| Psoas Muscle Cross-Sectional Area and | ||
| Outcomes Following Colorectal Cancer Surgery | ||
| Matthew Mouat 1 , Ashok Gunawardene 2 , Lisa Sweetman1 , Elizabeth Dennett1,2 , | ||
| and Peter Larsen2* | ||
| ISSN: 2754-8880 | ||
| Published 00 11 0000 | * Correspondingauthor: Associate Professor Peter Larsen, Department of Surgery | Anaesthesia, |
| University of Otago Wellington, New Zealand. Peter.Larsen@otago.ac.nz. | ||
| 1 Capital & Coast District Health Board, New Zealand | ||
| 2 Department of Surgery and Anaesthesia, University of Otago, Wellington, New Zealand | ||
| ORIGINAL | ||
| Abstract | ||
| Background: Frailty and functional status are established risk factors for postoperative morbidity | ||
| and mortality, but new data also suggest a link between sarcopenia and longer-term oncological | ||
| outcomes in colorectal cancer. Cross-sectional imaging is performed routinely prior to elective | ||
| resection and provides a means to measure psoas muscle cross-sectional area, which in turn is a | ||
| surrogate marker of sarcopenia. | ||
| Methods: A retrospective cohort study of patients undergoing elective surgery with curative intent | ||
| for colorectal cancer. Using automated software, psoas muscle cross-sectional area was measured | ||
| and the relationship with five-year disease-free survival was evaluated using Kaplan-Meier survival | ||
| curves. | ||
| Results: A significant relationship was found among patients with a low (below median) psoas | ||
| muscle cross-sectional area, HR 1.57 (95% CI 1.1-2.5) p=0.04. | ||
| Conclusion: This study demonstrated a potential relationship between psoas muscle cross- | ||
| sectional area and disease-free survival, highlighting the further utility of pre-operative staging | ||
| CT in predicting prognosis in patients with colorectal cancer. | ||
| Introduction | ||
| Assessing the likelihood of postoperative morbidity and mortality is critical to informing the | ||
| decision-making of both surgical teams and patients. One of the more complex tasks for clinicians | ||
| is assessing the overall physical health of the preoperative patient, or when thinking about potential | ||
| adverse outcomes, their frailty. Frailty can be described as “a state of a reduced physiologic reserve | ||
| OPEN ACCESS | associated with increased susceptibility to disability” (1). Methods for measurement of frailty or | |
| Edited by | functional status have included many variables such as the patient’s ability to perform activities | |
| A.Hussain | of daily living, cognition, falls, anaemia, weight loss, physical fitness, and underlying medical | |
| Submitted 30 Nov 2021 | conditions (1; 2; 3; 4; 5). One aspect of frailty is the loss of lean muscle mass, and many studies have | |
| shown that this can be used as a predictor of adverse post-surgical outcomes (4; 6; 7; 8; 9; 10; 11). | ||
| Accepted 04 Dec 2021 | A simple and reproducible method for loss of muscle mass is a measurement of the cross-sectional | |
| Citation | area of the psoas muscle in the lumbar spine (8; 9; 12). | |
| Matthew Mouat, Ashok | ||
| Gunawardene, Lisa | Colorectal cancer is the second leading cause of cancer-related deaths in New Zealand. The | |
| Sweetman, Elizabeth | incidence of colorectal cancer progressively increases with age. Over ninety percent of cases | |
| Dennett, Peter Larsen.Psoas Muscle | in New Zealand occur after the age of 50, and three-quarters of those patients are older than | |
| Cross-Sectional Area and | 65 (13). This age-related increase means that the greatest need for colorectal cancer surgery is in | |
| Outcomes Following | older patients who are also more likely to be frail, conferring a higher risk of adverse postoperative | |
| Colorectal Cancer Surgery: | outcomes. Loss of lean muscle mass in this population has been associated with poor short-term | |
| BJOSS::2021:(1);39-45 | ||
| outcomes, but not with a longer-term prognosis. To determine whether loss of mean muscle mass |
| does predict longer-term outcomes, this study examined whether measurements of psoas muscle |
| cross-sectional area in colorectal cancer surgery patients was a predictor of 5-year disease-free |
| survival. |
| Methods |
| We retrospectively collated a cohort of all patients undergoing surgery with curative intent for |
| colorectal at Wellington Hospital over the years 2010, 2011, and 2012. Baseline demographics |
| and outcomes were recorded for all patients. Disease-free survival was defined as having neither |
| recurrence nor death. Time-to-recurrence was calculated from the date of surgery to either |
| histological confirmation or clinical-radiological evidence of loco-regional or metastatic disease |
| recurrence on review at a multi-disciplinary meeting, where the date of the meeting was taken as |
| the end-point (14). Patients that were alive and without evidence of disease recurrence on 1st |
| November 2016 were censored. |
| For each patient, we accessed preoperative CT imaging which had been performed either in |
| Wellington Hospital on 16 slice Siemens or GE CT scanners or by a local private radiology provider |
| on 32 or 64 slice CT scanners. The images for these CT scans were then uploaded onto the |
| workstation for the current 320 slices Toshiba Aquilion One Genesis CT at Wellington Hospital |
| and the images were evaluated using the Toshiba workstation software. This software allowed |
