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Background: RECIST may not be optimal for assessing treatment response with current systemic regimens. We evaluated RECIST, morphologic, and pathologically documented response (pathological response) in patients with initially unresectable colorectal cancer liver-only metastases (CRLM)., Patients and Methods: Four hundred and eighty-nine patients from the phase III CAIRO5 trial were included who were treated with FOLFOX/FOLFIRI/FOLFOXIRI and bevacizumab or panitumumab. The association of the different response tools with overall survival (OS) was evaluated for all patients, and with early recurrence (<6 months) for patients after complete local treatment., Results: In the overall population, suboptimal [hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.83-1.47] and optimal (HR 0.95, 95% CI 0.74-1.22) morphologic response were not associated with OS compared with no response. RECIST partial response (HR 0.61, 95% CI 0.49-0.76) and progressive disease (HR 5.77, 95% CI 3.97-8.39) were associated with OS compared with stable disease. In 242 patients who underwent local treatment, suboptimal (HR 1.22, 95% CI 0.76-1.96) and optimal (HR 1.28, 95% CI 0.89-1.86) morphologic response were not associated with OS compared with no response. RECIST partial response was not significantly associated with OS (HR 0.73, 95% CI 0.52-1.01), whereas progressive disease was (HR 19.74, 95% CI 5.75-67.78), compared with stable disease. While major pathological response (HR 0.66, 95% CI 0.44-0.99) was associated with OS, partial pathological response (HR 0.82, 95% CI 0.57-1.19) was not, compared with no pathological response. Pathological response, but not morphologic response and RECIST, was significantly associated with early recurrence (P < 0.001) which occurred in 13/58 (22%) patients with major response, 29/61 (48%) patients with partial response, and 51/88 (58%) patients with no response., Conclusions: Our results show that RECIST but not morphologic response was prognostic for OS. In patients eligible for local treatment, neither RECIST nor morphologic response were associated with early recurrence. Pathological response was associated with early recurrence but is only available post-operatively. Hence, novel preoperative parameters are warranted to predict early recurrence and prevent potentially futile liver surgery., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Minimally invasive ablative treatments, such as radiofrequency ablation (RFA), are increasingly used in the curative treatment of patients with colorectal liver metastases (CRLM). Selection bias plays an important role in the evaluation of early and late results between RFA and surgery. The purpose of this study was to evaluate recurrences and oncological survival following these two treatment modalities using single pair propensity score matching., Methods: Between 2000 and 2018, patients curatively treated for CRLM were included in a multicentre database. Patients were excluded when receiving two-staged treatment, synchronous treatment with primary tumor or combination of modalities. Propensity score matching was used to minimize influence of known covariates, i.e., age, ASA, FONG CRS, location and T-stage of the primary tumor., Results: Before matching, the RFA group contained 39 patients and the surgery group 982 patients, after matching both groups contained 36 patients. After matching, mean age was 69 years (53-86) for RFA and 68 (50-86) for surgery, with a mean tumor size of respectively 2.5 cm (0.8-6.5) and 3.4 cm (1-7.5). Both groups showed similar complication rate according to Clavien-Dindo (17vs.33%; p = 0.18), recurrence rate (58vs.64%; p = 0.09) without significant differences in 5-year DFS and OS (RFA compared to surgery respectively 25vs.37%; p = 0.09 and 42vs.53%; p = 0.09)., Conclusion: After propensity score matching, RFA showed lower complications and similar oncological survival compared to surgical resection. In patients who are suboptimal candidates for surgery, RFA seems to be a good and safe alternative., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Targeted therapy against tumor angiogenesis is widely used in clinical practice for patients with colorectal liver metastases (CRLM). Possible predictive biomarkers for tumor angiogenesis, such as, microvessel density (MVD), hypoxia and cell proliferation, can be determined using immunohistochemical staining. However, patients ineligible for surgical treatment need to undergo invasive diagnostic interventions in order to determine these biomarkers. CT perfusion (CTP) is an emerging functional imaging technique, which can non-invasively determine vascular properties of solid tumors. The purpose of this study was to evaluate CTP with histological biomarkers in CRLM., Material and Methods: Patients with CRLM underwent CTP one day before liver surgery. CTP analysis was performed on the entire volume of the largest metastases in each patient. Dual-input maximum slope analysis was used and data concerning arterial flow (AF), portal flow (PF) and perfusion index (PI) were recorded. Immunohistochemical staining with CD34, M75/CA-IX and MIB-1 was performed on the rim in the midsection of the tumor to determine respectively MVD, hypoxia and cell proliferation., Results: Twenty CRLM in 20 patients were studied. Mean size of the largest CRLM was 37 mm (95% CI 21-54 mm). Mean AF and PF were respectively 64 ml/min/100ml (95% CI 48-79) and 30 ml/min/100ml (95% CI 22-38). Mean PI was 68% (95% CI 62-73). No significant correlation was found between tumor growth patterns and CTP (p = 0.95). MVD did not significantly correlate to AF (r = 0.05; p = 0.84), PF (r = 0.17; p = 0.47) and PI (r = -0.12; p = 0.63). Cell proliferation also did not significantly correlate to AF (r = 0.07; p = 0.78), PF (r = -0.01; p = 0.95) and PI (r = 0.15; p = 0.52). Hypoxia did not significantly correlate to AF (r = -0.05; p = 0.83), however, significantly to PF (r = 0.51; p = 0.02) and a trend to negative correlation with PF (r = -0.43; p = 0.06). However, after controlling the false discovery rate, no significant correlation between CTP and used immunohistochemical biomarkers was found., Conclusion: In conclusion, this feasibility study found a trend to negative correlation between PI and hypoxia, CTP might therefore possibly evaluate this prognostic marker in CRLM non-invasively. However, CTP is not an appropriate technique for the assessment of microvessels or cell proliferation in CRLM., Competing Interests: The authors have declared that no competing interests exist.

