Pub Date : 2024-11-10DOI: 10.1016/j.clcc.2024.10.003
Jian Li , YI BA , Rongbo Lin , Xiao Ke , Xianli yin , Jieer Ying , Ying Cheng , Nong Xu , Jiangming Xu , Yali Shen , Jianfeng Zhou , Jufeng Wang , Xiaoping Qian , Rong wu , Yanqiao Zhang , Lin Shen
Background
Patients with recurrent or metastatic advanced colorectal cancer (mCRC) often face the clinical dilemma as this unresectable disease is continuously progressing and endangering the patients’ lives. In the current study, we explored the clinical feasibility of KH903 in combination with FOLFIRI chemotherapy as a new clinical indication for mCRC.
Methods
Patients (N = 122) were randomized 1:1 to 4mg/kg q1w KH903 or 5mg/kg q2w KH903, and both groups of patients were treated with the fixed regimen of FOLFIRI (every 2 weeks) along with the KH903 therapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were Overall Survival (OS), objective response rate (ORR), and disease control rate (DCR).
Results
As of December 30, 2020, median (m)PFS was 5.68 months (95% CI, 4.67-7.13) with 4mg/kg q1w versus 5.19 months (95% CI, 4.04, 5.78) with 5mg/kg q2w (HR, 0.76; 95% CI, 0.50-1.16),and mOS was 13.14 months (95% CI, 10.61-19.52) versus 16.03 months (95% CI, 10.28- NE), respectively (HR, 1.11; 95% CI, 0.65-1.89), The ORR was 15.9% and 11.9% for both groups, respectively, and The DCR for both groups was 85.7% and 83.1%, respectively. Grade 3 or higher treatment-related adverse event rates for both groups were 68.3% vs.52.5%, respectively.
Conclusions
KH903 in combination with FORFIRI in second-line treatment of patients with mCRC showed prolonged mPFS and mOS, comparing to the similar agents (Avastin®, ZALTRAP®, Cyramza®) and no new safety signals were observed.
{"title":"Efficacy and Safety of KH903 Plus FOLFIRI as a Second-Line Treatment in Unresectable Recurrent or Metastatic Colorectal Cancer: A Randomized Phase 2 Study","authors":"Jian Li , YI BA , Rongbo Lin , Xiao Ke , Xianli yin , Jieer Ying , Ying Cheng , Nong Xu , Jiangming Xu , Yali Shen , Jianfeng Zhou , Jufeng Wang , Xiaoping Qian , Rong wu , Yanqiao Zhang , Lin Shen","doi":"10.1016/j.clcc.2024.10.003","DOIUrl":"10.1016/j.clcc.2024.10.003","url":null,"abstract":"<div><h3>Background</h3><div>Patients with recurrent or metastatic advanced colorectal cancer (mCRC) often face the clinical dilemma as this unresectable disease is continuously progressing and endangering the patients’ lives. In the current study, we explored the clinical feasibility of KH903 in combination with FOLFIRI chemotherapy as a new clinical indication for mCRC.</div></div><div><h3>Methods</h3><div>Patients (<em>N</em> = 122) were randomized 1:1 to 4mg/kg q1w KH903 or 5mg/kg q2w KH903, and both groups of patients were treated with the fixed regimen of FOLFIRI (every 2 weeks) along with the KH903 therapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were Overall Survival (OS), objective response rate (ORR), and disease control rate (DCR).</div></div><div><h3>Results</h3><div>As of December 30, 2020, median (m)PFS was 5.68 months (95% CI, 4.67-7.13) with 4mg/kg q1w versus 5.19 months (95% CI, 4.04, 5.78) with 5mg/kg q2w (HR, 0.76; 95% CI, 0.50-1.16),and mOS was 13.14 months (95% CI, 10.61-19.52) versus 16.03 months (95% CI, 10.28- NE), respectively (HR, 1.11; 95% CI, 0.65-1.89), The ORR was 15.9% and 11.9% for both groups, respectively, and The DCR for both groups was 85.7% and 83.1%, respectively. Grade 3 or higher treatment-related adverse event rates for both groups were 68.3% vs.52.5%, respectively.</div></div><div><h3>Conclusions</h3><div>KH903 in combination with FORFIRI in second-line treatment of patients with mCRC showed prolonged mPFS and mOS, comparing to the similar agents (Avastin®, ZALTRAP®, Cyramza®) and no new safety signals were observed.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 89-97"},"PeriodicalIF":3.3,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1016/j.clcc.2024.10.002
Sara Bastian , Markus Joerger , Lisa Holer , Daniela Bärtschi , Matthias Guckenberger , Wolfram Jochum , Dieter Koeberle , Alexander R. Siebenhüner , Andreas Wicki , Martin D. Berger , Ralph C. Winterhalder , Carlo R. Largiadèr , Melanie Löffler , Katarzyna Mosna-Firlejczyk , Angela Fischer Maranta , Bernhard C. Pestalozzi , Chantal Csajka , Roger von Moos , Swiss Group for Clinical Cancer Research (SAKK)
Background
The multi tyrosine kinase inhibitor regorafenib is active in metastatic colorectal cancer. Improvement in clinical outcome by adding regorafenib to long-course chemoradiotherapy (LcCRT) was investigated in molecularly undefined LARC.