| for the region of interest (ROI) measurement of both psoas muscles at the level of the inferior |
| endplate of L3 using maximum and minimum Hounsfield unit (HU) thresholds Figure 1. The range |
| of values used for measurement of psoas cross-sectional area was between +150HU and -29 |
| HU (12). Measurements were taken by a single observer, a final year diagnostic radiology trainee. |
| The ROI was defined manually using a drawing tool on the Toshiba software. Any operator error |
| that inadvertently included bone (vertebral body or osteophyte) or retroperitoneal fat within the |
| ROI was minimized by the HU threshold settings. |
| Figure 1. CT image for a representative subject at the inferior endplate of L3. The region of |
| interest was defined manually (defined here as the green line). The Toshiba software then |
| detected muscle tissue on the basis of HU threshold settings (area shaded pink), excluding |
| bone or retroperitoneal fat. |
| Measurement error was further minimized by using multi-planar reconstruction software to |
| account for curvature (anteroposterior or lateral) of the patient’s lumbar spine, to standardize |
| the level of measurement to the inferior endplate of L3. Repeat measurements were performed |
| on images for 10 subjects selected at random, with the investigator blinded to the original |
| measurement. The percentage variance between initial and repeat measurement averaged 1.7%, |
| with a maximum variance of 5.9%. |
| 40/45 |
| We took the average of left and right psoas muscle area and divided this by patient height to give | |
| total psoas muscle (TPA) area (15). Sarcopenia was defined using gender-specific cutoff points of | |
| <38.5cm2/m2 for female patientsand <54.5cm2/m2 for male patients based on an international | |
| consensus group definition (16). | |
| Statistical analysis | |
| Continuous variables are expressed as mean + standard deviation, and categorical variables are | |
| expressed as numbers (percentage). We examined disease-free survival based on quartiles and | |
| median cut-points for BMI and TPA, and those with and without sarcopenia. P values >0.05 were | |
| taken as statistically significant. Data analysis was performed using SPSS. | |
| Results | |
| During the study period, 237 patients underwent curative-intent surgery for the colorectal cancer | |
| cohort. Of this group, 218 patients had preoperative CT scans that were accessible and were | |
| included in the study. Demographic features of the patient cohort are given in Table 1. The mean | |
| age was 69, 49% were male, and 74% had colon cancer. | |
| Table 1. Demographical and clinical characteristics of the patients | |
| All (n=218) | |
| Age | 69 (12) |
| Male Gender | 108 (49%) |
| BMI | 27 (7) |
| CCI | |
| 0 | 117(54%) |
| 1 | 46 (21%) |
| 2 | 32 (15%) |
| 3+ | 23 (10%) |
| Tumour Location Colon | 161 (74%) |
| Rectum | 57 (26%) |
| Cancer Stage | |
| 1 | 37 (17%) |
| 2 | 84 (39%) |
| 3 | 87 (40%) |
| 4 | 10 (5%) |
| Adjuvant Therapy | 69 (32%) |
| The mean TPA in the cohort was 58.1 +/- 17.2 cm2/m2 and the mean BMI was 27.2 +/- 6.9 kg/m2. | |
| While there was a correlation between BMI and TPA, this relationship was relatively weak (r=0.36, | |
| p=0.0001, Pearson’s Correlation) Figure 2. There was a weak inverse relationship between TPA | |
| and age, and TPA was greater in male patients (67.9 +/- 16.1 cm2/m2 versus 47.4 +/- 11.1 cm2/m2, | |
| p=0.0001, unpaired t-test). TPA was also greater in male patients than female patients and had a | |
| weak inverse relationship with age (r=-0.22, p=0.001, Pearson’s Correlation). TPA did not differ | |
| by cancer stage, or between patients with colon or rectal cancer. | |
| Applying the consensus definition of sarcopenia to the population, 23 patients were defined as | |
| sarcopenic. This group was older than the rest of the cohort (mean age 74+/-7 versus 69+/-12, | |
| p=0.04) but did not differ from the rest of the cohort significantly by BMI. | |
| At 5 years, disease free survival in the cohort was 62%. We examined rates of disease-free | |
| survival against TPA by quartile and by median Figure 3 and observed that there was a statistical | |
| difference in outcome in the group divided by median score. Those in the lower half had a 5-year | |
| disease-free survival of 55% compared to 66% in those in the upper half, giving a hazard ratio of | |
| 41/45 | |
| Figure 2. A shows the relationship between TPA in cm2/m2 and BMI in kg/m2 (r=0.36, p=0.0001, |
| Pearson’s Correlation). B shows the relationship between age and TPA (r=-0.22, p=0.001, |
| Pearson’s Correlation). C shows the difference in TPA between male and female patients |
| (p=0.0001, unpaired t-test) |
| 1.57 (95% CI 1.1 to 2.5) associated with being in the lower half of TPA scores (p=0.04, Mantel-Cox |
| test). There was no significant difference in disease-free survival against BMI by either quartile |
| or by median Figure 4. In those with sarcopenia, we observed a 5-year disease-free survival |
| rate of 54%, compared to 62% in those nonsarcopenic. This difference was not statistically |
| significant Figure 5. |
| Figure 3. Disease free survival in the population segregated on the basis of TPA quartiles (A) |
| and by the median (B). There was a significant difference between the survival curves |
