Wendtner Clemens-M, Abdel-Rahman Sultan, Krych Matthäus, Baumert Jens, Lindner Lars H, Baur Andrea, Hiddemann Wolfgang, Issels Rolf D
Department of Internal Medicine III, Diagnostic Radiology and Institute for Biostatistics and Epidemiology, Klinikum Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany.
J Clin Oncol. 2002 Jul 15;20(14):3156-64. doi: 10.1200/JCO.2002.07.146.
To determine the efficacy of neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for local tumor control and overall survival (OS) in adult patients with retroperitoneal or visceral (RP/V) high-risk soft tissue sarcomas (HR-STS).
From 1991 to 1997, 58 patients with HR-STS at RP/V sites were prospectively treated with four cycles of etoposide, ifosfamide, and doxorubicin combined with RHT followed by surgery, adjuvant chemotherapy, and radiation.
Objective response rate assessable in 40 patients was 13% (five partial responses). Including minor responses (n = 8), the radiographic response rate was 33%. The pathologic response rate assessable in 26 patients after surgical resection was 42%. Median OS was 31 months. At a median observation time of 74 months, 5-year probability of local failure-free survival (LFFS), distant metastasis-free survival, event-free survival, and OS were 25%, 51%, 20%, and 32%, respectively. Averaged minimum temperatures (T(min)) and time-averaged temperatures achieved in 50% (T(50)) and 90% (T(90)) of all measured tumor sites differed significantly between responders and nonresponders (T(min), 39.3 degrees C v 38.0 degrees C; P =.002; T(50), 40.9 degrees C v 40.3 degrees C; P =.038; T(90), 40.1 degrees C v 39.3 degrees C; P =.017). At 5-year follow-up, probability of LFFS (59% v 0%; P <.001) and OS (60% v 10%; P <.001) was significantly in favor of patients responding to neoadjuvant thermochemotherapy.
Response to neoadjuvant chemotherapy combined with RHT is predictive for an improved local tumor control resulting in a long-term survival benefit for patients with HR-STS at unfavorable RP/V sites; however, the impact of RHT has to be defined in a randomized phase III trial.
确定新辅助化疗联合区域热疗(RHT)对成人腹膜后或内脏(RP/V)高危软组织肉瘤(HR-STS)患者局部肿瘤控制和总生存期(OS)的疗效。
1991年至1997年,58例RP/V部位HR-STS患者前瞻性接受了四个周期的依托泊苷、异环磷酰胺和阿霉素联合RHT治疗,随后进行手术、辅助化疗和放疗。
40例患者可评估的客观缓解率为13%(5例部分缓解)。包括轻微缓解(n = 8),影像学缓解率为33%。手术切除后26例患者可评估的病理缓解率为42%。中位OS为31个月。在中位观察时间74个月时,5年局部无复发生存率(LFFS)、无远处转移生存率、无事件生存率和OS分别为25%、51%、20%和32%。反应者和无反应者在所有测量肿瘤部位的平均最低温度(T(min))以及达到50%(T(50))和90%(T(90))的时间平均温度存在显著差异(T(min),39.3℃对38.0℃;P = 0.002;T(50),40.9℃对40.3℃;P = 0.038;T(90),40.1℃对39.3℃;P = 0.017)。在5年随访时,LFFS概率(59%对0%;P < 0.001)和OS概率(60%对10%;P < 0.001)显著有利于对新辅助热化疗有反应的患者。
对新辅助化疗联合RHT的反应可预测局部肿瘤控制的改善,从而为处于不利RP/V部位的HR-STS患者带来长期生存益处;然而,RHT的影响必须在随机III期试验中确定。