Skeletal Muscle Index And Ovarian Cancer Prognosis: A Meta-Analysis
Overview
In this study, a meta-analysis was carried out to determine the correlation between low skeletal muscle index (SMI) and the clinicopathological features and prognosis of patients with ovarian cancer.
Advances in the ability to predict the overall survival rate and prognosis of ovarian cancer would be beneficial in order to counsel patients better and manage their care.
Introduction
Ovarian cancer
Ovarian cancer simply put, is a malignant disease of the ovary. It is also one of the leading causes of mortality in females. Its high mortality rate is recorded in the United States as the commonest cause of death among women with gynecological tumors. This is because there are inadequate screening modalities, vague presenting symptoms, and as a result, patients present late with more advanced disease.
Skeletal muscle index (SMI) is a measure of the whole body muscle mass. It is estimated using computed tomography (CT) scans best at the third lumbar spine. Several studies have previously suggested a correlation between skeletal muscle index and the disease progression of several malignancies. These studies were based on the premise that certain malignancies in their more advanced stage result in a progressive loss of muscle mass and function, also known as sarcopenia.
With this in mind, the primary objective of this study was to determine the correlation between low skeletal muscle index and the clinicopathologic features and prognosis of patients with ovarian cancer.
Sarcopenia
Sarcopenia is a medical condition involving a progressive loss of muscle mass and functionality. Here, there is progressive muscle atrophy. Sarcopenia occurs physiologically in the elderly people as part of the aging process. It is also a consistent clinical feature of cancer malnutrition, which is seen in cancer patients with advanced stage disease. A 38.6% incidence of sarcopenia was recorded amongst 6894 cancer patients in a study review involving 35 articles.
Skeletal Muscle Index
Skeletal muscle index is used to quantify the mass and functionality of the muscle fibers. In other words, it assesses the skeletal muscle mass and confirms or rules out sarcopenia. It is measured via computed tomographic imaging (CT-scan) of the muscle, preferably over the lower L3 segment. The aim of this study was to analyze the correlation between the skeletal muscle index and the ovarian cancer disease progression.
Methods
This meta-analysis utilized a systematic literature search using three databases, which are PubMed, EMBASE and Cochrane, and was conducted on June 10, 2022. Certain keywords were used to aid in the search, and they include: skeletal muscle, ovarian cancer, ovarian malignancy, ovarian tumor and cachexia.
This literature review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA).
This meta-analysis is registered with the PROSPERO International Prospective Register of Systematic Reviews, CRD42022369501.
Inclusion Criteria
The analysis included studies written in English language, involving humans with ovarian cancer who were receiving treatment. These studies must have also demonstrated sarcopenia using skeletal muscle index with overall survival rate or chemotherapy-related toxicity as the reported outcomes.
Exclusion Criteria
Studies using computed tomography (CT) studies of the psoas muscle only, and studies that were review articles, conference abstracts or case reports were excluded. In addition, studies involving cohorts of less than five patients, or with incomplete or insufficient data were excluded.
Limitations
This analysis was limited to studies with skeletal muscle index measurements of the total skeletal muscle area including the erector spinae, the psoas, quadratus lumborum, etc. Due to the wide cutoff for assessing sarcopenia from SMI, its prevalence amongst the patients in this study had a wide range of 11.4% to 63.7%.
Study Quality Assessment
Methodological quality assessment was carried out using the Newcastle-Ottawa Scale (NOS). Here, high-quality studies have a score of 7 and above, a moderate quality study scoring between 5 and 7, and a low-quality study scoring less than 5. This scoring system was based on patient selection, study comparability and endpoint.
Results
Included Studies
- 1286 studies resulted from the comprehensive literature search medical databases.
- 81 full-text articles were considered for use this analysis based on inclusion criteria.
- 68 studies were screened out based on the exclusion criteria, leaving 13 studies to be used for this analysis.
- The 13 studies included were published between 2015 and 2022.
Patient Characteristics
- The included studies had a sample size ranging from 69 to 323 women, with a total of 1814 patients.
- Patients had a mean age range of 54.5 ± 10.5 to 66.5 ± 0.8 years, and mean body mass index (BMI) ranging from 22.3 ± 3.3 to 25.9 ± 0.5 kg/m².
- All patients in the included studies have had tumor debulking surgery, alongside adjuvant or neoadjuvant chemotherapy.
- The included studies involved SMI measurements at L3 and osteopenia which was demonstrated with a cutoff of 38.5 to 41.5 cm²/m².
The correlation between Low Skeletal Muscle Index and Body Mass Index
5 of the 13 studies assessed the correlation between low SMI and BMI.
Patients were divided into two categories; those with low SMI and those with high SMI.
Each of these groups were further divided into two based on their BMI; those with BMI less than 25 kg/m² and those with BMI greater than 25 kg/m².
Based on these studies, there was a clinically significant correlation between SMI levels and BMI values in these patients. It was demonstrated that patients with low SMI usually had lower BMI values (P<0.00001 with an OR:5.08 and 95% CI:3.54–7.30).
The correlation between Low Skeletal Muscle Index and Clinicopathological Features
Studies were reviewed to analyze the relationship between low SMI and the clinicopathological features of ovarian cancer.
The features assessed included:
- The FIGO stage of the tumor
- The histopathologic type of the tumor
- The histopathological tumor grade
- Intraoperative R0 cell reduction
It was noted that 127 patients were in stage I-II, while 638 patients were in stage III-IV cancer.
These studies demonstrated a correlation between SMI and clinicopathological features.
Low SMI was associated with advanced cancer stage, and as such, patients were less likely to achieve R0 cytoreduction.
6 included studies analyzed R0 cytoreduction in patients with low SMI, and showed that a slightly higher number with low SMI could not achieve R0 cytoreduction.
Pathological grade of the tumor was seen to have no correlation with low SMI as demonstrated in 6 studies.
Histopathologic types of ovarian cancer were also shown to have no correlation with low SMI as demonstrated in 5 studies.
The correlation between Low Skeletal Muscle Index and Chemotherapy-related Toxicity
In analysis involving 3 studies, it was demonstrated that chemotherapy-related toxicity had no correlation with low SMI in patients with ovarian cancer.
The correlation between Low Skeletal Muscle Index and Progression-Free Survival (PFS)
An analysis of 3 studies involving 424 patients showed a strong correlation between low SMI and PFS.
The correlation between Low Skeletal Muscle Index and Overall Survival (OS)
An analysis of 8 studies involving 1356 patients demonstrated that a low SMI reduced the 5-year survival rate of patients with ovarian cancer. Thus, there is a strong correlation between low SMI and lower 5-year OS rate.
Discussion
This analysis was aimed at demonstrating the correlation between CT-assessed skeletal muscle index and the clinical features and prognosis of patients with ovarian cancer.
Evidence obtained from a total of 13 studies showed that sarcopenia defined by low SMI was associated with lower PFS and OS, as well as low BMI, advanced FIGO stage and less R0 cytoreduction.
Women with low BMI, advanced FIGO stage and less R0 cytoreduction usually had poor nutritional intake and extensive disease which usually lead to sarcopenia.
Final Thoughts
This analysis suggested that CT-assessed sarcopenia at L3 was common among women with ovarian cancer, especially those with more advanced cancer stage.
It was demonstrated in this study that a low SMI is not only associated with decreased progression-free survival and overall survival, but also a decreased BMI, more advanced FIGO stage and reduced ability to achieve R0 cytoreduction. These factors lead to a poorer prognosis in patients with ovarian cancer.
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