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

2016 ◽  
Vol 34 (12) ◽  
pp. 1339-1344 ◽  
Author(s):  
Susanne Blauwhoff-Buskermolen ◽  
Kathelijn S. Versteeg ◽  
Marian A.E. de van der Schueren ◽  
Nicole R. den Braver ◽  
Johannes Berkhof ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Computed Tomography ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Muscle Mass ◽  
Palliative Chemotherapy ◽  
Survival Rates ◽  
Lumbar Vertebra ◽  
Muscle Loss ◽  
Muscle Area

Purpose Low muscle mass is present in approximately 40% of patients with metastatic colorectal cancer (mCRC) and may be associated with poor outcome. We studied change in skeletal muscle during palliative chemotherapy in patients with mCRC and its association with treatment modifications and overall survival. Patients and Methods In 67 patients with mCRC (mean age ± standard deviation, 66.4 ± 10.6 years; 63% male), muscle area (square centimeters) was assessed using computed tomography scans of the third lumbar vertebra before and during palliative chemotherapy. Treatment modifications resulting from toxicity were evaluated, including delay, dose reduction, or termination of chemotherapy. Multiple regression analyses were performed for the association between change in muscle area and treatment modification and secondly overall survival. Results Muscle area of patients with mCRC decreased significantly during 3 months of chemotherapy by 6.1% (95% CI, −8.4 to −3.8; P < .001). Change in muscle area was not associated with treatment modifications. However, patients with muscle loss during treatment of 9% or more (lowest tertile) had significantly lower survival rates than patients with muscle loss of less than 9% (at 6 months, 33% v 69% of patients alive; at 1 year, 17% v 49% of patients alive; log-rank P = .001). Muscle loss of 9% or more remained independently associated with survival when adjusted for sex, age, baseline lactate dehydrogenase concentration, comorbidity, mono-organ or multiorgan metastases, treatment line, and tumor progression at first evaluation by computed tomography scan (hazard ratio, 4.47; 95% CI, 2.21 to 9.05; P < .001). Conclusion 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.

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 Loss of adipose tissue mass during chemotherapy predicts reduced survival in patients with colorectal cancer treated with palliative intent

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Erin Stella Sullivan ◽  
Louise E. Daly ◽  
Éadaoin B Ní Bhuachalla ◽  
Samantha J. Cushen ◽  
Derek G. Power ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Body Composition ◽  
Muscle Mass ◽  
Fat Mass ◽  
Palliative Chemotherapy ◽  
Poor Survival ◽  
Palliative Intent ◽  
The Impact ◽  
Baseline Bmi

AbstractObesity is an established risk factor for colorectal cancer (CRC), however little is known about changes in body composition during chemotherapy and its impact on survival. The aim of this study was to examine in patients with CRC: (1) The prevalence of abnormal body composition phenotypes, (2) The impact of baseline body composition on overall survival, (3) Changes in body composition throughout treatment and its impact on overall survival.A prospective study of adult CRC patients undergoing chemotherapy between 2012–2016 was conducted. Longitudinal changes in body composition were examined using computed tomography (CT) images at two timepoints (interval 7 months, IQR: 5–9 months) using paired t-tests. Sarcopenia and low muscle attenuation (MA) were defined using published cut-offs. Cox proportional-hazards models were used to estimate mortality hazard ratios, adjusted for known prognostic covariates – stage, age, sex, performance status & systemic inflammation.In total, 268 patients were recruited (66% male, mean age 63 years) and 51% were undergoing chemotherapy with a palliative intent. At baseline, 4% were underweight (BMI < 20 kg/m2), 38% had a normal BMI, and 58% were overweight/obese. Despite this, 38% had cancer cachexia, 34% were sarcopenic and 43% had low MA. Neither sarcopenia, sarcopenic obesity nor cachexia at baseline predicted survival. Over 100 days, 68% were muscle stable (± 1 kg), while 25% lost > 1 kg and 7% gained > 1 kg. Fat mass remained stable ± 1 kg in 49%, while 28% lost > 1 kg and 23% gained > 1 kg. When adjusted for known prognostic covariates, baseline BMI (20–25 kg/m2) in those having palliative chemotherapy was independently associated with reduced survival compared to those with BMI indicating overweight (BMI 25–30 kg/m2) [HR: 1.80 (95% CI: 1.04–3.14), p = 0.037]. In those undergoing chemotherapy with palliative intent, a loss of > 6.4% subcutaneous fat (Q1 SAT) over 100 days was predictive of poor survival versus those with small losses, remaining stable or gaining SAT (Q2-4), independent of changes in muscle mass [HR: 2.22 (95% CI: 1.07–4.62), p = 0.033].Patients with CRC, particularly those treated with a palliative intent, experience significant losses in muscle and fat mass during chemotherapy. Loss of SAT mass during palliative chemotherapy is prognostic of poor survival, independent of changes in muscle mass. Baseline BMI in the overweight range confers a survival advantage. Nutritional strategies to prevent or attenuate weight loss during chemotherapy are advisable especially in the context of advanced CRC.

