapeutic efficacy and minimize risks.Future directions include refining the role of neoadjuvant therapies in clinical practice,expanding the use of immunotherapy,and exploring innovative combinations of systemic and targeted approaches to enhance survival and quality of life in patients with LACC.This review examines the current evidence supporting neoadjuvant approaches in pMMR and dMMR colon cancer,emphasizing their potential benefits and challenges.展开更多
文摘1文献来源Le D T,Kim T W,Van Cutsem E,et al.PhaseⅡopen⁃label study of pembrolizumab in treatment⁃refractory,microsatellite instability⁃high/mismatch repair⁃deficient metastatic colorectal cancer:KEYNOTE⁃164[J].J Clin Oncol,2019,38(1):11-19.2证据水平2a。3背景•微卫星高度不稳定性(microsatellite instability high,MSI⁃H)或错配修复功能缺陷(mismatch repair⁃deficient,dMMR)结直肠癌患者的预后比微卫星稳定(microsatellite stability,MSS)结直肠癌患者的预后差。
文摘Brain metastasis in colorectal cancer is a rare occurrence with poor prognosis and limited treatment options.This case report presents a unique and previously unreported case of brain metastasis in a patient with dMMR(DNA mismatch repair-deficient)colorectal cancer.The patient,a 70-year-old male,initially presented with abdominal pain and was diagnosed with moderately differentiated adenocarcinoma of the right colon.Following surgical resection and adjuvant chemotherapy,the patient developed cognitive decline and was found to have a metastatic lesion in the left temporal lobe.Immunohistochemical analysis revealed MSH2 positivity and MSH6,MLH1,and PMS2 negativity,indicating dMMR status.Further genetic testing showed wild-type Kras,Nras,and Braf,and high tumor mutational burden(TMB).The patient was subsequently treated with pembrolizumab immunotherapy,resulting in a significant improvement of symptoms and a reduction in the size of brain metastasis.This case highlights the rarity and challenging management of brain metastasis in colorectal cancer,particularly in the context of dMMR tumors.The successful use of immunotherapy in this case provides valuable insights into the potential efficacy of immune-based treatments for dMMR colorectal cancer with brain metastasis,underscoring the need for further research in this field.
文摘1文献来源Chalabi M,Fanchi L F,Dijkstra K K,et al.Neoadjuvant immunotherapy leads to pathological responses in MMR⁃proficient and MMR⁃deficient early⁃stage colon cancers[J].Nat Med,2020,26(4):566-576.2证据水平1b。3背景•程序性死亡受体⁃1(programmed cell death 1,PD⁃1)和细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte⁃associated antigen⁃4,CTLA⁃4)抑制剂的治疗方案对错配修复功能缺陷(mismatch repair⁃deficient,dMMR)的晚期结直肠癌非常有效,但在错配修复功能完整(proficient mismatch repair,pMMR)的晚期结直肠癌患者中疗效不佳。
基金Supported by the National Natural Science Foundation of China,No.82173156Beijing Hospitals Authority Clinical Medicine Development of Special Funding,No.ZYLX202116.
文摘BACKGROUND Programmed death protein(PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient(dMMR)/microsatellite instability-high(MSI-H)gastrointestinal malignancies such gastric and colorectal cancer.However,the data on preoperative immunotherapy are limited.AIM To evaluate the short-term efficacy and toxicity of preoperative PD-1 blockade immunotherapy.METHODS In this retrospective study,we enrolled 36 patients with dMMR/MSI-H gastrointestinal malignancies.All the patients received PD-1 blockade with or without chemotherapy of CapOx regime preoperatively.PD1 blockade 200 mg was given intravenously over 30 min on day 1 of each 21-d cycle.RESULTS Three patients with locally advanced gastric cancer achieved pathological complete response(pCR).Three patients with locally advanced duodenal carcinoma achieved clinical complete response(cCR),followed by watch and wait.Eight of 16 patients with locally advanced colon cancer achieved pCR.All four patients with liver metastasis from colon cancer reached CR,including three with pCR and one with cCR.pCR was achieved in two of five patients with nonliver metastatic colorectal cancer.CR was achieved in four of five patients with low rectal cancer,including three with cCR and one with pCR.cCR was achieved in seven of 36 cases,among which,six were selected for watch and wait strategy.No cCR was observed in gastric or colon cancer.CONCLUSION Preoperative PD-1 blockade immunotherapy in dMMR/MSI-H gastrointestinal malignancies can achieve a high CR,especially in patients with duodenal or low rectal cancer,and can achieve high organ function protection.
文摘Colon cancer is a leading cause of cancer-related mortality worldwide,with surgical resection followed by adjuvant chemotherapy being the traditional standard for localized disease.However,the emergence of neoadjuvant therapies has introduced new possibilities for improving outcomes in locally advanced colon cancer(LACC).Neoadjuvant chemotherapy has demonstrated promising results in tumor downstaging,improved resectability,and reduced recurrence rates,as highlighted in trials like FOxTROT(Fluoropyrimidine oxaliplatin and targeted receptor pre-operative therapy),OPTICAL(A phase III study to evaluate the 3-year disease-free survival in patients with locally advanced colon cancer receiving either perioperative or postoperative chemotherapy with FOLFOX or CAPOX regimens),and NeoCol(Neoadjuvant chemotherapy versus standard treatment in patients with locally advanced colon cancer).For deficient mismatch repair(dMMR)tumors,neoadjuvant immunotherapy,exemplified by the NICHE(Neoadjuvant immune checkpoint inhibition and novel IO combinations in early-stage colon cancer)trial,has shown good pathologic response rates.Despite these advancements,challenges such as disease progression during treatment,staging inaccuracies,and chemotherapy-related toxicities underscore the need for precise patient selection and monitoring.Immunotherapy offers significant potential for dMMR tumors,potentially leading to non-surgical management strategies,while neoadjuvant chemotherapy presents a viable option for MMR-proficient(pMMR)patients,improving long-term outcomes in select populations.As the landscape of LACC management evolves,this review emphasizes the importance of personalized treatment strategies informed by biomarkers such as MMR status to maximize therapeutic efficacy and minimize risks.Future directions include refining the role of neoadjuvant therapies in clinical practice,expanding the use of immunotherapy,and exploring innovative combinations of systemic and targeted approaches to enhance survival and quality of life in patients with LACC.This review examines the current evidence supporting neoadjuvant approaches in pMMR and dMMR colon cancer,emphasizing their potential benefits and challenges.
