SUPERFICIAL AND SEMIDEEP434 MHZ RADIATIVE HYPERTHERMIA

ALBA ON 4000D CLINICAL INDICATIONSWITHOUT HT

Standard therapy DNA damage DNA repair Sub-lethal DNA damage

HYPERTHERMIA CLINICAL EVIDENCE

Several phase III randomized clinical studies have

already shown the benefits of adding hyperthermia

to standard therapies (chemo-radiotherapy).

Response rates, local control and overall survival

are often 1.5 times higher than with radiotherapy or

chemotherapy alone, without inducing additional

side effects [1,3].

RT dose (Gy)

“shoulder”

RT

Potentially lethal DNA damage

Fraction surviving

cells

Effect without HT Effect with HT

HYPERTHERMIARADIO-BIOLOGICAL RATIONALE

Hyperthermia (HT), heating tumors in the range

41-43°C, is a powerful radio and chemosensitizer.

The effectiveness of HT as well as its safety, in

combination with radiotherapy and chemotherapy,

has already been proven in phase III clinical trials

[1,3], particularly in patients with very large or very

advanced stages of cancer and recurrent tumors.

HT enhances the effect of radiotherapy on the tumor,

without additional toxicity for healthy tissues, by

means of three synergistic mechanisms:

(1) Inhibition of DNA damage repair: HT enhances

the effectiveness of radiotherapy by inhibiting repair

of DNA damage [2,4,5,6].

(2) Direct cell killing: HT selectively kills radioresistant

hypoxic tumor cells [2]

(3) Reoxygenation: HT increases tissue perfusion

resulting in reoxygenation, thereby reducing hypoxia

and increasing radiosensitivity [2,6,7]

With regards to chemotherapy, hyperthermia targets

its action within the heated tumor region without

affecting systemic toxicity[8]. It has also been shown

that local hyperthermia has the capability of inducing

systemic anti-tumor immune responses [1].

CH

RT

COMPLETE RESPONSE

WITH HT

Standard therapy plus hyperthermia HT induced re-oxygenation, direct

cell killing, increased intratumoral

drug uptake, enhanced tumor DNA

damage

DNA repair inhibition Sub-lethal DNA damage becomes lethal

RT dose (Gy)

RT

RT + HT

Fraction surviving

cells

100

10-1

10-2

10-3

10-4

2 4 6 8

CHO2

HT

RT

Head and Neck tumors

Breast tumors

Melanoma

Soft tuissue sarcoma

Chest wall recurrences

Cutaneous lymphoma

ALBA ON 4000D is certified to treat:

32

4 5

“SAR absorption comparison between a Radiative 434MHz microstrip type applicator vs 13.56 MHz capacitive

electro hyperthermia electrodes”

The curved ALBA ON 4000D

applicators are designed to adapt

to the curved anatomy of the

patient.

ALFA66 cm²

BETA96 cm²

GAMMA216 cm²

DELTA440 cm²

ALBA ON 4000D TECHNOLOGY

The ALBA ON 4000D is a radiative hyperthermia system working at a fixed frequency of 434MHz. The unit is

equipped with radiative technology curved microstrip applicators with an integrated water bolus to safely and

effectively heat targets, in the range of 41-43°c, for 60 minutes, as required by the ESHO (European Society for

Hyperthermic Oncology) guidelines (9).

EFFECTIVE POWER DEPOSITION

The multiple radiative microstrip applicators of ALBA ON 4000D are curved at a fixed radius and are perfectly tuned

at 434MHz. The high efficiency and homogeneity (no hot-spots) allow hyperthermia treatments at a depth of up to

40 mm +/- 5 mm as demonstrated both in phantoms (10,11) and in patients (12,13).

40mm +\- 5 mmDEPTH

6 7

As an option ALBA ON 4000D can be connected to an external ultrasound scanner useful also to position applicator

and temperature sensors on the target

Heating with a capacitive system yields the maximum SAR in the fat layer, whereas the radiative CFMA has its

maximum in muscle tissue.

POSITIONING SOLUTIONS

ALBA ON 4000D is supplied with specific tools which display the EFS (Effective Field Size) in 2D and the E-Field direction

of each applicator. These tools allow both a correct selection of the best applicator with respect to the lesion geometry

and the perfect alignment of the max SAR of the applicator with the central axis of the lesion.

