Unresectable Colorectal Metastases Research Articles

Liver transplantation for non-resectable colorectal liver metastasis: where we are and where we are going.

Almost 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastasis (LM). Although their only long-term curative treatment is surgery, less than half of these patients can be eventually resected. Therefore, palliative chemotherapy is offered as a definitive option, though with poor results. Recently, the University of Oslo group has published encouraging results in the treatment of these patients with liver transplantation (LT), whereby worldwide interest in this option has been renewed. A literature review of LT for patients with unresectable colorectal metastasis was performed. This included information regarding patient selection, complications, overall survival (OS) and disease-free survival (DFS), immunosuppression, chemotherapy, and description of the ongoing trials. Improvements in OS and DFS have been observed in consecutive published prospective trials, as patient selection has been refined. Papers reporting OS of patients who randomly presented similar selection criteria also exhibited good results. LT within the available therapeutic options in patients with CRC-LM seems to be a compelling alternative in carefully selected patients. The ongoing trials will provide valuable information regarding selection criteria, immunosuppressive therapy and different modalities of adjuvant chemotherapy, which are, to our knowledge, the vital platform of LT in CRC-LM. Although some of the developing techniques involve living donors, graft availability for these patients remains a matter of major concern.

Personalizing Locoregional Therapy for Patients with Metastatic Colorectal Cancer

The management of metastatic colorectal liver disease has improved overall survival by multidisciplinary approach utilizing systemic treatment followed by local control of metastatic disease. There has been an evolution of local control therapy which has expanded the new armamentarium for treatment of resectable and unresectable liver disease. The review article will address the various types of locoregional therapy and various indications for its use. The application of ablative therapies combined with resections has allowed single-stage resection for patients with bilobar disease with excellent safety and efficacy. In patients with unresectable colorectal metastasis to the liver, chemo- and radio-embolization have provided improved survival outcome compared to systemic chemotherapy alone. Locoregional therapy for metastatic colorectal liver disease can improve outcome as an adjunctive role in combination with resection or as a sole therapy for patients with unresectable disease.

Timing of Two‐stage Liver Resection during Chemotherapy for Otherwise Unresectable Colorectal Metastases

Tumor downsizing by effective chemotherapy while increasing remnant liver volume by two-stage hepatectomy can expand eligibility for resection of otherwise unresectable liver metastases. However, optimal timing of two-stage hepatectomy with respect to chemotherapy is undetermined. We retrospectively analyzed the effect of timing of two-stage hepatectomy and chemotherapy using data from 95 patients whose colorectal liver metastases initially were considered unresectable. In 21 of 22 (95 %) patients whose first liver resection preceded chemotherapy (Hx-CTx group) and in 39 of 73 (53 %) patients whose chemotherapy preceded surgery (CTx-Hx group), macroscopic complete resection ultimately was achieved (P < 0.01). Overall and disease-free survivals were comparable between groups. However, overall survival of patients not achieving complete resection in the CTx-Hx group was significantly poorer than that for patients achieving complete resection (P < 0.01). When the 21 patients with complete resection in the Hx-CTx group were compared to the 39 patients with complete resection in the CTx-Hx group, no difference in overall or disease-free survival was observed (P = 0.12 and P = 0.24, respectively), although poor response to chemotherapy was more frequent in the Hx-CTx group. Optimal timing of hepatectomy and chemotherapy is difficult to specify, but performing the initial resection in a two-stage hepatectomy before chemotherapy may increase likelihood of macroscopic complete resection, even in patients with a poor response to chemotherapy or with limited courses of chemotherapy.

Efficacy of intraoperative radiofrequency ablation (IRFA) combined or not with resection to treat unresectable colorectal metastases, with or without preoperative chemotherapy: The ARF2003 Study (NTC 00210106): Preliminary results

4095 Background: Only few patients suffering from colorectal metastases (CRM) can have surgery and thus hope for a 40% 5-year survival rate. Adding IRFA to resection may improve the efficacy of surgery. Methods: The primary objective was to evaluate the efficacy of IRFA combined or not with resection in terms of 3-month complete hepatic response (CHR) in patients with unresectable CRM. Secondary endpoints were overall survival (OS), disease-free survival (DFS), morbidity and quality of life. A phase II study based on a Simon's two-stage design was conducted in 6 university French hospitals. Number of subjects estimated was 53, with 19 for the 1st stage. At the end of the 1st stage, 12 CHR were required to continue recruiting. At the end of 2nd stage, 37 CHR would be required to claim efficacy. Results: Fifteen of the first 19 patients exhibited CHR allowing the study to pursue accrual which ended in Nov 08; some patients are still followed up. As of Nov 08, data had been collected on 47 patients (mean age 61 years): 6 had RFA alone (13%), 37 had RFA and resections (82%), 2 could not be treated (4%). Median number of CRM was 5 (1–12). All had chemotherapy pre-op and 12 post-op (29%). Three-month data were available for 36 patients: 1 patient died on the 3rd week following intervention. Scans were available for 35 patients (independently reviewed). Of these, 29 had CHR (83%); 13 had 3-month morbidity (37%). The median follow-up was 15 months. One-year OS and DFS rates were 92.3% and 26% respectively. Analysis on all 53 patients will be communicated in June 09. Conclusions: These preliminary results suggest that IRFA combined or not to resection may be efficient in treating unresectable diseases despite their more aggressive pattern. This corroborates the EORTCC CLOCC Trial findings which demonstrated IRFA superiority upon chemotherapy alone. IRFA could thus be valuably associated to resection in treating patients with colorectal metastases that resection alone could not handle. No significant financial relationships to disclose.

236 ORAL Efficiency of radiofrequency ablation combined or not with resection to treat unresectable colorectal metastases, with or without preop chemotherapy: the ARF2003 Study (NTC 00210106). Results of the intermediate analysis

236 ORAL Efficiency of radiofrequency ablation combined or not with resection to treat unresectable colorectal metastases, with or without preop chemotherapy: the ARF2003 Study (NTC 00210106). Results of the intermediate analysis

Long-term results of resection following downstaging of initially unresectable colorectal metastases

Colorectal carcinoma is a significant health problem with over half of all patients experiencing systemic metastasis. Fortunately for these patients, the recent introduction of more effective systemic chemotherapy drugs has ushered in a new and exciting era in the treatment of metastastic colorectal cancer. Not only have these novel regimens improved the outlook for patients with unresectable disease, lengthening the median survival from 10 months to 24 months, they are allowing patients previously thought to be unresectable the opportunity for a potentially curative hepatic resection. A growing literature has been written describing chemotherapy response rates in patients who were initially considered “unresectable” and describing the long-term outcome for the subset of these responders who are resected. This report summarizes this literature, focusing on the prognostic factors that have been identified to determine which patients receive the most and those who receive the least benefit from resection following treatment with systemic chemotherapy.