Background: Approximately 20% of patients with colorectal cancer present with synchronous liver metastases (sCRLM). These patients can be treated with a "one-step procedure" or staged resection, with or without radiofrequency ablation (RFA). Colorectal surgery in combination with intraoperative RFA leads to concerns regarding postoperative complications and survival. The purpose was to evaluate the one-step procedure with or without RFA in patients with sCRLM., Materials and Methods: Between January 2000 and September 2018, patients with sCRLM were selected in two tertiary referral centers and retrospectively analyzed. Postoperative morbidity and survival were analyzed., Results: From a total of 410 patients presenting with sCRLM, 329 patients underwent a staged resection and 81 a one-step procedure. The 3-year overall survival (OS) was respectively 66% and 69% for one-step procedure and staged resection (P = 0.24). A total of 18 patients underwent RFA during the one step procedure. No significant differences were shown in postoperative complications whether intraoperative RFA was used in patients with sCRLM. In the one-step procedure, the 3-year OS was respectively 43% and 72% wheter patients did or did not receive RFA (P = 0.19)., Conclusion: OS for patients with sCRLM was similar for both one-step procedure and staged resection. Intraoperative RFA for sCRLM is technically safe., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: There is an ongoing controversy surrounding portal vein embolization (PVE) regarding the short-term safety of PVE and long-term oncological benefit. This study aims to compare survival outcomes of patients subjected to major liver resection for colorectal liver metastases (CRLM) with or without PVE., Methods: All consecutive patients who underwent major liver resection for CRLM in four high volume liver centres between January 2000 and December 2015 were included. Major liver resection was defined as resection of at least three Couinaud liver segments. To reduce selection bias, propensity score matching was performed for PVE and non-PVE patients with overall and disease-free survival as primary endpoints. For matching, all patients who underwent PVE followed by a major liver resection were selected. Patients were matched to patients who had undergone major liver resection without PVE., Results: Of 745 patients undergoing major liver resection for CRLM, 53 patients (7%) underwent PVE before liver resection. In the overall cohorts, PVE patients had inferior DFS and a trend towards inferior OS. A total of 46 PVE patients were matched to 46 non-PVE patients to create comparable cohorts and between these two matched cohorts no differences in DFS (3-year DFS 16% vs 9%, p = 0.776) or OS (5-year OS 14% vs 14%, p = 0.866) were found., Conclusions: This retrospective, matched analysis does not suggest a negative impact of PVE on long-term outcomes after liver resection in patients with CRLM., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: The combination of resection and radiofrequency ablation (RFA) may provide an alternative treatment for patients with unresectable colorectal liver metastases (CRLM). Although the results in literature look promising, uncertainty exists with regard to complication risks and survival for this therapy., Methods: From January 2000 to May 2013, patients were included in a prospective multicenter database when treated for CRLM. Exclusion criteria were: two-staged treatment, synchronous resection of liver metastases and primary tumor, loss to follow-up or extrahepatic metastases. Patients were divided in a resection-only group (ROG) and combination group (CG). Outcome variables were retrospectively analyzed., Results: In CG, 98 patients were included versus 534 patients in ROG. There were no differences in general patient characteristics. Patients in CG had a higher Fong clinical risk score (CRS; P = 0.001), better ASA classification (P = 0.04) and received more neoadjuvant chemotherapy (P = 0.001). There was no difference in postoperative morbidity or 90-day mortality. The 5-year disease-free survival (DFS) for CG and ROG was 25% and 36.1% (P = 0.03), respectively. For the 5-year overall survival (OS) this was respectively 42% and 62.2% (P = 0.001). On multivariate analysis, Fong CRS was a significant predictor for DFS. For OS, Fong CRS, ASA class IV and the combination therapy were significant predictors., Conclusion: The combination of hepatic resection and intraoperative RFA is a safe procedure, without increase in postoperative morbidity or mortality. Combining RFA and resection in one session is a valid treatment option for patients who would otherwise be inoperable., (Copyright © 2016 Elsevier Ltd. All rights reserved.)