scholarly journals Trajectory of skeletal muscle index (SMI) loss during palliative systemic treatment (Tx) predicts time to progression (TTP) in metastatic colorectal cancer (mCRC) patients

2018 ◽  
Vol 29 ◽  
pp. viii619
Author(s):  
S.A. Kurk ◽  
R.K. Stellato ◽  
P.H.M. Peeters ◽  
M. Oskam ◽  
B.D. Dorresteijn ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Skeletal Muscle ◽  
Metastatic Colorectal Cancer ◽  
Systemic Treatment ◽  
Time To Progression ◽  
Skeletal Muscle Index

Skeletal muscle loss under chemotherapy and its association with survival and systemic treatment toxicity in metastatic colorectal cancer: An AGEO prospective multicenter study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4025-4025 ◽  
Author(s):  
Claire Gallois ◽  
Camille Bourillon ◽  
Edouard Auclin ◽  
Pascal Artru ◽  
Astrid Lievre ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Skeletal Muscle ◽  
Multivariate Analysis ◽  
Metastatic Colorectal Cancer ◽  
Survival Outcomes ◽  
Muscle Loss ◽  
Skeletal Muscle Index ◽  
Nutritional Factors ◽  
Multicenter Observational Study ◽  
Skeletal Muscle Loss

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.

Impact of skeletal muscle index (SMI) loss during palliative systemic treatment (Tx) on time to progression and overall survival (OS) in metastatic colorectal cancer (mCRC) patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10087-10087 ◽  
Author(s):  
Sophie Kurk ◽  
Petra H.M. Peeters ◽  
Rebecca K. Stellato ◽  
Bram Dorresteijn ◽  
Marion Jourdan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Overall Survival ◽  
Disease Progression ◽  
Cox Regression ◽  
Systemic Treatment ◽  
P Value ◽  
Multiple Time ◽  
Time To Progression ◽  
Skeletal Muscle Index ◽  
The Impact

10087 Background: Evidence for a strong link between skeletal muscle depletion and poor outcomes in mCRC is growing. However, the impact of SMI changes over time on progression and OS during palliative systemic Tx is not known. The CAIRO3 study (Simkens et al. Lancet 2015) randomized 556 mCRC patients after 6 cycles capecitabine+oxaliplatin+bevacizumab (CAPOX-B) to maintenance CAP-B Tx (Main) vs. observation (Obs). Upon 1st disease progression (PD1), CAPOX-B or other treatment was reintroduced until 2nddisease progression (PD2). This is the first analysis using scan data of multiple time-points to investigate SMI changes during palliative systemic treatment Tx and its association with survival. Methods: 1227 CT-scans of a random selection of 416 CAIRO3 patients (mean age 64±9 years, Main n = 206; Obs n = 210) were analyzed for SMI (skeletal muscle area at the L3 level in cm2/m2). Using mixed model analysis, SMI changes were analyzed for two intervals; interval 1: from randomization to PD1, and interval 2: from PD1 to PD2. Three Cox regression models were used to study the association between SMI loss and time to PD2 and death for interval 1, and time to death for interval 2. Main and Obs groups were combined in the analyses since the p-value for interaction was not significant. Hazard ratios (HR) were reported per 2 units change in SMI. Results: Median times from randomization to PD1, PD2 and death were 7.7, 13.5 and 24 months resp. During interval 1 (less intensive or no Tx) patients gained SMI on average (1.2 units; 95%CI 0.6-1.8), but 23% of patients still lost SMI. SMI loss was associated with shorter time to PD2 (HR 0.88; 0.81-0.98, p= .01), but not with shorter OS (HR 0.94; 0.86-1.02, p= .17). During interval 2 (more intensive Tx) average SMI loss was -2.2 units ( 1.5-2.8) and 63% of patients lost SMI. SMI loss was associated with shorter OS (HR 0.73; 0.62-0.86, p< .00). Conclusions: Loss of SMI was related to shorter time to progression during first line less intensive main Tx or obs and shorter overall survival during more intensive reinduction Tx. This large longitudinal study suggests that SMI preservation may be a therapeutic goal. Clinical trial information: NCT00442637.

scholarly journals Prognostic Value of Sarcopenia in Metastatic Colorectal Cancer Patients Treated with Trifluridine/Tipiracil

