Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer

Blauwhoff‐Buskermolen, Susanne; Versteeg, Kathelijn S.; Schueren, Marian A.E. de van der; Braver, Nicolette R. den; Berkhof, Johannes; Langius, J.A.E.; Verheul, Henk M.W.

doi:10.1200/jco.2015.63.6043

Cited by 307 publications

(305 citation statements)

References 37 publications

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“…A random sample of 140 slices was analysed twice by the same analyst and another time by a second trained analyst, during which both analysts were blinded for patient ID and the outcome of the first analysis. Mean coefficients of 1.7% and 1.2% were found for interobserver and intraobserver variation, respectively, which are consistent with other reports in literature 5, 15…”

Section: Methodssupporting

confidence: 92%

“…Previously, it has been questioned whether these cut‐off points are generalizable to other ethnicities 31, 32, 33. In addition, average Western Europeans are taller and less overweight compared with North Americans, and low SMM in Western European patient cohorts was not always associated with treatment‐related toxicities and reduced overall survival times 15. Recently, new sarcopenia definitions in stages I–III of CRC patients have been proposed,34 but further large‐scale studies are warranted to reach consensus on definitions of sarcopenia in European populations of mCRC patients.…”

Section: Discussionmentioning

confidence: 99%

“…In this model, we included the subgroup of patients with the additional SMM measurements available at these time points and modelled SMM changes from randomization until 9 and 18 weeks thereafter. Finally, to get insight in the correlation between changes in SMM and changes in body weight, Pearson's correlation coefficient was used separately for men and women as differences between sexes were previously described 15. All P ‐values were two‐sided, and the level of significance was considered at P < 0.05.…”

Section: Methodsmentioning

confidence: 99%

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Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients

Kurk

Peeters

Dorresteijn

et al. 2018

J cachexia sarcopenia muscle

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BackgroundObservational studies suggest that loss of skeletal muscle mass (SMM) is associated with chemotherapy‐related toxicity, poor quality of life, and poor survival in metastatic colorectal cancer (mCRC) patients. Little is known about the evolution of SMM during palliative systemic therapy. We investigated changes in SMM during various consecutive palliative systemic treatment regimens using repeated abdominal computed tomography scans of mCRC patients who participated in the randomized phase 3 CAIRO3 study.MethodsIn the CAIRO3 study, mCRC patients with stable disease or better after 6 cycles of first‐line treatment with capecitabine + oxaliplatin + bevacizumab (CAPOX‐B) were randomized between maintenance treatment with capecitabine + bevacizumab (CAP‐B) or observation. Upon first disease progression, in both groups, CAPOX‐B or other treatment was reintroduced until the second disease progression, which was the primary study endpoint. We analysed 1355 computed tomography scans of 450 (81%) CAIRO3 patients (64 ± 9.0 years, CAP‐B n = 223; observation n = 227) for SMM at four time points (i.e. prior to the start of pre‐randomization initial treatment, at randomization, and at first and at second disease progression) using the Slice‐o‐matic software and single slice evaluation at the lumbar 3 level. By using accepted and widely used formulas, whole body SMM was calculated. A linear mixed effects model, adjusted for relevant confounders, was used to assess SMM changes for the total group and within and between study arms.ResultsDuring 6 cycles of initial treatment with CAPOX‐B prior to randomization, SMM decreased significantly in all patients [CAP‐B arm: −0.53 kg (95% CI −1.12; −0.07) and observation arm: −0.85 kg (−1.45; −0.25)]. After randomization, SMM recovered during CAP‐B treatment by 1.32 kg (0.73; 1.90) and observation by 1.20 kg (0.63; 1.78) (median time from randomization to first disease progression 8.6 and 4.1 months for CAP‐B arm and observation arm, respectively). After first progression and during reintroduction treatment with CAPOX‐B or other treatment, SMM again decreased significantly and comparable in both arms, CAP‐B: −2.71 kg (−3.37; −2.03), and observation: −2.01 kg (−2.64; −1.41) (median time from first progression until second progression CAP‐B arm: 4.7 months and observation arm: 6.6 months).ConclusionsThis longitudinal study provides a unique insight in SMM changes in mCRC patients during palliative systemic treatment regimens, including observation. Our data show that muscle loss is reversible and may be influenced by the intensity of systemic regimens. Although studies have shown prognostic capacity for SMM, the effects of subsequent changes in SMM are unknown and may be clues for new future therapeutic interventions.

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Section: Methodssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients

Kurk

Peeters

Dorresteijn

et al. 2018

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

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“…For example, in patients receiving systemic chemotherapy for colorectal cancer, loss of ≥ 9 % muscle mass during a 3 month period was independently predictive of lower survival at 6 months compared to patients who had < 9 % loss, 33 % versus 69 %, respectively, despite no difference in treatment modifications [31]. Similar associations have been described in patients with HNSCC.…”

Section: Main Textsupporting

confidence: 61%

A review of weight loss and sarcopenia in patients with head and neck cancer treated with chemoradiation

2016

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Background: Concurrent chemotherapy and radiation (CTRT) improves disease-free survival in locally advanced head and neck cancer but is associated with numerous acute and chronic toxicities resulting in substantial alterations in body mass and composition. We aim to summarize the current evidence on body composition changes experienced by patients undergoing CTRT, examine the impact of these changes on clinical outcomes and address potential interventions aimed at mitigating the loss. Main Body: Loss of 20 % of pre-CTRT weight predicts poorer treatment tolerance and 30-day mortality. While clinical practice focuses on body weight, emerging data indicates that CTRT causes profound adverse changes in lean body mass (sarcopenia). Higher prevalence of sarcopenia predicts poorer disease-free survival as well as overall survival, lower quality of life and functional performance. The magnitude of CTRT-induced sarcopenia is the equivalent to that observed in a decade of aging in a healthy adult. Alterations in body composition are only explained, in part, by decreased caloric intake; other significant predictors include body mass index, stage, and dysphagia. Lifestyle interventions aimed at preventing loss of whole-body and especially lean mass include nutritional counseling, nutritional supplements, dietary supplements and exercise training. Personalized nutritional counseling has been associated with improvement in quality of life, while the benefits of feeding tube placement are inconsistent. There are inconsistently reported benefits of resistance training in this population. Conclusion: Patients with head and neck cancer undergoing CTRT therapy experience dramatic shifts in body composition, including sarcopenia, which can negatively impact clinical outcomes. Efforts to understand the magnitude, clinical importance and mechanisms of sarcopenia are needed to inform a more personalized approach to mitigating the body composition changes associated with CTRT.

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“…The benefits of regorafenib and TAS-102 for OS of patients with mCRC was demonstrated in 2 phase III randomized controlled trials, CORRECT [4] and RECOURCE [5]. As a result, rego-DOI: 10.1159/000494417 rafenib and TAS-102 are now established as additional treatment options for patients with mCRC refractory to previous standard chemotherapy and for best supportive care. However, there are no reliable biomarkers to identify patients likely to respond to salvage-line chemotherapy.…”

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

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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.

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Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer

Abstract: Muscle area decreased significantly during chemotherapy and was independently associated with survival in patients with mCRC. Further clinical evaluation is required to determine whether nutritional interventions and exercise training may preserve muscle area and thereby improve outcome.

Cited by 307 publications

References 37 publications

Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients

Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients

A review of weight loss and sarcopenia in patients with head and neck cancer treated with chemoradiation

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

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