Number Of Liver Metastases Research Articles

The feasibility and potential benefit of preoperative chemotherapy for colorectal liver metastasis (CLM): a single-centered retrospective study

The benefit of neo-adjuvant chemotherapy for liver-limited metastatic colorectal cancer is still controversial. This study defined the resectability regardless of the size and number of liver metastases, and attempted curative hepatic resection in all cases. Sixty-four patients that tolerated chemotherapy were diagnosed with CLM (colorectal liver metastases) without extrahepatic metastase from January 2007 to November 2010, and received an oxaliplatin-based regimen. This study assessed the resectability after chemotherapy, and the patients were divided in two groups; the resected and unresected group. Sixteen patients underwent hepatic resection without chemotherapy. Thirty-five patients underwent surgical resection (resected group) and twenty-nine patients were considered unresectable (unresected group). All 35 patients in the resected group safely received oxaliplatin-based chemotherapy safely without serious adverse effects. No serious postoperative complications were observed. The median overall survival (MST) was significantly higher in the resected than in the unresected group (56.93 [95% CI 38.13-75.73] and 25.07 months [95% CI 17.87-32.26], respectively; P < 0.001). The median disease-free survival was 20.2 [95% CI 8.82-31.65] months in the resected group. Preoperative chemotherapy for CLM is well tolerated and does not increase postoperative complications. Curative surgery with preoperative chemotherapy has the potential to improve the overall survival in patients with CLM.

IS9-2 - Survival Investigation in Patients with Colorectal Liver Metastasis: A Single-Institution Analysis

ABSTRACT Background To investigate survival in patients with colorectal liver metastasis (CRLM) and identify risk factors associated with survival. Methods A total of 1613 consecutive patients with CRLM in Zhongshan Hospital between 2000 and 2010 were retrospectively analyzed. The prognostic value of different factors was studied through univariate and multivariate analyses. Results Synchronous liver metastasis (SLM), female, grade III–IV, T4 and N positive of primary tumor, bilobar disease, number of liver metastases ≥4, size of largest liver metastases ≥5 cm, CEA ≥5 ng/ml and CA19–9 ≥ 37 µg/ml were predictors of adverse outcome using univariate analysis. The median survival and 5-year survival rate for patients after resection of liver metastases was 49.8 months and 47%, better than that for those after other therapy. Expansion of the indications for liver resection, simultaneous or staged resection of primary tumor and liver metastases and preoperative neoadjuvant therapy had no effect on survival. Sixty-four initially unresectable patients underwent surgery after convertible therapy and demonstrated a median survival of 36.9 months and a 5-year survival of 30%, better than that of unresectable patients without surgery. By multivariate analysis, SLM, poorly differentiated primary tumor, number of liver metastases ≥4, size of largest liver metastases ≥5 cm, and no surgical treatment of liver metastases were found to be independent predictors. Assigning one point to each of above factors, the total was divided into six groups with distinct 5-year survival rates: 0 points (77%), 1 point (57%), 2 points (38%), 3 points (12%), 4 points (4%) and 5 points (0%) (P Conclusions Patients with CRLM could get long-term survival benefit from different types of therapy used to treat the liver metastases, and resection of resectable and initially unresectable liver metastases was the optimal strategy. Long-term survival outcome can be predicted from the above five factors.

Efficacy of minimally invasive therapies on unresectable pancreatic cancer

For patients with unresectable pancreatic cancer, current chemotherapies have negligible survival benefits. Thus, developing effective minimally invasive therapies is currently underway. This study was conducted to evaluate the efficacy of transarterial chemoembolization plus radiofrequency ablation and/or 125I radioactive seed implantation on unresectable pancreatic cancer. We analyzed the outcome of 71 patients with unresectable pancreatic carcinoma who underwent chemoembolization plus radiofrequency ablation and/or radioactive seed implantation. Of the 71 patients, the median survival was 11 months, and the 1-, 2-, and 3-year overall survival rates were 32.4%, 9.9%, and 6.6% respectively. Patients who had no metastasis, who had oligonodular liver metastases (≤3 lesions), and who had multinodular liver metastases (>3 lesions) had median survival of 12, 18, and 8 months, respectively, and 1-year overall survival rates of 50.0%, 68.8%, and 5.7%, respectively. Although the survival of patients without liver metastases was worse than that of patients with oligonodular liver metastasis, the result was not significant (P = 0.239). In contrast, the metastasis-negative patients had significantly better survival than did patients with multinodular liver metastases (P < 0.001). Patients with oligonodular liver lesions had a significanthg longer median survival than did patients with multinodular lesions (P < 0.001). In conclusion, combined minimally invasive therapies had good efficacy on unresectable pancreatic cancer and resulted in a good control of liver metastases. In addition, the number of liver metastases was a significant factor in predicting prognosis and response to treatment.

