Comparison of the clinical performance of a hybrid Alba 4D and the AMC-4 locoregional hyperthermia systems.

OBJECTIVE: The in-house developed 70 MHz AMC-4 locoregional hyperthermia system has been in clinical use since 1984. This device was recently commercialized as the Alba 4D (Medlogix®, Rome, Italy), with a similar geometrical 4-waveguide design. At the time of this study a hybrid Alba 4D was installed at our center, which incorporated elements of the AMC-4. This study aims to compare clinical performance of both devices. METHODS: During one year after clinical acceptance of the hybrid Alba 4D, both devices were used for treatment delivery in patients scheduled for locoregional hyperthermia. Each patient started with the AMC-4, next sessions were allocated to either device. Possible differences between Alba 4D and AMC-4 sessions in power, achieved temperature T0, T10, T50, T90, T100, treatment time and complaints per session, were evaluated using linear mixed models (LMMs) for repeated measures with patient as random effect. RESULTS: From March 2018 to April 2019, eleven patients with cervical, pancreatic, vaginal carcinoma and uterine leiomyosarcoma received 27 locoregional hyperthermia sessions with the Alba 4D and 34 sessions with the AMC-4. Median number of sessions per patient was 5 (range 3-13). Treatment results for both devices were not significantly different: T50 was 40.5 ± 1.0 °C vs. 40.8 ± 0.7 °C, applied power was 500 ± 79 W vs. 526 ± 108 W, for the Alba 4D vs. AMC-4, respectively. CONCLUSION: Results of the first patients treated with the hybrid Alba 4D demonstrated comparable clinical performance of the Alba 4D and AMC-4 locoregional hyperthermia systems, and both devices are expected to yield similar favorable clinical results.

A randomized phase-II study of reirradiation and hyperthermia versus reirradiation and hyperthermia plus chemotherapy for locally recurrent breast cancer in previously irradiated area.

BACKGROUND: In patients with inoperable local regional recurrences of breast cancer in previously irradiated areas, local control is difficult to maintain and treatment options are limited. The Dutch standard treatment for such recurrences is reirradiation combined with hyperthermia. Apart from enhancing the effect of reirradiation, hyperthermia is also known to improve local effects of chemotherapy like cisplatin. This randomized phase-II trial compares reirradiation and hyperthermia versus the same treatment combined with cisplatin. PATIENTS AND METHODS: From December 2010 up to January 2019, 49 patients were randomized, 27 in the standard arm and 22 in the combined arm. A total of 32 Gy was given in eight fractions of 4 Gy in 4 weeks, at two fractions per week. After January 2015, the radiation schedule was changed to 46 Gy in 23 fractions of 2 Gy, at five fractions per week. Hyperthermia was added once a week after radiotherapy. The combined arm was treated with four cycles of weekly cisplatin 40 mg/m2. RESULTS: Complete response rate was 60.9% in the standard arm and 61.1% in the combined arm (p = 0.87). Partial response rate was 30.4% in the standard arm and 33.3% in the combined arm (p = 0.79). One-year overall survival was 63.4% in the standard arm and 57.4% in the combined arm. One-year local progression-free interval was 81.5% in the standard arm and 88.1% in the combined arm (p = 0.95). Twenty-five percentage of patients in the standard arm experienced grade 3 or 4 acute toxicity and 29% of patients in the combined arm (p = 0.79). CONCLUSION: No potential benefit could be detected of adding cisplatin to reirradiation and hyperthermia in patients with recurrent breast cancer in a previously irradiated area. With or without cisplatin, most patients had subsequent local control until last follow-up or death.

Post-operative re-irradiation with hyperthermia in locoregional breast cancer recurrence: Temperature matters.

PURPOSE: To investigate the impact of hyperthermia thermal dose (TD) on locoregional control (LRC), overall survival (OS) and toxicity in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and hyperthermia. METHODS: In this retrospective study, 112 women with resected locoregional recurrent breast cancer treated in 2010-2017 with postoperative re-irradiation 8frx4Gy (n = 34) or 23frx2Gy (n = 78), combined with 4-5 weekly hyperthermia sessions guided by invasive thermometry, were subdivided into 'low' (n = 56) and 'high' TD (n = 56) groups by the best session with highest median cumulative equivalent minutes at 43 °C (Best CEM43T50) < 7.2 min and ≥7.2 min, respectively. Actuarial LRC, OS and late toxicity incidence were analyzed. Backward multivariable Cox regression and inverse probability weighting (IPW) analysis were performed. RESULTS: TD subgroups showed no significant differences in patient/treatment characteristics. Median follow-up was 43 months (range 1-107 months). High vs. low TD was associated with LRC (p = 0.0013), but not with OS (p = 0.29) or late toxicity (p = 0.58). Three-year LRC was 74.0% vs. 92.3% in the low and high TD group, respectively (p = 0.008). After three years, 25.0% and 0.9% of the patients had late toxicity grade 3 and 4, respectively. Multivariable analysis showed that distant metastasis (HR 17.6; 95%CI 5.2-60.2), lymph node involvement (HR 2.9; 95%CI 1.2-7.2), recurrence site (chest wall vs. breast; HR 4.6; 95%CI 1.8-11.6) and TD (low vs. high; HR 4.1; 95%CI 1.4-11.5) were associated with LRC. TD was associated with LRC in IPW analysis (p = 0.0018). CONCLUSIONS: High thermal dose (best CEM43T50 ≥ 7.2 min) was associated with significantly higher LRC for patients with locoregional recurrent breast cancer treated with postoperative re-irradiation and hyperthermia, without augmenting toxicity.

