Loss of muscle mass as outcome measures and factors associated with it
| First author (year) | Patients | Study | Comparison | Result | ||||
|---|---|---|---|---|---|---|---|---|
| n (M/F) | Tumour, stage | Muscle mass measurement(s) | Method of measurement | Design | Controls | |||
| McMillan (2001)57 | 40 (40/0) | NSCLC n=11, upper GI n=22, colon n=7 All locally advanced or metastatic | BCM | Total body potassium | Cross sectional | Nil | The inter-relationship between albumin, body cell mass and the systemic inflammatory response | Albumin concentrations correlated with BCM (r=0.686, p<0.001) and negatively correlated with CRP (r=−0.545, p<0.001) |
| Crown (2002)58 | 30 (NR/NR) | NSCLC in all Inoperable, stage NR | FFM, MUAC | BIA, upper arm measurements | Case-control, longitudinal over 2 years | n=30 HV | ILGF system and cancer cachexia | More LC than HV had MAMC in the lowest quartile (p<0.05) at baseline, Male LC patients had lower FFM than male HV (p<0.05) at baseline, No significant longitudinal trend observed in IGFBP-3 and IL-6 and nutritional status, p=NS |
| Jagoe (2002)59 | 36 (27/9) | Mix of NSCLC and SCLC Stage 1–21 Stage 2–6 Stage 3–6 Stage 4–2 | FFMi | BIA, Four skinfold method, %BFMAMA | Cross sectional | n=10 patients referred for thoracotomy for non-malignant conditions | Ubiquitin-proteasome and lysosomal proteolytic pathway gene expression in LC and association with LMM | Cathepsin B expression in LC inversely related to FFMi, p=0.003; Cathepsin-B expression increased in ‘depleted FFMi cancer patients’ vs controls p=0.003; No relationship between cathepsin B expression and %BFMAMA, p=NS |
| Wieland (2007)60 | 286 (NR/NR) | NSCLC n=181, stage IIIB or IV | SMA at T4 | CT at T4 | Longitudinal | n=7 HV | Establish prevalence of PIF in patients with cancer, and its association with muscle loss | In patients with NSCLC: PIF unrelated to survival and muscle loss, p=NS; PIF positive patients rate of loss of muscle mass per 100 days −3.4±2.1% vs PIF negative patients −2.4±1.7%, p=NS |
| Martinez-Hernandez (2012)61 | 21 (19/2) | LC n=13, GI cancer n=6, Other cancer n=2 Stage according to tumour group NR | FFM | BIA | Longitudinal | n=8 HV | The role of IL-15) in patients with cachectic cancer | At weeks 4 and 8, patients with cancer lost FFM in tandem with decreasing IL-15 levels, r=0.514 and r=0.535, both p<0.05 |
| Op den Kamp (2012)55 | 16 (15/1) | NSCLC in all Stage I–II—11 Stage IIIA—2 Stage IIIB—3 | FFMi | DEXA | Cross sectional | n=10 HV | Skeletal muscle NF-κB and ubiquitin proteasome system activity in precachexia | FFMi no significant difference in precachectic cancer vs controls, p=NS; NF-κB, UPS E3-ligase and 26S proteasome activity not raised in patients with precachectic cancer, all p=NS |
| Vigano (2009)52 | N=172 (101/71) | NSCLC n=64, All stage III and IV. Metastatic GI cancer n=108 | LBM, ALM | DEXA (n=64) | Cross sectional | Nil | ACE gene polymorphism (insertion2-II, insertion/deletion-ID, deletion2-DD) on nutritional status | Trend (p=0.07) towards lower LBM in ID compared to II groups |
| Op den Kamp (2013)62 | 26 (17/9) | NSCLC Stage IIIB—10 Stage IV—16 | FFMi, AMMi | DEXA | Cross sectional | n=10 HV | Expression of signalling molecules in protein metabolism in LC cachexia | AMMi 20% lower in cachectic group compared with controls, p<0.05; Akt concentration increased in cachectic group (p<0.05), but no downstream signal phosphorylation, that is, impaired anabolic activity |
