Adeline Dolly1, Thierry Lecomte2, Olivier Bouché3, Christophe Borg4, Eric Terrebonne5, Jean-Yves Douillard6, Romain Chautard2, William Raoul7, David Ternant8, Julie Leger9, Aurore Bleuzen10, Jean-François Dumas1, Stéphane Servais11, Vickie E Baracos12. 1. INSERM UMR1069, "Nutrition, Croissance et Cancer", University of Tours, France. 2. Department of Hepatogastroenterology and Digestive Oncology, Hôpital Trousseau, CHRU de Tours, 37044, Tours, Cedex 09, France; EA GICC 7501, University of Tours, 10 Boulevard Tonnellé, 37000, Tours, France. 3. Department of Hepatogastroenterology, Hôpital Robert Debré, CHU de Reims, Avenue Général Koenig, 51092, Reims, Cedex, France. 4. Department of Medical Oncology, Hôpital Jean Minjoz, CHRU de Besançon, 3 Boulevard Alexandre Fleming, 25000, Besançon, France. 5. Department of Hepatogastroenterology and Digestive Oncology, Hôpital du Haut Lêvèque, CHU de Bordeaux, Avenue Magellan, 33604, Pessac Cedex, France. 6. Department of Medical Oncology, ICO René Gauducheau, 44805, Saint-Herblain, France. 7. EA GICC 7501, University of Tours, 10 Boulevard Tonnellé, 37000, Tours, France. 8. EA GICC 7501, University of Tours, 10 Boulevard Tonnellé, 37000, Tours, France; Department of Pharmacology & Toxicology, Hôpital Bretonneau, CHRU de Tours, 37044, Tours, Cedex 09, France. 9. INSERM CIC 1415, CHRU de Tours, CHRU de Tours, 37044, Tours, Cedex 09, France. 10. Department of Radiology, Hôpital Bretonneau, CHRU de Tours, CHRU de Tours, 37044, Tours, Cedex 09, France. 11. INSERM UMR1069, "Nutrition, Croissance et Cancer", University of Tours, France. Electronic address: stephane.servais@univ-tours.fr. 12. Department of Oncology, Division of Palliative Care Medicine, University of Alberta, Edmonton, Canada. Electronic address: vickie.baracos@ualberta.ca.
Abstract
BACKGROUND: Changes in skeletal muscle mass (SMM), total adipose tissue mass (TAT) or bone mineral density (BMD) have been described in patients with cancer undergoing various treatments; simultaneous variations of all 3 tissues has not been reported. METHODS: Data were prospectively collected in a clinical study (NCT00489697) including patients with liver metastases of colorectal cancer who received 4 cycles of bevacizumab in combination with cytotoxic chemotherapy. Computerized tomography (CT) at baseline and after chemotherapy was used to quantify skeletal muscle and adipose tissue cross-sectional areas, and mean lumbar spine BMD using validated approaches. RESULTS: After exclusion of patients lacking adequate CT images or missing data, 72 subjects were included. Patients were 63% male, aged 63.2 ± 10.3 years, 100% had liver metastases and 54%, 24% and 22% respectively has 0, 1 and ≥2 extrahepatic metastases. 100% tolerated 4 cycles of treatment and none showed progressive disease at the end of treatment. The scan interval was 70 days (95% CI, 62.3 to 80.5). Thresholds for loss of tissue were defined as loss ≥ measurement error. 10% of patients showed no loss of any tissue and a further 43% lost one tissue (SMM, TAT or BMD); 47% of patients lost 2 tissues (16.5% lost SMM + TAT, 8% lost SMM + BMD, 10% lost TAT + BMD) or all 3 tissues (12.5%). Catabolic behavior (2 or 3 tissue loss vs 0 or 1 tissue loss) associated with disease burden, including unresectable primary tumor (p = 0.010), presence of extrahepatic (EH) metastases (p = 0.039) and number of EH metastases (p = 0.004). No association was found between the number of tissues lost and treatment response, which was uniformly high, or treatment toxicity, which was uniformly low. CONCLUSION: Multiple tissues can be measured in routine CT images and these show considerable inter-individual variation. Substantial losses in some individuals appear to associate with disease burden.
BACKGROUND: Changes in skeletal muscle mass (SMM), total adipose tissue mass (TAT) or bone mineral density (BMD) have been described in patients with cancer undergoing various treatments; simultaneous variations of all 3 tissues has not been reported. METHODS: Data were prospectively collected in a clinical study (NCT00489697) including patients with liver metastases of colorectal cancer who received 4 cycles of bevacizumab in combination with cytotoxic chemotherapy. Computerized tomography (CT) at baseline and after chemotherapy was used to quantify skeletal muscle and adipose tissue cross-sectional areas, and mean lumbar spine BMD using validated approaches. RESULTS: After exclusion of patients lacking adequate CT images or missing data, 72 subjects were included. Patients were 63% male, aged 63.2 ± 10.3 years, 100% had liver metastases and 54%, 24% and 22% respectively has 0, 1 and ≥2 extrahepatic metastases. 100% tolerated 4 cycles of treatment and none showed progressive disease at the end of treatment. The scan interval was 70 days (95% CI, 62.3 to 80.5). Thresholds for loss of tissue were defined as loss ≥ measurement error. 10% of patients showed no loss of any tissue and a further 43% lost one tissue (SMM, TAT or BMD); 47% of patients lost 2 tissues (16.5% lost SMM + TAT, 8% lost SMM + BMD, 10% lost TAT + BMD) or all 3 tissues (12.5%). Catabolic behavior (2 or 3 tissue loss vs 0 or 1 tissue loss) associated with disease burden, including unresectable primary tumor (p = 0.010), presence of extrahepatic (EH) metastases (p = 0.039) and number of EH metastases (p = 0.004). No association was found between the number of tissues lost and treatment response, which was uniformly high, or treatment toxicity, which was uniformly low. CONCLUSION: Multiple tissues can be measured in routine CT images and these show considerable inter-individual variation. Substantial losses in some individuals appear to associate with disease burden.