Pectoralis muscle wasting during chemotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24069-e24069
Author(s):  
Jason Wiederin ◽  
Christina Gu ◽  
Patricia Jewett ◽  
Anne Hudson Blaes
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Muscle Mass ◽  
Body Surface ◽  
Cox Regression ◽  
Nonlinear Effects ◽  
Pectoralis Muscle ◽  
Muscle Loss ◽  
Muscle Area

e24069 Background: Chemotherapy is often followed by muscle mass loss which has been associated with frailty. We explored factors associated with change in pectoralis muscle mass after chemotherapy. We hypothesized greater muscle loss with time would be associated with poorer overall survival. Methods: We identified individuals with breast cancer (N = 221), sarcoma (N = 115), and lymphoma (N = 216) who received chemotherapy at the University of Minnesota MHealth Fairview and had CT scans before and after chemotherapy. Right pectoralis muscle area was measured using CORESLICER and indexed to body surface (right pectoralis muscle area [cm2] / body surface [m2]). We calculated quartiles of the indexed pectoralis measure. We restricted our analyses to participants who received a follow-up CT within two years after starting chemotherapy. In a multivariate linear regression, we explored associations of sex, age, BMI, ever-smoking, time since start of chemotherapy, indexed baseline muscle area, stage, type of diagnosis, and cumulative anthracycline dose with relative (%) change in muscle area. In a Cox regression we tested the association of relative muscle change with overall mortality. We used cubic splines to test for nonlinear effects. Results: Of 477 participants (66% female; mean age 61.3 (10.1) years), 366 received anthracyclines, 61 Trastuzumab, and 60 both. The average loss in right pectoral muscle area was -10% for women and -12% for men. We detected nonlinear effects of indexed baseline muscle area, P = 0.03. In a model using quartiles of indexed baseline muscle area, significant predictors of muscle loss included sex (women vs. men, -9.0%, 95% confidence interval (CI) -14.2- -3.7%, P = 0.0008), larger indexed baseline muscle area (quartiles 2, 3, 4 compared with quartile 1, change range -7 - -24%, 95% CI range, -2 - -30%, P-range < 0.0001 – 0.006), smoking (ever vs. never, -4.1%, 95% CI -7.6 - -0.7%, P = 0.02), and diagnosis (sarcoma vs breast cancer, -5.7%, 95% CI -11.1 - -0.3%, P = 0.04). There was no significant association between muscle change and overall survival (median follow-up time 4.1). Conclusions: Being female, larger baseline muscle mass (per m2 body surface), ever-smoking, and a sarcoma diagnosis were associated with greater relative muscle loss after chemotherapy. More data is needed to understand the course of sarcopenia in terms of recovery and survivorship. [Table: see text]

