Purchasing of the ALBA Hyperthermia System for the Radiation Oncology Department of S. Camillo Medical Hospital, Rome

Project location: ITALY, Rome
Project start date: July 2009 - Project end date: This project covers various years
Project number: 2009-12
Beneficiary: ASPRO Onlus

[2010-75]

In consideration of the Oncological Hyperthermia Service offered by the San Camillo-Forlanini Hospital, thanks to the contribution of the Nando Peretti Foundation, having seen the effectiveness of treatments already achieved with this method and the increasing number of patients who come to the San Camillo-Forlanini Hospital to perform this kind of treatment, together with the traditional therapies, it became necessary to improve the existing staff adding two technicians into the hyperthermia unit of the radiotherapy department, with the purpose to create an excellence in the breast cancer and chest wall recurrencies treatment.

The second NPF grant was then initially used to guarantee the presence of:

1. A new radiotherapist medical technician, qualified to perform oncological hyperthermia. The radiotherapist medical technician is the medical operator qualified to perform all the kind of therapies that need ionizing artificial or natural radiations, thermal energies, ultrasonic sources.
2. A biomedical engineer in charge to integrate the hyperthermia treatment with the traditional therapies performing specific treatment planning systems to prepare, check, evaluate and register the hyperthermia treatment session and to collect the data to optimize the hyperthermia treatment for follow-up studies. The biomedical engineer is the interface between the clinical staff working in a hospital and the technological innovations that are available for the health of the population.

In the Department of Radiotherapy San Camillo-Forlanini Hospital in Rome, during the period between January 2011 and June 2011 eight sessions of hyperthermia in combination with radiation therapy were performed.

The sessions were given to patients with recurrent breast cancer (ductal carcinoma histologically) who have already undergone quadrantectomy surgery and post-operative radiotherapy at the onset of the illness and again been subjected to surgical resection of local recurrence in the scar.

Radiation treatment has been set using energy photons of 6 MV with variable collimators, for a total dose of 40 Gy delivered in 20 fractions.

Irradiation treatments up to a maximum of 1 hour were perfomed by superficial/deep seeds hyperthermia applications with the Alba Hyperthermia System, which operates at a frequency of 434 MHz and equipped with a generator can supply a maximum power of 200 W. Hyperthermia sessions were performed 1-2 times a week at a distance of 48-72 hours, in order to limit the phenomenon of heat tolerance, that the physiological increase cellular resistance to heat in the hours immediately following therapy. The irradiation of tissues was obtained by applicators CCMA (Contact Curved Microstrip Applicator) in particular, using the antenna Beta, able to cover a treatment area of 240 cm2, with an EFS (Effective Field Size) of 96 cm2. During the treatment a bolus containing deionized water was placed between the applicator and the patient, in order to improve the coupling, allowing the maximum power transfer between antenna and tissue, and in order to avoid excessive heating of the skin and subcutaneous adipose tissue. A minimum temperature of 41oC was set as a target temperature level of the lesion. The total duration of treatment was chosen equal to 1 hour, with a range of 5 / 10 minutes necessary to achieve initial transient hyperthermic temperatures. The average power was set at 65 W (50-80W).

During treatment, four T-type thermocouple sensors were used for detecting the temperature reached the surface. To view and accurately locate the lesion we have used a sonographic system directly connected to the hyperthermia apparatus and integrated with the owner of handling software.

Tolerance to treatment was evaluated according to the scale of toxicity CTC v3.0. The analysis resulted in an acute skin toxicity G1. It was not possible to evaluate the late toxicity related to combined treatment for brevity of follow-up.

During the period of use of the system Alba, has been required discontinuation of treatment due to a technical failure of equipment by structural alteration of the applicator CCMA (contact Curved Microstrip Applicator) of 240 cm2 (antenna Beta) with consequent modification of the transmission power antenna to the tissues. It has therefore been necessary to stop any further applications with resulting impact on continuity of treatment.

In the final months of the NPF-sponsored project, it became necessary to replace the two technicians with a medical figure, who could work on the scientific dissemination of project results in order to improve the application, the study and the diffusion of the hyperthermia device and its use. The second installment of the NPF grant was then used to sponsor a ten-month scholarship for a young doctor, Giovanni De Pascalis M.D., who worked to an in-depth analysis of the use and knowledge of this technology.

