3519 Background: Prognostic factors of survival have been extensively reported after resection of colorectal liver metastases. However, a specific analysis of patients (pts) submitted to preoperative chemotherapy (PCT), with the real impact of type and modalities of treatment on patient outcome is lacking.
METHODS: From Jan 1995 to June 2010, 10,436 pts from 151 centers and 39 countries were entered into LiverMetSurvey an international, prospective registry designed to assess the efficacy of multimodality treatment for colorectal liver metastases (CLM). Among this cohort, 4,444 pts (49.9%) received PCT. There were 38% of men and mean age was 61. Prognostic factors of overall (OS) and disease-free (DFS) survivals were determined including characteristics of primary tumor, of metastasis, initial resectability, type and duration of PCT, using multivariate analyses.
RESULTS: Metastases were initially resectable in 63%, originated in the rectum in 33% and were synchronous in 69% of pts. 33% pts had ≥ 3 CLM, bilateral in 49% and with a size > 5cm in 30%. PCT was oxaliplatin-based in 36%, irinotecan-based in 12% and both drug-based in 3% of pts. Targeted therapy was used in combination with oxaliplatin (11%), irinotecan (9%) or both (1%). Median, 5-year and 10-year OS were 43 months, 39%, and 23%, respectively. Median, 5-year and 10-year DFS were 17 months, 21%, and 15%, respectively. Variables independently associated with poor OS included metastatic primary lymph nodes (p=0.005), abnormal CEA levels (p<0.001), metastases >3 (p=0.006), concomitant extrahepatic metastases (p<0.001), tumoral progression while on PCT (p=0.03), the use of >1 line of PCT (p<0.001) and R2 resection (p<0.001). The use of > 6 cycles of PCT was additionally associated to a poor DFS (p=0.004). Neither the type of conventional PCT nor the combined use of targeted agents independently influenced outcome following resection.
CONCLUSIONS: PCT is used in half of pts overall, 63% of whom with initially resectable CLM. The type of PCT does not influence the outcome provided that resection is achieved. However, the shorter is the PCT and the more limited is the number of lines, the best is the survival after surgery.
CONCLUSION: As shown by the significant influence of metastatic sites, some P die from their advanced systemic disease situation before they would experience cerebral progression, in part explaining the influence of systemic treatment. In other individuals however, intensified local treatment and systemic treatment appear to influence both cTTP and OS significantly, implicating a direct influence of systemic therapy on BM. This might result from an impaired blood brain barrier around metastatic sites, making sufficient tissue concentrations of cytotoxic agents possible. No significant financial relationships to disclose.
TREATMENT: Rx 375 mg/m(2) IV at day 1; concomitant therapy: Rasburicase, steroids only for anaphylaxis, intrathecal (IT) triple drug at days 1, 3 for CNS pts only. Begin of chemotherapy at day 5. Response evaluation: product of 2 perpendicular diameters of 1 - 3 index lesions/% blasts in BM/PB within 24 h prior to Rx and at day 5: responder (RP): at least 1 lesion with at least objective effect (decrease of ≥25%) and no progress (increase of ≥25 %) at other sites. Study plan: Simon 2-stage phase II with α and β = 5%. Response rate (RR) for poor activity was set to 45%, for good activity 65%. 33 pts entered the first stage, final evaluation after 79 pts.