Session Item

The treatment of unresectable local recurrences of superficial tumors in pre-irradiated areas is a major challenge when the option of re-irradiation (re-RT) using standard dose is questionable due to expected unacceptable toxicity.

A novel treatment protocol of contact-free thermography-controlled superficial hyperthermia (HT) using water-filtered infrared-A (wIRA) irradiation immediately followed by hypofractionated re-RT of 20 Gy total dose (5 x 4 Gy, 1x/week) has shown a most favorable toxicity/efficacy profile in the treatment of large-sized, locally recurrent breast cancer (Notter et al., Cancers 2020).

Different (radio-)sensitizing mechanisms of HT require different temperature ranges. Whereas the inhibition of DNA repair requires HT-levels ≥41.5°C, O₂-dependent mechanisms can already operate at ≥39°C, and may be counteracted at temperatures ≥43°C. Using mild HT immediately before re-RT, O₂-dependent radiosensitizing mechanisms thus may play a key role.

Experiments on healthy volunteers were performed using the wIRA-hyperthermia system hydrosun^®TWH1500 (Hydrosun, Germany) with approval of the local ethics committee. At automatically controlled maximum skin surface temperatures of 43°C, temperature profiles within the abdominal wall were measured with fiber optic sensors (OTG-M600, Opsens, Canada) at defined tissue depths of 1-20 mm. Corresponding pO₂ values were assessed with the OxyLite-Pro system (Oxford Optronix, UK). Hyperspectral tissue imaging (TIVITA, Diaspective Vision, Germany) was used to visualize the HbO₂- oxygenation status of upper skin layers, and of superficial tumors in selected patients.

Within 5-12 min of wIRA-exposure, mean skin surface temperatures increased from 34.6 to 41.6°C. Upon steady state conditions, mean maximum temperatures of 41.8°C were found at a tissue depth of 1 mm, with a steady decline in deeper layers (41.6°C @ 5 mm, 40.8°C @ 10 mm, 40.6°C @ 15 mm, 40.1°C @ 20 mm). Tissue heating was accompanied by a significant increase in tissue pO₂, e.g., at a depth of 13 mm mean pO₂ rose from 46 to 81 mmHg. In the post-heating phase (+15 min), pO₂ was still elevated (72 mmHg), even though tissue temperatures had returned to normothermia (36.7°C). pO₂ values remained above baseline for 30-60 min post-heat. Non-invasive HbO₂ monitoring in the subpapillary dermis layer of normal skin and in recurrent breast cancers confirmed the improved O₂ status caused by wIRA-HT.

wIRA-hyperthermia (T = 39-43°C) leads to a distinct pO₂ rise in superficial tissues, which is essential for radiosensitization. This benefit of improved tissue oxygenation is only present if HT is applied shortly before radiotherapy. Effective HT levels needed for inhibition of DNA repair could be observed up to a tissue depth of ≈5 mm, as present, e.g., in lymphangiosis carcinomatosa. Effective HT levels for improved oxygenation (T ≥ 39°C) can be measured up to a tissue depth of ≈30 mm.