Baratti D, Kusamura S, Cabras A D, Dileo P, Laterza B, Deraco M
Department of Surgery, National Cancer Institute, Milan, Italy.
Ann Surg Oncol. 2009 Feb;16(2):463-72. doi: 10.1245/s10434-008-0219-1. Epub 2008 Dec 12.
Improved survival has been reported for diffuse malignant peritoneal mesothelioma (DMPM) treated by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). The issue of treatment failure has never been extensively addressed. The present study assessed the failure pattern, management, and outcome of progressive DMPM following comprehensive treatment. Clinical data on 70 patients with DMPM undergoing cytoreduction and HIPEC were prospectively collected; after a median follow-up of 43 months, disease progression occurred in 38 patients. Progressive disease distribution in 13 abdominopelvic regions was analyzed. In 28 patients undergoing adequate cytoreduction (residual tumor < or =2.5 mm), clinicopathological factors correlating to disease progression in each region were investigated. Median time to progression was 9 months [95% confidence interval (CI) 1.6-35.9]. Median survival from progression was 8 months (95% CI 4-16.2). The failure pattern was categorized as peritoneal progression (n = 31), liver metastases (n = 1), abdominal lymph-node involvement (n = 2), pleural seeding (n = 4). Small bowel was the single site most commonly involved (n = 27). Residual tumor < or =2.5 mm (versus no visible) was the only independent risk factor for disease progression in epigastric region (P = 0.047), upper ileum (P = 0.029), upper jejunum (P = 0.034), and lower jejunum (P = 0.002). Progressive disease was treated with second HIPEC in 3 patients, debulking in 4, systemic chemotherapy in 16, and supportive care in 15. At multivariate analysis, time to progression <9 months (P = 0.009), poor performance status (P = 0.005), and supportive care (P = 0.003) correlated to reduced survival from progression. We conclude that minimal residual disease, compared with macroscopically complete cytoreduction, correlated to failure in critical anatomical areas, suggesting the need for maximal cytoreductive surgical efforts. In selected patients, aggressive management of progressive disease seems worthwhile.
据报道，经细胞减灭术和腹腔内热灌注化疗（HIPEC）治疗的弥漫性恶性腹膜间皮瘤（DMPM）患者生存率有所提高。治疗失败的问题从未得到广泛探讨。本研究评估了综合治疗后进展期DMPM的失败模式、处理方法及结局。前瞻性收集了70例行细胞减灭术和HIPEC的DMPM患者的临床资料；中位随访43个月后，38例患者出现疾病进展。分析了13个腹盆腔区域的疾病进展分布情况。对28例行充分细胞减灭术（残留肿瘤≤2.5 mm）的患者，研究了各区域与疾病进展相关的临床病理因素。进展的中位时间为9个月[95%置信区间（CI）1.6 - 35.9]。进展后的中位生存期为8个月（95% CI 4 - 16.2）。失败模式分为腹膜进展（n = 31）、肝转移（n = 1）、腹部淋巴结受累（n = 2）、胸膜播散（n = 4）。小肠是最常受累的单一部位（n = 27）。残留肿瘤≤2.5 mm（相对于无可见残留）是上腹部区域（P = 0.047）、回肠上段（P = 0.029）、空肠上段（P = 0.034）和空肠下段（P = 0.002）疾病进展的唯一独立危险因素。3例进展期疾病患者接受了第二次HIPEC治疗，4例接受了减瘤手术，16例接受了全身化疗，15例接受了支持治疗。多因素分析显示，进展时间<9个月（P = 0.009）、体能状态差（P = 0.005）和支持治疗（P = 0.003）与进展后的生存期缩短相关。我们得出结论，与宏观上完全细胞减灭术相比，最小残留病灶与关键解剖区域的治疗失败相关，这表明需要最大程度地进行细胞减灭性手术。在部分患者中，积极处理进展期疾病似乎是值得的。