Methods
Patients with T3-4 and/or N+ but M0 rectal cancer were included. Neoadjuvant LcRCT consisted in capecitabine (C) 825mg/m2 d1-d38 and 28 fractions of 1.8Gy (50.4Gy). Regorafenib was added d1-14 and d22-35 in 3 dose escalation (DE) cohorts (40mg/80mg/120mg). The recommended dose (RD) was used for the expansion (EXP) cohort. Primary endpoints were dose-limiting toxicity (DLT) for DE and pathological response (near-complete regression [npCR] or complete regression [pCR]) for EXP.
Results
Overall, 25 patients were included. Two DLTs occurred at the regorafenib dose level of 120 mg, thereby establishing the RD at 80mg daily. Among the 19 patients who were treated at the RD, 8 (42.1%; 1-sided 80% confidence interval [CI] (lower bound): 30.7%; 95% CI, 20.3%-66.5%) reached the primary endpoint (5 [26.3%] had npCR and 3 [15.8%] pCR). One additional patient received no surgery due to clinical complete response. All patients had R0 resections and clear circumferential margins. Postoperative complications occurred in 6 patients (35.3%). The most common grade ≥ 3 treatment-related adverse event in the EXP cohort was diarrhea (2 patients).
Conclusion
Adding regorafenib 80 mg to LcCRT in LARC resulted in both primary endpoints being met and yielded an expected pathological response rate. Toxicity was manageable, and postoperative complications were as expected.
{"title":"Neoadjuvant Treatment With Regorafenib and Capecitabine Combined With Radiotherapy in Locally Advanced Rectal Cancer: A Multicenter Phase Ib Trial (RECAP)–SAKK 41/16","authors":"Sara Bastian , Markus Joerger , Lisa Holer , Daniela Bärtschi , Matthias Guckenberger , Wolfram Jochum , Dieter Koeberle , Alexander R. Siebenhüner , Andreas Wicki , Martin D. Berger , Ralph C. Winterhalder , Carlo R. Largiadèr , Melanie Löffler , Katarzyna Mosna-Firlejczyk , Angela Fischer Maranta , Bernhard C. Pestalozzi , Chantal Csajka , Roger von Moos , Swiss Group for Clinical Cancer Research (SAKK)","doi":"10.1016/j.clcc.2024.10.002","DOIUrl":"10.1016/j.clcc.2024.10.002","url":null,"abstract":"<div><h3>Background</h3><div>The multi tyrosine kinase inhibitor regorafenib is active in metastatic colorectal cancer. Improvement in clinical outcome by adding regorafenib to long-course chemoradiotherapy (LcCRT) was investigated in molecularly undefined LARC.</div></div><div><h3>Methods</h3><div>Patients with T3-4 and/or N+ but M0 rectal cancer were included. Neoadjuvant LcRCT consisted in capecitabine (C) 825mg/m<sup>2</sup> d1-d38 and 28 fractions of 1.8Gy (50.4Gy). Regorafenib was added d1-14 and d22-35 in 3 dose escalation (DE) cohorts (40mg/80mg/120mg). The recommended dose (RD) was used for the expansion (EXP) cohort. Primary endpoints were dose-limiting toxicity (DLT) for DE and pathological response (near-complete regression [npCR] or complete regression [pCR]) for EXP.</div></div><div><h3>Results</h3><div>Overall, 25 patients were included. Two DLTs occurred at the regorafenib dose level of 120 mg, thereby establishing the RD at 80mg daily. Among the 19 patients who were treated at the RD, 8 (42.1%; 1-sided 80% confidence interval [CI] (lower bound): 30.7%; 95% CI, 20.3%-66.5%) reached the primary endpoint (5 [26.3%] had npCR and 3 [15.8%] pCR). One additional patient received no surgery due to clinical complete response. All patients had R0 resections and clear circumferential margins. Postoperative complications occurred in 6 patients (35.3%). The most common grade ≥ 3 treatment-related adverse event in the EXP cohort was diarrhea (2 patients).</div></div><div><h3>Conclusion</h3><div>Adding regorafenib 80 mg to LcCRT in LARC resulted in both primary endpoints being met and yielded an expected pathological response rate. Toxicity was manageable, and postoperative complications were as expected.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 82-88.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1016/j.clcc.2024.10.001
Grace Y. Kim , Azim Jalali , Grace Gard , Justin M. Yeung , Hieu Chau , Lucy Gately , Nezor Houli , Ian T. Jones , Suzanne Kosmider , Belinda Lee , Margaret Lee , Louise Nott , Jeremy D. Shapiro , Jeanne Tie , Benjamin Thomson , Yat Hang To , Vanessa Wong , Rachel Wong , Catherine Dunn , Julie Johns , Peter Gibbs
Background
Surgery improves long-term survival for resectable, liver-only metastatic colorectal cancer (mCRC). With no consensus definition of “resectable” disease, decisions regarding resectability are reliant on the expertise and judgement of the treating clinician working in consultation with a multidisciplinary team (MDT). This study examines the clinical outcome versus initial assessment of resectability in an Australian population with mCRC.
Patients and Methods
Patients with liver-only mCRC diagnosed January 2009 to December 2022 were identified from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry. Patients were classified based on prospectively documented treatment assessment as “resectable,” “potentially resectable,” or “unresectable.” The correlation between initial assessment of resectability and clinical outcome, and any impact of clinicopathologic factors were examined. Kaplan-Meier analysis assessed overall survival based on initial resectability assessment and resection status.
