Date Published: October 10, 2018
Publisher: Public Library of Science
Author(s): Panita Limpawattana, Daris Theerakulpisut, Kosin Wirasorn, Aumkhae Sookprasert, Narong Khuntikeo, Jarin Chindaprasirt, Pankaj K Singh.
Low skeletal muscle mass is frequently observed in cancer patients and is known to be a poor prognostic factor for survival outcomes. The purposes of our study were to determine the prevalence of sarcopenia and its relation to mortality in biliary tract cancer. Body composition measurements (skeletal muscle index, total fat mass, bone mineral content) were evaluated by using dual-energy x-ray absorptiometry in 75 biliary tract cancer patients before chemotherapy. Muscle strength was measured by handgrip strength and gait speed. Overall survival and its associated factors were determined. The mean appendicular muscle mass was 17.8±2.7 kg in men and 14.0±2.1 kg in women (p < 0.05). Sarcopenia was diagnosed in 46 patients (61.3%) and higher proportion of men was classified as sarcopenia than women (69.0% vs 35.3%, p < 0.05). Multivariable analysis adjusted for chemotherapy regimen and age revealed that high appendicular muscle mass independently predicted better survival outcomes (HR 0.40; 95% CI, 0.18 to 0.88; p = 0.023). Sarcopenia is common in biliary tract cancer patients and low appendicular muscle mass was associated with poor survival outcome.
Biliary tract cancer is common in Thailand, but the prevalence is increasing worldwide [1, 2]. Even though there is a screening program, most of the tumors detected are in advanced stage . Most BTC patients are not eligible for curative resection resulting in a dismal prognosis, with a median survival of 8–12 months despite palliative chemotherapy . The pooled analysis of two randomized phase III trials showed the superior survival with cisplatin-gemcitabine group with a median survival of 11.6 months compared with 8.0 months in gemcitabine alone group . However, the response rate was only 19% in the bile duct tumor subgroup and there were nearly 70% of patients suffered from grade 3 or 4 adverse events . Unquestionably, we have restricted access to predict who will get the largest survival benefit prior to the treatment.
This single-center, prospective study included patients with BTC undergoing first-line chemotherapy with fluoropyrimidine or gemcitabine-based regimen from January 2016 to September 2017 in Srinagarind Hospital, Khon Kaen University. Inclusion criteria were age of at least 18 years old, histological or cytological proven biliary tract cancer, ECOG performance status of 0–1, and adequate organ function. Patients were excluded if they had a second malignancy, had other active medical illnesses, were unable to undergo the dual-energy X-ray absorptiometry (DXA), or had conditions that would affect the DXA results. Gemcitabine was administered weekly with either cisplatin or carboplatin as physician’s choice (8 cycles of 1000 mg/m2 day 1, 8 per 3 weeks) i.e., a total of 24 weeks. Another regimen was platinum combined with 5-fluorouracil 1000 mg/m2 every 3 weeks i.e., a total of 24 weeks. This study was approved by the Khon Kaen University Ethics Committee as instituted by the Declaration of Helsinki (Number HE581333). Written informed consents were obtained from all patients.
A total number of 75 biliary tract cancer patients were included, of which 35 were intrahepatic tumor and 38 were either perihilar or distal type. The median age was 57 years (range, 43–77 years); 58 patients (77.3%) were men (Table 1). In total, 20 patients (27%) received less than half of planned chemotherapy, resulting in a median of 4 cycles of chemotherapy in the entire cohort. Sixty patients (80%) were treated with platinum/5-fluorouracil while 15 patients (20%) underwent treatment with platinum/gemcitabine.
To our knowledge, this is one of the first studies exploring the relationship between body composition and survival in biliary tract cancer. We noted several findings of interest. First, in this cohort, sarcopenia at diagnosis was 61.3% and skeletal muscle mass depletion at diagnosis predicted worse survival for advanced biliary tract cancer patients.
Sarcopenia was common in BTC even in good performance status patients. Low muscle mass was associated with advanced age, female gender, and low BMI and it was an independent prognostic factor for survival. Since there is no molecular biomarker that predict outcome of chemotherapy, body composition should be considered as a potential marker. As such, we propose that interventions to modify skeletal muscle wasting may result in better outcome before and during chemotherapy.