644 - Outcome of Patients with Colorectal Liver Metastasis: Analysis of 1613 Consecutive Cases

ABSTRACT Objective To evaluate the long-time outcome of patients with colorectal liver metastasis (CRLM) undergoing different types of therapy and identify prognosis factors. Methods From 2000 to 2010, 1613 consecutive patients with CRLM were identified. Clinicopathological and outcome data were collected and analyzed by univariate and multivariate analyses. Results Synchronous liver metastasis (SLM), female, grade III-IV, T4 and N positive of primary tumor, bilobar disease, number of liver metastases ≥ 4, size of largest liver metastases ≥ 5 cm, serum CEA level ≥5 ng/ml and CA19-9 level ≥ 37u/ml were the predictors of adverse outcome using univariate analysis. The median survival and five-year survival rate for patients after resection of liver metastases was 49.8 months and 47%, better than that for those after other therapy. In addition, patients without treatment had the poorest survival. Sixty-four initially unresectable patients underwent surgery after conversion therapy with a median survival of 36.9 months and a five-year survival of 30%. By multivariate analysis, SLM, poorly differentiated primary tumor, number of liver metastases ≥ 4, size of largest liver metastases ≥ 5 cm, and no surgical treatment of liver metastases were found to be independent predictors of poor survival. Conclusions Patients with CRLM could get long-term survival benefit from different types of therapy, and resection of liver metastases was the optimal strategy. A predictive model using these above five factors may be of use in stratifying patients who may benefit from intensive surveillance and adjuvant therapy. Disclosure All authors have declared no conflicts of interest.

Factors that influence survival in colorectal cancer with synchronous distant metastasis

BackgroundTreatments for the purposes of curing or more effectively managing metastatic colorectal cancer (CRC) are evolving. Our study focused on patients with primary CRC with synchronous distant metastasis, and we analyzed the factors influencing patient survival. MethodsData review was conducted retrospectively. Clinicopathological parameters included age, sex, site of primary cancer, tumor cell differentiation, number of liver metastasis, presence of extrahepatic metastasis, treatment of liver metastasis, pre-treatment carcinoembryonic antigen (CEA) level, status of treatment response, salvage treatment and survival. ResultsA total of 420 patients were identified and considered for our study. Of those, 275 patients (65.4%) had liver-only metastasis, 100 patients (23.8%) had concomitant lung metastasis, and 40 patients (9.5%) had other metastases. Additionally, 145 patients (34.5%) had liver-directed treatment including surgical resection (28.5%), radiofrequency ablation (RFA) (10.6%) and transcatheter arterial chemoembolization (TAE) (1.2%). There were 80 patients (19%) with CEA levels < 10, 135 patients (32.1%) with CEA 10–100, and 165 patients (39.2%) with CEA > 100. There were 200 patients (47.6%) who had received chemotherapy, 130 patients (30.9%) with target therapy, and 40 patients (9.5%) who had not undergone any salvage treatment. Three significant factors were identified, including treatment of liver metastasis (p=0.027), pre-treatment CEA (p=0.04), and salvage treatment (p=0.005). ConclusionWe demonstrated three factors influencing patient survival including treatment of liver metastasis, pre-treatment CEA level, and salvage treatment. Aggressive treatment of liver metastasis including surgical resection or RFA combined with chemotherapeutic agents appear to provide an increased rate of survival to patients.

PWE-145 Prognostic factors influencing survival after liver resection for colorectal metastasis

IntroductionA variety of factors have been identified in the literature which influence survival following resection of colorectal liver metastases (CRLM). The aim of this study was to identify those factors...