| segregated by the median, with a hazard ratio of 1.57 (95% CI 1.1 to 2.5) associated with being |
| in the lower half of TPA scores (p=0.04, Mantel-Cox test |
| Discussion |
| We have observed that low TPA is a predictor of poor 5-year disease-free survival in patients |
| with colorectal cancer and a similar trend observed in analysis by sarcopenia, but the rate of |
| sarcopenia was low and this result was not statistically significant. TPA did differ by gender, and |
| was correlated with BMI and inversely correlated with age although these were weak relationships. |
| We observed that preoperative TPA was a statistically significant predictor of 5-year disease- |
| free survival in colorectal cancer surgical patients. Patients in the high TPA group had a 66% |
| 42/45 |
| Figure 4. Disease free survival in the population segregated on the basis of BMI quartiles (A) |
| and by the median (B). There were no significant differences in survival between these groups |
| Figure 5. Disease free survival of groups with (n=23) and without (n=195) sarcopenia on the |
| basis of TPA measurement. There was no statistical difference in survival outcomes between |
| these groups |
| 5-year survival compared with 55% in the low TPA group. While TPA was related to BMI, we did |
| not observe the same association between BMI and disease-free survival, indicating that TPA |
| measurement is providing information that is not gained from simple measurement of BMI. |
| The association between TPA and outcome is consistent with the findings of multiple previous |
| studies linking low preoperative TPA to poor short-term post-surgical outcomes (4; 6; 7; 9; 11). |
| While the majority of literature examining TPA in cancer patients has focused on short-term |
| outcomes, a previous study in oesophageal cancer patients observed that low TPA was associated |
| with worse 3-year survival (17). The only other study we are aware of to examine long term |
| outcomes in colorectal cancer patients found no significant survival differences between those |
| with and without sarcopenia, however, this was in a cohort of patients who had undergone liver |
| resection for metastatic colorectal cancer, as opposed to surgery for the primary mass (7). |
| The findings of this study suggest that in addition to the previously demonstrated increased |
| likelihood of adverse short-term outcomes, patients with low TPA have reduced 5-year survival. |
| This provides additional information to clinicians and patients for the purposes of operative |
| risk stratification and informed decision-making. It also reinforces the need to optimize patient |
| resilience (reduce frailty) prior to surgery whenever possible. |
| Measurement of TPA is simple to perform and multiple studies have shown high inter-observer |
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| reliability with minimal training (9; 11; 12). Jones et al also demonstrated that a simplified two-axis |
| cross-sectional measurement significantly correlates with the measurements made using more |
| complex software, as used in this study (9). This further simplifies the quantification of TPA |
| and reduces additional software costs. The measurements take no more than a few minutes to |
| perform and could easily be included in a template report for colorectal cancer staging CT scans. |
| It is not clear what the optimal threshold for determining low TPA should be. The international |
| consensus document defines CT-based criteria for sarcopenia (16), but these come from a single |
| study examining sarcopenia in obese cancer patients (15). A variety of different thresholds have |
| been applied in the literature (9; 17; 18), and our quartile data suggest a graded risk may exist |
| across the spectrum of TPA. Routine reporting of TPA in colorectal staging CT scans would provide |
| large population data that could address how to quantify TPA. Gender and age-specific criteria |
| may be appropriate, as our data show a degree of correlation with these demographic variables. |
| The study has several limitations. The data were collected retrospectively, which may affect |
| its quality. Using only the area of the psoas muscles at the level of L3 as an indirect marker |
| of sarcopenia and therefore frailty provides an incomplete assessment of patient health and |
| functional status, and although it has been shown to correlate well with more comprehensive |
| measures of sarcopenia, the addition of more variables such as body fat (to evaluate for the |
| presence of sarcopenic obesity) may increase the predictive value (9; 15). Another limitation is |
| that while the cohort is larger than some, with 218 patients, there were only 23 patients that met |
| the criteria for sarcopenia, limiting the power of the findings for this group. The study was also |
| insufficient in size to allow for detailed analysis of subgroups based on cancer stage, although |
| TPA did not differ by this variable suggesting that our observed results were not attributable to |
| the cancer stage alone. |
| Conclusion |
| Low TPA is a predictor of reduced 5-year survival in colorectal cancer surgical patients. Mea- |
| surement of TPA on CT is reliable, quick, and easy to perform, and could be used to assist in |
| preoperative risk assessment and planning. |
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