Repeat Curative Intent Liver Surgery is Safe and Effective for Recurrent Colorectal Liver Metastasis: Results from an International Multi-institutional Analysis

Jong, Mechteld C. de; Mayo, Skye C.; Pulitano, Carlo; Lanella, Serena; Ribero, Dario; Strub, Jennifer; Hubert, Catherine; Gigot, J. F.; Schulick, Richard D.; Choti, Michael A.; Aldrighetti, Luca; Mentha, Gilles; Capussotti, Lorenzo; Pawlik, Timothy M.

doi:10.1007/s11605-009-1050-0

Cited by 171 publications

(147 citation statements)

References 52 publications

(81 reference statements)

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“…Repeat hepatectomy is independently associated with favorable long-term outcome in patients with colorectal liver metastases in the repeat hepatectomy group remain to be clearly identified, with a plethora of significant prognostic variables identified in different studies [6,7,10,15,16,[18][19][20][21][22].…”

Section: Original Researchmentioning

confidence: 99%

“…There were 308 (63.1%) men and 180 (36.9%) women. At index hepatectomy, the median number of tumors on preoperative imaging was two (range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Tumor size ranged from 5 to 150 mm, with a median size of 35 mm.…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…Unfortunately, cancer recurs in up to 75% of patients following hepatectomy, in the remnant liver and/or other sites [5]. Over the past three decades, however, repeat hepatectomy has emerged as a viable therapy for recurrent CRLM [6][7][8][9][10]. The rationale of repeat hepatectomy is supported by the observation that the liver is often the sole site of disease recurrence.…”

Section: Introductionmentioning

confidence: 99%

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Repeat hepatectomy is independently associated with favorable long‐term outcome in patients with colorectal liver metastases

et al. 2017

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Up to three-quarters of patients undergoing liver resection for colorectal liver metastases (CRLM) develop intrahepatic recurrence. Repeat hepatic resection appears to provide the optimal chance of cure for these patients. The aim of this study was to analyze short-and long-term outcomes following index and repeat hepatectomy for CRLM. Clinicopathological data were obtained from a prospectively maintained database. Perioperative variables and outcomes were compared using the Chi-squared test. Variables associated with long-term survival following index and second hepatectomy were identified by Cox regression analyses. Over the study period, 488 patients underwent hepatic resection for CRLM, with 71 patients undergoing repeat hepatectomy. There was no significant difference in rates of morbidity (P = 0.135), major morbidity (P = 0.638), or mortality (P = 0.623) when index and second hepatectomy were compared. Performance of repeat hepatectomy was independently associated with increased overall and cancer-specific survival following index hepatectomy. Short diseasefree interval between index and second hepatectomy, number of liver metastases >1, and resection of extrahepatic disease were independently associated with shortened survival following repeat resection. Repeat hepatectomy for recurrent CRLM offers short-term outcomes equivalent to those of patients undergoing index hepatectomy, while being independently associated with improved longterm patient survival. Cancer MedicineOpen Access 332

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Section: Original Researchmentioning

confidence: 99%

Section: Patient Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Repeat hepatectomy is independently associated with favorable long‐term outcome in patients with colorectal liver metastases

et al. 2017

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“…Several studies have demonstrated the efficacy of repeat surgical resection or ablation for the treatment of colorectal liver metastasis and hepatocellular carcinoma; however, there is a paucity of data on the management of recurrent ICC. [16][17][18] Given this, the objective of the current study was to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. Specifically, using a large multi-institutional cohort of patients, we sought to determine the rate and the pattern of recurrent disease following curative-intent surgery for ICC, as well as define the therapy-specific outcome of patients treated for recurrent disease.…”

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confidence: 99%

Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma following previous curative intent surgical resection.