Thermal Skin Damage During Reirradiation and Hyperthermia Is Time-Temperature Dependent.

PURPOSE: To investigate the relationship of thermal skin damage (TSD) to time-temperature isoeffect levels for patients with breast cancer recurrence treated with reirradiation plus hyperthermia (reRT + HT), and to investigate whether the treatment history of previous treatments (scar tissue) is a risk factor for TSD. METHODS AND MATERIALS: In this observational study, temperature characteristics of hyperthermia sessions were analyzed in 262 patients with recurrent breast cancer treated in the AMC between 2010 and 2014 with reirradiation and weekly hyperthermia for 1 hour. Skin temperature was measured using a median of 42 (range, 29-82) measurement points per hyperthermia session. RESULTS: Sixty-eight patients (26%) developed 79 sites of TSD, after the first (n=26), second (n=17), third (n=27), and fourth (n=9) hyperthermia session. Seventy percent of TSD occurred on or near scar tissue. Scar tissue reached higher temperatures than other skin tissue (0.4°C, P<.001). A total of 102 measurement points corresponded to actual TSD sites in 35 of 79 sessions in which TSD developed. Thermal skin damage sites had much higher maximum temperatures than non-TSD sites (2.8°C, P<.001). Generalized linear mixed models showed that the probability of TSD is related to temperature and thermal dose values (P<.001) and that scar tissue is more at risk (odds ratio 0.4, P<.001). Limiting the maximum temperature of a measurement point to 43.7°C would mean that the probability of observing TSD was at most 5%. CONCLUSION: Thermal skin damage during reRT + HT for recurrent breast cancer was related to higher local temperatures and time-temperature isoeffect levels. Scar tissue reached higher temperatures than other skin tissue, and TSD occurred at lower temperatures and thermal dose values in scar tissue compared with other skin tissue. Indeed, TSD developed often on and around scar tissue from previous surgical procedures.

A flexible 70 MHz phase-controlled double waveguide system for hyperthermia treatment of superficial tumours with deep infiltration.

PURPOSE: Superficial tumours with deep infiltration in the upper 15 cm of the trunk cannot be treated adequately with existing hyperthermia systems. The aim of this study was to develop, characterise and evaluate a new flexible two-channel hyperthermia system (AMC-2) for tumours in this region. MATERIALS AND METHODS: The two-channel AMC-2 system has two horizontally revolving and height adjustable 70 MHz waveguides. Three different interchangeable antennas with sizes 20 × 34, 15 × 34 and 8.5 × 34 cm were developed and their electrical properties were determined. The performance of the AMC-2 system was tested by measurements of the electric field distribution in a saline water filled elliptical phantom, using an electric field vector probe. Clinical feasibility was demonstrated by treatment of a melanoma in the axillary region. RESULTS: Phantom measurements showed a good performance for all waveguides. The large reflection of the smallest antenna has to be compensated by increased forward power. Field patterns become asymmetrical when using smaller top antennas, necessitating phase corrections. The clinical application showed that tumours deeper than 4 cm can be heated adequately. A median tumour temperature of 42 °C can be reached up to 12 cm depth with adequate antenna positioning and phase-amplitude steering. CONCLUSIONS: This 70 MHz AMC-2 waveguide system is a useful addition to existing loco-regional hyperthermia equipment as it is capable of heating axillary tumours and other tumours deeper than 4 cm.

Reirradiation and hyperthermia for radiation-associated sarcoma.

BACKGROUND: The objective of this study was to evaluate the role of reirradiation and hyperthermia in the treatment of radiation-associated sarcoma (RAS) in the thoracic region, which is an increasing, yet extremely rare condition with a poor prognosis. METHODS: Between 1979 and 2009, 16 patients with RAS in the thoracic region were treated in the Academic Medical Center and the Institute Verbeeten with reirradiation and hyperthermia. In 13 patients, this treatment was given for unresectable disease and 3 times after resection as adjuvant treatment. The median latency period between the original malignancy diagnosis and the RAS diagnosis was 86 months (range 19-212 months). Histology was angiosarcoma in 11 patients (69%). The literature on reirradiation with or without hyperthermia for RAS was reviewed. RESULTS: The median survival was 15.5 months (range, 3-204 months). Four patients were not evaluable for response. The response rate for the remaining 12 patients was 75% (7 complete responses and 2 partial responses). Six patients remained free of local failure until death (5 months and 7 months) or last follow-up (8 months, 11 months, 39 months, and 68 months). CONCLUSIONS: The current study indicates that combined reirradiation and hyperthermia for RAS in the thoracic region is feasible. The high response rate and the possibility of durable local control suggest that this treatment is promising.