Results
Of 4437 patients with mCRC identified through TRACC, 1250 (28%) had liver-only disease at presentation, with 497 (43%), 277 (24%), and 374 (33%) classified as “unresectable,” “potentially resectable,” and “resectable,” respectively. In total, 516 (41%) ultimately underwent surgical resection, including 30 (6%) of the “initially unresectable,” 148 (53%) of the “potentially resectable,” and 338 (90%) of the “resectable” at a median of 9.5, 5.9, and 2.4 months from the diagnosis of liver metastases, respectively. Resection in the “unresectable” patient population was associated with younger age (mean age 63 vs. 69, P = .0006), better performance status (ECOG 0-1 100% vs. 74%, P = .0017), and fewer comorbidities (Charlson index 0-3 in 73% vs. 53%, P = .0296) compared with no resection. Median overall survival was longer for resected versus nonresected patients across all categories: “unresectable” (59.2 vs. 17.6 months, P < .0001), “potentially resectable” (57.2 vs. 22.8 months, P < .0001), and “resectable” (108 vs. 55 months, P < .0001).
Conclusions
This real-world study demonstrates the potential for “initially unresectable” patients to become surgical candidates following systemic therapy, more likely in younger and fitter patients, with overall excellent survival outcomes in resected patients. This highlights the value of routine, repeated MDT assessments for patients with liver-only disease who are continuing to respond to systemic therapy, even for those initially considered never to be surgical candidates.
{"title":"Initial Assessment of Resectability of Colorectal Cancer Liver Metastases Versus Clinical Outcome","authors":"Grace Y. Kim , Azim Jalali , Grace Gard , Justin M. Yeung , Hieu Chau , Lucy Gately , Nezor Houli , Ian T. Jones , Suzanne Kosmider , Belinda Lee , Margaret Lee , Louise Nott , Jeremy D. Shapiro , Jeanne Tie , Benjamin Thomson , Yat Hang To , Vanessa Wong , Rachel Wong , Catherine Dunn , Julie Johns , Peter Gibbs","doi":"10.1016/j.clcc.2024.10.001","DOIUrl":"10.1016/j.clcc.2024.10.001","url":null,"abstract":"<div><h3>Background</h3><div>Surgery improves long-term survival for resectable, liver-only metastatic colorectal cancer (mCRC). With no consensus definition of “resectable” disease, decisions regarding resectability are reliant on the expertise and judgement of the treating clinician working in consultation with a multidisciplinary team (MDT). This study examines the clinical outcome versus initial assessment of resectability in an Australian population with mCRC.</div></div><div><h3>Patients and Methods</h3><div>Patients with liver-only mCRC diagnosed January 2009 to December 2022 were identified from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry. Patients were classified based on prospectively documented treatment assessment as “resectable,” “potentially resectable,” or “unresectable.” The correlation between initial assessment of resectability and clinical outcome, and any impact of clinicopathologic factors were examined. Kaplan-Meier analysis assessed overall survival based on initial resectability assessment and resection status.</div></div><div><h3>Results</h3><div>Of 4437 patients with mCRC identified through TRACC, 1250 (28%) had liver-only disease at presentation, with 497 (43%), 277 (24%), and 374 (33%) classified as “unresectable,” “potentially resectable,” and “resectable,” respectively. In total, 516 (41%) ultimately underwent surgical resection, including 30 (6%) of the “initially unresectable,” 148 (53%) of the “potentially resectable,” and 338 (90%) of the “resectable” at a median of 9.5, 5.9, and 2.4 months from the diagnosis of liver metastases, respectively. Resection in the “unresectable” patient population was associated with younger age (mean age 63 vs. 69, <em>P</em> = .0006), better performance status (ECOG 0-1 100% vs. 74%, <em>P</em> = .0017), and fewer comorbidities (Charlson index 0-3 in 73% vs. 53%, <em>P</em> = .0296) compared with no resection. Median overall survival was longer for resected versus nonresected patients across all categories: “unresectable” (59.2 vs. 17.6 months, <em>P</em> < .0001), “potentially resectable” (57.2 vs. 22.8 months, <em>P</em> < .0001), and “resectable” (108 vs. 55 months, <em>P</em> < .0001).</div></div><div><h3>Conclusions</h3><div>This real-world study demonstrates the potential for “initially unresectable” patients to become surgical candidates following systemic therapy, more likely in younger and fitter patients, with overall excellent survival outcomes in resected patients. This highlights the value of routine, repeated MDT assessments for patients with liver-only disease who are continuing to respond to systemic therapy, even for those initially considered never to be surgical candidates.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 72-81"},"PeriodicalIF":3.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-05DOI: 10.1016/j.clcc.2024.09.003
Ellen Hein Nordvig , Gull-Mai Bergliot Grønbæk , Zahra Khalid Al-Uboody , Jakob Lykke , Jakob Hagen Vasehus Schou , Laurids Østergaard Poulsen
Introduction
Total neoadjuvant treatment (TNT) with induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) has improved long-term outcomes for patients with locally advanced rectal cancer (LARC). However, long-term outcomes have not been investigated for patients with incomplete (R1) resection separately. This study investigates overall survival (OS), disease-free survival (DFS) and local and distant recurrence rates in patients with R1 resection after preoperative treatment with ICT and CRT or CRT.
Patients and methods
From the NORD database 689 patients with LARC who received treatment between 2006 and 2017 were screened for inclusion. All patients with R1 resection were included. ICT consisted of at least 1 cycle of capecitabine and oxaliplatin (CAPOX) and was followed by radiotherapy concomitant with capecitabine.
Results
Among 46 patients with R1 resection, 27 (59%) received both ICT and CRT, and 19 (41%) patients received CRT. The 5-year OS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 37% (95% CI, 15%-59%) (CRT) (P = .25) and 5-year DFS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 32% (95% CI, 11%-53%) (CRT) (P = .22). The local recurrence rates showed a small nonstatistical significant difference in local control in the ICT group: 15% compared to 26% in the CRT group (P = .22). Distant recurrence rates were similar: 41% (ICT + CRT) versus 47% (CRT) (P = .48).