Spolverato

Kim

Alexandrescu

et al. 2015

JCO

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349 Background: Many patients develop recurrence following resection of intrahepatic cholangiocarcinoma(ICC). Management and outcomes of patients with recurrent ICC following previous curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. Methods: Between 1990-2013, 542 patients who underwent surgery for ICC were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence and recurrence-related management were recorded and analyzed. Results: At initial surgery, treatment was resection only(96.1%) or resection+RFA(3.9%). Overall 5-year survival was 25.9%; 376(69.4%) patients recurred with a median disease-free survival of 11.0 months. Vascular invasion(hazard ratio [HR]=1.43), nodal metastasis(HR=1.40) and poor differentiation(HR=1.30) were predictive of recurrence(all P<0.05). First recurrence site was intrahepatic only (62.0%), extrahepatic only (14.1%), or intra- and extrahepatic(23.9%). Overall 259(68.9%) patients received treatment for recurrent ICC, while 117(31.1%) received best supportive care(BSC). Among patients who received treatment for recurrent disease, therapy consisted of systemic chemotherapy only(49.4%), repeat liver-directed therapy (25.9%), or systemic chemotherapy+liver-directed therapy(24.7%). Repeat liver-directed therapy consisted of repeat hepatic resection±ablation(30.5%), ablation alone (21.4%), and intra-arterial therapy(IAT)(48.1%). Among patients who recurred, median survival from the time of the recurrence was 11.0 months(BSC-7.7 months, systemic chemotherapy only-10.0 months, liver-directed therapy-18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 7.6 months for patients who had IAT(P<0.001). Conclusions: Recurrence following resection of ICC is common, occurring in up to two-thirds of patients. When recurrence occurs, prognosis is poor. In well-selected patients with liver only recurrence, resection+chemotherapy may offer a modest survival benefit.

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“…However colorectal cancer (CRC), the third most common cancer worldwide, commonly metastasizes to the liver, which is the leading cause of CRC mortality. 3,4 The current therapeutic options for HCC and liver metastasis from CRC (LM-CRC) include surgery (resection and liver transplantation) and local (ablative) therapy. Unfortunately, less than 20% of HCC patients are eligible for curative procedures 5 because most of them have advanced disease at the time of diagnosis.…”

Section: Introductionmentioning

confidence: 99%

GITR engagement in combination with CTLA-4 blockade completely abrogates immunosuppression mediated by human liver tumor-derived regulatory T cellsex vivo

et al. 2015

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Sprengers (2015) GITR engagement in combination with CTLA-4 blockade completely abrogates immunosuppression mediated by human liver tumor-derived regulatory T cells ex vivo, OncoImmunology, 4:12, e1051297, DOI: 10.1080/2162402X.2015 Keywords: cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor (GITR), hepatocellular carcinoma (HCC), liver metastases from colorectal cancer (LM-CRC), regulatory T cells (Treg)In liver cancer tumor-infiltrating regulatory T cells (Ti-Treg) are potent suppressors of tumor-specific T-cell responses and express high levels of the Treg-associated molecules cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and glucocorticoid-induced tumor necrosis factor receptor (GITR). In this study, we have evaluated the capacity of GITRligation, CTLA-4-blockade and a combination of both treatments to alleviate immunosuppression mediated by Ti-Treg. Using ex vivo isolated cells from individuals with hepatocellular carcinoma (HCC) or liver metastases from colorectal cancer (LM-CRC) we show that treatment with a soluble form of the natural ligand of GITR (GITRL), or with blocking antibodies to CTLA-4, reduces the suppression mediated by human liver tumor-infiltrating CD4 C Foxp3C Treg, thereby restoring proliferation and cytokine production by effector T cells. Importantly, combined treatment with low doses of both molecules exhibited stronger recovery of T cell function compared with either treatment alone. Our data suggest that in patients with primary and secondary liver cancer both GITR-ligation and anti-CTLA-4 mAb can improve the antitumor immunity by abrogating Ti-Treg mediated suppression.

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Repeat Curative Intent Liver Surgery is Safe and Effective for Recurrent Colorectal Liver Metastasis: Results from an International Multi-institutional Analysis

Abstract: Repeat CIS for recurrent colorectal liver metastasis can be performed with low morbidity and near-zero mortality. Patients with no extra-hepatic disease are best candidates for repeat CIS. In these patients, repeat CIS can offer the chance of long-term survival.

Cited by 171 publications

References 52 publications

Repeat hepatectomy is independently associated with favorable long‐term outcome in patients with colorectal liver metastases

Repeat hepatectomy is independently associated with favorable long‐term outcome in patients with colorectal liver metastases

Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma following previous curative intent surgical resection.

GITR engagement in combination with CTLA-4 blockade completely abrogates immunosuppression mediated by human liver tumor-derived regulatory T cellsex vivo

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