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 Table of Contents  
Year : 2019  |  Volume : 8  |  Issue : 3  |  Page : 69-73

The influence of neoadjuvant chemoradiotherapy on muscle mass in patients with rectal cancer

Division of GastroIntestinal Surgery, Wirral University Teaching Hospital, UK

Date of Submission31-May-2019
Date of Decision23-Jul-2019
Date of Acceptance15-Sep-2019
Date of Web Publication24-Oct-2019

Correspondence Address:
Mr. Gregory Simpson
Division of Gastrointestinal Surgery, Wirral University Teaching Hospital
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/WJCS.WJCS_12_19

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Background: The psoas major muscle accurately represents overall skeletal muscle mass. The skeletal muscle mass volume is related to outcomes in multiple surgical procedures including colorectal cancer. However, neoadjuvant chemoradiotherapy for rectal cancer may adversely affect muscle mass. Objective: Assess the effect of neoadjuvant chemoradiotherapy on muscle mass in rectal cancer patients as well as on outcomes. Design: Retrospective study. Setting: A large UK District General Hospital. Patients and Methods: Analysis of all rectal cancer patients between 2014 and 2017. Psoas major was measured at the L3 level using pre- and post-neoadjuvant chemoradiotherapy images. Psoas major to L3 cross-sectional area (PML3) was calculated for each patient. Main Outcome Measures: 30-day and 90-day mortality, inpatient stay, and postoperative complications. Sample Size: One hundred and twenty-one rectal cancer patients. Results: Median age was 72 years (IQR: 64–78 years). Male:Female ratio was 82:39. 30-day mortality was 0%, and 90-day mortality was 0.83%. Sixty-one patients underwent neoadjuvant chemoradiotherapy (50.4%). Thirty-one patients underwent abdominoperineal excision of the rectum (APER) (25.6%), 1 underwent proctocolectomy (0.83%), 1 underwent completion proctectomy (0.83%), and 88 patients underwent anterior resection (72.7%). Significant muscle loss occurred during neoadjuvant therapy (median loss: 25.9%, IQR: 12.6–36.8%) (P < 0.0001). No correlation was observed between PML3 and inpatient stay. Patients with PML3 in the lowest quartile had a chest infection rate of 11.1% and a complication rate of 37.1% rather than 6.2% and 26.8%, respectively, for those in the upper quartiles. Anastomotic leak rate in the PML3 lowest quartile was 23.5% compared to 11.4% in patients in the upper quartiles. Conclusion: Patients who received neoadjuvant chemoradiotherapy had a significant reduction in muscle mass. Muscle mass loss can be overcome with a prehabilitation program that may reduce muscle loss and improve outcomes. Limitations: Due to a low event-rate of anastomotic leak, it is difficult to show statistical significance with a patient cohort of this size. Conflict of Interest: None.

Keywords: Muscle mass, neoadjuvant chemoradiotherapy, rectal cancer, sarcopenia

How to cite this article:
Simpson G, Marks T, Blacker S, Magee C, Wilson J. The influence of neoadjuvant chemoradiotherapy on muscle mass in patients with rectal cancer. World J Colorectal Surg 2019;8:69-73

How to cite this URL:
Simpson G, Marks T, Blacker S, Magee C, Wilson J. The influence of neoadjuvant chemoradiotherapy on muscle mass in patients with rectal cancer. World J Colorectal Surg [serial online] 2019 [cited 2020 Aug 5];8:69-73. Available from: http://www.wjcs.us.com/text.asp?2019/8/3/69/269880

  Introduction Top

Colorectal cancer is a leading cause of cancer-related deaths worldwide. Moreover, the management of locally advanced rectal cancer remains a challenge. Conventionally, rectal cancer is treated using a multimodal approach involving surgery, radiotherapy, and chemotherapy; however, the timing of surgery, neoadjuvant protocols, and the surgical technique used (inter alia, open, robotic, laparoscopic, and TaTME) are still debatable.

Decisions regarding surgical units are affected by complex, older patients, and excess information regarding tumor-specific molecular biology. However, there is an increasing interest in patient-related factors that can influence the surgical outcomes, of which “prehabilitation” has shown promise in colorectal and other gastrointestinal cancers.

Sarcopenia is the age-related progressive loss of muscle mass and strength. Sarcopenia and skeletal muscle mass are related to outcome in multiple specialties, including colorectal cancer[1],[2],[3],[4],[5] and emergency surgery,[6] though no consensus is available regarding a cut-off value to define sarcopenia.

