scholarly journals Trajectory of body mass and skeletal muscle indices and disease progression in metastatic colorectal cancer patients

2019 ◽  
Vol 110 (6) ◽  
pp. 1395-1403 ◽  
Author(s):  
Sophie A Kurk ◽  
Rebecca K Stellato ◽  
Petra H M Peeters ◽  
Bram Dorresteijn ◽  
Marion Jourdan ◽  
...  

ABSTRACT Background Knowledge of the evolution of BMI and skeletal muscle index (SMI) measurements during advanced cancer and their relationships with disease progression (PD) is relevant to improve the timing of interventions that may improve cachexia-associated outcomes. Objectives We investigated BMI and SMI trajectories and their associations with PD in metastatic colorectal cancer (mCRC) patients during consecutive palliative systemic regimens. Methods In a secondary analysis of the primary CAIRO3 trial, we included 533 mCRC patients with BMI measurements repeated every 3 wk and 95 randomly selected patients with SMI measurements repeated every 9 wk. We studied 2 periods: p1, during first-line maintenance capecitabine + bevacizumab or observation until the first progression of disease (PD1); and p2, during capecitabine + oxaliplatin + bevacizumab or another reintroduction treatment from PD1 until the second progression of disease (PD2). BMI and SMI trajectories were modeled separately throughout both periods, and joint longitudinal-survival modeling was used to investigate the relationships between slopes in BMI and SMI with PD at 9 and 3 wk pre-PD. A multivariate longitudinal joint model was used to investigate the association between the BMI trajectory and PD at time of PD, independent of SMI. Results During p1, the slopes in BMI and SMI were associated with early PD1 [HRs for 9-wk BMI: 1.54 (95% CI: 1.33, 1.76); 9-wk SMI: 1.38 (95% CI: 0.87, 1.89), NS; 3-wk BMI: 1.74 (95% CI: 1.48, 1.99); 3-wk SMI: 2.65 (95% CI: 1.97, 3.32)]. During p2, only the slope in SMI was related to PD2 [9-wk BMI: 1.09 (95%: CI: 0.73, 1.45), NS; 9-wk SMI: 1.64 (95% CI: 1.25, 2.04); 3-wk BMI: 1.17 (95% CI: 0.77, 1.57); 3-wk SMI: 1.11 (95% CI: 0.70, 1.53)]. In models mutually adjusting for BMI and SMI, SMI was associated with PD in p1 [p1 ( n = 95), HR BMI: 1.32 (95% CI: 0.74, 2.39), NS; p1, HR SMI: 1.50 (95% CI: 1.04, 2.14); p2 ( n = 50), BMI: 0.98 (95% CI: 0.55, 1.75), NS; p2, HR SMI: 1.11 (95% CI: 0.61, 2.05), NS]. Conclusions In mCRC patients during palliative systemic treatment, SMI losses, irrespective of BMI losses, may be a marker for the early initiation of cachexia interventions.

2019 ◽  
Vol 9 (3) ◽  
pp. 1033-1043 ◽  
Author(s):  
Sophie A. Kurk ◽  
Petra H. M. Peeters ◽  
Bram Dorresteijn ◽  
Pim A. Jong ◽  
Marion Jourdan ◽  
...  

2018 ◽  
Vol 9 (5) ◽  
pp. 909-919 ◽  
Author(s):  
Sophie A. Kurk ◽  
Petra H.M. Peeters ◽  
Bram Dorresteijn ◽  
Pim A. de Jong ◽  
Marion Jourdan ◽  
...  

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 633-633 ◽  
Author(s):  
Grant Richard Williams ◽  
Allison Mary Deal ◽  
Shlomit S. Shachar ◽  
Christine Marie Walko ◽  
Jai Narendra Patel ◽  
...  

633 Background: Great heterogeneity exists in the ability of adults with cancer to tolerate treatment. Variability in body composition may affect rates of metabolism of cytotoxic agents and contribute to the variable chemotherapy toxicity observed. The goal of this study was to explore the impact of body composition, in particular sarcopenia, on the pharmacokinetics of 5-fluorouracil (5FU) in a cohort of patients receiving FOLFOX +/- bevacizumab for colorectal cancer. Methods: We performed a secondary analysis of a completed multicenter trial that investigated pharmacokinetic-guided 5FU in patients receiving mFOLFOX6 +/- bevacizumab [Patel et al. The Oncologist 2014]. Computed Tomography (CT) images that were performed as part of routine care were used to for body composition analysis. Skeletal muscle area (SMA) and density (SMD) were analyzed from CT scan L3 lumbar segments using radiological software. SMA and height (m2) were used to calculate skeletal muscle index (SMI = SMA/m2). Skeletal Muscle Gauge (SMG) was created by multiplying SMI x SMD. Differences were compared using two group t-tests and fisher’s exact tests. Results: Of the 70 patients from the original study, 25 had available CT imaging. The mean age was 59, 52% female, 80% Caucasian, and 92% with either stage III or IV disease. Eleven patients (44%) had grade 3/4 toxicity, and 12 patients were identified as sarcopenic (48%) [per Martin et al. JCO 2013]. Sarcopenic patients had numerically higher first cycle 5FU AUCs compared to non-sarcopenic patients (19.3 vs. 17.3 AUC, p= 0.43) and higher grade 3/4 toxicities (50 vs 38.5%, p= 0.70). Patients with low SMG ( < 1475 AU) had higher grade 3/4 toxicities (62 vs 25%, p= 0.11) and higher hematologic toxicities (46 v 8%, p= 0.07). Conclusions: CRC patients with sarcopenia had numerically higher first cycle AUCs of 5FU and a higher incidence of severe toxicities; however, this was not statistically significant, possibly due to limited sample size. SMG, an integrated muscle measure, was more highly correlated with toxicity outcomes than either SMI or SMD alone. Further research exploring the role of body composition in pharmacokinetics is needed with a focus on alternative dosing strategies in sarcopenic patients.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4025-4025 ◽  
Author(s):  
Claire Gallois ◽  
Camille Bourillon ◽  
Edouard Auclin ◽  
Pascal Artru ◽  
Astrid Lievre ◽  
...  

