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. 2022 Jan 26;14(3):625. doi: 10.3390/cancers14030625

Table 8.

Retrospective clinical studies using RT in combination with HT.

Author(s) Cancer Site, n RT Dose (Gy)
/Fractions		 Temperature
Metrics (°C)		 HT
Session		 ttreat
(min)		 Thermal
Dose (min)		 tint
(min)		 Sequence Clinical Outcome
(Comment)
Franckena et al. [36] Locally advanced cervix cancer,
n = 420		 46.0–50.4
/23–28
with
HDR-IRT 11
(192 Ir):
17.0/2
weekly
or LDR-IRT 12:
18.0/3
weekly
or LDR:
30 Gy in
60 h		 n.r. Ntotal:
5
Nweek:
1		 60 CEM43°CT90 †:
5.05 ± 4.18 min		 n.r. n.r.

  • CR 1: 78%, PR 2: 16%, SD 3: 3%, PD 4: 1%.

  • 1-year PTC 5: 65% (95% CI: 60–70%), 5-year PTC: 53% (95% CI: 47–58%).

  • 1 year DSS 6: 75% (95% CI: 71–79%) and 5-year DSS: 47% (95% CI: 41–53%).

  • Toxicity of grade I: 51% (80/153), grade II: 39% (60/153), grade III: 9%(16/153) and grade IV: 0.6% (1/153).

  • Tumor stage, performance status, radiotherapy dose and tumor size, CEM43°CT90 and TRISE emerged as significant predictors of the various end-points.
Kroesen et al. [33] Locally advanced
cervix cancer,
n = 400		 46.0 -50.4
/23–28
with
HDR-IRT
(192 Ir):
17.0/2
or MRI-IRT
7.0/3–4		 n.r. Ntotal:
5
Nweek:
1		 60 CEM43°CT90 †:
3.40 (1.89–5.83)
TRISE †:
3.46 (2.93–3.86)		 30–230 HT after RT

  • TRISE and CEM43T90 had a significant effect on LC (univariate and multivariate analyses).

  • TRISE, and IGBT showed a significant effect on DFS 7, DSS, and OS 8 (univariate analyses).

  • tint grouped based on median value in short tint (30–74 min) and long tint (75–220 min) were not significant predictor of LC, DFS, DSS and OS.

  • The incidence of late grade III toxicity did not differ between low or high TRISE or low or high tint patients.
van Leeuwen et al. [22] Locally advanced
cervix cancer,
n = 58		 46.0–50.4
/23–28
with
PDR:
24		 n.r. Ntotal:
4–5
Nweek:
1		 60 n.r. 33.8–125.2 † HT after RT

  • 3-year IFR 9:18% (0–35%) in the short tint (≤ 79.2 min) group and 53% (18–82%) in the long tint (>79.2 min) group.

  • 5-year OS: 52% (35–77%).

  • OS ‡: 61 months (38–83 months) in the short tint group and 19 months (13–26 months) in the long tint group.

  • No difference in toxicity was observed between short and long tint group.
Franckena et al. [120] Locally advanced
cervix cancer,
n = 378		 46.0–50.4
/23–28
with
HDR-IRT (192 Ir):
17.0/2
or
18.0–21.0/3
or
20.0–24.0/1
or
HDR:
30.0/1		 Tavg †: 40.6 Ntotal:
5
Nweek:
1		 60 n.r. 30–240 HT after RT

  • CR: 77%.

  • 5- year PTC: 53% for all patients (95% CI, 48–59) and 5-year DSS: 47% (95% CI, 41–53).

  • Ntotal significant influence on CR, DSS and OS (univariate analysis) and on CR and DSS (multivariate analysis).
Oldenborg et al. [121] Recurrent breast
cancer, n = 78		 32.0/8 T90 †: 41.1
(37.7–42.4)
T50 †: 42.2
(39.0–43.4)
T10 †: 43.2
(41.0–44.5)		 Ntotal:
4
Nweek:
1		 60 CEM43°CT90 †:
22.3 (1.5–107.7)
CEM43°CT50 †:
37.3 (3.3–96.0)		 60 HT after RT

  • 3- and 5-year OS: 66% and 49%, respectively.

  • 3- and 5-year LC: 78% and 65%, respectively.

  • The only significant prognostic factor: time between primary and recurrent disease (multivariate analyses)

  • CEM43°CT90 was not analyzed because skin temperature measurements are poor indicators of tumor temperature.
Datta et al. [49] Muscle invasive bladder cancer,
n = 18		 unifocal
cancer:
48.0/16
multifocal
cancer:
50.0/20		 Tavg †:
40.5 ± 0.5
Tmin †:
36.7 ± 0.3
Tmax †:
42.0 ± 0.6		 Ntotal:
4
Nweek:
1		 60 CEM43°C:
59.8 ± 45.6		 15–20 HT before RT

  • 16/21 patients were free from local recurrence until their last follow-up or death.

  • Temperature attained during ttreat was significantly lower in patients with local failure.

  • AUC > 37 °C and AUC ≥ 39 °C were significantly lower in patients who had a local relapse.

  • Nweek and Ntotal, no significant differences between CEM43°C and CEM43°C for T > 37 °C.

  • Tavg: significantly greater in patients with no local bladder failure for both individual and Ntotal.
Leopold et al. [32] Soft tissue sarcoma, n = 45 50.0–50.4
/25–28		 T90 ‡: 39.5
T50 ‡: 41.6
T10 ‡: 43.0
Tmin ‡: 37.7
Tmax ‡: 44.0		 Group A:
Ntotal:
5
Nweek:
1
Group B:
Ntotal:
10
Nweek:
2		 60 n.r. 30–60 HT after RT

  • Strongest predictive value for cumulative minimum T90, average min T90, cumulative minutes of T50, and average minutes T50: 40.5 °C, 40.5 °C, 41.5 °C, and 41.5 °C, respectively.

  • Nweek: 2 were superior to Nweek: 1 with respect to the degree of histopathologic changes, but not predictive.

  • T50 and T90 are substantially temperature distribution descriptors.
Ohguri et al. [94] Non-small cell lung cancer,
n = 35		 45.0–80.0
/23–30		 Tmax ‡: 43.2 (38.9–48.1)
Tavg ‡: 42.6 (38.8–47.0)
Tmin ‡: 41.7 (38.6–45.6)		 Ntotal ‡:
11
(3–17)
Nweek:
1–2		 40–70 n.r. 15 HT after RT

  • CR: 2%, PR: 66%, and NC 10: 14%.

  • Median OS, local recurrence–free, and distant metastasis–free survival times: 14.1, 7.7, and 6.1 months, respectively.

  • Acute toxicity: 14% and late toxicity: 17%.

  • All thermal parameters, Tmin, Tavg and Tmax of intraesophageal temperature significantly correlated with median radiofrequency-output power.

n: number of patients assigned to be treated with HT in combination with RT; †: mean value (±standard deviation) or mean value (range); ‡: median (range); n.r.: not reported; 1 CR: complete response; 2 PR: partial response; 3 SD: stable disease; 4 PD: progressive disease; 5 PTC: pelvic tumor control; 6 DSS: disease specific survival; 7 DFS: disease free survival; 8 OS:overall survival; 9 IFR: in-field recurrence; 10 NC: no change; 11 HDR-IRT: high dose rate interventional radiotherapy; 12 LDR-IRT: low dose rate interventional radiotherapy.