Background: The regional chronomodulated hepatic arterial infusion chemotherapy (HAIC) is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, especially for th...Background: The regional chronomodulated hepatic arterial infusion chemotherapy (HAIC) is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, especially for the conversion into resectability. Aim: To demonstrate that chronomodulated HAI triplet chemotherapy according to OPTILIV protocol is well tolerated and displayed high antitumor activity in this heavily-pretreated patient. Case Presentation: A 54 years old patient from Russia was treated for a tumor in the ascending colon presented with 13 hepatic metastases ranging from 0.3 to 2.7 cm in diameter. He underwent a laparoscopic right hemicolectomy, 12 cycles of FOLFIRINOX combined to bevacizumab for the last 5 cycles, resulting in a partial response according to CT scan. It was decided to perform a two-stage hepatectomy at Paul Brousse hospital: left partial hepatectomy allowed the excision of 9 lesions. Radio frequency ablation was performed in 2 nodular lesions. Afterwards, the patient received 5 cycles of chronomodulated triplet chemotherapy into the hepatic artery, according to the OPTILIV protocol design, yet without cetuximab, because of the KRAS mutation in the liver metastases, with a partial re-sponse. The patient could then undergo the second stage of the planned right hepatectomy, which turned out to be an R0 resection followed by receiving three courses of chronomodulated HAIC. Disease progression was documented after 3 months. Chronomodulated FOLFIRI chemotherapy was re-started intravenously, in combination with Aflibercept and it was associated with further disease progression. The genetic analysis of our patient’s cancer revealed a high level of MSI. The patient was included in the Phase 2 CheckMate-142 trial and received nivolumab 3 mg/kg every 2 weeks within 3 months. Treatment was discontinued due to ineffectiveness. Then the patient underwent radiotherapy geared towards reduction of pain. Afterwards, the patient died from the disease progression 2 years after the beginning of treatment. Conclusion: In this article, the authors report a clinical case with chronomodulated HAIC as rescue therapy in a heavily pretreated patient with metastatic colorectal cancer, allowing to achieve an objective response despite prior progression on FOLFIRINOX (the same triplet chemo by IV route). This strategy permitted to overcome drug resistance and to perform further complete resection of the liver me-tastases with prolonged patient survival. Thus, chronomodulated HAI is useful in patients with liver metastases from colorectal cancer and de-serves to be further assessed prospectively in clinical trials chemotherapy.展开更多
In the study by Wu et al,patients with unresectable hepatocellular carcinoma were subjected to transarterial chemoembolization(TACE)as a conversion therapy in order to render their tumors suitable for resection.A nomo...In the study by Wu et al,patients with unresectable hepatocellular carcinoma were subjected to transarterial chemoembolization(TACE)as a conversion therapy in order to render their tumors suitable for resection.A nomogram was devised and shown to be effective in predicting the survival of these patients.Generalization of the results,however,is questionable since the study subjects consisted of patients who had resection after TACE while excluding patients with the same disease but not suitable for TACE.Immunotherapy can be considered to be an option for conversion therapy.However,markers for determining responses to a conversion therapy and for guiding the decision between TACE and sequential immunotherapy have been lacking.The question of whether effective conversion therapy can truly enhance overall survival remains unanswered.展开更多
Colorectal carcinoma(CRC)is one of the leading causes of cancer-related deaths worldwide,and up to 50%of patients with CRC develop colorectal liver metastases(CRLM).For these patients,surgical resection remains the on...Colorectal carcinoma(CRC)is one of the leading causes of cancer-related deaths worldwide,and up to 50%of patients with CRC develop colorectal liver metastases(CRLM).For these patients,surgical resection remains the only opportunity for cure and long-term survival.Over the past few decades,outcomes of patients with metastatic CRC have improved significantly due to advances in systemic therapy,as well as improvements in operative technique and perioperative care.Chemotherapy in the modern era of oxaliplatin-and irinotecancontaining regimens has been augmented by the introduction of targeted biologics and immunotherapeutic agents.The increasing efficacy of contemporary systemic therapies has led to an expansion in the proportion of patients eligible for curative-intent surgery.Consequently,the use of neoadjuvant strategies is becoming progressively more established.For patients with CRLM,the primary advantage of neoadjuvant chemotherapy(NCT)is the potential to down-stage metastatic disease in order to facilitate hepatic resection.On the other hand,the routine use of NCT for patients with resectable metastases remains controversial,especially given the potential risk of inducing chemotherapy-associated liver injury prior to hepatectomy.Current guidelines recommend upfront surgery in patients with initially resectable disease and low operative risk,reserving NCT for patients with borderline resectable or unresectable disease and high operative risk.Patients undergoing NCT require close monitoring for tumor response and conversion of CRLM to resectability.In light of the growing number of treatment options available to patients with metastatic CRC,it is generally agreed that these patients are best served at tertiary centers with an expert multidisciplinary team.展开更多