Sarcopenia is prevalent among elderly people diagnosed with colorectal cancer.[7] Lower levels of skeletal muscle mass are associated with increased hospital stay and re-admission,[8],[9] poorer survival, and increased rates of postoperative morbidity,[10],[11],[12],[13] requiring routine preoperative sarcopenia and muscle-mass assessment.[14] Patients who experience deterioration in muscle mass have increased morbidity and mortality.[15],[16],[17]

The psoas muscle measured using CT is a simple and reliable measure for overall skeletal muscle mass and sarcopenia measurement.[4],[18],[19],[20] There are multiple methods of muscle mass measurement including MRI, DEXA, CT, ultrasound, bioelectric impedance, anthropometric analysis, and biochemical markers;[21],[22],[23] however, routine use of CT imaging during preoperative assessment makes this method easy to use, with no additional cost.

Rectal cancer patients undergoing neoadjuvant chemoradiotherapy have readily available pre and posttreatment CT images, making them an excellent group to investigate muscle mass.

In this study, we aim to investigate the prevalence of sarcopenia in a UK population of patients undergoing surgical intervention for rectal cancer and the impact of neoadjuvant chemotherapy on skeletal muscle mass and postoperative outcomes.

  Patients and Methods Top

In this study, we included all patients who underwent surgical resection for rectal cancer with curative intent who were identified from a prospectively maintained database of patients diagnosed between 2014 and 2017 at a single center.

Demographic, histological, clinical, biochemical, and operative data were collected and analyzed by accessing patient clinical notes and electronic records.

Outcome measures were inpatient, 30-day, and 90-day mortality, length of stay (LOS), postoperative chest infection, anastomotic leak, and postoperative complications.

Radiological analysis

All patients underwent staging CT-imaging at the same center using the same CT scanning equipment. Because the psoas major muscle significantly predicts whole-body muscle mass,[24],[25] it was utilized as a marker for whole-body muscle mass.

Psoas major and lumbar vertebral body cross-sectional area were calculated at the level of the third lumbar vertebral body inferior end plate. All patients included in this study had preoperative CT images at the level of the L3 inferior end plate analyzed. PML3 ratios were calculated preoperatively for each patient. In patients who underwent neoadjuvant chemoradiotherapy, images at the level of the L3 inferior end plate were analyzed before commencement and after completion of neoadjuvant chemoradiotherapy to assess the effect of neoadjuvant chemoradiotherapy on PML3 as a representation of muscle mass loss.

Psoas major was normalized to total body size using the cross-sectional area of the corresponding L3 vertebrae as a marker of body size.

Area of interest was marked by two trained investigators, and calculated in millimeter squared (Cerner RadNet Software, MO, USA). Psoas major to lumbar vertebral body ratio (PML3 ratio) was calculated for each patient. In addition, psoas major density was calculated using mean Hounsfield units for the cross-sectional area of the psoas major at the level of the inferior end plate of L3.

Statistical analysis

Statistical analysis was performed using GraphPad

(San Diego, Ca, USA).

Mann–Whitney U test was used to compare PML3 values in patients before commencement of neoadjuvant chemoradiotherapy with PML3 values after completion of NACRT. Spearman's rank correlation coefficient was utilized to assess correlation. Categorical data were analyzed using the Chi-square test. Analysis included comparison of those patients in the bottom quartile with respect to PML3 ratio compared to patients in the upper third quartiles.

  Results Top

Baseline characteristics

[Table 1] demonstrates the baseline characteristics of patients. One hundred and twenty-one patients (39 female and 82 male) underwent surgery for rectal cancer between 2014 and 2017. Median age was 72 years (Interquartile range, IQR: 64–78 years). The 30-day mortality rate was 0%. One patient died within 90 days postoperatively (0.83%). The median inpatient stay was 8 days (IQR: 6–11.75 days).
Table 1: Baseline characteristics

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Surgical approach

[Table 2] shows the operative approach. [Figure 1] shows the operative procedures performed.
Table 2: Surgical approach

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Figure 1: Procedures performed

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Tumor characteristics

See [Table 3].
Table 3: Tumor characteristics

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Patients receiving neoadjuvant chemoradiotherapy vs. patients who received no neoadjuvant therapy

[Table 4] shows the outcomes of patients who received neoadjuvant chemoradiotherapy compared to those who did not receive it.
Table 4: Patients receiving neoadjuvant chemoradiotherapy vs patients not receiving neoadjuvant chemoradiotherapy

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PML3 ratio during neoadjuvant chemoradiotherapy

The median baseline PML3 ratio for all patients was 0.61 (interquartile range IQR: 0.49–0.76).