RADIATIVE VS CAPACITIVE

ALBA Radiative curved applicators guarantee a very favorable SAR (Specific Absorption Rate) both on muscle and

heterogeneous tissue targets and a very low power density in fat tissue. This uniqueness results in more favorable

SAR and temperature distribution for superficial tumor locations, compared to Capacitive Electro-Hyperthermia

electrodes characterized by a power absorption in the poorly perfused fat tissue much higher than in muscle tissue,

which produces lower target temperatures with the risk of overheating heterogeneous normal tissue (14).

Results - Applicators on Phatom 3

8 9

The pre-treatment picture of the target area with

the points of interest where temperature sensors

have been positioned is downloaded onto the ALBA

ON 4000D Treatment SW to show in real time the

temperature reached on the specific target.

Temperature readings recorded throughout the

treatment are stored in the database for post

processing data analysis.

DOSIMETRY

An embedded multichannel thermometer detects real time temperature readings in up to 32 sensors positioned

on the patient skin or in the target volumes. Totally immune to radiofrequency interference, the ALBA ON 4000D

thermometer guarantees very fast detection of the temperature sensors at the remarkable precision of +/- 0.2°C.

Alfa applicator on a head

and neck lesion.

Beta applicator on a

supraclavicular lesion.

Gamma applicator on a chest wall

recurrence.

The modular ALBA ON 4000D platform allows for the

simultaneous use of two applicators, also of different

sizes if necessary, on the same patient to treat larger

lesions on a chest wall recurrence.

A single external PC console synchronizes the use

of two ALBA ON 4000D systems treating different

locations on a patient with an independent control of

power and water temperature for each applicator/

lesion.

ERGONOMY

ALBA ON 4000D is user-friendly, intuitive and easy to install in any outpatient room. It is mounted on wheels which

allow the operator to move the unit according to the need. The mechanic structure and its ergonomy makes it easier

for the operator to interact with the patient for the treatment of different anatomic sites.

10 11

An example of a 3D temperature simulation of Plan2Heat based on a patient specific 3D CT Scan image and a 3D

ALBA Applicator SAR simulation.

CT scan of patient target Dielectric tissue type property assignment according to

automatic Hounsfield unit recognition

Temperature simulation performed by Plan2Heat

44°C.42°C40°C38°target

QUALITY ASSURANCE

Temperature accuracy and efficient SAR deposition are key elements to be controlled during the lifetime of the

ALBA ON 4000D. Quality assessment, according to ESHO guidelines (15), can be performed using a specific kit to

calibrate all temperature sensors and a dedicated anatomic phantom (muscle type) for ALBA applicator 3D SAR

evaluation.

TPS

ALBA ON 4000D can be provided with a hyperthermia treatment planning software PLAN2HEAT in continuous

development in collaboration with Amsterdam UMC (Amsterdam University Medical Center). The goal is to find the

optimal setting to maximize the power deposition in the target area while preserving the surrounding healthy tissue.

PLAN2HEAT is able to calculate the power absorption, the consequent temperature distribution and the optimized

setting in a 3D patient-specific anatomy model generated from patient CT/MRI images.

12 13

ALBA DATA MANAGEMENT SYSTEM

The ALBA ON 4000D Data Management System offers an integrated data management solution which allows to

import patient data as DICOM Worklist and export treatment reports in PDF to Hospital Information System (HIS).

Treatment of raw-data is stored in standard xml files. This allows for post-processing and simplifies data sharing

which is useful for data analysis within clinical trials.

INTEGRATION WITH RADIOTHERAPY PACS SYSTEM

The ALBA ON 4000D software is designed to be fully integrated with the radiotherapy PACS systems in order to

introduce hyperthermia more easily into the radiotherapy workflow from treatment planning to the treatment itself.

HT - TPS

HT Treatment

14 15

BIBLIOGRAPHY

1. Datta NR, Ordóñez SG, Gaipl US, Paulides

MM, Crezee H, Gellermann J, Marder D, Puric

E, Bodis S. Local hyperthermia combined with

radiotherapy and-/or chemotherapy: recent

advances and promises for the future. Cancer

Treat Rev. 2015 Nov; 41(9):742-53.

2. Hans Crezee, Caspar M. van Leeuwen,

Arlene L. Oei, Lukas J.A. Stalpers, Arjan

Bel, Nicolaas A. Franken & H. Petra Kok.

Thermoradiotherapy planning: Integration in

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of Hyperthermia Vol. 32 , Iss. 1,2016.

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European Organization for the Research and

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