| Harvie (2003)29 | 50 (32/18) | NSCLC in all, stage III and IV | FFM | Four skinfold method | Longitudinal | Nil | Exploration of gender-specific differences in body composition and REE prechemotherapy and postchemotherapy | Trend for FFM to decrease (p=0.063) and FFM decreased (p<0.05) in men after chemotherapy. No significant difference in FFM or REE in women |
| Harvie (2005)63 | 43 (28/15) | NSCLC in all, stage III and IV. Alongside this metastatic breast and melanoma patients evaluated separately | FFM | Four skinfold method | Longitudinal | Nil | Relationship between energy intake, REE and acute phase response vs changes in body composition over course of chemotherapy | No significant change in FFM over the course of chemotherapy, and no significant relationship with energy intake, REE or CRP (all p=NS) |
| Bovio (2008)64 | 144 (92/52) | LC n=46, colon n=22, HCC n=11, other n=65 Stage NR | AMA | Upper arm measurements | Cross sectional | Nil | Evaluation of nutritional status in patients with advanced cancer | 63% men vs 19% women had AMA<5th centile (p<0.01) |
| Baracos (2010)25 | 441 (229/212) | NSCLC in all Stage III—206 Stage IV—235 | SMA at L3 | CT of L3 | Cross sectional | Nil | The use of CT images in evaluating body composition in NSCLC | 61.1% men in cohort were sarcopenic, 31.3% of women sarcopenic, p<0.001 |
| Martin (2013)65 | 1473 (828/645) | Colorectal cancer n=773, LC n=440, other GI cancer n=260 Stage according to cancer NR | SMA at L3, SMAi | CT of L3 | Longitudinal | Nil | Prognostic significance of weight loss, muscle mass index and muscle attenuation | Concordance model using variables of BMI, weight loss, MI and MA found a concordance statistic (predictive accuracy of survival) of 0.92 Regardless of BMI, pts with weight loss, low MI and MA reduced survival (8.4 months), compared to those with none of these features (28.4 months), p<0.001 |
| Prado (2013)66 | 368 (216/152) | NSCLC n=242 GI tract cancer n=126 | SMA at L3 | CT of L3 | Longitudinal | Nil | Clinical course of skeletal muscle wasting in advanced cancer | Being <90 days from death increases risk of muscle loss, OR 2.67, p=0.002; and decreases chance of muscle gain, OR=0.37, p=0.002 |
| Hansell (1986)67 | 98 (63/35) | Colorectal cancer n=55, gastric cancer n=24, LC n=12, other cancer n=7 Stage NR | LBM, MUAC | Tritiated saline, upper arm measurements | Cross sectional | n=38 non-malignant illnesses | REE in weight-losing patients with cancer WLC=weight-losing patients with cancer, WSC=weight-stable patients with cancer, WSC on=weight-stable controls | WLC compared to WSC had lower LBM (p<0.005); WLC compared to WSC and WSC on lower MAMC (p<0.0005); WLC had increased REE/kg bodyweight compared with both WS groups (p<0.005); No significant difference when REE is expressed in terms of kg LBM; WLC had positive relationship with REE, r=0.83, p<0.001 |
| Fredrix (1990)68 | 39 (GCR 13/9, LC 16/1) | LC n=17 GCR—n=22 Stage NR | FFM | BIA | Cross sectional | n=40 healthy | REE and weight loss | FFM: LC 50.4±8.9, Controls 51.1±9.6, p=NS; REE/FFM: LC 33.5±5.4, Controls 29.6±2.9, p<0.01 |
| Staal-van den Brekel (1997)69 | 12 (10/2) | All SCLC | FFM | BIA | Longitudinal | Nil | Assess REE and systemic inflammation prechemotherapy and postchemotherapy | No change in FFM postchemotherapy (p=NS). Absolute REE and REE adjusted for FFM decreased postchemotherapy (p<0.005) |
| Simons (1997)70 | 21 (21/0) | NSCLC n=19 Stage I—3 Stage III—5 Stage IV—11 SCLC n=2 Limited stage—2 | FFM, FFMi | DEXA | Cross sectional | Nil | Relationship between DL expression, body composition and REE | DL vs non-DL no significant difference between groups with regards FFM, FFMi, and REE/FFM, all p=NS |
