Progression of Colorectal Liver Metastases from the End of Chemotherapy to Resection: A New Contraindication to Surgery?

BACKGROUND: Not all patients with resectable colorectal liver metastases (CLM) benefit from liver resection (LR); only patients with disease progression during chemotherapy are excluded from surgery. OBJECTIVE: This study was performed to determine whether tumor behavior (stable disease/progression) from the end of chemotherapy to LR impacts prognosis. METHODS: Patients undergoing LR after tumor response or stabilization during chemotherapy were considered. Overall, 128 patients who underwent examination by two imaging modalities (computed tomography/magnetic resonance imaging) after chemotherapy with a > 3-week interval between the two imaging modalities were analyzed. Any variation in CLM size was registered. Tumor progression was defined according to the response evaluation criteria in solid tumors (RECIST) criteria. RESULTS: Among 128 patients with stable disease or partial response to preoperative chemotherapy, 32 (25%) developed disease progression in the chemotherapy to LR interval, with a disease progression rate of 17% when this interval was < 8 weeks. Survival was lower among patients with progression than those with stable disease [3-year overall survival (OS) 23.0 vs. 52.4%, and recurrence-free survival (RFS) 6.3% vs. 21.6%; p < 0.001]. Survival was extremely poor in patients with early progression (< 8 weeks) (0.0% 2-year OS, 12.5% 6-month RFS). Disease progression in the chemotherapy to LR interval was an independent negative prognostic factor for OS and RFS [hazard ratio 3.144 and 2.350, respectively; p < 0.001]. CONCLUSIONS: Early disease progression in the chemotherapy to LR interval occurred in approximately 15% of patients and was associated with extremely poor survival. Even if these data require validation, the risk for early disease progression after chemotherapy should be considered, and, if progression is evident, the indication for surgery should be cautiously evaluated.

The Impact of Different Patterns of Residual Disease on Long-Term Oncological Outcomes in Breast Cancer Patients Treated with Neo-Adjuvant Chemotherapy.

BACKGROUNDS: The majority of breast cancer (BC) patients treated with neo-adjuvant chemotherapy (NAC) achieves a pathologic partial response with different patterns of residual disease. No clear correlation between these patterns and oncological results was described. Our aims were to define the predictive factors for different patterns of residual disease and compare the outcomes between the scattered versus the circumscribed pattern. METHODS: We reviewed 219 postoperative surgical specimens. Patients were divided into two groups: scattered versus circumscribed. Disease-free survival (DFS), distant DFS (DDFS), and overall survival (OS) were analyzed. RESULTS: The scattered and circumscribed patterns were assessed in 111 (50.7%) and 108 (49.3%) patients. Two independent predictive factors for the circumscribed pattern were identified: discontinuation of NAC cycles (p = 0.011), and tumor size post-NAC >18 mm (p = 0.022). No difference was observed in terms of DFS and DDFS. Patients with the scattered pattern exhibited a statistically significant better OS. Discontinuation of NAC cycles, tumor size >18 mm, triple-negative BC, and ypN+ were associated with increased recurrence and poorer survival. CONCLUSIONS: Discontinuation of NAC cycles and tumor size are independent factors associated with patterns of residual disease. The scattered pattern presents better survival. Understanding the relationship between NAC, the residual pattern, and differences in survival outcomes offers the potential to optimize the therapeutic approaches.

Hepatic and Extrahepatic Colorectal Metastases Have Discordant Responses to Systemic Therapy. Pathology Data from Patients Undergoing Simultaneous Resection of Multiple Tumor Sites.

BACKGROUND: Systemic therapy is the standard treatment for patients with hepatic and extrahepatic colorectal metastases. It is assumed to have the same effectiveness on all disease foci, independent of the involved organ. The present study aims to compare the response rates of hepatic and extrahepatic metastases to systemic therapy. METHODS: All consecutive patients undergoing simultaneous resection of hepatic and extrahepatic metastases from colorectal cancer after oxaliplatin- and/or irinotecan-based preoperative chemotherapy were analyzed. All specimens were reviewed. Pathological response to chemotherapy was classified according to tumor regression grade (TRG). RESULTS: We analyzed 45 patients undergoing resection of 134 hepatic and 72 extrahepatic metastases. Lung and lymph node metastases had lower response rates to chemotherapy than liver metastases (TRG 4-5 95% and 100% vs. 67%, p = 0.008, and p = 0.006). Peritoneal metastases had a higher pathological response rate than liver metastases (TRG 1-3 66% vs. 33%, p < 0.001) and non-hepatic non-peritoneal metastases (3%, p < 0.001). Metastases site was an independent predictor of pathological response to systemic therapy. CONCLUSIONS: Response to chemotherapy of distant metastases from colorectal cancer varies in different organs. Systemic treatment is highly effective for peritoneal metastases, more so than liver metastases, while it has a very poor impact on lung and lymph node metastases.