Immune checkpoints and liver resection after neoadjuvant chemotherapy including bevacizumab in patients with colorectal liver metastases

281 Background: The long-term outcome of patients resected for colorectal liver metastases (CLM) after neoadjuvant chemotherapy (CHT) depends by several tumoral and non-tumoral factors, such as the immune response to the tumor and to the CHT. The aim of this study was to investigate the impact of the pathological and immunological response in patients undergoing liver resection for CLM after CHT in regards to the long-term outcome. Methods: The immunoreactivity to CD3+ and NKp46+ cells inside the tumor, at the border between the tumor and the normal liver, and inside the normal liver was tested by computer-assisted image analyses in 121 patients undergoing liver resection for CLM between 2005 and 2013 preoperatively treated with oxaliplatin or irinotecan with or without bevacizumab or cetuximab. The survival was assessed in relation to several prognostic factors and to that immunoreactivity. Results: At univariate analysis T1/T2- and N0-status of the primary tumor, metachronous CLM, the radiological response, and the higher density of intratumoral CD3+ ( > 1%) and of NKp46+ (mean > 1) were found to be significantly associated with prolonged survival, but only intratumoral CD3+ ( > 1%) and NKp46+ (mean > 1) were significant on multivariate analysis (P = 0.005 and P = 0.004 respectively). On logistic regression analysis the metachronous CLM (OR = 2.781; P = 0.002), the use of irinotecan and cetuximab (OR = 3.891; P = 0.001) and the radiological response (OR = 3.219; P = 0.001) were found to be associated with increasing density of intratumoral CD3+ and NKp46+ cells. No significant associations were found with CLM number or size, CEA, or number of CHT courses. Combining the intratumoral CD3+ and NKp46+ cells density we defined four stages of survival (P = 0.003): patients presenting intratumoral CD3+ ( > 1%) and NKp46+ (mean > 1) had 100% overall survival at 5 years. Conclusions: Intratumoral CD3+ and NKp46+ cells density is a crucial prognostic factor in patients undergoing hepatic resection for CLM after CHT, and the kind of CHT seems related to their density. Further external validations are required to confirm our promising findings.

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Impact of Neoadjuvant Chemotherapy on the Postoperative Outcomes of Patients Undergoing Liver Resection for Colorectal Liver Metastases: A Population-Based Propensity-Matched Analysis

Journal of the American College of Surgeons ◽

10.1016/j.jamcollsurg.2019.03.011 ◽

2019 ◽

Vol 229 (1) ◽

pp. 69-77.e2 ◽

Cited By ~ 6

Author(s):

Jason T. Wiseman ◽

Francisco Guzman-Pruneda ◽

Dimitrios Xourafas ◽

Yun Shin Chun ◽

Aslam Ejaz ◽

...

Keyword(s):

Liver Resection ◽

Neoadjuvant Chemotherapy ◽

Liver Metastases ◽

Colorectal Liver Metastases ◽

Population Based ◽

Postoperative Outcomes

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Radiofrequency ablation of colorectal liver metastases

Perspectives in Surgery ◽

10.33699/pis.2019.98.10.399-403 ◽

2019 ◽

Vol 98 (10) ◽

Keyword(s):

Radiofrequency Ablation ◽

Liver Resection ◽

Liver Metastases ◽

Colorectal Liver Metastases ◽

Survival Rates ◽

Postoperative Mortality ◽

Disease Free Survival ◽

Female Ratio ◽

Liver Resections ◽

Multi Stage

Introduction: Radical liver resection is the only method for the treatment of patients with colorectal liver metastases (CLM); however, only 20–30% of patients with CLMs can be radically treated. Radiofrequency ablation (RFA) is one of the possible methods of palliative treatment in such patients. Methods: RFA was performed in 381 patients with CLMs between 01 Jan 2001 and 31 Dec 2018. The mean age of the patients was 65.2±8.7 years. The male to female ratio was 2:1. Open laparotomy was done in 238 (62.5%) patients and the CT-navigated transcutaneous approach was used in 143 (37.5%) patients. CLMs <5 cm (usually <3 cm) in diameter were the indication for RFA. We used RFA as the only method in 334 (87.6%) patients; RFA in combination with resection was used in 36 (9.4%), and with multi-stage resection in 11 (3%) patients. We performed RFA in a solitary CLM in 170 (44.6%) patients, and in 2−5 CLMs in 211 (55.6%) patients. We performed computed tomography in each patient 48 hours after procedure. Results: The 30-day postoperative mortality was zero. Complications were present in 4.8% of transcutaneous and in 14.2% of open procedures, respectively, in the 30-day postoperative period. One-, 3-, 5- and 10-year overall survival rates were 94.8, 66.8, 43.9 and 16.6%, respectively, in patients undergoing RFA, and 90.6, 69.1, 52.8 and 39.2%, respectively, in patients with liver resections. Disease free survival was 63.2, 30.1, 18.4 and 13.1%, respectively, in the same patients after RFA, and 71.1, 33.3, 22.8 and 15.5%, respectively, after liver resections. Conclusion: RFA is a palliative thermal ablation method, which is one of therapeutic options in patients with radically non-resectable CLMs. RFA is useful especially in a non-resectable, or resectable (but for the price of large liver resection) solitary CLM <3 cm in diameter and in CLM relapses. RFA is also part of multi-stage liver procedures.

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