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
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。
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.
