Despite advances in the management of patients with locally advanced,non-metastatic rectal adenocarcinoma(LARC),prognosis remains largely unsatisfactory due to a high rate of distant relapse.In fact,currently availabl...Despite advances in the management of patients with locally advanced,non-metastatic rectal adenocarcinoma(LARC),prognosis remains largely unsatisfactory due to a high rate of distant relapse.In fact,currently available neoadjuvant protocols,represented by fluoropyrimidine-based chemo-radiotherapy(CT-RT)or short-course RT,together with improved surgical techniques,have largely reduced the risk of local relapse,with limited impact on distant recurrence.Available results of phaseⅢtrials with additional cytotoxic agents combined with standard CT-RT are disappointing,as no significant reduction in the risk of recurrence has been demonstrated.In order to improve the control of micrometastatic disease,integrating targeted agents into neoadjuvant treatment protocols thus offers a rational approach.In particular,the antiangiogenic agent bevacizumab has demonstrated synergistic activity with both CT and RT in pre-clinical and clinical models,and thusmay represent a suitable companion in the neoadjuvant treatment of LARC.Preliminary results of phase?Ⅰ-Ⅱclinical studies are promising and suggest potential clinical parameters and molecular predictive biomarkers useful for patient selection:treatment personalization is indeed the key in order to maximize the benefit while reducing the risk of more complex neoadjuvant treatment schedules.展开更多
In the following review we intend to ascertain the optimal neoadjuvant therapy inpatients with locally advanced rectal cancer. In 2004, a study revealed thatchemoradiotherapy (CRT) resulted in better local control whe...In the following review we intend to ascertain the optimal neoadjuvant therapy inpatients with locally advanced rectal cancer. In 2004, a study revealed thatchemoradiotherapy (CRT) resulted in better local control when performedpreoperatively rather than postoperatively, thus neoadjuvant treatment wasestablished as a standard treatment. Subsequently, the Polish study and the Trans-Tasman Radiation Oncology Group showed no statistically significant differencebetween concomitant CRT over 5 wk vs short-course radiotherapy (RT).Therefore, both were established as standard neoadjuvant treatments. Later, theStockholm III study demonstrated that short-course RT had a higher completepathological response than long-course RT. It also showed that a delay betweenRT and surgery presented fewer complications. This opened a window of time toprovide an early and effective systemic treatment to prevent distant metastases.Studies show that short-course RT plus oxaliplatin-based chemotherapy couldachieve this. When comparing this total neoadjuvant treatment (TNT) vsconcomitant CRT, the former showed greater complete pathological response andlower acute toxicity. Studies presented during 2020 have also shown the benefitsof TNT in terms of complete pathological response, as well as disease andmetastasis-free survival. Our review suggests that probably TNT should be thenew standard treatment for these patients. However, we will have to wait for thefull text publications of these studies to confirm this statement.展开更多
Fifteen percent to twenty-five percent of patients affected by colorectal cancer presents with liver metastases at diagnosis. In resectable cases, surgery is the only potentially curative treatment and achieves surviv...Fifteen percent to twenty-five percent of patients affected by colorectal cancer presents with liver metastases at diagnosis. In resectable cases, surgery is the only potentially curative treatment and achieves survival rates up to 50% at 5 years. Management is complex, as colorectal resection, liver resection, chemotherapy, and, in locally advanced mid/low rectal tumors, radiotherapy have to be integrated. Modern medical practice usually relies on evidence-based protocols. Levels of evidence for synchronous metastases are poor:published studies include few recent prospective series and several retrospective analyses collecting a limited number of patients across long periods of time. Data are difficult to be generalized and are mainly representative of single centre's experience, biased by local recruitment, indications and surgical technique. In this context, surgeons have to renounce to "evidence-based medicine" and to adopt a sort of "experience-based medicine". Anyway, some suggestions are possible. Simultaneous colorectal and liver resection can be safely performed whenever minor hepatectomies are planned, while a case-by-case evaluation is mandatory in case of more complex procedures. Neoadjuvant chemotherapy is preferentially scheduled for patients with advanced metastatic tumors to assess disease biology and to control lesions. It can be safely performed with primarytumor in situ , even planning simultaneous resection at its end. Locally advanced mid/low rectal tumor represents a further indication to neoadjuvant therapies, even if treatment's schedule is not yet standardized. In summary, several issues have to be solved, but every single HPB centre should define its proper strategy to optimize patient's selection, disease control and safety and completeness of surgery.展开更多