Outcome of patients with colorectal liver metastasis: Analysis of 1,613 consecutive cases.

e14000 Background: To evaluate the long-time outcome of patients with colorectal liver metastasis (CRLM) undergoing different types of therapy and identify factors associated with prognosis. Methods: From 2000 to 2010, a total of 1,613 patients with CRLM were identified in Zhongshan Hospital. Clinicopathological and outcome data were collected and analyzed by univariate and multivariate analyses. Results: Of 1,613 patients the median survival was 23.1 months and the five-year survival rate was 23%. Synchronous liver metastasis (SLM), female, grade III-IV, T4 and N + of primary tumor, bilobar disease, number of liver metastases ≥ 4, size of largest liver metastases ≥ 5 cm, CEA ≥5 ng/ml and CA19-9 ≥ 37u/ml were the predictors of adverse outcome using univariate analysis. The median survival and five-year survival rate for patients after resection of liver metastases was 49.8 months and 47%, compared with 22.2 months and 19% for those after systemic chemotherapy alone, 19.0 months and 13% for those after hepatic arterial chemotherapy alone, 22.8 months and 10% for those after systemic chemotherapy combined with hepatic arterial chemotherapy, and 28.5 months and 6% for those after local regional treatment alone (p&lt; 0.010). In addition, patients without treatment had the poorest survival rate (9.6 months and 0%). 64 initially unresectable patients underwent surgery after convertible therapy and had a median survival of 36.9 months and a five-year survival of 30%, which was better than that of unresectable patients who did not undergo surgery (18.2 months and 10%). By multivariate analysis, SLM, poorly differentiated primary tumor, number of liver metastases ≥ 4, size of largest liver metastases ≥ 5 cm, and no surgical treatment of liver metastases were found to be independent predictors of poor survival. Conclusions: Patients with CRLM could get long-term survival benefit from different types of therapy, and resection of resectable and initially unresectable liver metastases was the optimal strategy. The disease-free interval from primary to liver metastases, the differentiation of the primary tumor, the number and size of liver metastases and the types of therapy used to treat liver metastases were independent prognostic factors.

Liver Resection for Multiple Colorectal Liver Metastases with Surgery Up‐front Approach: Bi‐institutional Analysis of 736 Consecutive Cases

Preoperative chemotherapy has become more common in the management of multiple resectable colorectal liver metastases; however, the benefit is unclear. This study examined clinical outcomes following liver resection for multiple colorectal liver metastases with the surgery up-front approach. Data collected prospectively over a 16-year period for 736 patients who underwent hepatic resection at two different centers were reviewed. Patients were divided into three groups depending on the number of tumors as follows: group A, between one and three tumors (n = 493); group B, between four and seven tumors (n = 141); and group C, eight or more tumors (n = 102). The 5-year overall and recurrence-free survival rates were 51 and 21 %, respectively, for the entire patient cohort, 56 and 29 % in group A, 41 and 12 % in group B, and 33 and 1.7 % in group C. Multivariate analysis showed that decreased survival was associated with positive lymph node metastasis of the primary tumor, the presence of extrahepatic tumors, a maximum liver tumor size >5 cm, and tumor exposure during liver resection. In patients with multiple liver metastases, the number of liver metastases has less impact on the prognosis than other prognostic factors. Complete resection with repeat metastasectomy offers a chance of cure even in patients with numerous colorectal liver metastases (i.e., those with eight or more nodules). A further prospective study is necessary to clarify the optimal setting of preoperative chemotherapy.

Abstract 3840: Evaluation of the synergetic effect of a combination of dehydroxymethylepoxyquinomicin and gemcitabine on liver metastasis of pancreatic cancer

