Hyperthermia and radiotherapy with or without chemotherapy in locally advanced cervical cancer: a systematic review with conventional and network meta-analyses

Figures & data

Figure 1. Flow chart indicating study selection procedure for hyperthermia with radiotherapy and/or chemotherapy in cervical cancers for conventional meta-analysis and network meta-analyses.

Table 1. Characteristics of the studies included in the present systematic review and meta-analysis pertaining to (a) HTRT vs. RT and (b) HTCTRT vs. RT and (c) HTRT vs. CTRT.

	Patient characteristics			Radiotherapy					Loco-regional hyperthermia				Chemotherapy
Trial	Stage	Total	% in< stageIIB	Ext RT (Gy)	Ext RT(dose/fr.)	BT (Gy)		BT (dose/fr.)	Order of HTand RT	Time(min)	Temp.(°C)	No./week	Drugs,dose,frequency	Nos.
(a) HTRT vs. RT
Harima et al. [14]	IIIB	40	0.0	52.20	1.80	30.0 (H)		7.5	RT → HT	60	40.6	1	–	–
Franckena et al. [13]	IIB–IVA	114	0.0	46–50.4	1.8–2.0	17.0 (H) 18.0 (H)20–30 (M)		8.5 6.0 20–30	RT → HT	60	42.0	1	–	–
Vasanthan et al. [16]	IIB–IVA	110	0.0	50 (0–70)	1.8–2.0	Varied across centres		Varied across centres	RT → HT	60	41.6	1	–	–
Chen et al. [11]	IIB–IIIB	60	0.0	40	2.00	25–60 (H)		5–10	RT → HT	45	42	2	–	–
Sharma et al. [17]	IIA–IIIB	42	7.1	45	2.25	35.0 (L)		35	HT → RT	30	42–43	3	–	–
Datta et al. [15]	IIIB	53	0.0	60–70	2.00	–		–	HT → RT	45	42.5	2	–	–
(b) HTCTRT vs. RT
Chen et al. [11]	IIB–IIIB	60	0.0	40	2.00	25–60 (H)	5–10		RT → HT	45	42	2	CDDP: 30 mg D1–3, 5-FU: 500 mg D1–3, VCR: 1 mg D8,15	2
(c) HTRT vs. CTRT
Chen et al. [11]	IIB–IIIB	60	0.0	40	2.00	25–60 (H)	5–10		RT → HT	45	42	2	CDDP: 30 mg D1–3, 5-FU: 500 mg D1–3, VCR: 1 mg D8,15	2
Lutgens et al. [21]	IB2–IVA	84	30.1	50	2.00	21 (H) 32 (L/P) 29 (M/P)	7.0 16–32 14.5–29		RT → HT	60	–	1	CDDP: 40 mg/m^2 weekly	5

RT: radiotherapy; HT: hyperthermia; HTRT: thermoradiotherapy; HTCTRT: thermochemoradiotherapy; BT: brachytherapy; NA: not available; H: high-dose rate; M: medium-dose rate; L: low-dose rate; P: pulsed-dose rate; CDDP: cisplatin; 5-FU: 5-fluorouracil; VCR: vincristine; D: day; for HTCTRT vs. CTRT, the eight trials have not been detailed here as these are published in Chinese medical journals and the original articles were not available. Their summary outcomes as listed in Yan et al. [12] have been taken for computation in network meta-analysis.

Figure 3. Funnel plots corresponding to the risk difference for (a) complete response; (b) long-term loco-regional control; (c) number of patients alive; (d) acute toxicity; and (e) late toxicity for trials included in thermoradiotherapy (HTRT) vs. radiotherapy (RT). Kendall?s τ and p values for each plot are also shown.

Figure 4. Network meta-analysis for complete response with trials using thermoradiotherapy (HTRT), thermochemoradiotherapy (HTCTRT), chemoradiotherapy (CTRT) and radiotherapy (RT) alone. (a) Network diagram showing the number of trials and patients included in each set of randomised groups; (b) league table with odds ratios and 95% credible interval (95% Cr.I) with pairwise comparison. Random effects model with vague priors has been used for computation of odds ratios.

Figure 5. Rankograms for complete response computed using random effects model for subgroups of thermoradiotherapy (HTRT), thermochemoradiotherapy (HTCTRT), chemoradiotherapy (CTRT) and radiotherapy (RT) alone. The rankings have been based on the surface under the cumulative ranking (SUCRA) values with the best rank obtained by the modality with the highest SUCRA value.

Table 2. Summary of the network meta-analysis characteristics for complete response and patients alive for various treatment arms: thermoradiotherapy (HTRT), thermochemoradiotherapy (HTCTRT), chemoradiotherapy (CTRT) and radiotherapy (RT) alone.

	Network meta-analysis characteristics
Parameters	Completeresponse	Patientsalive
Number of interventions	4	4
Number of studies	13	12
Total number of patients in the network	1000	807
Total number of events in the network	659	596
Total possible pairwise comparison	6	6
Total pairwise comparison with direct data	6	3
Number of two-arm studies	12	12
Number of multi-arm studies	1	0
Number of studies with no zero events	13	12
Number of studies with at least one zero event	0	0
Number of studies with all zero events	0	0

Figure 6. Network meta-analysis for patients alive with trials using thermoradiotherapy (HTRT), thermochemoradiotherapy (HTCTRT), chemoradiotherapy (CTRT) and radiotherapy (RT) alone. (a) Network diagram showing the number of trials and patients included in each set of randomised groups; (b) league table with odds ratios and 95% credible interval (95% Cr.I) with pairwise comparison. Random effects model with vague priors has been used for computation of odds ratios.

Figure 7. Rankograms for patients alive computed using random effects model for subgroups of thermoradiotherapy (HTRT), thermochemoradiotherapy (HTCTRT), chemoradiotherapy (CTRT) and radiotherapy (RT) alone. The rankings have been based on the surface under the cumulative ranking (SUCRA) values with the best rank obtained by the modality with the highest SUCRA value.

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