Is hyperthermia combined with radiotherapy adequate in elderly patients with muscle-invasive bladder cancers? Thermo-radiobiological implications from an audit of initial results

Figures & data

Table 1. Patient and treatment characteristics. Numbers in parenthesis indicate the minimum and maximum values.

Parameters	All patients (n = 20)	HTRT group (n = 8)	HTCTRT group (n = 12)	p value
Age (years)	79.2 ± 6.1 (65–87)	82.4 ± 4.8 (74–87)	77.1 ± 6.2 (64–85)	0.062^+
Sex
Male	16	7	9	ns*
Female	4	1	3
KPS
60	2	2	0	ns*
70	2	0	2
80	3	1	2
90	13	5	8
Tumour stage
1	1	1	0	ns*
2	17	6	11
3	1	1	0
4	1	0	1
Nodal stage
x	3	1	2	ns*
0	15	6	9
1	1	1	0
2	0	0	0
3	1	0	1
Metastases stage
x	3	1	2	ns*
0	17	7	10
Tumour grade
2	1	0	1	ns*
3	19	8	11
Number of lesions
Solitary	14	5	9	ns*
Multiple	6	3	3
Extent of TUR-BT
Complete	14	5	9	ns*
Partial	6	3	3
Total RT dose (Gy)	54.6 ± 4.2 (48.0–59.4)	51.0 ± 3.4 (48.0–58.2)	57.1 ± 2.7 (50.4–59.4)	<0.001^+
Pelvic RT dose (Gy)	44.6 ± 4.6 (36.0–50.4)	44.1 ± 6.9 (36.0–50.0)	45.0 ± 2.3 (39.6–50.4)	ns+
Pelvic RT dose/fraction (Gy)	2.06 ± 0.4 (1.8–3.0)	2.45 ± 0.4 (1.8–3.0)	1.8 ± 0.0 (1.8)	<0.001^+
Boost RT dose (Gy)‡	10.0 ± 6.4 (0.0–19.8)	6.9 ± 7.6 (0.0–18)	12.1 ± 4.6 (0.0–19.8)	0.072^+
Boost RT dose/fraction (Gy)‡	1.6 ± 1.0 (0.0–3.0)	1.2 ± 1.4 (0.0–3.0)	1.8 ± 0.6 (0.0–2.2)	ns^+
Overall treatment time (days)	38.7 ± 8.3 (25.0–55.0)	30.9 ± 6.9 (25.0–44.0)	43.9 ± 4.0 (40.0–55.0)	<0.001^+
Nos. of hyperthermia sessions	5.3 ± 0.8 (4.0–6.0)	4.6 ± 0.7 (4.0–6.0)	5.7 ± 0.6 (4.0–6.0)	0.002^+
Bladder Tmean (°C)	41.8 ± 0.5 (40.6–42.7)	41.8 ± 0.4 (41.1–42.5)	41.8 ± 0.6 (40.6–42.7)	ns^+
Bladder Tmin (°C)	40.8 ± 0.7 (39.0–42.1)	40.9 ± 0.5 (40.1–41.8)	40.8 ± 0.9 (39.0–42.1)	ns^+
Bladder Tmax (°C)	42.8 ± 0.5 (41.8–43.7)	42.8 ± 0.6 (42.1–43.7)	42.8 ± 0.5 (41.8–43.5)	ns^+
Chemotherapy drugs
Cisplatin	2	–	2	–
Carboplatin	10	–	10
Number of chemotherapy cycles			6.0 ± 0.4 (5.0–7.0)

HTRT: thermoradiotherapy; HTCTRT: thermochemoradiotherapy; KPS: Karnofsky performance status; T, temperature; TUR-BT, transurethral resection of bladder tumour.

p values are for HTRT versus HTCTRT groups; ns, not significant.

‡Four patients of HTRT and one patient of HTCTRT did not receive any boost. They have been considered as 0 dose for the computation.

*χ² test; ⁺t-test.

Table 2. Biological effective dose (BED) and thermo-radiobiological effective dose (TBED) for patients treated with thermoradiotherapy (HTRT) and thermochemoradiotherapy (HTCTRT).

Parameters	HTRT group (Mean ± SD)	HTCTRT group (Mean ± SD)	p value^+
BEDpelvis (without time factor correction) (Gy15)	51.3 ± 8.0	50.4 ± 2.6	ns
BEDboost (without time factor correction) (Gy15)	8.0 ± 8.7	13.7 ± 5.2	ns
Time factor correction (Gy)	1.5 ± 2.4	6.3 ± 1.6	<0.001
Total BED (without time factor correction) (Gy15)	59.3 ± 2.6	64.1 ± 3.1	0.002
Total BED (with time factor correction) (Gy15)	57.8 ± 0.8	57.8 ± 2.8	ns
TBEDpelvis (without time factor correction) (Gy3)	80.0 ± 13.3	72.0 ± 3.7	0.06
TBEDboost (without time factor correction) (Gy3)	12.5 ± 13.4	20.1 ± 7.6	ns
Total TBED (without time factor correction) (Gy3)	92.5 ± 3.2	92.1 ± 4.7	ns
Total TBED (with time factor correction) (Gy3)	91.0 ± 4.4	85.8 ± 4.3	0.018

⁺t test; BED has been calculated with α/β = 15 Gy⁻¹; TBED has been calculated with α/β = 3 Gy⁻¹.

For details on the computation of BED, TBED and time factor correction, please refer to text and equations (1(1) ), (2(2) ) and (3).

Figure 1. Survival curves for all (n = 20), thermoradiotherapy (HTRT) and thermochemoradiotherapy (HTCTRT) patients for (a) bladder preservation (HTRT versus HTCTRT, log rank p not significant), (b) local disease-free survival (HTRT versus HTCTRT, log rank p = 0.076), (c) cause-specific survival (HTRT versus HTCTRT, log rank p not significant), and (d) overall survival (HTRT versus HTCTRT, log rank p not significant).

Figure 2. Local disease-free survival curves for all 20 patients grouped as (a) patients with biological effective dose (BED) with time factor correction: <58.1 versus >58.1 Gy₁₅ (log rank p not significant), and (b) patients with thermo-radiobiological effective dose (TBED) with time factor correction (see text for details): <88.7 versus >88.7 Gy₃ (log rank p = 0.05).