Critical Analysis of Electromagnetic Hyperthermia Randomized Trials: Dubious Effect and Multiple Biases

Table 1

Randomized clinical trials on superficial local hyperthermia published after 1990.

Trial	Kapp et al. [7]	Perez et al. [5]	Emami et al. [8]	Engin et al. [9]	Vernon et al. [10]	Overgaard et al. [11]	Jones et al. [12]
Organization	Stanford University	Mallinckrodt Institute of Radiology	Mallinckrodt Institute of Radiology	Thomas Jefferson University	Some European and Canadian centers	Danish Cancer Society	Duke University
Country	USA	USA	USA	USA	Europe/Canada	Europe	USA
Year of publication	1990	1991	1992	1993	1996	1996	2005
Design	Monocenter	Monocenter	Monocenter	Monocenter	Multicenter	Multicenter	Monocenter
Number of patients	70	307	173	41	236	70	108
Number of tumors	179	N/D	240	44	N/D	134	N/D
Type of tumors	Chest wall, neck nodes, melanoma	Chest wall, neck nodes, melanoma	Superficial	Chest wall, neck nodes	Chest wall	Melanoma	Chest wall, neck nodes, melanoma
Therapy
HT+	RT + HT 42.5°C (6 HTs)	RT + HT 42.5°C × 45–60′ (2 HTs)	RT + HT 42.5°C (8 HTs)	RT + HT 42.5°C (8 HTs)	RT + HT 42.5°C	RT + HT 43°C × 60′ (3 HTs)	RT + HT 10 < CEM43°C  𝑇90 < 100 (10 HTs)
HT−	RT + HT 42.5°C (2 HTs)	RT only	RT + HT 42.5°C (4 HTs)	RT + HT 42.5°C (4 HTs)	RT only	RT	RT
Complete local response (%)
HT+	52%	32%	57.8%	55%	59%	62% (immed.)/46% (2 yr)	66%
HT−	51%	30%	54.7%	59%	41%	35% (immed.)/28% (2 yr)	42%
Overall survival
HT+	N/D	Statistically insignificant	Statistically insignificant	N/D	Statistically insignificant	Statistically insignificant	Statistically insignificant
HT−
Disease-free survival
HT+	N/D	Enhanced	N/D	N/D	Enhanced	N/D	Enhanced
HT−
Burns
HT+	N/D	30%	N/D	40%	11%	N/D	46%
HT−		0%		40%	2%		5.7%
Complications (overall)
HT+	5% needed medication; 3% needed surgery	N/D	18% of severe complications	N/D	Pain	27% pain, incl. 8% moderate and 6% severe	16% needed pause of treatment
Authors estimation	Negative	Negative	Negative	Negative	Positive	Positive	Positive
Final estimation	Negative	Negative	Negative	Negative	Dubious	Dubious	Dubious