Conclusion
There was no significant difference in OS, DFS or local and distant recurrence rates between patients who received ICT + CRT versus patients who received CRT only.
{"title":"Long-Term Outcomes in Patients With Locally Advanced Rectal Cancer Following R1 Resection After Either Induction Chemotherapy and Chemoradiotherapy or Chemoradiotherapy Alone","authors":"Ellen Hein Nordvig , Gull-Mai Bergliot Grønbæk , Zahra Khalid Al-Uboody , Jakob Lykke , Jakob Hagen Vasehus Schou , Laurids Østergaard Poulsen","doi":"10.1016/j.clcc.2024.09.003","DOIUrl":"10.1016/j.clcc.2024.09.003","url":null,"abstract":"<div><h3>Introduction</h3><div>Total neoadjuvant treatment (TNT) with induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) has improved long-term outcomes for patients with locally advanced rectal cancer (LARC). However, long-term outcomes have not been investigated for patients with incomplete (R1) resection separately. This study investigates overall survival (OS), disease-free survival (DFS) and local and distant recurrence rates in patients with R1 resection after preoperative treatment with ICT and CRT or CRT.</div></div><div><h3>Patients and methods</h3><div>From the NORD database 689 patients with LARC who received treatment between 2006 and 2017 were screened for inclusion. All patients with R1 resection were included. ICT consisted of at least 1 cycle of capecitabine and oxaliplatin (CAPOX) and was followed by radiotherapy concomitant with capecitabine.</div></div><div><h3>Results</h3><div>Among 46 patients with R1 resection, 27 (59%) received both ICT and CRT, and 19 (41%) patients received CRT. The 5-year OS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 37% (95% CI, 15%-59%) (CRT) (<em>P =</em> .25) and 5-year DFS was 44% (95% CI, 26%-63%) (ICT + CRT) versus 32% (95% CI, 11%-53%) (CRT) (<em>P =</em> .22). The local recurrence rates showed a small nonstatistical significant difference in local control in the ICT group: 15% compared to 26% in the CRT group (<em>P</em> = .22). Distant recurrence rates were similar: 41% (ICT + CRT) versus 47% (CRT) (<em>P =</em> .48).</div></div><div><h3>Conclusion</h3><div>There was no significant difference in OS, DFS or local and distant recurrence rates between patients who received ICT + CRT versus patients who received CRT only.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 64-71"},"PeriodicalIF":3.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25DOI: 10.1016/j.clcc.2024.09.001
Yingqian Zhou , Xiaoyu Xie , Xi Chen , Qiongwei Tang , Zerong Cai , Yifeng Zou , Zhaoliang Yu , Yufeng Chen
Background
Para-aortic lymph node metastasis (PALNM) is a rare occurrence in colorectal cancer (CRC), and the high risk of radical lymphadenectomy leads to persistent debate about the best treatment strategy. This study aims to evaluate the predictor for PALNM and the clinical value of para-aortic lymph node dissection (PALND) in CRC patients with radiologically suspected synchronous PALNM.
Methods
Patients who have synchronous radiologically suspected PALNM and underwent primary tumor resection were included. Logistic regression and receiver operating characteristic curve analysis were used to assess the predictive value of lymph node short axis in preoperative CT, identifying the optimal cut-off value. Propensity score matching and Cox regression explored factors affecting overall and disease-free survival, while Kaplan-Meier curves and decision tree models identified patient characteristics suitable for synchronous para-aortic lymph node dissection.
Results
A total of 578 patients were enrolled, and 125 patients received synchronous PALND. We found that simultaneous PALND significantly improved overall survival (HR, 0.56; 95% CI, 0.35-0.91; P = .019) in multivariate analysis, while disease-free survival showed no significant difference (P = .41). The short axis diameter of PALN on preoperative CT is a crucial predictor of PALNM (P < .001, AUC = 0.759) with a threshold of > 7 mm. N-stage and distant metastasis were included as independent predictors in the diagnostic model to enhance accuracy. A larger short axis diameter of PALN correlated with advanced tumor stage and poorer prognosis. Subgroup analysis revealed that PALND offers survival benefits for colorectal cancer patients at all stages with a short axis diameter >10 mm on preoperative CT (P = .037) and for stage III patients with a diameter between 7 to10 mm (P < .001, AUC = 0.810).
Conclusion
Synchronous PALND can improve overall survival in CRC patients with suspected PALNM, with the maximum short axis diameter of PALN serving as a key criterion for selecting patients for surgery.
