晚期卵巢癌惡質病之檢視

Cachexia in advanced ovarian cancer

晚期卵巢癌患者常合併惡質病（cachexia），此為一種由慢性發炎、代謝重編程與骨骼肌耗損所共同驅動之多因素全身性症候群，臨床表現包括體重下降、肌肉質量流失、脂肪組織減少及食慾不振。與單純營養不良不同，惡質病之核心病理在於進行性骨骼肌耗損，其發生涉及腫瘤負荷、宿主發炎反應及能量代謝異常之複雜交互作用，且無法單純藉由增加營養攝取加以逆轉。在分子層面，IL-6、TNF-α等促發炎細胞因子可活化STAT3與NF-κB訊號路徑，促使泛素蛋白酶體系統與自噬溶酶體系統活化，加速肌肉蛋白質分解；與此同時，IGF-1／AKT／mTOR訊號軸受到抑制，蛋白質合成能力下降，形成「分解增加、合成不足」之代謝失衡。TGF-β家族成員（包括Myostatin與Activin A）亦透過SMAD2／3訊號路徑抑制肌肉生長，進一步加劇肌肉萎縮。此外，脂肪組織棕色化與靜息能量消耗增加，被認為是惡質病發展之早期重要事件。臨床研究方面，肌少症已被確立為晚期漿液性卵巢癌之獨立不良預後因子，其預測價值更優於體重或BMI。Megestrol acetate等藥物雖可改善食慾與整體體重，但對瘦體重（lean body mass）之保存效果有限，顯示單一治療策略難以全面逆轉惡質病之多重病理機轉。未來治療方向應整合抗發炎、代謝調節與肌肉保護等多重介入策略，並結合影像學評估與分子標記進行個體化風險分層，以期改善患者之存活率與生活品質。

Cachexia is a prevalent and clinically consequential complication in patients with advanced ovarian cancer. Unlike simple malnutrition, cachexia is a multifactorial systemic syndrome characterized by progressive skeletal muscle wasting driven by chronic inflammation and metabolic dysregulation―changes that cannot be fully reversed by nutritional supplementation alone. Proinflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), activate catabolic signaling cascades involving STAT3 and NF-κB, leading to enhanced muscle protein degradation through the ubi-quitin―proteasome and autophagy―lysosome systems. Simultaneously, sup-pression of the IGF-1/AKT/mTOR axis impairs protein synthesis, creating a state of metabolic imbalance. Members of the TGF-βsuperfamily―namely Myostatin and Activin A―further inhibit muscle growth via SMAD2/3 signal-ing. Adipose tissue browning and increased resting energy expenditure repre-sent early systemic manifestations of this process. Clinically, sarcopenia has emerged as an independent adverse prognostic factor in advanced ovarian cancer, offering superior risk stratification over body weight or body mass index. Although agents such as megestrol acetate may improve appetite and overall body weight, their benefit on lean body mass remains limited. A multi-modal therapeutic approach integrating anti-inflammatory, metabolic, and muscle-preserving interventions―guided by imaging-based muscle assessment and molecular biomarkers―is therefore essential to improve patient survival and quality of life.