By the literature we know that after mastectomy and adjuvant radiotherapy, relapse rates are of 5-15% and chest wall involvement is 60-95% of the cases. Chest wall recurrence can often cause symptoms that adversely affect the quality of life. The presence of a chest wall recurrence is regarded as a poor prognostic indicator with a total of 5 years survival rates range from 20 to 45%. Radio-hyperthermia has his own rationale in these patients because the warm directed to the relapse influence radiobiological mechanisms who control radiotherapeutic damages. Most publications speaking of radio-hyperthermia chest wall recurrence from breast cancer report an local control and overall survival improvement compared to re-irradiation alone. Literature reports that this kind of combined therapy is linked to low rate of early and late toxicities compared to radiotherapy alone.

Based on the considered literature, the project financed by Nando Peretti Foundation has been directed to the study and the hi-depth analysis of the knowledge of the re-irradiation with radio-hyperthermia of chest wall recurrences.

Since December 2011, Doctor Giovanni De Pascalis M.D. has been working on the hyperthermic treatment delivery for patients who underwent radiotherapy. In the period from December 15th 2011 to October 15th 2012 he made 58 superficial hyperthermic applications.

Every treatment was preceded by an ultrasound scan evaluation to well define depth and extension of the treatment region. Radiotherapy course is made by 20 fractions of 2 Gy for a total dose of 40 Gy using electron beam of 6 MeV directed to the chest wall recurrence. The radiotherapy is made every day from Monday to Friday. Every Tuesday and Thursday the patients undergo hyperthermia. This treatment is made not more than a hour late from radiotherapy and it lasts 60 minutes. So the patient goes to the hyperthermic room and lays on a couch. The operator put the termocouples (superficial thermometer) to detect the real temperature on the skin and the applicator (warm and radio-frequency delivered) on the chest wall based on the planning made during the first treatment of which we have a photographic documentation. When we get 40 oC of superficial temperature, hyperthermic treatment starts. During the treatment the operator follows the curves of the temperature registered by the termocouples on the display, taking care that its value is in the referring range and that the patient doesn't suffer from excessive warm.

The irradiation of tissues was obtained by applicators CCMA (Contact Curved Microstrip Applicator) in particular, using the Beta applicator, able to cover a treatment area of 240 cm2, with an EFS (Effective Field Size) of 96 cm2. One patient was treated with the Gamma applicator, with an area equal to 420 cm2 and an EFS of 216 cm2.

Doctor De Pascalis has also followed every patient after the end of the therapy, initially once a month and later on a three-month basis.

Tolerance to treatment was evaluated according to the CTC v3.0 scale of toxicity. The analysis showed that three patients reported two G1 acute dermal toxicity, while in one patient there was a dermal toxicity G2 and in one patient was a dermal G3 toxicity. The results obtained were the following with a Complete Response (CR) after 12 months in two patients; Complete Response (CR) after 6 months in one patient; Partial Response (PR) after 6 months in one patient.

This activity has been documented and divulged in the followed ways:

1) Presentation entitled "Radio-hyperthermia in the chest wall recurrence" realized at Breakfast meeting on 29/03/2012 at S. Camillo-Forlanini Hospital in Rome in the presence of all the doctors working in the hospital.

2) Publication of the poster (Abstract number 10057) entitled "Radio-hyperthermia (RT-HT) in the retreatment of superficial breast cancer recurrences" (First author : Giovanni De Pascalis) showed at 11th

International Congress of Hyperthermic Oncology and 29 the Japanese Congress of Thermal Medicine (ICHO&JCTM 2012) realized in Kyoto from 28th to 31st of August 2012.

3) Publication of the poster entitled "The recurrence of breast cancer treated by radiotherapy (RT) and Hyperthermia (HT)" (First author : Giovanni De Pascalis) showed at XXIIo Congresso AIRO 2012 that will be in Roma from 17th to 20th November 2012 There will be a review on the thermometric evaluation in radio-hyperthermia in collaboration with Istituto per la Ricerca e la Cura del Cancro di Candiolo (Torino).

Radio-hyperthermia activity in the treatment of chest wall breast cancer recurrences is currently a strength of the S. Camillo forlanini Hospital in Rome. This project aims now at extending this treatment to melanoma malignance. Moreover, the best time and way to approach combined treatment with the traditional therapies has to be considered, to insert hyperthermia into routine work.