{"title":"Prognostic Impact of Para-Aortic Lymph Node Dissection in Colorectal Cancer Patients Suspected of Para-Aortic Lymph Node Metastasis: A Retrospective Cohort Study","authors":"Yingqian Zhou , Xiaoyu Xie , Xi Chen , Qiongwei Tang , Zerong Cai , Yifeng Zou , Zhaoliang Yu , Yufeng Chen","doi":"10.1016/j.clcc.2024.09.001","DOIUrl":"10.1016/j.clcc.2024.09.001","url":null,"abstract":"<div><h3>Background</h3><div>Para-aortic lymph node metastasis (PALNM) is a rare occurrence in colorectal cancer (CRC), and the high risk of radical lymphadenectomy leads to persistent debate about the best treatment strategy. This study aims to evaluate the predictor for PALNM and the clinical value of para-aortic lymph node dissection (PALND) in CRC patients with radiologically suspected synchronous PALNM.</div></div><div><h3>Methods</h3><div>Patients who have synchronous radiologically suspected PALNM and underwent primary tumor resection were included. Logistic regression and receiver operating characteristic curve analysis were used to assess the predictive value of lymph node short axis in preoperative CT, identifying the optimal cut-off value. Propensity score matching and Cox regression explored factors affecting overall and disease-free survival, while Kaplan-Meier curves and decision tree models identified patient characteristics suitable for synchronous para-aortic lymph node dissection.</div></div><div><h3>Results</h3><div>A total of 578 patients were enrolled, and 125 patients received synchronous PALND. We found that simultaneous PALND significantly improved overall survival (HR, 0.56; 95% CI, 0.35-0.91; <em>P</em> = .019) in multivariate analysis, while disease-free survival showed no significant difference (<em>P</em> = .41). The short axis diameter of PALN on preoperative CT is a crucial predictor of PALNM (<em>P</em> < .001, AUC = 0.759) with a threshold of > 7 mm. N-stage and distant metastasis were included as independent predictors in the diagnostic model to enhance accuracy. A larger short axis diameter of PALN correlated with advanced tumor stage and poorer prognosis. Subgroup analysis revealed that PALND offers survival benefits for colorectal cancer patients at all stages with a short axis diameter >10 mm on preoperative CT (<em>P</em> = .037) and for stage III patients with a diameter between 7 to10 mm (<em>P</em> < .001, AUC = 0.810).</div></div><div><h3>Conclusion</h3><div>Synchronous PALND can improve overall survival in CRC patients with suspected PALNM, with the maximum short axis diameter of PALN serving as a key criterion for selecting patients for surgery.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 48-55.e4"},"PeriodicalIF":3.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25DOI: 10.1016/j.clcc.2024.09.002
Sameh Hany Emile , Nir Horesh , Victor Strassmann , Zoe Garoufalia , Rachel Gefen , Peige Zhou , Steven D. Wexner
Background
The vast majority of colon cancers occur in pre-existing adenomas. Little is known about the impact of adenoma type on behavior and outcome of subsequent carcinomas. The present study aimed to assess characteristics, behavior, and outcome of colon adenocarcinoma based on histologic type of pre-existing adenoma.
Methods
US-National Cancer Database was searched between 2005 and 2019 for patients with colonic adenocarcinoma with known adenoma type who underwent colectomy. Patients were divided into 3 groups according to type of adenoma in which carcinoma developed: tubular adenoma (TA), villous adenoma (VA), and tubulovillous adenoma (TVA)-associated carcinomas. The main outcome of the study was 5-year overall survival (OS).
Results
66,854 patients were included. 79.3% of carcinomas originated from TVA, 10.2% from VA, and 0.5% from TA. Patients with adenocarcinoma in VA were more often female whereas carcinomas in TA affected patients of Asian race more often. Approximately one-third of carcinomas in villous and tubulovillous adenomas were in the cecum whereas one-third of carcinomas in tubular adenomas were in the sigmoid colon. More TA-associated carcinomas were of clinical T1-2 stage (30.2% vs. 20.8%; P < .001), clinical N0 stage (69% vs. 62.2%, P < .001), and high grade (15.9% vs. 11.5%, P < .001) compared to VA-associated carcinomas. Patients with TA-associated carcinomas had longer mean OS than patients with VA and TVA-associated carcinomas (130.1 vs. 116.9 vs. 123.5 months, P < .0001).
Conclusions
Adenocarcinomas that arose in TA had more T1-2 stage and N0 stage, higher grade, and longer OS than did adenocarcinomas that arose in VA and TVA.