Abstract Activation of the nuclear transcription factor-kappaB (NF-κB) has been implicated in the progression and metastasis of pancreatic cancer. This study was designed to evaluate the effects of a novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) in inhibition of liver metastasis of pancreatic cancer in a clinical liver metastasis-mimicking mouse model in which cancer cells were intra-portal injected under small laparotomy. Moreover, the synergistic effect of combination therapy with DHMEQ and gemcitabine (GEM) was investigated. Cytotoxicity of DHMEQ and GEM was evaluated by cell growth inhibition assay. Both DHMEQ and GEM monotherapies inhibited cell growth of the human pancreas cell line AsPC-1. However, there was no synergistic effect in the combination therapy. For the in vivo study, male BALB/c nude mice were xenografted with intra-portal vein injection of AsPC-1. Mice were divided into four groups: 1) control (without any treatment), 2) GEM-treated group, 3) DHMEQ-treated group, and 4) combined treatment group (GEM+DHMEQ). Mice were fed for four weeks, and the number of liver metastases, induction of apoptosis in metastasis focuses and angiogenesis were investigated after sacrifice. The number of liver metastasis was decreased significantly in GEM group, DHMEQ group and GEM+DHMEQ group compared with control group. Significant inductions of apoptosis were revealed in GEM group and DHMEQ group compared with control group, in which apoptosis bodies in metastasis sections were counted by using the TUNEL method. Moreover, combination therapy of DHMEQ+GEM resulted in the strongest inductions of apoptosis. Tumor vessels were identified by immunohistochemical staining of tumor metastasis sections with an antibody against CD31. There was a large reduction in the number of CD31-positive vessels in the tumor of DHMEQ or/and GEM-treated mice as compared with control group. However, there was an inconsistency in the results of cell growth inhibition assay (in vitro) and mice metastasis model (in vivo). Thus we evaluated effect of combination therapy in the invasive potential of tumor cells by using chemoinvasion assay. The invasion ability was significantly inhibited in the GEM group, DHMEQ group and GEM+DHMEQ group. Furthermore, real-time PCR was performed to evaluate expression of mRNA of MMP-9. The expression levels of MMP-9 were inhibited in respective groups in the same order. In conclusion, the anti-tumor effects of combination therapy were significant, as evidenced by angiogenesis inhibition, apoptosis induction and invasiveness inhibition rather than cell growth inhibition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3840. doi:1538-7445.AM2012-3840

Abstract 1418: Dll4-Fc, an inhibitor of Dll4-notch signaling, suppresses liver metastasis of small cell lung cancer cells through down-regulation of NF-kappa-B activity

Abstract Purpose: The Notch signaling regulates cell-fate decisions during development and postnatal life. Recent studies have demonstrated that the signaling through Notch and its ligand Dll4 in tumor endothelial cells plays an important role in cancer angiogenesis. Little is known, however, about the role of Dll4-Notch signaling between cancer cells, and how it affects on cancer metastasis. We therefore assessed the importance of cancer cell Dll4-Notch signaling in cancer metastasis produced by human small lung cancer cells. Experimental Design: On the basis of previous studies, we generated retroviral vectors encoding a soluble dimerized form of Dll4 fused to the human IgG1 Fc constant region (Dll4-Fc) that acts as a blocker of Dll4-Notch interactions. Dll4-Fc was introduced into human small cell lung cancer cell lines that express high level of Dll4 and Notch (SBC-3 and H1048 cells), and low level of Dll4 (SBC-5 cells). The cells were intravenously inoculated to natural killer cell-depleted SCID mice, and the multiple-organ metastases were evaluated. Result: The number of liver metastasis in the mice inoculated with SBC-3 and H1048 cells expressing Dll4-Fc were significantly lower than that of liver metastasis formed by control transfectant cells. However, the number of liver metastasis formed by SBC-5 cells was not significantly different between Dll4-Fc expressing and control cells, suggesting that Dll4-Notch signaling in cancer cells plays important role in liver metastasis of small cell lung cancer. Metastatic colonies in other organ such as lung, kidney and bone were not affected by Dll4-Fc overexpression in each cell lines. In order to study the molecular mechanism of the effect of Dll4-Fc on liver metastasis, genes associated with metastasis were screened by PCR array system. Seven genes (MMP7, IL1B, MMP1, S100A4, MMP10, CXCR4, SERPINE1) were down-regulated in Dll4-Fc-overexpressing SBC-3 and H1048, but not SBC-5 cells, compared with control transfectant cells. Since most of the selected genes were NF-kappa-B target genes, we explored whether NF-kappa-B is involved in cancer cell Dll4-Notch signaling. By using luciferase assay, we observed that NF-kappa-B activity was down-regulated in Dll4-Fc-overexpressing SBC-3 and H1048 cells, but not SBC-5 cells, compared with control transfectant cells, indicating that Dll4-Fc inhibits NF-kappa-B activity in small cell lung cancer cells by suppressing Dll4-Notch signaling. Conclusion: These results suggest that Dll4-Notch signaling in cancer cells plays a critical role in liver metastasis of small cell lung cancer, by regulating the NF-kappa-B signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1418. doi:1538-7445.AM2012-1418

