Nathanson S D, Haas G P, Bobrowski R, Lee M, Tilley B, Schultz L, Hetzel F
Int J Radiat Oncol Biol Phys. 1987 Feb;13(2):243-9. doi: 10.1016/0360-3016(87)90134-9.
The effects of local tumor hyperthermia on regional lymph node metastases are inconclusive. We studied the effects of hyperthermia on the incidence of popliteal, femoral, and abdominal lymph node metastases in C57BL/6 mice with primary B16 melanomas (F10 variant) growing subcutaneously in the left foot. Tumors were heated to 42.3, 43.5, and 44.2 degrees C for 90 minutes either 7 days after inoculation of 5 X 10(4) viable cells (microscopic tumor = mic) or when the tumors were approximately 3 mm in diameter (macroscopic tumor = mac). Femoral lymph node metastases occurred in 0/21 control animals and in 8/22 (36%), 11/19 (58%), and 11/17 (65%) animals whose primary tumors were heated to 42.3, 43.5, and 44.2 degrees C, respectively. For all three treatments, the increase in metastases as compared to controls was statistically significant (p less than 0.004, Fisher's exact test). The incidence of abdominal lymph node metastasis was slightly higher in the treated groups than controls. Twenty of 21 (95%) control mice developed popliteal lymph node metastases and hyperthermia-induced increases could not be demonstrated. Fifteen of 21 control mice killed 3 weeks after amputation of tumor-containing leg had pulmonary metastases with an average of 6 +/- 4 (standard deviation) lesions per affected mouse. Pulmonary metastases occurred in 22/22 (100%), 17/19 (89%), and 13/17 (76%) of mice whose tumors were heated to 42.3, 43.5, and 44.2 degrees C, respectively. The numbers of metastases for affected mice were significantly increased compared to controls for tumors heated to 43.5 and 44.2 degrees C (28 +/- 43, 43 +/- 52, 119 +/- 121, p greater than 0.02, p less than 0.006, p less than 0.002, for two sample T-test). While 0/8 mic tumors were cured 5/9 mac tumors heated to 44.2 degrees C disappeared (p less than 0.03, Fisher's exact test) and there was a growth delay in the remaining mice. Mic tumors, heated to 43.5 degrees C, had an accelerated onset of growth while mac tumors heated to this temperature had a slight growth delay. Growth of both mic and mac primary tumors heated to 42.3 degrees C was similar to controls. These results show that therapeutic and subtherapeutic local hyperthermia increases metastases to regional lymph nodes and to lungs even when primary tumor growth rate is partially or totally controlled.
局部肿瘤热疗对区域淋巴结转移的影响尚无定论。我们研究了热疗对C57BL/6小鼠腘窝、股部和腹部淋巴结转移发生率的影响，这些小鼠的左足皮下生长有原发性B16黑色素瘤（F10变体）。在接种5×10⁴个活细胞（微小肿瘤=mic）7天后，或者当肿瘤直径约为3mm（肉眼可见肿瘤=mac）时，将肿瘤加热至42.3、43.5和44.2摄氏度，持续90分钟。股部淋巴结转移在0/21只对照动物中出现，而在原发性肿瘤分别加热至42.3、43.5和44.2摄氏度的22只动物中有8只（36%）、19只中的11只（58%）和17只中的11只（65%）出现转移。对于所有这三种治疗，与对照组相比转移增加具有统计学意义（p<0.004，Fisher精确检验）。治疗组腹部淋巴结转移的发生率略高于对照组。21只对照小鼠中有20只（95%）发生腘窝淋巴结转移，未显示出热疗诱导的增加。在切除含肿瘤腿部3周后处死的21只对照小鼠中有15只出现肺转移，每只受影响小鼠平均有6±4（标准差）个病灶。肿瘤分别加热至42.3、43.5和44.2摄氏度的小鼠中，肺转移发生率分别为22/22（100%）、17/19（89%）和13/17（76%）。对于加热至43.5和44.2摄氏度的肿瘤，受影响小鼠的转移数量与对照组相比显著增加（两样本T检验，p>0.02、p<0.006、p<0.002）。虽然8个mic肿瘤中无治愈情况，但加热至44.2摄氏度的9个mac肿瘤中有5个消失（p<0.03，Fisher精确检验），其余小鼠出现生长延迟。加热至43.5摄氏度的mic肿瘤生长开始加速，而加热至该温度的mac肿瘤生长略有延迟。加热至42.3摄氏度的mic和mac原发性肿瘤的生长与对照组相似。这些结果表明，即使原发性肿瘤生长速率得到部分或完全控制，治疗性和亚治疗性局部热疗仍会增加区域淋巴结和肺部的转移。