2021 ◽  
Vol 10 (21) ◽  
pp. 5107
Author(s):  
Mateusz Malik ◽  
Maciej Michalak ◽  
Barbara Radecka ◽  
Marek Gełej ◽  
Aleksandra Jackowska ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Skeletal Muscle ◽  
Metastatic Colorectal Cancer ◽  
Performance Status ◽  
Lumbar Vertebra ◽  
Progression Free Survival ◽  
Muscle Area ◽  
Skeletal Muscle Index ◽  
Skeletal Mass

Sarcopenia is common in metastatic colorectal cancer (mCRC), increases the risk of treatment-related toxicity and reduces survival. Trifluridine/tipiracil (TT) chemotherapy significantly improved survival in refractory mCRC patients, but the prognostic and predictive role of pretherapeutic sarcopenia and variation in the skeletal muscle index (SMI) during this treatment has not been investigated so far. In this retrospective, observational study, clinical data on mCRC patients treated with TT at six cancer centres in Poland were collected. Computed tomography (CT) scans acquired at the time of initiation of TT (CT1) and on the first restaging (CT2), were evaluated. SMI was assessed based on the skeletal muscle area (SMA) at the level of the third lumbar vertebra. Progression-free survival (PFS) and overall survival (OS) were calculated from the treatment start. Neither initial sarcopenia nor ≥5% skeletal mass loss (SML) between CT1 and CT2 had a significant effect on PFS in treated patients (p = 0.5526 and p = 0.1092, respectively). In the multivariate analysis, reduced OS was found in patients with ≥5% SML (HR: 2.03 (1.11–3.72), p = 0.0039). We describe the prognostic role of sarcopenia beyond second line treatment and analyze other factors, such as performance status, tumor histological differentiation or carcinoembryonic antigen level that could predict TT treatment response.

scholarly journals Loss of skeletal muscle index and survival in patients with metastatic colorectal cancer: Secondary analysis of the phase 3 CAIRO3 trial

2019 ◽  
Vol 9 (3) ◽  
pp. 1033-1043 ◽  
Author(s):  
Sophie A. Kurk ◽  
Petra H. M. Peeters ◽  
Bram Dorresteijn ◽  
Pim A. Jong ◽  
Marion Jourdan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Skeletal Muscle ◽  
Metastatic Colorectal Cancer ◽  
Secondary Analysis ◽  
Phase 3 ◽  
Skeletal Muscle Index

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 ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Skeletal Muscle ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Secondary Analysis ◽  
Skeletal Muscle Index ◽  
Longitudinal Joint ◽  
Progression Of Disease ◽  
Survival Modeling ◽  
Colorectal Cancer Patients

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.

scholarly journals Factors Contributing to Cancer-Related Muscle Wasting During First-Line Systemic Treatment for Metastatic Colorectal Cancer

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Jeroen W G Derksen ◽  
Sophie A Kurk ◽  
Marieke J Oskam ◽  
Petra H M Peeters ◽  
Cornelis J A Punt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Computed Tomography ◽  
Metastatic Colorectal Cancer ◽  
Muscle Mass ◽  
Systemic Treatment ◽  
Tumor Resection ◽  
Adverse Outcomes ◽  
Muscle Loss ◽  
First Line ◽  
Skeletal Muscle Index

AbstractBackgroundIncreasing evidence indicates that loss of muscle mass is associated with adverse outcomes in metastatic colorectal cancer. Here, we investigate which demographic, lifestyle- (smoking), tumor-, and treatment-related factors are associated with muscle loss in patients with metastatic colorectal cancer during first-line palliative systemic treatment.MethodsData from 300 patients with computed tomography scans both at start and after six initial cycles of capecitabine plus oxaliplatin and bevacizumab was used (CAIRO3). From computed tomography, muscle mass normalized for stature (skeletal muscle index [SMI]) was calculated. A priori-selected variables were tested using multivariable linear regression models (P values ≤.05). Two models were developed: Model 1 contained variables measured at start and Model 2 contained variables assessed after initial therapy.ResultsIn Model 1, loss of SMI was statistically significantly associated with a higher initial SMI (−0.32%, 95% confidence interval [CI] = −0.45% to −0.19% per unit increase in initial SMI), smoking status (−2.74%, 95% CI = −5.29% to −0.19% for smokers), and interval of metastases (−3.02%, 95% CI = −5.50% to −0.53%) for metachronous vs synchronous metastases), and primary tumor resection was statistically significantly associated with a gain in SMI (2.17%, 95% CI = 0.13% to 4.21% for resection vs no resection). In Model 2, loss of SMI was statistically significantly associated with response to capecitabine plus oxaliplatin and bevacizumab (−2.48%, 95% CI = −4.33% to −0.62% for stable disease vs partial/complete response).ConclusionsOur results highlight, given the association of sarcopenia and survival, that patients with higher SMI should not be ignored. In addition, smoking is a potentially modifiable factor associated with muscle loss. The association between smoking and muscle loss might relate to worse clinical outcomes in smokers with metastatic colorectal cancer.

