Negative Impact of Skeletal Muscle Loss after Systemic Chemotherapy in Patients with Unresectable Colorectal Cancer

Miyamoto, Yuji; Baba, Yoshifumi; Sakamoto, Yasuo; Ohuchi, Mayuko; Tokunaga, Ryuma; Kurashige, Junji; Hiyoshi, Yukiharu; Iwagami, Shiro; Yoshida, Naoya; Watanabe, Masayuki; Baba, Hideo

doi:10.1371/journal.pone.0129742

Cited by 125 publications

(114 citation statements)

References 23 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous studies have reported that skeletal muscle mass at baseline is not associated with survival outcome in mCRC patients receiving front-line chemotherapy whereas skeletal muscle loss during chemotherapy clearly predicts long-term outcome [9][10][11]. These results contrast with our data.…”

Section: Discussioncontrasting

confidence: 99%

“…Recent studies have demonstrated that loss of skeletal muscle is a significant risk factor for short-and long-term outcomes after surgery for CRC [7,8]. In addition, It has been reported that changes in skeletal muscle mass during chemotherapy, but not changes before chemotherapy, is significantly associated with clinical outcome in mCRC patients treated with front-line chemotherapy [9][10][11]. However, the significance of alterations in skeletal muscle among patients with pretreatment refractory cancer, in whom cancer cachexia is a more common problem, remains unknown.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Low Skeletal Muscle Mass before Salvage-Line Chemotherapy Is a Poor Prognostic Factor in Patients with Refractory Metastatic Colorectal Cancer

et al. 2018

Self Cite

View full text Add to dashboard Cite

Background: Regorafenib and TAS-102 are standard salvage-line treatment options for patients with chemorefractory metastatic colorectal cancer (mCRC). We aimed to evaluate the prognostic significance of skeletal muscle mass in mCRC patients receiving these salvage-line therapies. Methods: We conducted a retrospective analysis of 52 patients with mCRC who received regorafenib or TAS-102 as salvage-line treatment. Skeletal muscle cross-sectional area was measured by pretreatment CT to obtain the skeletal muscle index (SMI, cm²/m²). We divided patients into 2 groups (low-SM/high-SMI) based on the median value of SMI. Result: The median SMI was 51.8 cm²/m² in males and 39.2 cm²/m² in females. In Kaplan-Meier analysis, patients in the low-SMI group showed significantly shorter overall survival (3.7 vs. 7.3 months, log-rank p = 0.002) and progression-free survival (1.9 vs. 2.8 months, log-rank test p = 0.009) than those in the high-SMI group. Subsequent multivariate analysis revealed that the SMI was an independent prognostic factor (hazard ratio = 2.381, 95% CI 1.189–4.944, p = 0.014). Patients in the low-SMI group had significantly more grade 3 or 4 adverse events than those in the high-SMI group (46 vs.12%, p = 0.013). Conclusion: Low skeletal muscle mass is a negative factor for survival outcomes in mCRC patients treated with salvage-line chemotherapy.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Low Skeletal Muscle Mass before Salvage-Line Chemotherapy Is a Poor Prognostic Factor in Patients with Refractory Metastatic Colorectal Cancer

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Lastly, several studies have proposed that cancer therapy may have direct effects on skeletal muscle or may cause a pro-inflammatory state that leads to proteolysis. Recent work highlights significant skeletal muscle loss during the course of chemotherapy (11, 37, 38). …”

Section: Discussionmentioning

confidence: 99%

Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study)

Caan

Meyerhardt

Kroenke

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

281

283

View full text Add to dashboard Cite

Background Body composition may partially explain the U-shaped association between BMI and colorectal cancer (CRC) survival. Methods Muscle and adiposity at CRC diagnosis and survival were examined in a retrospective cohort using Kaplan Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early stage (I-III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality (OM) and CRC specific mortality (CRCsM). Results Forty-two percent of patients were sarcopenic. During 6.0 years of follow-up, 788 deaths occurred, including 433 from CRC. Sarcopenic patients had a 27% (HR 1.27; 95% CI 1.09, 1.48) higher risk of OM, than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of OM (HR 1.64; 95% CI 1.05, 2.57) when compared to females with adequate muscle and lower adiposity. The lowest risk of OM was seen in patients with a BMI between 25-<30-kg/m2, a range associated with the greatest number of patients (58.6%) who were not at increased risk of OM due to either low muscle or high adiposity. Conclusions Sarcopenia is prevalent among non-metastatic CRC patients, and should, along with adiposity be a standard oncological marker. Impact Our findings suggest a biological explanation for the obesity paradox in CRC and refute the notion that the association between overweight and lower mortality is due solely to methodological biases.

show abstract

“…Adequate muscle mass, and possibly greater muscle mass than noncancer patients, has been shown to be a strong determinant of overall mortality in several studies of cancer patients. (28-39) Studies of CRC patients with advanced disease found that muscle wasting was associated with worse recurrence-free and/or overall survival(40) as well as poor response to chemotherapy. (41) Persons with low muscle mass experience elevated low-grade systemic inflammation,(42) and altered mitochondrial function,(43, 44) both of which may influence cancer progression .…”

Section: Discussionmentioning

confidence: 99%

Association of Weight Change after Colorectal Cancer Diagnosis and Outcomes in the Kaiser Permanente Northern California Population

Meyerhardt

Kroenke

Prado

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Background Higher body mass index (BMI) is associated with incident colorectal cancer (CRC) but not consistently with CRC survival. Whether weight gain or loss is associated with CRC survival is largely unknown. Methods We identified 2,781 patients from Kaiser Permanente Northern California diagnosed with stages I-III CRC between 2006-2011 with weight and height measurements within 3 months of diagnosis and ~18 months post diagnosis. We evaluated associations between weight change and CRC-specific and overall mortality, adjusted for sociodemographics, disease severity, and treatment. Results Following completion of treatment and recovery from stage I-III CRC, loss of at least 10% of baseline weight was associated with significantly worse CRC-specific mortality (hazard ratio [HR] 3.20; 95% confidence interval [CI], 2.33-4.39; P trend <0.0001) and overall mortality (HR 3.27; 95% CI, 2.56-4.18; P trend <0.0001). For every 5% loss of baseline weight, there was a 41% increased risk of CRC-specific mortality (95% CI, 29%-56%). Weight gain was not significantly associated with CRC-specific mortality (P trend=0.54) or overall mortality (P trend=0.27). The associations were largely unchanged after restricting analyses to exclude patients who died within 6 months and 12 months of the second weight measurement. No significant interactions were demonstrated for weight loss or gain by gender, stage, primary tumor location, or baseline BMI. Conclusions Weight loss after diagnosis was associated with worse CRC-specific mortality and overall mortality. Reverse causation does not appear to explain our findings. Impact Understanding mechanistic underpinnings for the association of weight to worse mortality is important to improving patient outcomes.

show abstract

Negative Impact of Skeletal Muscle Loss after Systemic Chemotherapy in Patients with Unresectable Colorectal Cancer

Cited by 125 publications

References 23 publications

Low Skeletal Muscle Mass before Salvage-Line Chemotherapy Is a Poor Prognostic Factor in Patients with Refractory Metastatic Colorectal Cancer

Low Skeletal Muscle Mass before Salvage-Line Chemotherapy Is a Poor Prognostic Factor in Patients with Refractory Metastatic Colorectal Cancer

Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study)

Association of Weight Change after Colorectal Cancer Diagnosis and Outcomes in the Kaiser Permanente Northern California Population

Contact Info

Product

Resources

About