文摘Despite advances in the management of patients with locally advanced,non-metastatic rectal adenocarcinoma(LARC),prognosis remains largely unsatisfactory due to a high rate of distant relapse.In fact,currently available neoadjuvant protocols,represented by fluoropyrimidine-based chemo-radiotherapy(CT-RT)or short-course RT,together with improved surgical techniques,have largely reduced the risk of local relapse,with limited impact on distant recurrence.Available results of phaseⅢtrials with additional cytotoxic agents combined with standard CT-RT are disappointing,as no significant reduction in the risk of recurrence has been demonstrated.In order to improve the control of micrometastatic disease,integrating targeted agents into neoadjuvant treatment protocols thus offers a rational approach.In particular,the antiangiogenic agent bevacizumab has demonstrated synergistic activity with both CT and RT in pre-clinical and clinical models,and thusmay represent a suitable companion in the neoadjuvant treatment of LARC.Preliminary results of phase?Ⅰ-Ⅱclinical studies are promising and suggest potential clinical parameters and molecular predictive biomarkers useful for patient selection:treatment personalization is indeed the key in order to maximize the benefit while reducing the risk of more complex neoadjuvant treatment schedules.
文摘In the following review we intend to ascertain the optimal neoadjuvant therapy inpatients with locally advanced rectal cancer. In 2004, a study revealed thatchemoradiotherapy (CRT) resulted in better local control when performedpreoperatively rather than postoperatively, thus neoadjuvant treatment wasestablished as a standard treatment. Subsequently, the Polish study and the Trans-Tasman Radiation Oncology Group showed no statistically significant differencebetween concomitant CRT over 5 wk vs short-course radiotherapy (RT).Therefore, both were established as standard neoadjuvant treatments. Later, theStockholm III study demonstrated that short-course RT had a higher completepathological response than long-course RT. It also showed that a delay betweenRT and surgery presented fewer complications. This opened a window of time toprovide an early and effective systemic treatment to prevent distant metastases.Studies show that short-course RT plus oxaliplatin-based chemotherapy couldachieve this. When comparing this total neoadjuvant treatment (TNT) vsconcomitant CRT, the former showed greater complete pathological response andlower acute toxicity. Studies presented during 2020 have also shown the benefitsof TNT in terms of complete pathological response, as well as disease andmetastasis-free survival. Our review suggests that probably TNT should be thenew standard treatment for these patients. However, we will have to wait for thefull text publications of these studies to confirm this statement.
文摘Fifteen percent to twenty-five percent of patients affected by colorectal cancer presents with liver metastases at diagnosis. In resectable cases, surgery is the only potentially curative treatment and achieves survival rates up to 50% at 5 years. Management is complex, as colorectal resection, liver resection, chemotherapy, and, in locally advanced mid/low rectal tumors, radiotherapy have to be integrated. Modern medical practice usually relies on evidence-based protocols. Levels of evidence for synchronous metastases are poor:published studies include few recent prospective series and several retrospective analyses collecting a limited number of patients across long periods of time. Data are difficult to be generalized and are mainly representative of single centre's experience, biased by local recruitment, indications and surgical technique. In this context, surgeons have to renounce to "evidence-based medicine" and to adopt a sort of "experience-based medicine". Anyway, some suggestions are possible. Simultaneous colorectal and liver resection can be safely performed whenever minor hepatectomies are planned, while a case-by-case evaluation is mandatory in case of more complex procedures. Neoadjuvant chemotherapy is preferentially scheduled for patients with advanced metastatic tumors to assess disease biology and to control lesions. It can be safely performed with primarytumor in situ , even planning simultaneous resection at its end. Locally advanced mid/low rectal tumor represents a further indication to neoadjuvant therapies, even if treatment's schedule is not yet standardized. In summary, several issues have to be solved, but every single HPB centre should define its proper strategy to optimize patient's selection, disease control and safety and completeness of surgery.
