Nalinie Joharatnam-Hogan1, William Wilson2, Kai Keen Shiu1, Giuseppe Kito Fusai3, Brian Davidson3, Daniel Hochhauser1, John Bridgewater1, Khurum Khan1,4,5,6. 1. Department of Gastrointestinal Oncology, University College London Hospital NHS Foundation Trust, London NW1 2PG, UK. 2. Department of Statistics, Cancer Research UK and UCL Cancer Trials Centre, London W1T 4TJ, UK. 3. HPB and Liver Transplant Unit, Royal Free London NHS Foundation Trust, London NW13 1QG, UK. 4. Research Department of Oncology, UCL Cancer Institute, London WC1E 6BT, UK. 5. Department of Medical Oncology, North Middlesex University Hospital, London N18 1QX, UK. 6. Department of Oncology, GI Cancer Lead North London & Oncology Research Lead North Middlesex University Hospital, London N18 1QX, UK.
Abstract
BACKGROUND: Despite notable advances in the management of metastatic colorectal cancer (mCRC) over the last two decades, treatment intent in the vast majority of patients remains palliative due to technically unresectable disease, extensive disease, or co-morbidities precluding major surgery. Up to 30% of individuals with mCRC are considered potentially suitable for primary or metastasis-directed multimodal therapy, including surgical resection, ablative techniques, or stereotactic radiotherapy (RT), with the aim of improving survival outcomes. We reviewed the potential benefits of multimodal therapy on the survival of patients with mCRC treated at the UCLH. METHODS: Clinical data on baseline characteristics, multimodal treatments, and survival outcomes were retrospectively collected from all patients with mCRC receiving systemic chemotherapy between January 2013 and April 2017. Primary outcome was the impact of multimodal therapy on overall survival, compared to systemic therapy alone, and the effect of different types of multimodal therapy on survival outcome, and was assessed using the Kaplan-Meier approach. All analyses were adjusted for age, gender, and side of primary tumour. RESULTS: One-hundred and twenty-five patients with mCRC were treated during the study period (median age: 62 years (range 19-89). The liver was the most frequent metastatic site (78%; 97/125). A total of 52% (65/125) had ≥2 lines of systemic chemotherapy. Of the 125 patients having systemic chemotherapy, 74 (59%) underwent multimodal treatment to the primary tumour or metastasis. Median overall survival (OS) was 25.7 months [95% Confidence Interval (CI) 21.5-29.0], and 3-year survival, 26%. Univariate analysis demonstrated that patients who had additional procedures (surgery/ablation/RT) were significantly less likely to die (Hazard Ratio (HR) 0.18, 95% CI 0.12-0.29, p < 0.0001) compared to those receiving systemic chemotherapy alone. Increasing number of multimodal procedures was associated with an incremental increase in survival-with median OS 28.4 m, 35.7 m, and 64.8 m, respectively, for 1, 2, or ≥3 procedures (log-rank p < 0.0001). After exclusion of those who received systemic chemotherapy only (n = 51), metastatic resections were associated with improved survival (adjusted HR 0.36, 95% CI 0.20-0.63, p < 0.0001), confirmed in multivariate analysis. Multiple single-organ procedures did not improve survival. CONCLUSION: Multimodal therapy for metastatic bowel cancer is associated with significant survival benefit. Resection/radical RT of the primary and resection of metastatic disease should be considered to improve survival outcomes following multidisciplinary team (MDT) discussion and individual assessment of fitness.
BACKGROUND: Despite notable advances in the management of metastatic colorectal cancer (mCRC) over the last two decades, treatment intent in the vast majority of patients remains palliative due to technically unresectable disease, extensive disease, or co-morbidities precluding major surgery. Up to 30% of individuals with mCRC are considered potentially suitable for primary or metastasis-directed multimodal therapy, including surgical resection, ablative techniques, or stereotactic radiotherapy (RT), with the aim of improving survival outcomes. We reviewed the potential benefits of multimodal therapy on the survival of patients with mCRC treated at the UCLH. METHODS: Clinical data on baseline characteristics, multimodal treatments, and survival outcomes were retrospectively collected from all patients with mCRC receiving systemic chemotherapy between January 2013 and April 2017. Primary outcome was the impact of multimodal therapy on overall survival, compared to systemic therapy alone, and the effect of different types of multimodal therapy on survival outcome, and was assessed using the Kaplan-Meier approach. All analyses were adjusted for age, gender, and side of primary tumour. RESULTS: One-hundred and twenty-five patients with mCRC were treated during the study period (median age: 62 years (range 19-89). The liver was the most frequent metastatic site (78%; 97/125). A total of 52% (65/125) had ≥2 lines of systemic chemotherapy. Of the 125 patients having systemic chemotherapy, 74 (59%) underwent multimodal treatment to the primary tumour or metastasis. Median overall survival (OS) was 25.7 months [95% Confidence Interval (CI) 21.5-29.0], and 3-year survival, 26%. Univariate analysis demonstrated that patients who had additional procedures (surgery/ablation/RT) were significantly less likely to die (Hazard Ratio (HR) 0.18, 95% CI 0.12-0.29, p < 0.0001) compared to those receiving systemic chemotherapy alone. Increasing number of multimodal procedures was associated with an incremental increase in survival-with median OS 28.4 m, 35.7 m, and 64.8 m, respectively, for 1, 2, or ≥3 procedures (log-rank p < 0.0001). After exclusion of those who received systemic chemotherapy only (n = 51), metastatic resections were associated with improved survival (adjusted HR 0.36, 95% CI 0.20-0.63, p < 0.0001), confirmed in multivariate analysis. Multiple single-organ procedures did not improve survival. CONCLUSION: Multimodal therapy for metastatic bowel cancer is associated with significant survival benefit. Resection/radical RT of the primary and resection of metastatic disease should be considered to improve survival outcomes following multidisciplinary team (MDT) discussion and individual assessment of fitness.
Authors: Sara Lindberg; Eva Onjukka; Peter Wersäll; Caroline Staff; Rolf Lewensohn; Giuseppe Masucci; Karin Lindberg Journal: Clin Transl Radiat Oncol Date: 2022-07-21