WO2023017551A1

WO2023017551A1 - Device for radiotherapy treatment

Info

Publication number: WO2023017551A1
Application number: PCT/IT2022/050227
Authority: WO
Inventors: Vincenzo PATERA; Luigi Palumbo; Mauro MIGLIORATI; Massimo DI FRANCESCO; Giuseppe FELICI; Salvatore Barone; Vincenzo Galasso
Original assignee: S.I.T.-Sordina Iort Technologies S.P.A.
Priority date: 2021-08-11
Filing date: 2022-08-09
Publication date: 2023-02-16
Also published as: IT202100021740A1

Abstract

The present invention relates to a device for radiotherapy treatment, in particular, an accelerating structure (10) comprising at least one radiofrequency accelerating cavity (12). Advantageously, the accelerating structure (10) is made of a low atomic number or Z material and comprises the deposition of a layer (11 ) of a further low atomic number or Z material, so as to reduce a weight of the accelerating structure (10), keeping it shielded, and reducing the scattered radiation to the patient.

Description

DEVICE FOR RADIOTHERAPY TREATMENT

The present invention relates to a device for radiotherapy treatment of oncological patients.

More in detail, the invention relates to a device for radiotherapy treatment, in particular, a linear accelerator, preferably for radiotherapy of the "Flash" type and for industrial applications.

It is well known that radiotherapy is a well-established tool in the treatment of oncological patients and together with surgery and chemotherapy has significantly improved both the final prognosis and the patients' quality of life.

The effectiveness associated with radiotherapy treatment lies in the ability to target diseased cells with a radiation dose high enough to be curative, while limiting damage to surrounding healthy tissue.

Several strategies are implemented to provide effective treatment: a) Optimisation of the ballistics of the beam: different ionising radiations and technologies are chosen according to the tumour to be treated, using, with the external beams, different input fields; in this way, 'conformed' dose distributions are obtained on the target to be treated, with a dosimetric saving of the adjacent healthy tissues.

(b) Optimisation of radiobiological parameters: whenever possible, the radiobiological data derived from the fact that healthy tissues recover better and earlier than diseased tissues from sub-lethal radiation damage at the cellular level are exploited. In this way, it is possible to be very effective on the tumour while limiting damage to healthy tissue, by fractioning the treatment dose. In fact, for example, a standard technique in radiotherapy is fractioned treatment in a series of 2 Gy treatments per day, to be repeated until the prescribed dose (60 - 80 Gy) is reached.

Ultimately, the efficacy of radiotherapy treatment is determined by the possibility of having a 'therapeutic window' (see the diagram in Figure 1 attached, where the 'therapeutic window' is defined as the distance between the curves) between the curative dose to the target (upper curve in Figure 1 ) and the damage to healthy tissue (lower curve in Figure 1 ). Prognosis is closely related to the existence of this 'therapeutic window'; cancers with a more complex prognosis are those where it is complicated, if not impossible, to deliver effective target doses (good probability of cure) without limiting complications.

Consider, by way of example but not exhaustively, pancreatic cancer, which today has a decidedly inauspicious prognosis, characterised by a five-year survival rate of less than 20%, even in the most favourable cases.

The treatment of these difficult tumours, which have withstood the impressive technological development in the field since the 1980s, requires new ideas, techniques and discoveries.

Radiotherapy is currently administered through multiple devices: radioisotopes, linear accelerators in electron and/or X-ray mode, cyclotrons for protons and/or carbon ions.

However, all these technologies are united by a dose rate that varies but is essentially limited to a few Gy per minute.

Some research demonstrated an unexpected and potentially revolutionary phenomenon: by using a much higher dose rate, defined as the 'Flash' effect, and amounting to around 40 Gy/s, which is higher than the standard by a factor of more than 1000, the ratio of damage to diseased cells compared to healthy tissue was no longer that achievable with standard dose rates, but much more advantageous. For example, it was possible to completely cure lung cancer in guinea pigs without the side effects of the standard technique.

Through this research, it was shown that in the 'Flash' range, the so- called 'therapeutic window' (see diagram in Figure 1 ) was significantly larger, suggesting a higher probability of a positive prognosis for tumours that were not yet curable, thus making what is not curable today curable, and significantly improving the quality of life of cancer patients.