4025 Background: We showed in a previous work that “Patient Generated-Subjective Global Assessment” (PG-SGA) was independently associated with survival and treatment toxicities in non-pretreated metastatic colorectal cancer (mCRC) patients. We have evaluated here if muscle mass in these patients can provide useful additional information for clinical practice. The objective of the present work was to evaluate the association between baseline sarcopenia, and the variation of the Skeletal Muscle Index (SMI) under treatment with survival and chemotherapy-related toxicities in our population of non-pretreated mCRC patients. Methods: This prospective multicenter observational study enrolled non-pretreated mCRC patients. Measurement of SMI was performed on routine CT scan at day 0 (D0) and day 60 (D60). PG-SGA score and other nutritional factors were collected at D0. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start. Treatment related toxicities were registered according to the NCI CTCAE v4.0. Results: 149 patients were included in eight French centers from 7/2013 to 11/2016. Sarcopenia at baseline was not significantly associated with survival outcomes or chemotherapy-related toxicities. The best cut-point value of SMI variation (between D0 and D60) for OS prediction obtained with a log-rank maximisation method was -14%. The decrease in SMI > 14%, with a median follow-up of 23 months, was significantly associated with shorter PFS (6 vs 9 mo; HR 1.8, 95%CI 1.1-3.1, p = 0.02) and OS (8.5 vs 26 mo; HR 2.4, 95%CI 1.3-4.4, p = 0.004), independently of hypoalbuminemia and malnutrition defined by PG-SGA, in multivariate analysis. 40% of patients with a SMI decrease > 14%, and 22% of patients with a SMI increase or stable or decrease < 14% developed grade ≥ 2 clinical toxicities (OR 3.0, 95%CI 1.2-7.7, p = 0.02), but the difference was not statistically significant in multivariate analysis (OR 2.3. 95%CI 0.8-6.7, p = 0.1). Conclusions: To our knowledge, this study is the first study assessing the association of skeletal muscle loss with survival and treatment toxicities in patients with mCRC prospectively. In our population of non pre-treated mCRC patients, baseline sarcopenia was not associated with poor survival outcomes, but the decrease in SMI > 14% during the first two months of treatment was significantly associated with decreased PFS and OS, independently of other prognostic and nutritional factors.


2021 ◽  
Author(s):  
Takahiro Manabe ◽  
Yasumasa Takii ◽  
Hidehito Oyanagi ◽  
Hitoshi Nogami ◽  
Satoshi Maruyama

Abstract Background: Despite marked recent advances in chemotherapy, few reports have focused on the prognosis for patients with metastatic colorectal cancer (mCRC) achieving complete response (CR) after systemic chemotherapy. This study investigated the clinical course of mCRC patients achieving CR and evaluated the role of CR in chemotherapy.Methods: This retrospective study searched a prospectively maintained database at the author’s institute to identify medical records for mCRC patients achieving CR after systematic chemotherapy from January 2007 to March 2020.Results: The search yielded 23 patients with confirmed CR to systemic chemotherapy. Median time to CR from treatment initiation was 6.8 months. Maintenance chemotherapy was continued for 22 of 23 patients. Median duration of maintenance chemotherapy was 11.1 months. Disease progression occurred for 17 (73.9%) patients at a median 48.1-month follow-up. Median progression-free survival was 26.6 months. Median overall survival was 91.7 months.Conclusions: Patients with CR to chemotherapy had a high probability of disease progression, but a relatively long-term prognosis. Treatment strategies after achievement of CR should be based an understanding of the high potential that tumor cells will remain. Use of maintenance chemotherapy after achievement of CR is still unclear, the recent data do not demonstrate a negative impact for continuing maintenance chemotherapy after CR.


2019 ◽  
Vol 10 (4) ◽  
pp. 803-813 ◽  
Author(s):  
Sophie Kurk ◽  
Petra Peeters ◽  
Rebecca Stellato ◽  
B. Dorresteijn ◽  
Pim Jong ◽  
...  

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