背景：绝大多数结肠癌都发生在已存在的腺瘤上。人们对腺瘤类型对后续癌变的行为和结果的影响知之甚少。本研究旨在根据原有腺瘤的组织学类型评估结肠腺癌的特征、行为和预后：方法：检索2005年至2019年期间美国国家癌症数据库中已知腺瘤类型并接受结肠切除术的结肠腺癌患者。根据发生癌变的腺瘤类型将患者分为三组：管状腺瘤（TA）、绒毛状腺瘤（VA）和管状腺瘤（TVA）相关癌。研究的主要结果是5年总生存率（OS）：结果：共纳入 66 854 名患者。79.3%的癌细胞来自TVA，10.2%来自VA，0.5%来自TA。VA腺癌患者多为女性，而TA腺癌患者多为亚洲人。在绒毛状腺瘤和管状腺瘤中，大约三分之一的癌细胞位于盲肠，而在管状腺瘤中，三分之一的癌细胞位于乙状结肠。与VA相关癌相比，更多TA相关癌属于临床T1-2期（30.2%对20.8%；P < .001）、临床N0期（69%对62.2%，P < .001）和高级别（15.9%对11.5%，P < .001）。与VA和TVA相关癌患者相比，TA相关癌患者的平均生存期更长（130.1个月 vs. 116.9个月 vs. 123.5个月，P < .0001）：结论：与发生在VA和TVA的腺癌相比，发生在TA的腺癌有更多的T1-2期和N0期、更高的分级和更长的OS。
{"title":"A National Cancer Database Analysis of the Characteristics and Outcome of Colon Cancer According to Type of Preexisting Adenoma","authors":"Sameh Hany Emile , Nir Horesh , Victor Strassmann , Zoe Garoufalia , Rachel Gefen , Peige Zhou , Steven D. Wexner","doi":"10.1016/j.clcc.2024.09.002","DOIUrl":"10.1016/j.clcc.2024.09.002","url":null,"abstract":"<div><h3>Background</h3><div>The vast majority of colon cancers occur in pre-existing adenomas. Little is known about the impact of adenoma type on behavior and outcome of subsequent carcinomas. The present study aimed to assess characteristics, behavior, and outcome of colon adenocarcinoma based on histologic type of pre-existing adenoma.</div></div><div><h3>Methods</h3><div>US-National Cancer Database was searched between 2005 and 2019 for patients with colonic adenocarcinoma with known adenoma type who underwent colectomy. Patients were divided into 3 groups according to type of adenoma in which carcinoma developed: tubular adenoma (TA), villous adenoma (VA), and tubulovillous adenoma (TVA)-associated carcinomas. The main outcome of the study was 5-year overall survival (OS).</div></div><div><h3>Results</h3><div>66,854 patients were included. 79.3% of carcinomas originated from TVA, 10.2% from VA, and 0.5% from TA. Patients with adenocarcinoma in VA were more often female whereas carcinomas in TA affected patients of Asian race more often. Approximately one-third of carcinomas in villous and tubulovillous adenomas were in the cecum whereas one-third of carcinomas in tubular adenomas were in the sigmoid colon. More TA-associated carcinomas were of clinical T1-2 stage (30.2% vs. 20.8%; <em>P</em> < .001), clinical N0 stage (69% vs. 62.2%, <em>P</em> < .001), and high grade (15.9% vs. 11.5%, <em>P</em> < .001) compared to VA-associated carcinomas. Patients with TA-associated carcinomas had longer mean OS than patients with VA and TVA-associated carcinomas (130.1 vs. 116.9 vs. 123.5 months, <em>P</em> < .0001).</div></div><div><h3>Conclusions</h3><div>Adenocarcinomas that arose in TA had more T1-2 stage and N0 stage, higher grade, and longer OS than did adenocarcinomas that arose in VA and TVA.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 56-63"},"PeriodicalIF":3.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Whether HCV infection is associated with colorectal cancer (CRC) development remains inconclusive.
Methods
A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database was conducted.
Results
From 2003 to 2012, 1:2:2 propensity score-matched HCV-treated [interferon-based therapy ≥ 6 months, surveys for CRC (n = 9017), colon cancer (CC) (n = 9,022) and rectal cancer (RC) (n = 9,033), HCV-untreated and HCV-uninfected cohorts CRC (n = 18034), CC (n = 18,044) and RC (n = 18,066) were enrolled. The HCV-uninfected cohort had the lowest cumulative incidence of CRC (0.117%; 95% CI: 0.062%-0.207%), whereas the HCV-treated (0.966%; 0.375-2.122%) and HCV-untreated (0.807%; 0.485%-1.280%) cohorts had similar incidences (P = .0662); HCV infection [reference: HCV-untreated cohort, HCV-treated: hazard ratio (HR): 0.598; 95% CI HR: 0.337-1.059; HCV-uninfected: 0.250; 0.138-0.456] and age ≥ 49 years (3.128;1.751-5.59) were associated with CRC development. The HCV-untreated cohort had the highest cumulative incidence of CC (0.883%; 0.371-1.839%), while HCV-treated (0.478%; 0.110-1.518%) and HCV-uninfected cohorts (0.147%; 0.071-0.284%) had similar incidences (P = .4853); HCV infection (HCV-treated: 0.474; 0.232-0.971; HCV-uninfected: 0.338; 0.184-0.62), male sex (2.18; 1.301-3.654), age≥ 49 years (4.818; 2.123-10.936) and diabetes (1.983; 1.205-3.262) were associated with CC development. A higher RC cumulative incidence was noted in the HCV-untreated cohort (0.332%; 0.151-0.664%) than in the HCV-uninfected cohort (0.116%; 0.054-0.232%) (P = .0352); HCV infection (HCV-treated: 0.691; 0.295-1.617; HCV-uninfected: 0.424; 0.207-0.867), age ≥ 49 years (3.745, 1.576-8.898) and stroke (3.162; 1.366-7.322) were associated with RC development.
Conclusions
The baseline associations were HCV infection and age ≥ 49 years with CRC; male sex and diabetes with CC; and stroke with RC. Anti-HCV therapy might reverse the risk of HCV-related CC but not RC.