Generally, the scattered radiation generated by a medical linear accelerator can be divided into the following different categories:

(1 ) Direct beam; this component is not present in an IORT treatment as the beam is entirely collimated on the target and absorbed;

(2) Leakage radiation (LR); (3) Patient-produced radiation (patient scattered radiation PSR); the PSR has a 'cardioid' shape and peaks along the beam direction;

(4) Wall scattered radiation (wall scattered radiation WSR); in general, for each point the WSR can be expressed as the sum of LR and PSR;

(5) Secondary radiation (including photonutrons and gamma rays by neutron capture) produced in the radiating head or by interaction with elements in the room.

It is therefore clear that it is crucial to minimise the leakage or LR leakage radiation component in order to minimise the total amount of scattered radiation, since the radiation scattered by the PSR patient is in no way modifiable.

Furthermore, in medical linacs the LR leakage radiation is significantly higher than the scattered radiation from the PSR patient, in particular, up to four orders of magnitude higher, with the sole exception of IORT accelerators.

In particular, scattered radiation poses two different problems: a. the radiation protection of the patient; b. the radiation protection of the operators.

The radiation protection of the patient implies the need to shield the LR leakage radiation to reduce it below stringent limits set by regulations, as can be seen in figure 2. In particular, in figure 2, the electron gun is indicated with the numerical reference 100, the electron path from the electron gun 100 with the reference 101 , and the target with 102. Also in figure 2, reference 103 indicates the protective shielding and reference 104 the measurement limit for escape radiation outside a patient plane 105.

Again in Figure 2, reference 106 indicates the isocentre defined by the intersection between the reference axis X and the patient plane 105; finally, reference 107 indicates the normal treatment distance, which is the distance between the target 102 and the patient plane 105.

What has been described above, makes clear the need to limit the LR leakage radiation as much as possible, thus allowing the size and weight of the mechanical structure housing the linac to be optimised while respecting the regulatory limits for patient radiation protection.

Thus, both for IORT applications (energy less than or equal to 12 MeV) and for VHEE Very High Energy Electrons applications with external beams (energy between 50 and 250 MeV) the need to shield LR plays a fundamental role.

Thus, the possibility of limiting or even eliminating the shielding of the linac makes medical devices simpler, lighter and cheaper by de-facto affecting the actual possibility of clinical practice.

A further relevant issue is that of beam acceleration in the accelerating structure. Indeed, part of the accelerated electron beam interacts with the copper accelerating structure, producing X-rays via Bremsstrahlung. This phenomenon is clearly illustrated in Figures 3A-3D, which show, by way of example only, a 10 MeV liac with Emax= 27 MV/m on the axis and electron gun (e-gun) 12 KV 50000 e-. In detail, these figures show, starting from the second RF cavity of the particle accelerator to the last, how approximately 20% of the injected beam is lost. In detail, a significant portion of these electrons interacts unfavourably with the linac, generating the leakage radiation or LR leakage, discussed in the previous section.

In addition to the above, producing a dose per pulse sufficient to cause the flash effect requires the acceleration of high beam currents, significantly higher than is common in radiotherapy.

This naturally causes increased scattering between the electron beam and the accelerating copper structure, resulting in increased production of high-energy photons due to Bremsstrahlung.

The main purpose of the present invention, therefore, is to realise a device for radiotherapy treatment, which is such that it overcomes the problems of the known art.

A further purpose of the present invention is to realise a device for radiotherapy treatment of the compact type and which gives the possibility of implementing a correct and precise positioning of the linac without oversizing the relevant structure. A further scope of the present invention is to realise a device for radiotherapy treatment which is such that it can operate in "Flash" mode, both intraoperatively, VHEE and in industrial applications, such as a linac for non-destructive testing.

A further scope of the present invention is to realise a device for the radiotherapy treatment of oncological patients, which allows to drastically reduce the LR leakage radiation to the patient and the reduction of the necessary shielding in the bunker.

Not least of the objects of the present invention is also to realise a device for the radiotherapy treatment of oncological patients which allows, in particular for medical IORT linear accelerators, to reduce the weight of the structure, the necessary shielding and to overcome the problem of triggering, as will be further explained below.

These and other purposes are achieved by a device for the radiotherapy treatment of oncological patients according to claim 1 appended hereto; other detailed technical characteristics are contained in subsequent claims.

