结肠癌肝转移美国治疗方法

2019-01-31

正文


节选文献翻译:
同时性肝转移:结直肠癌确诊时发现的或结直肠癌原发灶根治性切除术后6个月内发生的肝转移。
异时性肝转移:结直肠癌根治术6个月后发生的肝转移。


异时转移性病灶的检查和处理[1]
根据相关文献报道,有关增强CT或MRI发现的异时性转移病灶,若转移病灶外科手术治疗可行,为了搞清楚病灶侵袭范围,则对选择的病人应进行PET-CT检查。PET / CT用于标示病灶侵袭范围并确定可能的肝外转移灶以排除手术治疗。特别要指出的是,乔伊斯等人报道了术前PET检查改变或排除了25%的准备实时治疗性肝切除手术的患者。最近一项随机临床试验评估了对可切除的异时性转移患者进行PET / CT检查的作用,尽管PET/CT对生存率没有影响,但在行PET / CT后有8%的患者的手术治疗方案发生了改变。
与被诊断的IV期疾病的其他患者一样,应针对肿瘤(转移灶或原发灶)进行KRAS/NRAS基因检测,以确定抗EGFR药物是否可以成为潜在的选择。对野生型KRAS/NRAS基因患者,虽然BRAF基因分型可以考虑,但此项检测目前是可选的,但不是决定是否使用抗EGFR药物的必须检查项目。
推荐多学科联合会诊,包括术前请有肝胆和肺转移灶手术经验的外科医生评估。通过对患者化疗史的评估和是否行结肠切除术,异时性转移灶的治疗方案和同时性转移灶是不同的。
根据之前是否接受过化疗,可将可切除病灶的患者进行分类。对于可切除的转移性病灶患者,采用手术联合6个月的围手术期化疗(术前或术后或二者联合),根据前期治疗选择化疗方案。对于无化疗史的患者,首选FOLFOX或CapeOx方案,FLOX、卡培他滨和5-FU/LV作为2线方案选择。在某些异时性病灶患者中,不推荐围手术期化疗。特别指出,既往接受过化疗和手术切除的患者可以进行观察随访,或者疾病进展时给予患者有效的治疗方案,这一原则对于术前肿瘤长大的患者的治疗方案也同样如此(在这些患者中推荐使用生物制剂,2B类证据)。对于之前采用了基于奥沙利铂的治疗方案的患者,首选观察随访。此外,对于接受新辅助治疗的患者,观察随访也是合适的选择。
通过影像学检查确定患有不可切除的病灶的患者(包括那些被认为有潜在可逆性病灶的患者),应根据先前的化疗史,接受积极的全身治疗方案。对于仅有肝转移的患者,可选择HAI治疗(肝动脉灌注化疗,译者注)联合或不联合全身5-FU/LV方案(2B类),该治疗需要在有外科和肿瘤治疗经验的中心进行。接受姑息性化疗的患者应大约每2-3个月进行CT或MRI扫描检查。
根据文献报道,可选择的方案如下:[1]
1. 一线推荐药物:
FOLFIRI或伊立替康;
FOLFIRI +(贝伐单抗[首选]或ZIV-阿普西柏或雷莫芦单抗)
伊立替康+(贝伐单抗[首选]或ZIV-阿普西柏或雷莫芦单抗)
FOLFIRI +(西妥昔单抗或帕尼单抗)*(仅KRAS / NRAS WT)
伊立替康+(西妥昔单抗或帕尼单抗)*(仅KRAS / NRAS WT)
伊立替康 +(西妥昔单抗或帕尼单抗)+威罗菲尼(BRAF V600E正突变)
(纳武单抗或派姆单抗)(仅限dMMR / MSI-H)
2. 二线推荐药物:
伊立替康+(西妥昔单抗或帕尼单抗) *(仅限KRAS / NRAS WT)
瑞戈非尼
三氟尿苷+地匹福林、(纳武单抗或派姆单抗)*(仅限dMMR / MSI-H)
3. 三线推荐药物:
瑞戈非尼
三氟尿苷+地匹福林


文献原文:
Workup and Management of Metachronous Metastatic Disease On documentation of metachronous, potentially resectable, metastatic disease with dedicated contrast-enhanced CT or MRI, characterization of the disease extent using PET/CT scan should be considered in select cases if a surgical cure of M1 disease is feasible. PET/CT is used at this juncture to promptly characterize the extent of metastatic disease, and to identify possible sites of extrahepatic disease that could preclude surgery. Specifically, Joyce et al reported that the preoperative[1] PET changed or precluded curative-intent liver resection in 25% of patients. A recent randomized clinical trial assessed the role of PET/CT in the workup of patients with resectable metachronous metastases. While there was no impact of PET/CT on survival, surgical management was changed in 8% of patients after PET/CT.
As with other conditions in which stage IV disease is diagnosed, a tumor analysis (metastases or original primary) for KRAS/NRAS genotype should be performed to define whether anti-EGFR agents can be considered among the potential options. Although BRAF genotyping can be considered for patients with tumors characterized by the wildtype KRAS/NRAS genes, this testing is currently optional and not a necessary part of deciding whether to use anti-EGFR agents (see The Role of KRAS, NRAS, and BRAF Status).distinguished from that of synchronous disease through also includingan evaluation of the chemotherapy history of the patient and through the absence of colectomy.
Patients with resectable disease are classified according to whether they have undergone previous chemotherapy. For patients who have resectable metastatic disease, treatment is resection with 6 months of perioperative chemotherapy (pre- or postoperative or a combination of both), with choice of regimens based on previous therapy. For patients without a history of chemotherapy use, FOLFOX or CapeOx is preferred, with FLOX, capecitabine, and 5-FU/LV as category 2B options. There are also cases when perioperative chemotherapy is not recommended in metachronous disease. In particular, patients with a history of previous chemotherapy and an upfront resection can be observed or may be given an active regimen for advanced disease, and the same is true for patients whose tumors grew on therapy before resection (category 2B for the use of biologic agents in these settings).
Observation is preferred if oxaliplatin-based therapy was previously administered. In addition, observation is an appropriate option for patients whose tumors grew through neoadjuvant treatment. Patients determined to have unresectable disease through crosssectional imaging scan (including those considered potentially convertible) should receive an active systemic therapy regimen based on prior chemotherapy history (see Therapy After Progression, above). In the case of liver metastases only, HAI therapy with or without systemic 5-FU/LV (category 2B) is an option at centers with experience in the surgical and medical oncologic aspects of this procedure. Patients receiving palliative chemotherapy should be monitored with CT or MRI scans approximately every 2 to 3 months.


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