{"title":"Different Metabolic Associations of Hepatitis C With Colon and Rectal Cancers: A 9-Year Nationwide Population-Based Cohort Study","authors":"Chun-Wei Chen , Jur- Shan Cheng , Tsung-Hsing Chen , Chia-Jung Kuo , Hsin-Ping Ku , Rong-Nan Chien , Ming-Ling Chang","doi":"10.1016/j.clcc.2024.08.005","DOIUrl":"10.1016/j.clcc.2024.08.005","url":null,"abstract":"<div><h3>Background</h3><div>Whether HCV infection is associated with colorectal cancer (CRC) development remains inconclusive.</div></div><div><h3>Methods</h3><div>A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database was conducted.</div></div><div><h3>Results</h3><div>From 2003 to 2012, 1:2:2 propensity score-matched HCV-treated [interferon-based therapy ≥ 6 months, surveys for CRC (n = 9017), colon cancer (CC) (n = 9,022) and rectal cancer (RC) (n = 9,033), HCV-untreated and HCV-uninfected cohorts CRC (n = 18034), CC (n = 18,044) and RC (n = 18,066) were enrolled. The HCV-uninfected cohort had the lowest cumulative incidence of CRC (0.117%; 95% CI: 0.062%-0.207%), whereas the HCV-treated (0.966%; 0.375-2.122%) and HCV-untreated (0.807%; 0.485%-1.280%) cohorts had similar incidences (<em>P</em> = <em>.</em>0662); HCV infection [reference: HCV-untreated cohort, HCV-treated: hazard ratio (HR): 0.598; 95% CI HR: 0.337-1.059; HCV-uninfected: 0.250; 0.138-0.456] and age ≥ 49 years (3.128;1.751-5.59) were associated with CRC development. The HCV-untreated cohort had the highest cumulative incidence of CC (0.883%; 0.371-1.839%), while HCV-treated (0.478%; 0.110-1.518%) and HCV-uninfected cohorts (0.147%; 0.071-0.284%) had similar incidences (<em>P</em> = .4853); HCV infection (HCV-treated: 0.474; 0.232-0.971; HCV-uninfected: 0.338; 0.184-0.62), male sex (2.18; 1.301-3.654), age≥ 49 years (4.818; 2.123-10.936) and diabetes (1.983; 1.205-3.262) were associated with CC development. A higher RC cumulative incidence was noted in the HCV-untreated cohort (0.332%; 0.151-0.664%) than in the HCV-uninfected cohort (0.116%; 0.054-0.232%) (<em>P</em> = .0352); HCV infection (HCV-treated: 0.691; 0.295-1.617; HCV-uninfected: 0.424; 0.207-0.867), age ≥ 49 years (3.745, 1.576-8.898) and stroke (3.162; 1.366-7.322) were associated with RC development.</div></div><div><h3>Conclusions</h3><div>The baseline associations were HCV infection and age ≥ 49 years with CRC; male sex and diabetes with CC; and stroke with RC. Anti-HCV therapy might reverse the risk of HCV-related CC but not RC.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 39-47.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-03DOI: 10.1016/j.clcc.2024.08.004
Irene Assaf , Giacomo Bregni , Geraldine Anthoine , Thomas Aparicio , Pascal Artru , Meher Ben Abdelghani , Marc Buyse , Benoist Chibaudel , Elisabeth Coart , Marie Diaz , Camille Evrard , Karen Geboes , François Ghiringhelli , Francesco Puleo , Judith Raimbourg , Timon Vandamme , Marc Van den Eynde , Alain Hendlisz , Francesco Sclafani
Background
Evidence suggests that ctDNA may be a reliable biomarker to monitor metastatic colorectal cancer (CRC) evolution. Nevertheless, evidence on the potential of liquid biopsy in this setting is still low quality, mostly consisting of retrospective studies.
Methods
COPERNIC is an international, multicenter clinical trial. The pilot study aims to confirm the predictive potential of early on-treatment ctDNA dynamics, and inform the design of a larger ctDNA-driven trial. Advanced CRC patients who are candidates for ≥3rd lines of systemic therapy undergo longitudinal blood sample collection during treatment (day 1, 15 and 29 for 2- or 4-weekly treatment regimens; day 1, 22 and 43 for 3-weekly treatment regimens) and at each imaging assessment. ctDNA analyses are carried out with the FoundationOne Liquid CDx and FoundationOneMonitor assays, and ctDNA changes during treatment are correlated with radiologic response (as assessed every 8-12 weeks by RECIST v1.1). The primary objective is to select the optimal timepoint and cut-off value for early ctDNA changes (at day 15/22) to predict progressive disease as best radiological response with a high positive predictive value. The cut-off value for ctDNA will be defined based on nonparametric ROC-curves with bootstrapping. Based on the expected rate of progressive disease and statistical assumptions, 109 patients are needed to be screened to have 87 assessable patients. COPERNIC is sponsored by the Institut Jules Bordet, and supported by Roche and Foundation Medicine. Recruitment is open in 13 centres across Belgium and France. The study is registered with clinicaltrials.gov (NCT05487248).
{"title":"Rationale and Design of the COPERNIC Trial: A Study of On-treatment ctDNA Changes in Chemo-refractory Colorectal Cancer Patients","authors":"Irene Assaf , Giacomo Bregni , Geraldine Anthoine , Thomas Aparicio , Pascal Artru , Meher Ben Abdelghani , Marc Buyse , Benoist Chibaudel , Elisabeth Coart , Marie Diaz , Camille Evrard , Karen Geboes , François Ghiringhelli , Francesco Puleo , Judith Raimbourg , Timon Vandamme , Marc Van den Eynde , Alain Hendlisz , Francesco Sclafani","doi":"10.1016/j.clcc.2024.08.004","DOIUrl":"10.1016/j.clcc.2024.08.004","url":null,"abstract":"<div><h3>Background</h3><div>Evidence suggests that ctDNA may be a reliable biomarker to monitor metastatic colorectal cancer (CRC) evolution. Nevertheless, evidence on the potential of liquid biopsy in this setting is still low quality, mostly consisting of retrospective studies.</div></div><div><h3>Methods</h3><div>COPERNIC is an international, multicenter clinical trial. The pilot study aims to confirm the predictive potential of early on-treatment ctDNA dynamics, and inform the design of a larger ctDNA-driven trial. Advanced CRC patients who are candidates for ≥3rd lines of systemic therapy undergo longitudinal blood sample collection during treatment (day 1, 15 and 29 for 2- or 4-weekly treatment regimens; day 1, 22 and 43 for 3-weekly treatment regimens) and at each imaging assessment. ctDNA analyses are carried out with the FoundationOne Liquid CDx and FoundationOneMonitor assays, and ctDNA changes during treatment are correlated with radiologic response (as assessed every 8-12 weeks by RECIST v1.1). The primary objective is to select the optimal timepoint and cut-off value for early ctDNA changes (at day 15/22) to predict progressive disease as best radiological response with a high positive predictive value. The cut-off value for ctDNA will be defined based on nonparametric ROC-curves with bootstrapping. Based on the expected rate of progressive disease and statistical assumptions, 109 patients are needed to be screened to have 87 assessable patients. COPERNIC is sponsored by the Institut Jules Bordet, and supported by Roche and Foundation Medicine. Recruitment is open in 13 centres across Belgium and France. The study is registered with clinicaltrials.gov (NCT05487248).</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 101-105"},"PeriodicalIF":3.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1016/j.clcc.2024.08.006
Caroline B. Ledet , Ugur Sener , Derek R. Johnson , Kimberly Ku , Thorvardur R. Halfdanarson
•
Antiangiogenic agents are frequently used in the treatment of malignancies, such as colorectal cancer. Posterior reversible encephalopathy syndrome (PRES), a clinicoradiographic syndrome characterized by headache, encephalopathy, seizures, and characteristic magnetic resonance imaging (MRI) changes, is a rare but known complication of antiangiogenic therapies.