An embodiment still object of the present invention is a device for radiotherapy treatment, as will be more fully described herein, according to a preferred but not exclusive embodiment of the present invention and with reference to the accompanying drawings, wherein figure 1 schematically shows a diagram relating to the known concept of a "therapeutic window" in radiotherapy; figure 2 schematically shows an exemplary typology of radiation protection with LR leakage radiation shielding, in particular, for accelerators with energy up to 50 MeV see IEC 60601 -2-1 , § 201.10.1.2.104.1 and § 201.10.1.2.104.2

Figures 3A-3D schematically show the problem of beam acceleration within the accelerating structure, in particular, the fact that part of the beam interacts with the accelerating structure, getting lost and producing X- radiation through Bremsstrahlung;

Figures 4A-4B show, for illustrative purposes only, schematic simulations of what happens to the beam when the accelerating structure is made of low atomic number (Z) material with a deposition (coating) of a copper layer;

Figures 5A-5B show, similarly to Figures 4A-4B, for illustrative and exemplary purposes only, what happens to the beam when the low atomic number accelerating structure has an aluminium coating layer;

Figures 6A-6B show, as in the figures above, for illustrative purposes only, simulations of what happens to the beam when the low-Z accelerating structure has a carbon coating layer;

Figures 7A-7G show, again for illustrative and illustrative purposes only, a simulation of the spectra and angular distribution of photons from beams with different energies (5, 10, 50 and 100 MeV, respectively), interacting with 2 mm copper, aluminium and silicon carbide, respectively.

Figure 8 shows a schematic illustration of what happens, as an example, to an IORT machine, in which X-radiation is produced along the axis of the beam, according to the present invention;

Figure 9 is a schematic illustration of a cavity of the accelerating structure made of copper and low-Z material with deposition of a copper surface layer;

Figure 10A shows a further view of the cavity of figure 9, in particular, a side view and in longitudinal section;

Figure 10B shows a detail of Figure 10A, according to the present invention.

With reference to the figures, generically, the device for radiotherapy treatment is an accelerating structure and is identified by the numerical reference 10. More in detail, such an accelerating structure 10 is such as to operate, by way of example only, in "Flash" mode, both intraoperatively and VHEE and in industrial applications, such as in the case of a linac for nondestructive testing.

In particular, the problems outlined above in the description of the known art, can be overcome, advantageously, by means of a new technological paradigm comprising the realisation of the accelerating structure 10 in material with low atomic number Z with, on top, a thin deposition (coating), total or partial, as will be described later, of a further layer 1 1 of material with low atomic number (Z), preferably copper, to achieve all the optimal effects analysed above.

In fact, it is well known that the fraction of energy carried by electrons that is transformed into photons, identified by the radiative Stopping power depends on the atomic number Z quadratically:

As an example, as can be seen in Figures 4A-4B, 5A-5B and 6A-6B, a first semi-quantitative analysis is carried out using the data provided with respect to three different materials: copper, aluminium and carbon, respectively.

The data show the stopping power mass (Figures 4A, 5A and 6A) and the fraction of energy transformed into photons, i.e. the radiation yield, (Figures 4B, 5B and 6B).

Advantageously, these figures immediately show the advantage of using materials with a lower atomic number Z, considering Carbon as the 'optimum' material.

Also advantageously, confirming the above, a more precise analysis was obtained by means of Monte Carlo simulation with the Fluka code.

The graphs shown in Figures 7A-7G illustrate the spectra and angular distribution of photons produced by beams with different energies (5, 10, 50 and 100 MeV) interacting with 2 mm copper, aluminium and silicon carbide. As can be seen in Figures 7A-7G, reference A shows the curve representing the energy (Fig. 7A-7D) and/or angle (7E-7C) of the photon on copper, B on aluminium and C on silicon carbide.

In more detail, the analysis performed shows that the choice of materials with a low atomic number Z has a dual effect: not only is the production of X-rays significantly lower, but the angular distribution is also profoundly different. Just as an example, copper is such a material that it provides a much higher fraction of scattered electrons at angles greater than 20°. This requires more shielding of the particle accelerator 10, e.g. linac.

As can already be seen in figure 2, the EN 60601 -2-1 standard is also illustrated schematically in figure 8. In detail, this figure relates to a linac dedicated to IORT, although, advantageously, this concept is easily generalisable for a linac from VHEE as well as for a linac dedicated to industrial applications.

Advantageously, the material to be chosen for making the 'bulk' of the accelerator structure must have, by way of example only, the following technological requirements:

- Present adequate hardness and workability;

- Allow the deposition of materials with low atomic number Z, preferably copper on the surface; - Have a sufficiently low atomic number, e.g. compared to copper (Z

= 29)

- Maintain solid structure up to the temperatures required for solderbrazing processes between parts (T > 800 °C);

- Have good thermal conductivity (conversely, a specific cooling system is required inside the cavity to dissipate the heat generated by the radiofrequency needed to create the accelerating electric fields).