Use of VEGF expression to predict for first-line treatment chemotherapy regimen in metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14695-e14695
Author(s):  
Metin Ozkan ◽  
Veli Berk ◽  
Kemal Deniz ◽  
Halit Karaca ◽  
Mevlude Inanc ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Survival Rates ◽  
First Line ◽  
Vegf Expression ◽  
Treatment Protocols ◽  
Primary Tumors ◽  
Study Results ◽  
Low Expression

e14695 Background: In metastatic colorectal cancer treatment more successful results are achieved by adding anti-angiogenic therapy to the chemotherapy. Over expression of VEGF in colorectal cancer is known to be a poor prognosis factor but its effects on designating the therapy is not clear. In this study, results of the patients receiving FOLFIRI + Bevacizumab or XELOX + Bevacizumab were compared for VEGF expression. Methods: VEGF was assessed immunohistochemically in primary tumors of the 53 metastatic colorectal cancers. Severity and conformity of VEGF expression was evaluated. Results were used to assess the association with the therapy response, progression free survival (PFS) and overall survival (OS). Results: The median age of the patients was 55 (range, 32-79). In combination with bevacizumab 38 patients received FOLFIRI and 15 patients received XELOX. In 30 patients (57%) there was a strong expression of VEGF and in 23 patients (23%) the expression was weak. In the high VEGF expression group, PFS was 11 months in FOLFIRI receiving patients and 8 months in XELOX receiving ones but in low expression group PFS was 8 months in patients receiving either one of the two treatment protocols. In high expression group, PFS in FOLFIRI-bevacizumab combination receiving patients was different and this difference was statistically significant (p=0.009). Overall survival in FOLFIRI receiving patients with high VEGF expression was 26 months and with low VEGF expression it was 16 months (p=0.04). Median OS was not reached in the XELOX receiving patient group. FOLFIRI regime clinical benefit was 58% in high VEGF expression group whilst it was 34% in low expression group. This difference was not statistically significant but it was close to the significance threshold (p=0.06). There was no association between the therapy responses and VEGF expression of the 15 patients who received XELOX. Conclusions: There is no difference in efficacy between the first line chemotherapy regimens of the metastatic colorectal cancer. In this study, in metastatic colorectal patients with over expressed VEGF first line FOLFIRI-bevacizumab combination led to better response and survival rates.

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.

Intensive Systemic Chemotherapy Combined With Surgery for Metastatic Colorectal Cancer: Results of a Phase II Study

2005 ◽  
Vol 23 (3) ◽  
pp. 502-509 ◽  
Author(s):  
Julien Taïeb ◽  
Pascal Artru ◽  
François Paye ◽  
Christophe Louvet ◽  
Nathalie Perez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cancer Progression ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Curative Surgery ◽  
Free Survival ◽  
Disease Free

Purpose To evaluate the efficacy and tolerability of the metastatic irinotecan plus oxaliplatin (MIROX) strategy (adjuvant FOLFOX-7 followed by FOLFIRI), in patients with resectable metastatic colorectal cancer. Patients and Methods Forty-seven patients with resectable metastases of colorectal cancer were prospectively enrolled onto this study. Treatment consisted of six cycles of leucovorin 400 mg/m2, oxaliplatin 130 mg/m2 in a 120-minute infusion, and fluorouracil (FU) 2,400 mg/m2 in a 46-hour infusion, every 2 weeks (FOLFOX-7), followed by six cycles of leucovorin 400 mg/m2, irinotecan 180 mg/m2 in a 90-minute infusion, bolus FU 400 mg/m2, and FU 2,400 mg/m2 as a 46-hour infusion, every 2 weeks (FOLFIRI). Surgery was performed before chemotherapy in 25 patients and after six cycles of FOLFOX-7 in 22 patients (six cycles of FOLFIRI were administered after surgery). Results All but one of the patients underwent curative surgery. Two patients refused postoperative chemotherapy. Tolerability was generally good. The main toxicities were grade 3 to 4 neutropenia (13%) and thrombocytopenia (11%); no febrile neutropenia or bleeding occurred, and there were no deaths caused by toxicity. Two pathologically confirmed complete responses and 15 partial responses were obtained with FOLFOX-7 in the 22 patients who received this regimen before surgery (overall response rate, 77%; 95% CI, 68 to 86). The median disease-free survival time was 21 months; the median overall survival has not yet been reached. The 2-year overall and disease-free survival rates were 89% and 47%, respectively. Conclusion The MIROX strategy is feasible and well tolerated by patients with resectable metastatic colorectal cancer. Progression-free and overall survival rates are promising, with a median of 38 months of follow-up. This strategy currently is being compared with the leucovorin and FU regimen in a phase III trial.