In patients who underwent neoadjuvant chemoradiotherapy, baseline median PML3 ratio before surgical or neoadjuvant treatment was 0.66 (IQR: 0.51–0.81). However, following neoadjuvant chemoradiotherapy, PML3 ratio significantly decreased in comparison to pretreatment levels, with a median PML3 ratio of 0.48 (IQR: 0.38–0.56, P < 0.0001 MWU). [Figure 2] and [Figure 3] show the trend in PML3 ratios in patients before and after neoadjuvant chemoradiotherapy, respectively.
Figure 2: Pre-neoadjuvant chemoradiotherapy PML3 vs. Post-Neoadjuvant chemoradiotherapy PML3

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Figure 3: Box and whisker plot of PML3: pre vs. post neoadjuvant chemoradiotherapy

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PML3 as a predictor of outcome

Twenty-seven patients were identified with a PML3 of <0.42 (the lowest quartile).

Patients with a PML3 of <0.42 had a higher incidence of chest infection and overall complications (11% and 37%, respectively) compared to those with a PML3 >0.42 (6% and 27%, respectively), although this trend of higher complications in patients with lower PML3 values did not reach statistical significance.

For inpatients who underwent anterior resection, there was no correlation between PML3 ratio and duration of inpatient stay. Patients who underwent anterior resection with a preoperative PML3 >0.42 had a rate of anastomotic leak of 11.4% (8 of 70 patients) compared to patients with PML3 <0.42 who had a rate of anastomotic leak of 23.5% (4 of 17 patients). Similar rates of complications (PML3 <0.42 = 29.4% vs PML3 > 0.42 = 28.5%) and of chest infection (PML3 <0.42 = 5.9% vs PML3 >0.42 = 4.3%) were seen in both groups. [Table 5] demonstrates complications in this patient cohort.
Table 5: Postoperative complications (Clavien-Dindo Classification)

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In patients who underwent abdominoperineal resection of the rectum, there was no correlation between duration of inpatient stay and PML3 ratio. Additionally, no significant difference was seen in complication rates in this patient group.

PML3 Ratio and outcome after neoadjuvant chemoradiotherapy

In patients who experienced a 25% or greater reduction in PML3, the complication rate was greater than those who did not experience this decline (45.1% vs 34.6%, respectively). Rates of chest infection were similar between those who had a 25% decline in PML3 versus those who did not (6.7% vs. 11.1%, respectively), similarly median inpatient stay was similar between these two groups (9 days vs 8 days).

  Conclusion Top

The importance of skeletal muscle mass in a surgical patient has been described in numerous surgical subspecialties.[26],[27],[28],[29] However, worse outcomes have been encountered only in a sarcopenic patient. These findings have been mirrored in colorectal surgery, where sarcopenia was associated with increased morbidity, mortality, longer inpatient stay, and increased hospital re-admission rates.[8],[9],[10],[11],[12] The psoas muscle has proven to be an accurate marker of total body muscle mass,[24],[25] and it is easily quantified in a CRC population owing to the use of CT imaging as a staging modality. Multiple strategies to normalize the psoas major area to stature are described including height, body surface area, and cross-sectional area of the corresponding lumbar vertebrae;[30] however, we used normalization to L3 cross-sectional area as it allows a simple assessment of whole-body muscle mass from a single CT image.

We found out that muscle function and strength, in addition to muscle size, were important factors. Further research will involve understanding the significance of muscle function and figuring out the best method of quantification of muscle function for patients undergoing surgery for CRC.[31],[32]

Our data demonstrated higher rates of postoperative complications and anastomotic leak. However, our findings failed to achieve statistical significance. This may be due to insufficient patient numbers in our dataset. Furthermore, statistical significance is often not reached with outcomes measures, such as anastomotic leak, with a low event rate.

The principal finding in our study is that patients who undergo neoadjuvant chemoradiotherapy before surgery experience a significant reduction in skeletal muscle mass represented by a reduction in PML3 ratio. Studies among patients undergoing palliative chemotherapy have demonstrated that loss of muscle mass during oncologic treatment can be reversible.[33] The loss of skeletal muscle mass during neoadjuvant therapy could potentially be ameliorated by a prehabilitation program that incorporates exercise programs and nutritional support. This will reduce the possibility of poor outcome associated with preoperative sarcopenia and poor muscle mass. Rectal cancer treatment provides a unique chance to enhance patients, skeletal muscle mass and combat the effects of sarcopenia due to the use of neoadjuvant chemoradiotherapy, which provides a 3- to 4-month window of opportunity.

Furthermore, we aim to work in rectal cancer and sarcopenia by implementing a prehabilitation program. The program will assess if the patients can avoid the negative effects of neoadjuvant chemoradiotherapy on skeletal muscle mass and improve outcomes of patients undergoing surgery for rectal cancer.

Research involving human participants and/or animals

For this type of study, formal consent is not required.

Informed consent

Institutional review board and informed consent were obtained from all individual participants included in the study.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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