Outcomes of Sarcopenia Treatment for Malignant Bone and Soft Tissue Tumors in Elderly Patients
In 2021, the total Japanese population was 125 million, which included 36 and 18 million individuals in the ≥65 and ≥75 years’ age groups. The population of aging patients is increasing (1), and accordingly, the incidence of sarcopenia among patients has increased. Japan has a higher proportion of the elderly population in its so-called “super aging society,” and the proportion of the population ≥65 years was estimated to be 28.9% in 2021 (1).
To our knowledge, few studies have evaluated the relationship between sarcopenia and malignant bone and soft tissue tumors (4). This study aimed to investigate the impact of sarcopenia on the treatment outcomes of malignant bone and soft tissue tumors in elderly patients.
Patients and Methods
The following clinical data were obtained from the medical records: age, body mass index (BMI), Eastern Cooperative Oncology Group performance status (PS), tumor size, primary tumor site, tumor grade [based on the French Federation of Cancer Centers Sarcoma Group (FNCLCC) grading system (6) for soft tissue sarcomas (FNCLCC grade 2/3 and grade 1 tumors are considered “high grade” and “low grade”, respectively) and the grading system described by Broders (7) for bone tumors (grade ¾ and grade 1/2 tumours are considered “high grade” and “low grade”, respectively)]; laboratory values of albumin, hemoglobin, C-reactive protein (CRP), the neutrophil/lymphocyte ratio (NLR) (8), the platelet/lymphocyte ratio (PLR) (8), and the Modified Glasgow Prognostic Score (mGPS) (9); and whether chemotherapy was administered. We extracted data on the clinical perioperative information, including the operation time, blood loss, drainage interval, length of hospital stay, and hospital cost. Information about local recurrence, overall survival (OS), and outcomes were obtained from the patients' medical records. The preoperative status of the patients was evaluated using the following methods: the mGPS was calculated based on preoperative data (CRP >0.5 mg/l and albumin <3.5 g/dl: 2 points; CRP >0.5 mg/l or albumin <3.5 g/dl: 1 point; and CRP ≤0.5 mg/l and albumin ≥3.5 g/dl: 0 point); the score ranged from 0 to 2 points, where a higher score (mGPS 1 and 2 points) was associated with high risk of postoperative mortality (9). We evaluated NLR (neutrophils/lymphocytes in mm3/mm3), and PLR (platelets/lymphocytes in μl/mm3). Postoperative complications were recorded and defined as grade ≥3 based on the Common Terminology Criteria for Adverse Events (CTCAE v5.0; National Cancer Institute). We compared these factors between the sarcopenia and no sarcopenia groups.
This comparative retrospective study was approved by the Institutional Review Board (IRB) of our university and informed consent from the study participants was obtained.
Table I shows a comparison of the clinical and surgical characteristics of the sarcopenia and no-sarcopenia groups. Of the 76 patients treated for malignant bone and soft tissue tumours, 41 (54%) had sarcopenia, whereas 35 (46%) did not have sarcopenia. The median follow-up duration was 26.2 months (range=3.6-145.9 months) and 44.5 months (range=4.3-105.8 months) in the sarcopenia and no-sarcopenia groups, respectively. Histological subtyping of tumors in the overall study cohort showed the following distribution of tumor types: undifferentiated pleomorphic sarcoma (n=17; 22%), myxofibrosarcoma (n=11; 14%), dedifferentiated liposarcoma (n=8; 11%), myxoid liposarcoma (n=6; 8%), chordoma (n=2; 3%), osteosarcoma (n=2; 3%), and the others (chondrosarcoma, leiomyosarcoma, solitary fibrous tumor). The median (range) tumor size was 7.5 cm (range=1.5-25 cm) and 6.5 cm (range=2-20 cm) in the sarcopenia and no-sarcopenia groups, respectively. The majority of primary tumor sites was in the lower extremity (n=41; 54%). Tumour staging was based on the American Joint Committee Cancer (AJCC) 8th edition (10). The clinical stage of patients with soft tissue sarcoma was Stage IA (n=1; 1%), Stage IB (n=1; 1%), Stage II (n=20; 27%), Stage IIIA (n=18; 24%), Stage IIB (n=19; 25%), and Stage IV (n=6; 8%). The clinical stage of patients with bone sarcoma was Stage IA (n=2; 3%), Stage IB (n=1; 1%), Stage IIA (n=1; 1%), Stage IIB (n=1; 1%), Stage III (n=3; 5%), and Stage IV (n=2; 3%).
In the sarcopenia and no-sarcopenia groups, 21 (51%) and 20 (57%) patients, respectively, had primary tumor sites in the lower extremity. In addition, there were 37 and 33 patients with high-grade tumors in the sarcopenia and no-sarcopenia groups, respectively.
There was no significant difference in age, BMI, PS, albumin, mGPS, PLR, operation time, total blood loss, drainage interval, and median length of hospital stay between the sarcopenia and no-sarcopenia groups.