Abstract 1394: Acute bacterial infection increases lung cancer metastasis via toll-like receptors 2 and 4

Abstract INTRODUCTION: Surgery is required for curative treatment of lung cancer but is associated with a high rate of bacterial infections such as pneumonia. There is emerging clinical evidence to suggest that infectious complications may decrease survival after cancer surgery, but the mechanism is unclear. Interactions between bacteria and host cells are mediated by specialized pathogen recognition receptors, of which the Toll-like receptors (TLRs) are best characterized. We and others have shown that cancer cells express TLRs, but their function is largely unknown. The aim of this study is to investigate the mechanisms of bacterial infection-facilitated lung cancer metastasis with a particular focus on the role of TLRs. METHODS: Two lung cancer cell lines (murine H-59 and human A549) were incubated a) directly with heat-inactivated bacteria (S.pneumonia or E.coli) or purified bacterial antigens (lipopolysaccharide or lipoteichoic acid), or b) indirectly with an in vitro pneumonia model using conditioned media from pulmonary bronchial epithelial cells incubated with heat-inactivated bacteria or bacterial antigens. Migratory and metastatic ability of thus treated cells were determined in vitro (adhesion, migration) and in vivo (hepatic intravital microscopy and intra-splenic liver metastasis). A clinically relevant in vivo model of severe infection, cecal ligation and puncture (CLP) or sham control, was employed in some animals. To assess the role of TLRs, we used transgenic TLR4 knockout mice, and small molecule inhibiting molecules or antibodies of TLRs. RESULTS: Direct and indirect (in vitro pneumonia) infection of H-59 and A549 increased adhesion to extracellular matrix components approximately 2-8 fold and 2-4 fold over negative control, respectively. In vitro pneumonia increased in vitro migration of H-59 approximately 2-5 fold. Direct and indirect incubation of H-59 with S.pneumonia and E.coli increased the in vivo adhesion to liver sinusoids 2-4 fold. CLP (in vivo infection model) enhanced the in vivo adhesion of H-59 3-fold and increased number of liver metastases at 2 weeks post-injection approximately 12 fold. These effects were attenuated in TLR4 -/- mice and with TLR2 and TLR4 inhibition. CONCLUSION: Activation of TLR2 or TLR4 on lung cancer cells, either directly by S.pneumonia and E.coli, indirectly though activated bronchial epithelial cells, or via an in vivo infection, increases cancer cell adhesion, migration and metastasis. TLRs thus represent a potential therapeutic target in bacterial infection facilitated cancer metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1394. doi:1538-7445.AM2012-1394

Outcome of Patients with Colorectal Liver Metastasis: Analysis of 1,613 Consecutive Cases

This study was designed to evaluate the long-time outcome of patients with colorectal liver metastasis (CRLM) undergoing different types of therapy and identify prognosis factors. From 2000 to 2010, 1,613 consecutive patients with CRLM were identified. Clinicopathological and outcome data were collected and analyzed by univariate and multivariate analyses. Synchronous liver metastasis (SLM), female, grade III-IV, T4 and N positive of primary tumor, bilobar disease, number of liver metastases ≥ 4, size of largest liver metastases ≥ 5 cm, serum CEA level ≥ 5 ng/ml, and CA19-9 level ≥ 37 u/ml were the predictors of adverse outcome using univariate analysis. The median survival and 5-year survival rate for patients after resection of liver metastases was 49.8 months and 47%, better than that for those after other therapy. In addition, patients without treatment had the poorest survival. Sixty-four initially unresectable patients underwent surgery after conversion therapy with a median survival of 36.9 months and a 5-year survival of 30%. By multivariate analysis, SLM, poorly differentiated primary tumor, number of liver metastases ≥ 4, size of largest liver metastases ≥ 5 cm, and no surgical treatment of liver metastases were found to be independent predictors of poor survival. Patients with CRLM could get long-term survival benefit from different types of therapy, and resection of liver metastases was the optimal strategy. A predictive model using these above five factors may be of use in stratifying patients who may benefit from intensive surveillance and adjuvant therapy.

