Heating technology for malignant tumors: a review

Figures & data

Figure 1. (A) Characteristics of the three main treatment approaches in terms of temperature level. (B) Time to yield muscle fibrosis (continuous curve) or necrosis (dotted curve) at specific temperatures for hyperthermia and ablation (based on Dewhirst et al. [20]).

Figure 2. Schematic representation of the heating mechanisms of different clinical heating techniques: Electromagnetic (i.e., capacitive, radiofrequency, microwave, infrared and laser heating), focused ultrasound, hyperthermic perfusion and conductive heating.

Figure 3. Left: schematic overview of the heating depth from the skin and the tumor/target size that can be heated with various noninvasive heating techniques. Right: Schematic overview of the tumor/target size that can be heated with various invasive heating techniques.

Figure 4. Graphical representation of different heating techniques.

Table 1. General summary of heating techniques, typical goal temperatures, treatment scheme and duration, as well as experimental (italic) and clinically proven applications.

Protocol	Synergizing with	Technique		Temperature range (°C)	Duration session (min)	Number of sessions and frequency	Tumor sites: Proven/routine experimental	refs
Hyperthermia as sensitizer	Chemotherapy	Local	IHT	39–45	60	1–12 sessions before, during or after chemo
			SFUS	39–45	30–60		LI	[70]
			MNP	39–45	60
			Intraluminal	39–45	60		BL, RE	[71–76]
			Capacitive	39–45	60		HN	[77]
			Radiative	39–45	60
		Locoregional	Capacitive	39–45	60		BL, CE, LI, LU, OE, PA	[31,78–88]
			Radiative	39–45	60		BL, CE, EX, LI, OE, PA, PE, PO	[89–101]
			HIPEC	40–43	30–90	1 session during chemo	PE	[102–105]
			ILP	38–39	60–90	1 session during chemo	EX	[106,107]
		WBH		39–42	60–120	4-6 sessions during chemo	LU, PA, PO, RE	[35]
	Radiotherapy	Local	IHT	39–45	60	1–5 sessions, 1x/2x weekly during RT, before/after RT fraction	BR, HN, PR	[108–111]
			SFUS	39–45	60		PR
			MNP	39–45	60		BR, PR	[112,113]
			Intraluminal	39–45	60		OE, RE	[75,114,115]
			Capacitive	39–45	60		CW, HN,	[116–118]
			Radiative	39–45	60		CW, HN, IB, ME,	[119–126]
		Locoregional	Capacitive	39–45	60		BL, BO, CE, LI, LU, OE, PA, PR, RE	[79,81, 82,127–138]
			radiative	39–45	60		BL, CE, OE, LI, PA, PR, RE	[95,99,101,139–141]
Thermal ablation	n.a.	Local	IHT	50–100	<5	1 session	BO, BL, BR, HN, IB, LI, KI, LU, OE, PA, PR, TH	[142–169]
			SFUS	50–100	<5		BO, BR, CE, IB, LI, KI, OE, PA, PO, PR, TH	[158,170–192]
			IRE	50–100	<10		KI, LI, LU, PA, PR	[193–198]

BL: bladder; BO: bone (metastases; osteoid sarcoma); BR: brain; CE: cervix/uterus; CW: chest wall; EX: extremities; HN: head and neck; IB: intact breast; KI: kidney; LI: liver; LU: lung; ME: melanoma; OE: esophagus; PA: pancreas; PO: pelvis other (soft tissue sarcoma/pediatric tumors); PE: peritoneum; PR: prostate; RE: rectum; TH: thyroid.

Table 2. Overview of clinical applications of local, locoregional and whole-body heating techniques.

	Local hyperthermia and ablation										Locoregional hyperthermia				WBH	References
	IHT		SFUS		IRE	MNP			Superficial		EM Loco-regional		HIPEC	ILP
	HT	ABL	HT	ABL	ABL	HT	ABL	Intra-luminal	cap	rad	cap	rad
BL: Bladder		○						●			○	○				[55,71–74,81,96,97,132,139,166,199–202]
BO: Bone (metastases, osteoid osteoma)		○		●							●					[135,143,177]
BR: Brain	●	○		○			○									[110,112,164,165,173,203–206]
CE: Cervix/Uterus				●							○/●	●				[31,84,85,139,174–176,207,208]
CW: Chest wall									○	●						[117,118,122,209–213]
EX: Extremities												●		●		[89,106,107]
HN: Head and Neck	○	○							●	●/○						[111,116,121,125,126,150–153]
IB: Intact breast		○		○						○						[119,120,156,186]
KI: Kidney		○		○	○											[154,155,189,193,214]
LI: Liver		●	○	○	○						○	○				[50,70,82,83,101,145,146,159,163,193,196,215–219]
LU: Lung		●			○						○				○	[78–80,127–129,147–149,160–162,198,220,221]
ME: Melanoma										●						[123,124]
OE: Esophagus		●		○				○			○	○				[87,88,99,114,138,144,157,169,190]
PA: Pancreas		○		○	○						○	○			○	[86,93,95,137,158,185,193–195]
PE: Peritoneum												○	●			[94,100,102–104,222–226]
PO: Pelvis other: soft tissue sarcoma/ pediatric tumors				○								●			○	[89–92,187,188]
PR: Prostate	○	●/○		●	○	○					○	○				[108,109,113,130,131,140,141,167,168,170–172,178–184,197]
RE: Rectum								○			○	●			○	[35,75,76,115,133,134,139]
TH: Thyroid		●		○												[150–153,191]

Open circles represent explorative (small/few phase I/II) use and solid black circles represent many/large phase I/II trials, retrospective analyses or phase III evidence.

Figure 5. Trends in heating technologies, represented by a rough estimate of the number of publications from 1995 till present on whole body hyperthermia (WBH), hyperthermia combined with radiotherapy (HT + RT), hyperthermia combined with chemotherapy (HT + CHT), hyperthermic intraperitoneal chemotherapy (HIPEC) and thermal ablation. Search terms used in Web of Science were: (WBH OR whole body hyperthermia; (hyperthermia AND radiotherapy) OR thermoradiotherapy; (hyperthermia AND chemotherapy) OR thermochemotherapy; HIPEC OR Hyperthermic Intraperitoneal Chemotherapy; thermal ablation OR RFA OR MWA). NB: Although this search did probably not retrieve all relevant publications and some overlap is likely between topics (e.g., HT + CHT and HIPEC), this graph is indicative for the trends in interest for different heating techniques.

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