Concurrent losses of skeletal muscle mass, adipose tissue and bone mineral density during bevacizumab / cytotoxic chemotherapy treatment for metastatic colorectal cancer

Dolly, Adeline; Lecomte, Thierry; Bouché, Olivier; Borg, Christophe; Terrebonne, Éric; Douillard, Jean-Yves; Chautard, Romain; Raoul, William; Ternant, David; Léger, Julie; Bleuzen, A.; Dumas, Jean‐François; Servais, Stéphane; Baracos, Vickie E.

doi:10.1016/j.clnu.2020.02.017

Cited by 10 publications

(8 citation statements)

References 58 publications

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“…Recent studies suggest that bone loss begins before the loss of muscle mass, and thus may be an early marker of deconditioning that precedes sarcopenia in patients with end-stage liver disease (17,28). Cancer chemotherapies further accelerate bone loss through direct dysregulation of bone turnover and indirect mechanisms such as nephrotoxicity (14,30,31). Such therapies include antineoplastic drugs, such as platinumderived compounds, alkylating agents, antimetabolites, glucocorticoids, and targeted therapies.…”

Section: Discussionmentioning

confidence: 99%

“…Decreased bone mineral density (BMD) is another important survivorship issue in cancer care, rendering patients at risk for osteoporosis and consequent fractures that can compromise the quality of life and longevity (12). Skeletal complications in cancer patients primarily develop due to bone metastases, but other cancer-related factors as well as aging can cause disturbances in bone remodeling and resultant bone loss (13,14). However, except for cancers that frequently require antihormonal therapies, such as breast cancer and prostate cancer, limited studies have explored the implications of bone loss on outcomes of cancer patients.…”

Section: Introductionmentioning

confidence: 99%

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Computed tomography-measured bone mineral density as a surrogate marker of survival after resection of colorectal liver metastases

Ikuta¹,

Aihara²,

Nakajima³

et al. 2021

Ann Transl Med

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Background: Osteopenia/osteoporosis, characterized by low bone mineral density (BMD), is a potential prognostic factor in cancer patients. We conducted a retrospective single-institution study to evaluate the prognostic impact of preoperative low BMD on colorectal liver metastases (CRLM) in patients undergoing liver resection.Methods: BMD was assessed in 281 patients undergoing initial liver resection for CRLM by analyzing the preoperative computed tomography (CT) images at the level of the eleventh thoracic vertebra as the region of interest. Survival outcomes were compared between the two groups divided by the median BMD value and prognostic factors after surgery were assessed. Propensity score-based inverse probability weighting (IPW) was applied to adjust for between-group differences in baseline characteristics.Results: The low BMD group had significantly more older patients (≥75 years) (P=0.01) and a higher incidence of bilobar metastases (P=0.005) than the normal BMD group. After IPW adjustment, overall survival (OS) was significantly poorer (P=0.02) and recurrence-free survival was slightly poorer (P=0.05) in the low BMD group than in the normal BMD group. IPW-adjusted regression analysis revealed that low BMD was independently associated with an adverse OS (hazard ratio, 1.42; 95% CI, 1.04-1.93; P=0.03), in addition to other factors such as tumor number, extrahepatic disease, preoperative carcinoembryonic antigen level (≥5 ng/mL), and right-sided primary tumor location.Conclusions: Preoperative CT-measured low BMD can serve as a surrogate marker of adverse OS in CRLM patients undergoing liver resection. Prevention and early intervention for osteopenia/osteoporosis may be suggested for these patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Computed tomography-measured bone mineral density as a surrogate marker of survival after resection of colorectal liver metastases

Ikuta¹,

Aihara²,

Nakajima³

et al. 2021

Ann Transl Med

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“…In addition, SkM loss is also associated with reduced tolerance to anticancer treatments and exercise intolerance (fatigue) [ 11 , 12 , 91 ]. In most clinical studies ( Table 2 [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ,…”

