Radiotherapy with 8 MHz radiofrequency-capacitive regional hyperthermia for pain relief of unresectable and recurrent colorectal cancer

Figures & data

Table I.  Characteristis of patients and treatment.

Characteristic	All patients (n = 41)	Patients* (n = 27)
Gender: M/F	29/12	18/9
Age: <60/≧60	21/20	13/14
Performance score: 0–2/3–4	35/6	22/5
Tumour stage: Primary/Recurrent	4/37	4/23
Tumour size (mm): <60/≧60	19/22	13/14
Radiating pain to leg(s): Yes/No	18/23	10/17
Bone invasion: Yes/No	15/26	9/18
Metastatic disease**: Yes/No	16/25	11/16
Radiotherapy (Gy): <60/≧60	14/27	10/17
Number of hyperthermia treatments: <9/≧10	26/15	16/11
Strong superficial cooling: Yes/No	17/24	8/19
Chemotherapy: Yes/No	6/35	3/24

*Patients who underwent measurement of tumour temperature. **Outside treatment volume.

Table II.  Pain score and pain medication at the start of combined treatment.

Pain medication
Pain score	None	Step 1	Step 2	Step 3	Step 4
Mild	5	1	0	0	0
Moderate	7	4	3	1	0
Severe	1	3	1	5	0
Very severe	0	1	0	5	3
Excruciating	0	0	0	1	0

Step 1: paracetamol, nonsteroid anti-inflammatory drug; Step 2: paracetamol or nonsteroid anti-inflammatory drug plus codein; Step 3: oral morphinomimetics; and Step 4: parenteral morphinomimetics.

Table III.  Results of pain relief.

Pain relief	No. (%)
Complete response	9 (22)
Good response	15 (37)
Minor response	10 (24)
No change	6 (15)
Progressive pain	1 (2)

Table IV.  Separate data of pain score (a) and pain medication (b) for pre- and post-treatment.

(a)
Pain score of post-treatment
Pain score of pre-treatment	None	Mild	Moderate	Severe	Very severe	Excruciating
Mild	4	2	0	0	0	0
Moderate	9	3	2	1	0	0
Severe	1	4	2	3	0	0
Very severe	0	5	1	2	1	0
Excruciating	0	0	1	0	0	0

(b)
Pain medication of post-treatment
Pain medication of pre-treatment	None	Step 1	Step 2	Step 3	Step 4
None	13	0	0	0	0
Step 1	3	5	0	1	0
Step 2	0	1	3	0	0
Step 3	0	1	0	11	0
Step 4	0	1	0	1	1

Table V.  Multi-variate analysis by logistic regression to evaluate effects of certain factors on pain relief (complete response + good response) in all patients.

Characteristic	OR (95% CI)	p
Tumour size (mm): <60/≧60	1.2 (0.2–7.2)	0.82
Radiating pain to leg(s): Yes/No	7.9 (1.1–59.1)	<0.05
Bone invasion: No/Yes	2.7 (0.3–33.3)	0.40
Performance score: 0–2/3–4	4.5 (0.4–54.1)	0.23
Metastatic disease*: Yes/No	1.7 (0.3–9.0)	0.51
Radiotherapy (Gy): <60/≧60	2.1 (0.3–13.4)	0.50
No. of hyperthermia treatments: ≧10/<9	1.9 (0.3–12.5)	0.46
Strong superficial cooling: Yes/No	2.7 (0.5–15.2)	0.25
Chemotherapy: Yes/No	1.5 (0.1–15.8)	0.76

*Outside treatment volume. OR, odds ratio; CI, confidence interval.

Table VI.  Univariate and multi-variate analysis of certain factors on duration of pain relief in all patients.

Univariate			Multi-variate
Characteristic	Median duration of pain relief (months)	p	HR* (95% CI**)	p
Gender: M/F	6.8/7.0	0.92
Age: <60/≧60	6.5/10.1	0.66
Tumour size (mm): <60/≧60	7.1/6.9	0.99
Pain score***: Mild or moderate/others	8.5/6.6	0.07	1.7 (0.5–5.8)	0.37
Pain medication***: None or step 1/others	7.9/6.6	0.10	1.1 (0.3–4.1)	0.87
Radiating pain to leg(s): Yes/No	6.1/11.0	0.10	2.0 (0.9–4.7)	0.11
Bone invasion: Yes/No	6.0/8.6	0.10	1.3 (0.4–3.9)	0.68
Pain relief: CR + good response/others	7.0/6.8	0.95
Performance score: 0–2/3–4	7.1/6.7	0.41
Metastatic disease****: Yes/No	7.7/6.9	0.42
Radiotherapy (Gy): <60/≧60	5.5/8.1	0.55
No. of hyperthermia treatments: <9/≧10	6.8/7.1	0.97
Strong superficial cooling: Yes/No	10.6/6.6	0.33
Chemotherapy: Yes/No	4.1/7.0	0.77
Tumour response: CR + PR/NC + PD	14.4/6.8	0.12	1.9 (0.9–4.4)	0.11

