Hyperthermia and radiotherapy in the management of head and neck cancers: A systematic review and meta-analysis

Figures & data

Figure 1. Flow-chart indicating the study selection procedure.

Table 1. Summary of the key patient and treatment characteristics along with the outcome of the head and neck studies (radiotherapy versus radiotherapy and hyperthermia) included in the meta-analysis.

										RT group		RT + HT group
Author, year	Site	TNM stage	RT dose (Gy)	Type of HT	HT and RT sequence and time interval	Mean HT temperature (°C) and thermometry	HT duration (min)	HT sessions/ week	Total no. of HT sessions*	No. CR/ Total	% CR	No. CR/ Total	% CR	Remarks
Wen et al.,  2014 [21]	NP	II–IVa	60–80 (2 Gy/fr) with cobalt or linac, technique not stated	MW	Post-RT 10–60 min	44–52 °C at tumour surface, 98% of tumour surface at 44.4 °C	60	2	Mean: 6	23/49	46.9	34/49	69.4	Randomised; intracavitary HT; CR based on imaging studies; LPFS and PFS significantly better with HTRT (median PFS: 100 vs. 60 months, median LPFS 111 vs. 54 months for HTRT vs. RT respectively); toxicity assessed as per RTOG and NCI CTC criteria and similar for both groups
Huilgol et al.,  2010 [22]	OC OP HP	II–IV	Mean: 66.9–67.5 (2 Gy/fr) parallel opposed portals	RF	Post-RT Time interval not stated	Tav 42.3 °C single point invasive thermometry	30	1	5–7	11/26	42.3	22/28	78.6	Randomised; median survival better in HTRT group (241 days vs. 145 days for HTRT and RT respectively); toxicity assessment criteria not stated; toxicities comparable in both groups, no dose-limiting thermal burns or excessive mucosal or thermal toxicity reported
Valdagni et al.,  1994 [23]	NN (N3)	IV	64–70 (2–2.5  Gy/fr) single/ parallel opposed portals	RF	Post-RT 20–25 min	Tmin 42.5 °C multipoint invasive thermometry	Lowest temp of 42.5 °C maintained for 30 min	2	12	9/22	40.9	15/18	83.3	Randomised; 5-year LC: 24.2% vs. 68.6% with RT and HTRT respectively (p = 0.015); 5-year OS 53.3% vs. 0% with RT and HTRT respectively (p = 0.02); RTOG/EORTC criteria, acute toxicity similar in both arms except 1 patient had burns in HTRT group, 2 patients developed bone necrosis with HTRT attributed to nodes fixed to mandible
Perez et al.,  1991 [24]	HN	NA	32 (4 Gy/fr × 8) twice weekly single/ parallel opposed portals	MW	Post-RT 15–30 min	42.5 °C multipoint thermometry	60	2	8	21/60	35.0	18/53	33.9	Randomised; only HNC patients considered; outcomes reported as lesions; 30% received <90% of 32 Gy prescribed RT dose; only 52% of HTRT group received prescribed RT dose and 8 sessions of HT; toxicity score based on RTOG criteria; except for 30% incidence of thermal blisters acute and late toxicities comparable in both groups; separate survival outcomes for HNCs not stated
Datta et al.,  1990 [25]	OC OP	I–IV	60–65 (2 Gy/fr) parallel opposed portals	RF	Pre-RT immediate	42.5 °C single point invasive thermometry	20 min after attaining required temp	2	12	10/32	31.3	18/33	54.5	Randomised; response was better with HTRT in stages III/IV; DFS at 18 months 19% with RT vs. 33% with HTRT; toxicity assessment criteria not stated; toxicity comparable in both arms
Arcangeli et al.,  1987 [26]	NN	NA	60 (3 fr/day 1.5–2 Gy each) single/ parallel opposed portals	RF MW	Post-RT immediate	42.5 °C single or multipoint thermometry	45	3	7	18/43	41.9	30/38	78.9	Non-randomised; only head neck patients considered; CR rates given as number of lesions; LC at 2 years 58% vs. 14% with HTRT and RT respectively; toxicity assessment criteria not stated; no significant increase in toxicity seen with HT

HT, hyperthermia; RT, radiotherapy; HTRT, thermoradiotherapy; NA, not available; HNCs, head and neck cancers; NP, nasopharynx; OC, oral cavity; OP, oropharynx; HP, hypopharynx; NN, neck node; HN, head neck, no specific site stated; MW, microwave; RF, radiofrequency; RRT, radical radiotherapy; PRT, preoperative radiotherapy; CR, complete response; PFS, progression-free survival; LPFS, Local progression-free survival; DFS, disease-free survival; LC, local control; OS, overall survival.

Figure 2. Forest plots from the six individual two-arm studies depicting (a) the odds ratio, (b) risk ratio, (c) risk difference.

Figure 3. Funnel plots along with the Kendall’s tau and the p values for (a) odds ratio, (b) risk ratio and (c) risk difference for clinical trials with radiotherapy alone versus radiotherapy and hyperthermia.

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