Section: Overview Of Selected Studiesmentioning

confidence: 99%

Chemotherapy-Induced Molecular Changes in Skeletal Muscle

et al. 2023

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Paraneoplastic conditions such as cancer cachexia are often exacerbated by chemotherapy, which affects the patient’s quality of life as well as the response to therapy. The aim of this narrative review was to overview the body-composition-related changes and molecular effects of different chemotherapy agents used in cancer treatment on skeletal-muscle remodeling. A literature search was performed using the Web of Science, Scopus, and Science Direct databases and a total of 77 papers was retrieved. In general, the literature survey showed that the molecular changes induced by chemotherapy in skeletal muscle have been studied mainly in animal models and mostly in non-tumor-bearing rodents, whereas clinical studies have essentially assessed changes in body composition by computerized tomography. Data from preclinical studies showed that chemotherapy modulates several molecular pathways in skeletal muscle, including the ubiquitin–proteasome pathway, autophagy, IGF-1/PI3K/Akt/mTOR, IL-6/JAK/STAT, and NF-κB pathway; however, the newest chemotherapy agents are underexplored. In conclusion, chemotherapy exacerbates skeletal-muscle wasting in cancer patients; however, the incomplete characterization of the chemotherapy-related molecular effects on skeletal muscle makes the development of new preventive anti-wasting strategies difficult. Therefore, further investigation on molecular mechanisms and clinical studies are necessary.

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“…Endpoint scan timing was similarly variable, defined in seven instances by a single time point (e.g., 6 weeks) after treatment start 25,26,29,33,45,47,59 . Five studies defined endpoint as a window of time (e.g., 60–120 days) after treatment start 28,32,37,39,42 . Seven designs defined endpoint CT timing using a set number of chemotherapy cycles, ranging from one to six cycles; however, the length of one cycle was not often reported 23,34,40,50,51,54,55 .…”

Section: Study Design: Scan Timing and Intervalsmentioning

confidence: 99%

Call for standardization in assessment and reporting of muscle and adipose change using computed tomography analysis in oncology: A scoping review

Klassen,

Mazurak,

Thorlakson

et al. 2023

J cachexia sarcopenia muscle

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Investigators are increasingly measuring skeletal muscle (SM) and adipose tissue (AT) change during cancer treatment to understand impact on patient outcomes. Recent meta‐analyses have reported high heterogeneity in this literature, representing uncertainty in the resulting estimates. Using the setting of palliative‐intent chemotherapy as an exemplar, we aimed to systematically summarize the sources of variability among studies evaluating SM and AT change during cancer treatment and propose standards for future studies to enable reliable meta‐analysis. Studies that measured computed tomography‐defined SM and/or AT change in adult patients during palliative‐intent chemotherapy for solid tumours were included, with no date or geographical limiters. Of 2496 publications screened by abstract/title, 83 were reviewed in full text and 38 included for extraction, representing 34 unique cohorts across 8 tumour sites. The timing of baseline measurement was frequently defined as prior to treatment, while endpoint timing ranged from 6 weeks after treatment start to time of progression. Fewer than 50% specified the actual time interval between measurements. Measurement error was infrequently discussed (8/34). A single metric (cm2/m2, cm2 or %) was used to describe SM change in 18/34 cohorts, while multiple metrics were presented for 10/34 and no descriptive metrics for 6/34. AT change metrics and sex‐specific reporting were available for 10/34 cohorts. Associations between SM loss and overall survival were evaluated in 24 publications, with classification of SM loss ranging from any loss to >14% loss over variable time intervals. Age and sex were the most common covariates, with disease response in 50% of models. Despite a wealth of data and effort, heterogeneity in study design, reporting and statistical analysis hinders evidence synthesis regarding the severity and outcomes of SM and AT change during cancer treatment. Proposed standards for study design include selection of homogenous cohorts, clear definition of baseline/endpoint timing and attention to measurement error. Standard reporting should include baseline SM and AT by sex, actual scan interval, SM and AT change using multiple metrics and visualization of the range of change observed. Reporting by sex would advance understanding of sexual dimorphism in SM and AT change. Evaluating the impact of tissue change on outcomes requires adjustment for relevant covariates and concurrent disease response. Adoption of these standards by researchers and publishers would alter the current paradigm to enable meta‐analysis of future studies and move the field towards meaningful application of SM and AT change to clinical care.

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Concurrent losses of skeletal muscle mass, adipose tissue and bone mineral density during bevacizumab / cytotoxic chemotherapy treatment for metastatic colorectal cancer

Abstract: Please cite this article as: Dolly A et al., Concurrent losses of skeletal muscle mass, adipose tissue and bone mineral density during bevacizumab / cytotoxic chemotherapy treatment for metastatic colorectal cancer, Clinical Nutrition,

Cited by 10 publications

References 58 publications

Computed tomography-measured bone mineral density as a surrogate marker of survival after resection of colorectal liver metastases

Computed tomography-measured bone mineral density as a surrogate marker of survival after resection of colorectal liver metastases

Chemotherapy-Induced Molecular Changes in Skeletal Muscle

Call for standardization in assessment and reporting of muscle and adipose change using computed tomography analysis in oncology: A scoping review

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