Thigh sarcopenia and hypoalbuminemia predict impaired overall survival after infrainguinal revascularization in patients with critical limb ischemia

Vascular ◽  
2020 ◽  
Vol 28 (5) ◽  
pp. 542-547 ◽  
Author(s):  
Koichi Morisaki ◽  
Tadashi Furuyama ◽  
Yutaka Matsubara ◽  
Kentaro Inoue ◽  
Shun Kurose ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Overall Survival ◽  
Confidence Interval ◽  
Critical Limb Ischemia ◽  
Survival Rates ◽  
Limb Ischemia ◽  
Hazard Ratio ◽  
Thigh Muscle ◽  
Bone Area ◽  
Muscle Area

Objective This study was performed to determine whether thigh sarcopenia can serve as a clinically relevant predictor of postoperative complications and overall survival after revascularization in patients with critical limb ischemia. Methods Patients who underwent preoperative computed tomography followed by infrainguinal revascularization from 2006 to 2015 were retrospectively analyzed. An axial computed tomography image was obtained at the midpoint of a line extending from the superior border of the patella to the greater trochanter of the femur. The thigh muscle area and bone area were measured. Thigh sarcopenia was defined as thigh muscle area/thigh bone area of <9. Results We included 117 patients with critical limb ischemia who underwent infrainguinal revascularization. The overall survival rates at two years were 86.5% and 55.1% in the thigh sarcopenia (−) and (+) groups, respectively ( p < 0.01). The multivariate analysis showed that thigh sarcopenia (hazard ratio, 2.64; 95% confidence interval, 1.11–6.70; p = 0.03), cerebrovascular disease (hazard ratio, 3.18; 95% confidence interval, 1.31–7.36; p = 0.01), and serum albumin level (1 g/dL per increments) (hazard ratio, 0.41; 95% confidence interval, 0.21–0.81; p = 0.01) were the risk factors for overall survival two years after revascularization. Conclusion Thigh sarcopenia is a risk factor for two-year overall survival in patients with critical limb ischemia after infrainguinal revascularization.

scholarly journals Unresectable Metastatic Colorectal Cancer Treatment and Survival – Pauls Stradins Clinical University Hospital Experience

2012 ◽  
Vol 12 (1) ◽  
pp. 15-19
Author(s):  
Elīna Skuja ◽  
Gunta Purkalne ◽  
Edvins Miklasevics
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Metastatic Disease ◽  
Palliative Chemotherapy ◽  
Survival Rates ◽  
University Hospital ◽  
Disease Group ◽  
First Line ◽  
Colorectal Cancer Patients ◽  
Unresectable Metastatic Colorectal Cancer

SummaryIntroduction.Despite recent advances in the medical treatment of metastatic colorectal cancer (mCRC), which include oxaliplatinand irinotecan-based first-line regimens and the increasing use of targeted monoclonal antibodies, survival rates for patients with mCRC remain unacceptably low.Aim of the Study.Is to analyze survival in patients with unresectable metastatic colorectal cancer.Materials and Methods.Retrospective study of unresectable metastatic colorectal cancer patients who underwent palliative chemotherapy in Clinic of Oncology of PaulsStradins Clinical University Hospital from 2004 to 2011was done.Results.102 patients had a median PFS of 8 months and median OS of 16 months. Subgroup analysis revealed median PFS of 9 months in the synchronous metastatic disease group and 7 months in the metachronous metastatic disease group (p=0.0089) and median OS of 16 months and 12 months, respectively (p=0.0168).Median OS was 11 months in patients received only one line palliative chemotherapy compared to 19 months in patients received more than one line therapy (p<0.0001).Conclusions.The parameter of synchronous and metachronous metastases is of prognostic value in mCRC patients.Second line palliative chemotherapy prolongs overall survival in patient with mCRC.

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