BRAF mutation is a prognostic biomarker for colorectal liver metastasectomy

In metastatic colorectal cancer, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is a predictive biomarker for anti-epidermal growth factor receptor (EGFR) treatment and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) is a prognostic biomarker. We aimed to determine the impact of KRAS and BRAF mutation as determined from liver metastases specimens on overall survival (OS) in patients following colorectal liver metastasectomy. Liver metastases specimens (n = 292) obtained from patients after liver metastasectomy were used to determine the KRAS/BRAF genotype. Associations between clinicopathological parameters and KRAS/BRAF genotype were identified by univariate and multivariate analyses using the Cox proportional hazards model. The impact of KRAS/BRAF genotype on survival was analyzed using the Kaplan-Meier method. The 5-year survival rate of the cohort was 55.8%. The KRAS and BRAF mutation rates were 38.0 and 2.1%, respectively. BRAF genotype, but not KRAS, was found to be an independent prognostic biomarker (HR = 5.181, P = 0.002) after adjustment for other significant confounding clinicopathological variates: Number of liver metastases (HR = 1.983, P = 0.009), concomitant extrahepatic disease (HR = 1.858, P = 0.014), and surgical margin (HR = 3.241, P < 0.001). BRAF genotype was an independent prognostic biomarker in patients with liver metastases only after metastasectomy (HR = 6.245, P < 0.003). BRAF mutation is an independent prognostic biomarker for colorectal liver metastasectomy.

Minimally invasive liver surgery for metastases from colorectal cancer: oncologic outcome and prognostic factors

Few reports exist on long-term survival after minimally invasive liver surgery (MILS) for colorectal liver metastases (CRLM). No data are available assessing prognostic factors in the era of current modern treatment strategies. Between October 2002 and December 2008, 274 consecutive patients were analyzed on an intention-to-treat basis. Open liver surgery (OLS) was performed in 193 patients for a total of 437 metastases, and MILS was performed in 81 patients for 176 metastases. Systemic chemotherapy was administered preoperatively in 173 and postoperatively in 174 patients. The impact of 23 potential prognostic factors on disease-free (DFS) and overall survival (OS) was evaluated using univariable and multivariable Cox regression models. Postoperative complications were observed in 54 patients after OLS and in 11 after MILS (p = 0.016). The median postoperative length of hospital stay was 9 days after OLS and 5 days after MILS (p < 0.0001). For the entire patient population, the 5 year DFS and OS rates were 29.9 and 59.5%, respectively. No differences in survival between patients treated with MILS and OLS were observed (p = 0.63). In univariable analyses, the number of liver metastases and the overall Fong's clinical risk score (CRS) were the only two variables that predicted DFS (p ≤ 0.0035) and OS (p ≤ 0.0005). In multivariable analyses, the total CRS was the only independent predictor of both DFS (p = 0.0002) and OS (p = 0.002). The long-term oncologic outcome of surgically treated patients with CRLM is determined by the Fong's CRS. Although MILS does not influence long-term survival, it has a beneficial impact on the immediate postoperative clinical outcome.

Survival investigation in patients with colorectal liver metastasis: A single-institution analysis.

617 Background: To investigate survival in patients with colorectal liver metastasis (CRLM) and identify risk factors associated with survival. Methods: Clinical, pathologic, treatment and complete follow-up data were retrospectively collected from 1613 consecutive patients with CRLM in Zhongshan Hospital between 2000 and 2010. The prognostic value of different factors was studied through univariate and multivariate analyses. Results: The median survival was 22.0 mo and 5-yr survival rate was 16%. Survival of synchronous liver metastases (SLM) (21.2 mo and 16%) was lower than that of metachronous liver metastases (MLM) (30.1 mo and 23%, p&lt;0.01). Survival after resection of liver metastases was 49.8 mo and 37%, higher than that after chemotherapy (22.2 mo and 0%), that after intervention(19.0 mo and 11%), that after chemotherapy combined with intervention(22.8 mo and 10%)and that after local regional treatment (28.5 mo and 0%). Expansion of the indications for liver resection (38.0 vs 48.0 mo, 32% vs 40%), simultaneous or staged resection of primary colorectal tumor and liver metastases (47.0 vs 44.0 mo, 33% vs 35%) and preoperative neoadjuvant therapy (44.0 vs 48.0 mo, 38% vs 36%) had no significant effect on survival. 64 initially irresectable patients could undergo surgery after convertible therapy, with the median survival 36.9 mo and 5-yr survival 30%, better than that of unresectable patients (18.2 mo and 8%). Five factors were found to be significant and independent predictors of poor survival by multivariate analysis: SLM, poorly differentiated primary, number of liver metastases &gt;= 4, largest liver metastases &gt;= 5 cm, and no surgical treatment of liver metastases. Giving one point to each above factor, the population was divided into six groups with 5-yr survival rates: 0 (64%), 1 (44%), 2 (29%), 3 (4%), 4 (4%) and 5 (1%) (p&lt;0.01). Conclusions: Survival of SLM was lower than that of MLM. Resection of liver metastases provides good long-term survival benifit for patients with resectable and initially irresectable liver metastases. Expansion of the indications for liver resection is acceptable. Long-term survival outcome can be predicted from a risk factor scoring system.