*Hazards ratio; **Confidence interval; ***At the start of treatment; ****Outside treatment volume.

CR, complete response; PR, partial response; NC, no change; PD, progressive disease.

Table VII.  Univariate analysis of certain factors on duration of pain relief in patients who performed measurement of tumour temperature.

Characteristic	Median duration of pain relief (months)	p
Radiating pain to leg(s): Yes/No	5.8/14.4	0.06
Tumour response: CR + PR/NC + PD	14.4/7.1	0.43
Tmax: ≧43°C/<43°C	13.5/5.2	0.30
Tave: ≧42.5°C/<42.5°C	14.5/5.8	<0.05
Tmin: ≧42°C/<42°C	10.2/6.7	0.45

CR, complete response; PR, partial response; NC, no change; PD, progressive disease.

Table VIII.  Univariate analysis of certain factors on duration of pain relief in patients with radiating pain to leg(s).

Characteristic	Median duration of pain relief (months)	p
Radiotherapy (Gy): <60/≧60	4.9/6.7	0.08
No. of hyperthermia treatments: <8806;9/≧10	4.1/6.8	0.04
Strong superficial cooling: Yes/No	9.4/3.8	0.006
Chemotherapy: Yes/No	9.8/5.7	0.06

Figure 1. Duration of pain relief of patients with T_ave ≥ 42.5°C compared with that of patients with T_ave < 42.5°C using the Kaplan-Meier method and analysed with the log-rank test. The duration of patients with T_ave ≥ 42.5°C was significantly better than that of patients with T_ave < 42.5°C (p < 0.05).

Figure 2. As for the 18 patients with radiating pain to leg(s), strong superficial cooling (a) and higher number of hyperthermia treatments (b) were superior prognostic factor for the duration of pain relief using the Kaplan-Meier method and analysed with the log-rank test.

Table IX.  Pain relief, dulation of pain relief and tumour response after radiotherapy with or without hyperthermia for colorectal cancer in previous reports.

				Pain relief		Dulation of pain relief		Tumour response
Series	Year	No. of patients	Characteristic	RT alone	RT + HT	RT alone	RT + HT	RT alone	RT + HT
Williams et al. [44]	1956	82	recurrent	–	–	<6 months: 77%	–	87%	–
Smedal et al. [45]	1967	50	recurrent	–	–	<6 months: 50%	–	–	–
Ciatto and Pacini [46]	1982	55	recurrent	55%	–	<6 months: 66%	–	80%	–
James et al. [47]	1983	143	recurrent	–	–	median 3 months	–	70%	–
Overgaard et al. [10]	1984	89	unresectable, residual or recurrent	63%	–	>6 months or until death: 63%	–	–	–
Allum et al. [9]	1987	18	recurrent	–	–	median 3 months	–	–	–
Berdov and Menteshashvili [13]*	1990	114	preoperative, locally advances	32%	86%	–	–	CR 34%	CR 54%
Kakehi et al. [49]	1990	34	recurrent	–	56%	–	–	–	CR + PR 47%
Nishimura et al. [11]	1992	71	unresectable or recurrent	–	–	–	–	CR + PR 36%	CR + PR 54%
Gonzalez Gonzalez et al. [41]	1995	72	unresectable or recurrent	–	75%	–	median 12 months
Guiney et al. [48]	1997	118	recurrent	79%	–	–	–	–	–
van der Zee et al. [14], [40]*	2000	72	unresectable or recurrent	59%	68%	median 7 months	median 17 months	CR 16%	CR 21%
Juffermans et al. [15]	2003	54	reirradiation, unresectable or recurrent	–	84%	–	median 6 months	–	–
This study		41	unresectable or recurrent	–	83%	–	median 7 months	–	CR + PR 39%

*Randomized trial.

RT, radiotherapy; HT, hyperthermia; CR, complete response; PR, partial response.

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