Department of Surgery, Duke University Medical Center, 2301 Erwin Rd, Durham, NC 27710, USA.
JAMA Surg. 2013 Jun;148(6):493-8. doi: 10.1001/jamasurg.2013.695.
Although approximately 30% to 50% of patients experience a complete response after regional chemotherapy for in-transit melanoma, a subset of patients will develop rapidly progressive disease. In the current era of an expanding armamentarium, including both regional and systemic options for treating advanced melanoma, identifying perioperative factors that predict disease progression may obviate unnecessary morbidity associated with regional therapy and avoid delays in systemic therapy.
To identify patient-related clinical and pathological variables, as well as procedural factors, that correlate with disease progression.
Using a prospectively maintained database, we identified patients who either underwent first-time melphalan-based isolated limb infusion (ILI) or first-time hyperthermic isolated limb perfusion (HILP) for in-transit melanoma. Response was defined using modified Response Evaluation Criteria in Solid Tumors for cutaneous disease at 3 months after treatment. Survival analyses were performed using the Kaplan-Meier method, with the differences in survival curves compared using a log-rank test. Potential preoperative and procedural predictors of in-field progressive disease were analyzed using logistic regression.
Of the 258 patients included in the database, 215 were identified as having undergone first-time regional therapy. Of these 215 patients, 134 underwent ILI, and 81 underwent HILP.
Regional therapy (ILI or HILP).
Complete response or progressive disease.
Of 134 patients who underwent ILI, 43 (32.1%) experienced in-field progressive disease. Of 81 patients who underwent HILP, 9 (11.1%) experienced in-field progressive disease. The median survival for patients with in-field progressive disease was 20.3 months for the ILI cohort and 15.0 months for the HILP cohort. In general, patients with progressive disease were younger, with advanced-stage melanoma and increased tumor burden. Compared with patients who experienced a complete response, patients with in-field progressive disease after ILI were younger (odds ratio, 1.06 [95% CI, 0.90-0.98]; P = .002). For patients who underwent HILP, no clinically relevant preoperative predictors of in-field progressive disease were identified. Procedural variables, including chemotherapeutic dosing, degree of acidosis or base deficit achieved, and peak temperature attained, were not predictors of in-field progressive disease after ILI or HILP.
Patient, clinical, and procedural factors are unreliable predictors of in-field progressive disease after regional therapy in patients with in-transit melanoma. Defining the potential utility of molecular markers in predicting response or failure of regional therapy should be the focus of future research efforts.
尽管约有 30%至 50%的患者在接受局部化疗治疗转移性黑色素瘤后会出现完全缓解,但仍有一部分患者会出现疾病快速进展。在当前这个治疗转移性黑色素瘤的手段不断扩展的时代,包括局部和全身治疗方案,识别出与疾病进展相关的围手术期因素,可能避免与局部治疗相关的不必要的发病率,并避免延误全身治疗。
确定与疾病进展相关的患者相关的临床和病理变量以及手术因素。
我们使用前瞻性维护的数据库,确定了那些接受首次基于美法仑的孤立肢体灌注(ILI)或首次高热孤立肢体灌注(HILP)治疗转移性黑色素瘤的患者。在治疗后 3 个月,采用改良的实体瘤反应评估标准(RECIST)评估皮肤疾病的反应。使用 Kaplan-Meier 方法进行生存分析,并使用对数秩检验比较生存曲线的差异。使用逻辑回归分析对局部治疗中出现疾病进展的潜在术前和手术预测因素进行分析。
在数据库中,258 名患者中,有 215 名患者被确定为接受了首次局部治疗。在这 215 名患者中,有 134 名接受了 ILI,81 名接受了 HILP。
局部治疗(ILI 或 HILP)。
完全缓解或疾病进展。
在接受 ILI 的 134 名患者中,有 43 名(32.1%)出现了局部进展性疾病。在接受 HILP 的 81 名患者中,有 9 名(11.1%)出现了局部进展性疾病。ILI 组中出现局部进展性疾病的患者的中位生存时间为 20.3 个月,HILP 组为 15.0 个月。一般来说,出现进展性疾病的患者更年轻,且患有晚期黑色素瘤和更高的肿瘤负荷。与完全缓解的患者相比,接受 ILI 后出现局部进展性疾病的患者更年轻(比值比,1.06[95%CI,0.90-0.98];P=0.002)。对于接受 HILP 的患者,未发现与局部进展性疾病相关的有临床意义的术前预测因素。手术相关因素,包括化疗剂量、达到的酸中毒或碱缺失程度以及达到的峰值温度,均不能预测 ILI 或 HILP 后的局部进展性疾病。
在患有转移性黑色素瘤的患者中,患者、临床和手术因素不能可靠地预测局部治疗后的局部进展性疾病。确定分子标志物在预测局部治疗反应或失败方面的潜在效用,应该是未来研究工作的重点。