Radiofrequency ablation combined with systemic chemotherapy in nasopharyngeal carcinoma liver metastases improves response to treatment and survival outcomes

Systemic chemotherapy is the major treatment modality for nasopharyngeal carcinoma (NPC) liver metastases. We investigated the effectiveness of radiofrequency ablation (RFA) treatment, which has not been well explored in this disease. One-hundred and thirty-four cases of NPC with liver metastases treated with chemotherapy, chemotherapy with RFA, or RFA alone were retrospectively analyzed. Patient survival was evaluated by the log-rank test. Survival was analyses using the Kaplan-Meier method. Cox multivariate analyses of clinicopathological features and different treatment approaches were conducted. Local response rates were 58% in the RFA group, 78% in the chemotherapy group and 93% in the chemotherapy with RFA group (P < 0.001). Increased progression-free survival (PFS) and overall survival (OS) were observed in the chemotherapy with RFA group (P < 0.001). Cox multivariate analysis indicated that the number of liver metastases (1 vs. >1), the dimension of the largest liver metastases (≤3 cm vs. >3 cm), evaluation of treatment (response vs. no response) and disease-free survival (≤12 months vs. >12 months) were independent prognostic factors. RFA combined with chemotherapy is a promising treatment for NPC metastatic liver disease with improved local response, PFS, and OS compared to current chemotherapy protocols.

The prognostic significance of computerised tomography findings in women with liver metastases from breast cancer

Aims While computerised tomography (CT) is used for diagnosis and assessing response to treatment little work has been performed on the prognostic significance of the CT findings in women with liver metastases. The aim of this study was to assess if the CT findings in women diagnosed with liver metastases at the time of first presentation with metastatic breast cancer have any prognostic significance. Materials and methods The staging CT scans of 78 consecutive women diagnosed with liver metastases at the time of first presentation of metastatic breast cancer were reviewed independently by two radiologists who were blinded to survival and the histological features of the tumour. The number and enhancement characteristics of liver metastases, whether metastases were solitary, multiple or diffuse, the diameter of the largest and the sum of the diameter of the five largest lesions, an estimate of % involvement (<10%, 10–50%, >50%), and the presence of metastases at other sites were assessed. HER-2 and ER status and histological grade of the patient’s primary breast cancer were also recorded. Survival was ascertained from hospital records. The prognostic significance of these factors was assessed in a univariate and multivariate fashion. Results At univariate analysis, number of liver metastases, sum of the diameter of the five largest lesions, percentage estimated involvement, presence of ascites, chest metastases and HER-2 status were significantly associated with reduced survival. Liver metastasis pattern (i.e. whether discrete or multiple), enhancement characteristics, ER status and histological grade were not associated with a significant outcome. At multivariate analysis estimated percentage liver involvement and the presence of chest metastases retained prognostic significance. Estimated percentage involvement was reproducible with 90% concordance between the two observers. Conclusions The CT appearances of patients with liver metastases at first presentation with metastatic breast cancer provide prognostic information which may be clinically useful.