•
Fruquintinb is a tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF) receptors and has been recently approved for the treatment of colorectal cancer refractory to prior standard of care therapies. To date, only 1 other case of PRES associated with fruquintinib has been described. Our case highlights the possibility of PRES association with this novel antiangiogenic and emphasizes the importance of early recognition and management of this rare but potentially life-threatening treatment complication.
•
Our case underscores that prior tolerance of 1 antiangiogenic does not preclude occurrence of PRES associated with another agent from the same class.
{"title":"Fruquintinib-Associated Posterior Reversible Encephalopathy Syndrome in a Patient With Multiply Metastatic Rectal Cancer","authors":"Caroline B. Ledet , Ugur Sener , Derek R. Johnson , Kimberly Ku , Thorvardur R. Halfdanarson","doi":"10.1016/j.clcc.2024.08.006","DOIUrl":"10.1016/j.clcc.2024.08.006","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Antiangiogenic agents are frequently used in the treatment of malignancies, such as colorectal cancer. Posterior reversible encephalopathy syndrome (PRES), a clinicoradiographic syndrome characterized by headache, encephalopathy, seizures, and characteristic magnetic resonance imaging (MRI) changes, is a rare but known complication of antiangiogenic therapies.</div></span></li><li><span>•</span><span><div>Fruquintinb is a tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF) receptors and has been recently approved for the treatment of colorectal cancer refractory to prior standard of care therapies. To date, only 1 other case of PRES associated with fruquintinib has been described. Our case highlights the possibility of PRES association with this novel antiangiogenic and emphasizes the importance of early recognition and management of this rare but potentially life-threatening treatment complication.</div></span></li><li><span>•</span><span><div>Our case underscores that prior tolerance of 1 antiangiogenic does not preclude occurrence of PRES associated with another agent from the same class.</div></span></li></ul></div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 98-100"},"PeriodicalIF":3.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/j.clcc.2024.05.004
KRAS mutations contribute substantially to the overall colorectal cancer burden and have long been a focus of drug development efforts. After a lengthy preclinical road, KRAS inhibition via the G12C allele has finally become a therapeutic reality. Unlike in NSCLC, early studies of KRAS inhibitors in CRC struggled to demonstrate single agent activity. Investigation into these tissue-specific treatment differences has led to a deeper understanding of the complexities of MAPK signaling and the diverse adaptive feedback responses to KRAS inhibition. EGFR reactivation has emerged as a principal resistance mechanism to KRAS inhibitor monotherapy. Thus, the field has pivoted to dual EGFR/KRAS blockade with promising efficacy. Despite significant strides in the treatment of KRAS G12C mutated CRC, new challenges are on the horizon. Alternative RTK reactivation and countless acquired molecular resistance mechanisms have shifted the treatment goalpost. This review focuses on the historical and contemporary clinical strategies of targeting KRAS G12C alterations in CRC and highlights future directions to overcome treatment challenges.
{"title":"KRAS G12C Inhibitors in the Treatment of Metastatic Colorectal Cancer","authors":"","doi":"10.1016/j.clcc.2024.05.004","DOIUrl":"10.1016/j.clcc.2024.05.004","url":null,"abstract":"<div><p><span>KRAS mutations contribute substantially to the overall colorectal cancer burden and have long been a focus of </span>drug development<span><span> efforts. After a lengthy preclinical road, KRAS inhibition via the G12C allele has finally become a therapeutic reality. Unlike in NSCLC, early studies of KRAS inhibitors in CRC struggled to demonstrate single agent activity. Investigation into these tissue-specific treatment differences has led to a deeper understanding of the complexities of MAPK signaling and the diverse adaptive feedback responses to KRAS inhibition. EGFR reactivation has emerged as a principal resistance mechanism to KRAS inhibitor </span>monotherapy. Thus, the field has pivoted to dual EGFR/KRAS blockade with promising efficacy. Despite significant strides in the treatment of KRAS G12C mutated CRC, new challenges are on the horizon. Alternative RTK reactivation and countless acquired molecular resistance mechanisms have shifted the treatment goalpost. This review focuses on the historical and contemporary clinical strategies of targeting KRAS G12C alterations in CRC and highlights future directions to overcome treatment challenges.</span></p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 3","pages":"Pages 199-206"},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141031570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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