Below are the chemical and physical properties of some of the materials considered, starting with copper and ending with carbon, the most advantageous element in terms of low X-ray production.

Based on these data, silicon carbide may be a particularly interesting solution, due to its high hardness, high melting temperature and good thermal conductivity.

Advantageously, among the aforementioned low-Z materials, and also depending on the project's need for both the level of maximum radiation or leakage and the available budget, each of the materials analysed above can be used as an alternative to copper.

Additionally, as can be seen in the figures, the numerical reference 1 1 indicates a layer of low-Z material that is used as a covering/coating of the cavities 12 of the accelerating structure 10.

In detail, the definition of the thickness of the layer 1 1 of low atomic number material, preferably copper, must meet the following requirements:

1 . Being greater than the 'penetration thickness' of the electric field in the conductor, which is calculated as

where co is the frequency of the incident wave, /z₀ the vacuum permeability (1.256-1 O’⁶ H/m) and o the conductivity of the material ( for copper o ~ 5.88- 10⁷ Q-¹m-¹).

The condition is fulfilled for thicknesses greater than a few microns (3 pm for the S-band, 2998 MHz, 2.2 pm for the C-band, 5712 MHz, 1 .7 pm for the X-band, 9000 MHz);

1. Be capable of withstanding electrical discharges with typical intensities of 50 MV/m;

2. Be such as to allow Bremsstrahlung to be minimised.

Advantageously, an optimal solution is therefore represented by a layer 11 of cavity lining 12 having a thickness between 5 and 100 pm. In addition, with regard to the realisation of cavity 12, two types of solutions can be envisaged, depending on the different bulk materials:

- Integral realisation of the cavity 12 in low Z material coated with the layer 11 , preferably copper;

- Realisation in low-Z material only of the central part of cavity 12, where the probability of scattering with the electron beam is greater.

It should be noted that the realisation in low-Z material only of the central part of the cavity 12, as described in point 2 above, allows the brazing process to be left unaltered, e.g. of the linac, and that the brazing of the inner part is less critical, since it does not have to guarantee the vacuum seal.

Figures 9, 10A and 10B show, schematically, an example of the realisation of the central part of the radio-frequency cavity 12, having a layer 11 of low-Z material.

Naturally, the drawings refer, by way of example only, to a linac operating in the TT/2 mode, but obviously this solution is applicable to any type of linac, even for industrial applications and therefore for nondestructive testing.

Advantageously, such solutions allow a reduction in the weight of the accelerating structure 10 while keeping it shielded. Advantageously, there is a dramatic reduction in scattered radiation for the patient and a reduction in the shielding required in the bunker.

From the description made of the device for radiotherapy treatment of cancer patients, according to the invention and according to the examples illustrated in detail in the accompanying figures, the advantages obtained are clear.

Finally, all of the details described herein may be replaced by other technically equivalent elements; in particular, the invention thus conceived and illustrated herein is susceptible of numerous modifications and variations all within the scope of the inventive concept of the appended claims.

Claims

1 . Device (10) for a radiotherapy treatment, in particular, an accelerating structure of an electron beam, comprising at least one radiofrequency accelerating cavity (12), characterized in that it is made of a first material with atomic number or Z lower or equal to 29, and in which said cavity (12) comprises a deposition of a layer (1 1 ) of a second material with atomic number or Z lower than or equal to 29, in such a way as to reduce a weight of the accelerating structure (10), keeping it shielded, and reducing the scattered radiation to a patient.

2. Device (10) for the radiotherapy treatment as in claim 1 , characterized in that said cavity (12) in said first material is totally covered by said layer (1 1 ) of said second material.

3. Device (10) for the radiotherapy treatment as in claim 1 , characterized in that said cavity (12) in said first material is covered only in a central portion of said layer (1 1 ) with said second material.

4. Device (10) as per at least one of the preceding claims, characterized in that said first material and said second material have a melting temperature higher than 800 ° C.

5. Device (10) as per at least one of the preceding claims, characterized in that said layer (1 1 ) of second material has a thickness greater than a penetration thickness of an electric field in the conductor, preferably between 5 and 100 pm.

6. Device (10) as per at least one of the preceding claims, characterized in that said first material and said second material are made, independently, in one of the following materials: copper or aluminum or alumina (AI2O3) or silicon carbide (SiC) or Carbon.

7. Device (10) as per at least one of claims 1 -6, characterized in that said device (10) is inserted in a linac dedicated to IORT, or in a linac dedicated to VHEE, or in a linac dedicated to industrial applications and therefore for non-destructive testing.