| Simons (1999)71 | 20 (20/0) | NSCLC n=18 I–II—2 III—5 IV—11 SCLC n=2 | BCM, BCMi | DEXA | Cross sectional | Nil | Relationship between weight loss, low BCM and systemic inflammation | BCM lower in group with weight loss ≥10% compared to group with weight loss <10%, p=NS; Low BCMi associated with high REE/BCM, r=−0.54, p=0.03; BCMi positively correlated with Karnofsky PS, p=0.02 |
| Scott (2001)72 | 12 (12/0) | NSCLC in all, locally advanced | BCM | Total body potassium | Longitudinal | n=7, healthy participants | Inter-relationship between systemic inflammation and REE preonset and postonset of weight loss | Cancer group had lower REE (p<0.05) and BCM (p<0.001). Cancer group REE adjusted for BCM correlated with CRP concentrations (r=0.753, p<0.01) |
| Jatoi (2001)73 | 18 (10/8) | NSCLC in all Stage IA—6 Stage IB—3 Stage IIB—3 Stage IIIA—4 Stage IIIB—2 | FFM, BCM, LBM | DEXA, Potassium-40, tritium dilution | Cross sectional | n=18, HV | REE in non-metastatic NSCLC | REE in cancer vs controls significantly raised when adjusted for LBM, p=0.001; and also when adjusted for BCM, p=0.032 |
| Jagoe (2001)27 | 60 (43/17) | LC in all | FFM, MAMC, BFMAMA | BIA, four skinfold thickness, upper arm measurements | Cross sectional | n=22, mild COPD | Nutritional status of patients undergoing LC operations | No difference in FFMi and BFMAMA comparing LC and controls, all p=NS |
| Sarhill (2003)74 | n=352 but LC only 18% of cohort () | NR | MUAC, AMA | BIA (n=329) | Cross sectional | Nil | Prospective evaluation of nutritional status in advanced cancer | Cachexia group vs non-cachexia group, reduced AMA in 84% vs 69%, p=0.037 |
| Prado (2008)1 | n=250, with LC 60 (24%) of cohort (136/114) | TNM for cohort Stage I—24 Stage II—56 Stage III—74 Stage IV—96 | SMA and SMAi at L3 | CT of L3 | Cross sectional | Nil | Prevalence of sarcopaenic obesity and chemotherapy toxicity in this cohort OS=obese sarcopaenic ONonS=obese non-sarcopaenic | SMA in OS 128.1±29.1, ONonS 160±38.1, p<0.0001 SMAi in OS 43.3±6.3, ONonS 56.4±9.9; Median survival assoc with sarcopenia log rank, p<0.0001, OS 11.3 months and ONonS 21.6 months, p<0.0001 |
| Kilgour (2010)53 | n=84, with LC 16 (19%) of cohort (48/36) | Metastatic 57%, locally advanced 43%, stage NR | SMMI, ALM | DEXA | Cross sectional | Nil | Relationship of fatigue to muscle mass and strength | Brief fatigue index associated with SMMI (95% CI −8.4 to −1.3) p<0.01, and sarcopenia, p<0.01 |
| Peddle-McIntyre (2012)56 | 17 (7,10) | NSCLC n=16 Stage I–II—11 Stage III—5 Limited stage SCLC n=1 | LBM, ALM | DEXA | Longitudinal, duration 10 weeks | Nil | Resistance exercise training efficacy and feasibility in LC survivors | LBM and ALM no change from baseline to post training, all p=NS |
| Bauer (2005)75 | n=7, with NSCLC 2 (28.6%) of cohort | Adenocarcinoma pancreas n=5, NSCLC n=2 Stage NR | LBM | Deuterium dilution | Longitudinal, duration 10 weeks | Nil | Effect of nutrition counselling and EPA supplements on body composition | Change in LBM post intervention, p=NS |
| Fearon (2006)28 | 518 (355/163) | LC n=231 Upper GI cancer n=198 Other GI cancer n=89 Stage NR | LBM | BIA | RCT (double blind, placebo controlled, randomised) | Nil | Effect of 2 g and 4 g doses of EPA diester vs placebo in the process of cachexia | Group given 2 g EPA gained mean 0.9 kg LBM and group given 4 g EPA lost mean 0.1 kg LBM compared to placebo (p=NS) |
| Tozer (2008)54 | 66 (49/17); only 35 completed study | All LC Stage NR | BCM | NR | RCT (double blind, placebo controlled, randomised) | Nil | Effect of cysteine-rich protein supplement on body weight and body cell mass | Cysteine group +11.55±18.05% vs control group −5.47±34.63% after treatment (p=0.01), and compared to baseline (p=0.02) |
