Myerson R J, Straube W L, Moros E G, Emami B N, Lee H K, Perez C A, Taylor M E
Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University Medical Center, St. Louis, MO 63110, USA.
Int J Hyperthermia. 1999 Jul-Aug;15(4):251-66. doi: 10.1080/026567399285639.
In vitro and animal studies indicate that a moderate temperature of 41 degrees C maintained for approximately 1 h will provide radiosensitization if radiation (RT) and hyperthermia (HT) are delivered simultaneously, but not with sequential treatment. A minimum tumour temperature of 41 degrees C is a more feasible goal than the goal of >42 degrees C needed for sequential treatment.
Forty-four patients with 47 recurrent superficial cancers received simultaneous external beam radiotherapy and superficial hyperthermia on successive IRB approved phase I/II studies. All lesions had failed previous therapy, 35 were previously irradiated (mean dose 52.7 Gy). Hyperthermia was delivered with 915 MHz microwave or 1-3.5 MHz ultrasound using commercially available applicators. The average dimensions of 19 lesions treated with microwave were 4.7 x 3.6 x 1.7 cm and the average dimensions of 28 lesions treated with ultrasound were 8.0 x 6.1 x 2.9 cm. The most common sites were chest wall (15 cases) and head and neck (21 cases). Temperatures were monitored at an average of six intratumoral locations using multisensor probes. The median number of hyperthermia treatments was three and the median radiation dose 30 Gy. Radiation dose per fraction was 4 Gy with hyperthermia and 2 Gy or 4 Gy (depending on protocol) on non-hyperthermia days.
Six different measures of minimum monitored temperature and duration were found to be highly correlated with each other. There was nearly a one-to-one correspondence between minimum tumour time at or above 41 degrees C (Min t41) and minimum tumour Sapareto Dewey equivalent time at 42 degrees C (Min teq42). After four sessions 63% of cases had a per session average Sapareto Dewey equivalent time at 41 degrees C which exceeded 60 min in all monitored tumour locations. The complete and partial response rate in evaluable lesions were respectively 21/41 (51%) and 7/41 (17%) and were best correlated with site (chest wall showing best response). Toxicity consisted of 10/47 (21%) slow healing soft tissue ulcers which healed in all cases but required a median of 7 months. The most important predictors for chronic ulceration were cumulative radiation dose >80 Gy and complete response to treatment.
Minimum tumour temperatures maintained for durations compatible in vitro with thermal radiosensitization (if RT and HT are delivered simultaneously) are clinically feasible and tolerable for broad but superficial lesions amenable to externally applied ultrasound or microwave hyperthermia. The current in-house protocol is evaluating the impact of more than four hyperthermia sessions on the overall thermal dose distribution and toxicity.
体外和动物研究表明，如果放疗（RT）和热疗（HT）同时进行，维持约1小时的41摄氏度适度温度可产生放射增敏作用，但序贯治疗则不然。将肿瘤最低温度维持在41摄氏度比序贯治疗所需的高于42摄氏度的目标更可行。
44例患有47处复发性浅表癌的患者在相继获得机构审查委员会批准的I/II期研究中接受了同步外照射放疗和浅表热疗。所有病灶先前治疗均失败，35处曾接受过放疗（平均剂量52.7 Gy）。使用市售的施源器，通过915 MHz微波或1 - 3.5 MHz超声进行热疗。用微波治疗的19处病灶平均尺寸为4.7×3.6×1.7 cm，用超声治疗的28处病灶平均尺寸为8.0×6.1×2.9 cm。最常见的部位是胸壁（15例）和头颈部（21例）。使用多传感器探头平均在六个瘤内位置监测温度。热疗治疗的中位数为3次，放射剂量中位数为30 Gy。热疗日的分次放射剂量为4 Gy，非热疗日为2 Gy或4 Gy（取决于方案）。
发现监测到的最低温度和持续时间的六种不同测量方法彼此高度相关。肿瘤在41摄氏度及以上的最低时间（Min t41）与肿瘤在42摄氏度时的最低萨帕雷托 - 杜威等效时间（Min teq42）之间几乎呈一一对应关系。四次治疗后，63%的病例在所有监测的肿瘤部位，每次治疗的平均萨帕雷托 - 杜威等效时间在41摄氏度时超过60分钟。可评估病灶的完全缓解率和部分缓解率分别为21/41（51%）和7/41（17%），且与部位相关性最佳（胸壁显示出最佳反应）。毒性表现为10/47（21%）的软组织溃疡愈合缓慢，所有病例最终均愈合，但中位愈合时间为7个月。慢性溃疡最重要的预测因素是累积放射剂量>80 Gy和对治疗的完全反应。
对于适合外用超声或微波热疗的广泛浅表病灶，将肿瘤最低温度维持在体外与热放射增敏作用（如果放疗和热疗同时进行）相符的持续时间在临床上是可行且可耐受的。当前的内部方案正在评估超过四次热疗疗程对整体热剂量分布和毒性的影响。