scholarly journals Long Term Real-World Outcomes of Trifluridine/Tipiracil in Metastatic Colorectal Cancer—A Single UK Centre Experience

2021 ◽  
Vol 28 (3) ◽  
pp. 2260-2269
Author(s):  
Daniel Tong ◽  
Lei Wang ◽  
Jeewaka Mendis ◽  
Sharadah Essapen
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Systemic Treatment ◽  
Progression Free Survival ◽  
Median Number ◽  
Current Data ◽  
Real World Data

In the UK, Trifluridine-tipiracil (Lonsurf) is used to treat metastatic colorectal cancer in the third-line setting, after prior exposure to fluoropyrimidine-based regimes. Current data on the real-world use of Lonsurf lack long-term follow-up data. A retrospective evaluation of patients receiving Lonsurf at our Cancer Centre in 2016–2017 was performed, all with a minimum of two-year follow-up. Fifty-six patients were included in the review. The median number of cycles of Lonsurf administered was 3. Median follow-up was 6.0 months, with all patients deceased at the time of analysis. Median progression-free survival (PFS) was 3.2 months, and overall survival (OS) was 5.8 months. The median interval from Lonsurf discontinuation to death was two months, but seven patients received further systemic treatment and median OS gained was 12 months. Lonsurf offered a slightly better PFS but inferior OS to that of the RECOURSE trial, with PFS similar to real-world data previously presented. Interestingly, 12.5% had a PFS > 9 months, and this cohort had primarily left-sided and RAS wild-type disease. A subset received further systemic treatment on Lonsurf discontinuation with good additional OS benefit. Lonsurf may alter the course of disease for a subset of patients, and further treatment on progression can be considered in carefully selected patients.

Change in skeletal muscle index and its prognostic significance in conversion therapy for initially unresectable colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 56-56
Author(s):  
Hiroaki Nozawa ◽  
Shigenobu Emoto ◽  
Koji Murono ◽  
Yasutaka Shuno ◽  
Soichiro Ishihara
Keyword(s):  
Colorectal Cancer ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscles ◽  
Systemic Chemotherapy ◽  
Stage Iv ◽  
The Body ◽  
Pharmacological Intervention ◽  
Conversion Therapy ◽  
Skeletal Muscle Index

56 Background: Systemic chemotherapy can cause loss of skeletal muscle mass in colorectal cancer (CRC) patients in the neoadjuvant and palliative settings. However, it is largely unknown how the body composition is changed by chemotherapy rendering unresectable CRC to resectable disease or how it affects the prognosis. This study aimed at elucidating the effects of systemic chemotherapy on skeletal muscles and survival in stage IV CRC patients who underwent conversion therapy. Methods: We reviewed 98 stage IV CRC patients who received systemic chemotherapy in our hospital. According to the treatment setting, patients were divided into the ‘Conversion’, ‘Neoadjuvant chemotherapy (NAC)’, and ‘Palliation’ groups. The cross-sectional area of skeletal muscles at the third lumbar level and changes in the skeletal muscle index (SMI), defined as the area divided by height squared, during chemotherapy were compared among patient groups. The effects of these parameters on prognosis were analyzed in the Conversion group. Results: The mean SMI increased by 8.0% during chemotherapy in the Conversion group (n = 38), whereas it decreased by 6.2% in the NAC group (n = 18) and 3.7% in the Palliation group (n = 42, p < 0.0001). Moreover, patients with increased SMI during chemotherapy had a better overall survival (OS) than those whose SMI decreased in the Conversion group (p = 0.021). The increase in SMI was an independent predictor of favorable OS on multivariate analysis (hazard ratio: 0.26). Conclusions: Stage IV CRC patients who underwent conversion to resection often had an increased SMI. As such an increase in SMI further conveys a survival benefit in conversion therapy, it may be important to make efforts to preserve muscle mass by meticulous approaches, such as nutritional support, muscle exercise programs, and pharmacological intervention even during chemotherapy in patients with metastatic CRC.

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