| Murphy (2010)76 | 41 (19/22) | NSCLC in all Stage I—2 Stage II—2 Stage III—13 Stage IV—24 | SMA at L3 | CT of L3 | Longitudinal, cohort study over 2.5 months | Nil | Relationship between muscle mass, rate of muscle mass change, and plasma fatty acids | Sarcopenia at baseline in 63% men and 59% women; Patients with sarcopenia had lower plasma EPA (p=0.001), lower plasma DHA (p=0.003), and lower n-3 fatty acids (p=0.002) compared to non-sarcopenic patients |
| Murphy (2011)77 | 40 (21/19) | NSCLC in all Stage III—13 Stage IV—27 | SMA at L3 | CT of L3 | Longitudinal, duration 6 weeks Open label study | Nil controls; cohort divided into those receiving FO n=17 and SC n=24 | Effect of FO on body composition | Sarcopenic at baseline FO 46%, SC 46%; Muscle loss rate per 100 days, FO 0.1±1.6%, SC −6.8±2.6%, p<0.05; Positive relationship between plasma EPA concentration and rate of muscle gain, r2=0.55, p=0.01 |
| Winter (2012)78 | 10 (10/0) | NSCLC in all Stage IIIA—2 Stage IIIB—3 Stage IV—5 | LBM, AMMi | DEXA | Longitudinal | n=10 healthy men | Effect on protein anabolism in response to hyperaminoacidaemia, in cachexic insulin-resistant patients | Mean AMMi cancer group defined as sarcopenic, p=NS; Hyperaminoacidaemia stimulates a normal anabolic protein response, p<0.05 |
| Agteresch (2002)50 | 58 (38/20) | NSCLC in all including controls (RCT) All Stage IIIB or IV, breakdown NR | FFM, MUAC, BCM | Four skinfold thickness, deuterium dilution | Longitudinal, duration 28 weeks RCT | Randomised to ATP group n=28, to control group n=30, all NSCLC | Effect of ATP on body composition | FFM −0.5 kg in controls, but +0.1 kg in ATP group, between group difference p=0.02 MUAC −1.8% in controls, but +1.1% in ATP group, between group difference p=0.02 BCM −0.6% per 4 weeks in controls, but −0.1% in ATP group, between group diff p=0.054 |
| Beijer (2009)79 | n=100, with LC n=44 n=57 completed 8-week study period | LC in 44% (most frequent), colon cancer 13%, various other cancers 43% Stage NR ‘preterminal’ | MUAC | Upper arm measurements | Longitudinal, duration 8 weeks RCT | Baseline: ATP n=51, SC n=49; Completed study: ATP n=29, SC n=28 | Effect of ATP on nutritional status and survival | Post ATP loss of MUAC −2.24 mm, SC group −1.52 mm, p=NS Short term 0–8 weeks survival benefit with ATP (HR 0.17, p=0.023), and long term 0–6 months survival benefit (HR 0.35, p=0.025) |
ALM, appendicular lean mass; AMA, arm muscle area; AMMi, appendicular muscle mass index; BCM, body cell mass; BCMi, BCM index; BFMAMA, bone free mid arm muscle area; BIA, bioelectrical impedance analysis; BMI, body mass index; COPD, chronic obstructive pulmonary disease; CRP, C reactive protein; CT of L3, CT of the third lumbar space; DEXA, dual-energy X-ray absorptiometry; DL, detectable leptin; EPA, eicosapentaenoic acid; F, female; FFM, fat-free mass; FFMi, FFM index; FO, fish oil; GCR, gastric and colorectal cancer; GI, gastrointestinal; HV, healthy volunteers; IL-15, interleukin 15; ILGF, insulin-like growth factor; LBM, lean body mass; LC, lung cancer; M, male; MI, muscle index; MUAC, mid-upper arm circumference; MA, muscle area; NR, not recorded; NS, non-significant; NSCLC, non-small cell lung cancer; PS, performance status; RCT, randomised controlled trial; REE, resting energy expenditure; SCLC, small cell lung cancer; SMA at L3 or T4, skeletal muscle area at the level of the lumbar vertebra L3 or thoracic vertebra T4; SMAi, skeletal muscle area index; SMMI, skeletal muscle mass index; TNM, tumour, node, metastasis; HCC, hepatocellular carcinoma; MAMC, mid-arm circumference; PIF, proteolysis inducing factor.