In total, 69 patients received surgical treatment, of whom 83% had R0 resections (negative resection margins without tumours in the linked resection margin), 14% had R1 resections (microscopic residual tumour at the resection margin), and 3% had R2 resections (macroscopic residual tumour at the resection margin).
The average length of hospital stay was 34 and 33 days in the sarcopenia and no-sarcopenia groups, respectively. The mean hospital cost was USD19,523 and 16,285 in the sarcopenia and no-sarcopenia groups, respectively, and there was no significant between-group difference (
At the last follow-up, the status was as follows: clinical disease-free (CDF), 30 (39%); no evidence of disease (NED), 15 (20%); alive with disease (AWD), 18 (24%); died of disease (DOD), 11 (14%); and died of other disease (DOOD), 2 (3%).
In the sarcopenia and no-sarcopenia groups, 11 (27%) and 3 (9%) patients had local recurrences, respectively. Based on the local recurrence rate, six and two patients with malignant soft tissue tumours and malignant bone tumours, respectively, were excluded due to advanced stage cancer (Stage IV). The recurrence-free survival rates at 1, 2, and 5 years in the sarcopenia and no-sarcopenia groups were 76%, 68%, and 68%; and 93%, 93%, and 89%, respectively. The incidence of local recurrence was significantly higher in the sarcopenia group than in the no-sarcopenia group (
Irwin Rosenberg used “sarcopenia” to refer to age-related loss of skeletal muscle mass (2). For the diagnosis of sarcopenia, a single cross-sectional area at the level of the third or fourth lumbar vertebra on an axial CT is used as the gold standard imaging site. This is because CT is considered to be a very precise imaging tool that can distinguish fat from other soft tissues of the body, and a single abdominal cross-sectional image has been strongly related to the total skeletal muscle in a study (3). Calculation of the area of skeletal muscle mass using CT has been undertaken using various methods (3,4,6). Peng et al. investigated 259 patients who underwent liver resection for colorectal liver metastases (CRLM) by measuring TPA from CT images, and defined sarcopenia as a TPA of ≤5.0 cm2/m2, adjusted for height, as the most relevant cut-off value (6). In this study, we applied this definition of sarcopenia as a TPA of <5.0 cm2/m2, adjusted for height (cm2/m2). In this study, 51 out of 76 patients were assigned to the sarcopenia group.
Several treatment-related problems can occur in sarcopenic patients. Sarcopenia has a significantly negative effect on chemotherapy for patients with various cancers (11) and anticancer drugs induced frequent dose-limiting toxicities (DLT), such as diarrhoea and acute vascular toxicity, in patients with cancers (11). Furthermore, sarcopenia was associated with a poor survival rate and enhanced postoperative complications in patients with various types of cancer (3,11).
The preoperative status of patients was evaluated using the mGPS, NLR, PLR. The NLR is a ratio of the absolute number of neutrophils, which have a well-known protumorigenic role, and the absolute number of lymphocytes, which instead have an antitumorigenic role (8). High NLR was associated with worse outcomes in patients with cervical cancer (12) and gastric cancers with regard to OS and cancer specific survival (13). With regard to the indicators of the preoperative status of patients, such as mGPS, NLR, and PLR, we hypothesized that sarcopenia influences the immune system against malignant bone and soft tissue tumors. The results showed no significant differences between the sarcopenia and no-sarcopenia groups with regard to NLR, but there was a trend toward a higher NLR value in the sarcopenia group compared to the no-sarcopenia group (
With regard to malignant bone and soft tissue tumours, obtaining an adequate wide margin is essential for local control with surgical treatment (14). However, the sarcopenia group had a higher local recurrence rate than the no-sarcopenia group in this study, despite adequate wide resection and the absence of a statistically significant difference in surgical margins between the sarcopenia and no-sarcopenia groups (
The most interesting finding of this study was the extent of change in the TPA/m2 from the initial visit to the final follow-up. Regardless of the presence of sarcopenia, all patients experienced a significant postoperative decrease in skeletal muscle mass. The TPA/m2 of the patients with lower extremity tumors in the no-sarcopenia group had significantly decreased at the final follow-up (
This study has several limitations. First, the follow-up period was short; therefore, the OS and disease-free survival could have been underestimated. Second, the number of patients was small. Third, other parameters of sarcopenia, such as walking speed, grip strength, and levels of exhaustion, were not investigated in this study. Fourth, this study was a retrospective comparative study that was conducted in a single institution.
We investigated the impact of sarcopenia on surgical outcomes of malignant bone and soft tissue tumors based on a single-centre Japanese institutional experience with elderly patients. The incidence of postoperative complications and local recurrence was higher in the sarcopenia group compared to that in the no-sarcopenia group. A preoperative high NLR might possibly be a risk predictor for postoperative complications. This study demonstrated that the amount of skeletal muscle mass greatly decreased in patients aged 65 and older who underwent surgery.
Conflicts of Interest
The Authors have no conflicts of interest to declare regarding this study.
Yoshitaka Ban designed this study, analysed the data, prepared the figures, and wrote the original draft manuscript. All Authors reviewed the manuscript.