Risk factors for early recurrence after curative hepatectomy for colorectal liver metastases

With the broadening indications for hepatectomy to treat colorectal liver metastases (CRLM), early recurrence is a major problem. The aim of this study is to identify risk factors of early recurrence, defined as recurrence within 1 year after surgery. A retrospective analysis was performed on 121 consecutive patients who underwent hepatectomy for CRLM. Among 121 patients, 52 (43.0%) developed early recurrence. The independent risk factor for early recurrence was "number of liver metastases ≥ 3" (odds ratio 2.65). There were significantly more patients with liver recurrence (51.9%) and recurrence beyond curative surgical resection (63.5%) in those with early recurrence. In addition, patients with three or more liver metastases had significantly more liver recurrence (66.7%; P = 0.02) and recurrence beyond curative surgical resection (70.8%; P = 0.04). The overall survival rates of both patients with early recurrence (5-year survival rate 20%) and those with three or more liver metastases (5-year survival rate 24%) were significantly worse. The independent risk factor for early recurrence is the "number of liver metastases ≥ 3." Patients with three or more liver metastases have a significantly higher risk of liver recurrence and a higher rate of recurrence beyond curative surgical resection, and these are correlated with a poor prognosis.

Comparative analysis of radiofrequency ablation and surgical resection for colorectal liver metastases

PurposeTo evaluate the comparative therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection for the treatment of colorectal liver metastasis (CRLM).MethodsBetween 1996 and 2008, 177 patients underwent RFA, 278 underwent hepatic resection and 27 underwent combination therapy for CRLM. Comparative analysis of clinical outcomes was performed including number of liver metastases, tumor size, and time of CRLM.ResultsBased on multivariate analysis, overall survival (OS) correlated with the number of liver metastases and the use of combined chemotherapy (P < 0.001, respectively). Disease-free survival (DFS) also correlated with the number of liver metastases (P < 0.001). In the 226 patients with solitary CRLM < 3 cm, OS and DFS rates did not differ between the RFA group and the resection group (P = 0.962 and P = 0.980). In the 70 patients with solitary CRLM ≥ 3 cm, DFS was significantly lower in the RFA group as compared with the resection group (P = 0.015).ConclusionThe results indicate that RFA may be a safe alternative treatment for solitary CRLM less than 3 cm, with outcomes equivalent to those achieved with hepatic resection. A randomized controlled study comparing RFA and resection for patients with single small metastasis would help to determine the most efficient treatment modalities for CRLM.

Abstract P5-14-16: Resection of Breast Cancer Liver Metastases: Single Institution Experience

Abstract Background Metastatic breast cancer (MBC) is considered incurable and systemic treatment is usually given, even when liver metastasis is solitary and the only metastatic site. However, occasionally in selected, for surgery highly motivated patients, liver metastases resection is performed. The definitive disease outcome for those patients is rarely reported. The aim of this analysis is to evaluate outcomes for patients after breast cancer liver metastases resection. Patients and methods From December 2002-March 2010, 36 MBC patients were referred to surgery for liver metastases resection. Median age at MBC was 48 (range 29-71), median DFI from breast cancer diagnosis to metastases development was 36 (0-144 months). Steroid receptor status was positive (defined as ER and or PGR Qucik score ≥4) in 20 primary BC (74%), negative (Quick score&amp;lt;4) in 6 primary BC (22%), and unknown for 7 pts (22.5%). HER2 status was known for 24 pts (77.4%), and was positive (IHC 3+, and CISH+ for HER2 2+) in 5 pts. (21%), and negative in 19 pts (79%) Results Five pts were excluded because metastases in other organ sites were detected. In 3/31 pts who underwent surgery, inoperable multiple, metastases were intra-operatively confirmed despite initial diagnostic procedures indicate solitary lesions. Outcome for those patients is not shown in this analysis. In 3 pts, metastases were ruled out by biopsy during laparatomy. In 25 pts who underwent liver resection median number of liver metastases was 1 (range 1-5), median size 25 mm (7-50). All pts received systemic, postoperative chemotherapy, +/− treatment according to molecular characteristics of metastases (reported elsewhere). Outcome after liver resection: 7/25 (28%) patients are lost of follow-up; 3/25 (12%) died; NED stage (no evidence of disease) is achieved in 16/25 pts and 5/16 (31.5%) are still free of disease, for median 36 months. Conclusion Median 36 months after metastases resection,5/16 (31.5%) of patients remained in NED stage. That percentage of durable response is et least equal to systemic treatments response. It seems that there is a subgroup of patients who could benefit of metastases resection achieving long lasting NED stage. Still, the most important characteristics of this subgroup in not well recognized. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-16.