文摘Background: The regional chronomodulated hepatic arterial infusion chemotherapy (HAIC) is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, especially for the conversion into resectability. Aim: To demonstrate that chronomodulated HAI triplet chemotherapy according to OPTILIV protocol is well tolerated and displayed high antitumor activity in this heavily-pretreated patient. Case Presentation: A 54 years old patient from Russia was treated for a tumor in the ascending colon presented with 13 hepatic metastases ranging from 0.3 to 2.7 cm in diameter. He underwent a laparoscopic right hemicolectomy, 12 cycles of FOLFIRINOX combined to bevacizumab for the last 5 cycles, resulting in a partial response according to CT scan. It was decided to perform a two-stage hepatectomy at Paul Brousse hospital: left partial hepatectomy allowed the excision of 9 lesions. Radio frequency ablation was performed in 2 nodular lesions. Afterwards, the patient received 5 cycles of chronomodulated triplet chemotherapy into the hepatic artery, according to the OPTILIV protocol design, yet without cetuximab, because of the KRAS mutation in the liver metastases, with a partial re-sponse. The patient could then undergo the second stage of the planned right hepatectomy, which turned out to be an R0 resection followed by receiving three courses of chronomodulated HAIC. Disease progression was documented after 3 months. Chronomodulated FOLFIRI chemotherapy was re-started intravenously, in combination with Aflibercept and it was associated with further disease progression. The genetic analysis of our patient’s cancer revealed a high level of MSI. The patient was included in the Phase 2 CheckMate-142 trial and received nivolumab 3 mg/kg every 2 weeks within 3 months. Treatment was discontinued due to ineffectiveness. Then the patient underwent radiotherapy geared towards reduction of pain. Afterwards, the patient died from the disease progression 2 years after the beginning of treatment. Conclusion: In this article, the authors report a clinical case with chronomodulated HAIC as rescue therapy in a heavily pretreated patient with metastatic colorectal cancer, allowing to achieve an objective response despite prior progression on FOLFIRINOX (the same triplet chemo by IV route). This strategy permitted to overcome drug resistance and to perform further complete resection of the liver me-tastases with prolonged patient survival. Thus, chronomodulated HAI is useful in patients with liver metastases from colorectal cancer and de-serves to be further assessed prospectively in clinical trials chemotherapy.
文摘In the study by Wu et al,patients with unresectable hepatocellular carcinoma were subjected to transarterial chemoembolization(TACE)as a conversion therapy in order to render their tumors suitable for resection.A nomogram was devised and shown to be effective in predicting the survival of these patients.Generalization of the results,however,is questionable since the study subjects consisted of patients who had resection after TACE while excluding patients with the same disease but not suitable for TACE.Immunotherapy can be considered to be an option for conversion therapy.However,markers for determining responses to a conversion therapy and for guiding the decision between TACE and sequential immunotherapy have been lacking.The question of whether effective conversion therapy can truly enhance overall survival remains unanswered.
文摘Colorectal carcinoma(CRC)is one of the leading causes of cancer-related deaths worldwide,and up to 50%of patients with CRC develop colorectal liver metastases(CRLM).For these patients,surgical resection remains the only opportunity for cure and long-term survival.Over the past few decades,outcomes of patients with metastatic CRC have improved significantly due to advances in systemic therapy,as well as improvements in operative technique and perioperative care.Chemotherapy in the modern era of oxaliplatin-and irinotecancontaining regimens has been augmented by the introduction of targeted biologics and immunotherapeutic agents.The increasing efficacy of contemporary systemic therapies has led to an expansion in the proportion of patients eligible for curative-intent surgery.Consequently,the use of neoadjuvant strategies is becoming progressively more established.For patients with CRLM,the primary advantage of neoadjuvant chemotherapy(NCT)is the potential to down-stage metastatic disease in order to facilitate hepatic resection.On the other hand,the routine use of NCT for patients with resectable metastases remains controversial,especially given the potential risk of inducing chemotherapy-associated liver injury prior to hepatectomy.Current guidelines recommend upfront surgery in patients with initially resectable disease and low operative risk,reserving NCT for patients with borderline resectable or unresectable disease and high operative risk.Patients undergoing NCT require close monitoring for tumor response and conversion of CRLM to resectability.In light of the growing number of treatment options available to patients with metastatic CRC,it is generally agreed that these patients are best served at tertiary centers with an expert multidisciplinary team.
