Transcript non-melanoma skin cancer - INFN

PROTEL, A FEASIBILITY STUDY
EXPERIMENT PROTEL (PROtoni TErapia Locale). 2 years
Padova (C.N. P. Rossi)
LNL (R.L. G. Moschini)
Pavia ( D. Scannicchio) parteciperà nel secondo anno
1)PROTEL is a feasibility study of an innovative nuclear device to perform local proton
radiotherapy for brachytherapy and IORT* like applications. The device would exploit the
nuclear reaction 2H(3He,p)4He to obtain high energy protons (17 MeV), starting from low energy
3He ions (800 keV). These latter may be produced by a low cost portable compact accelerator
adequate for hospital usage.
2)PROTEL would provisionally use the existing LNL-AN2000 accelerator 3He ions for assessing
the therapeutic adequacy of this kind of proton radiation and testing key parts of the future
device. Moreover PROTEL would offer a conceptual design of a compact future accelerator and
a recommendation on the actual usage of this method.
(*IORT: Intra Operative Radio Therapy) `
Scientific Basis
Nuclear Instruments and Methods in Physics Research B 106 (1995) 606-617
The use of low energy, ion induced nuclear reactions for
proton radiotherapy applications
KM. Horn a * , B. Doyle a, M.N. Segal b, R.W. Hamm c, R.J. Adler d,
E. Glatstein e
a Sandia National Laboratories. USA
b Department of Otolaryngology, UniLersity of New Mexico Medical School. USA
C Accsys Technology Inc., USA
d North Star Research Corp., USA
e Department of Rad. Oncology, Universiiy of Texas Southwest Medical Center. USA
Needle for Radiotherapy
Low energy
RFQ
p(17.4 MeV)
10 mA
3He(0.8
MeV)
TiD2 (5-10 mm)
Reaction 2H(3He,p)4He
No industrial realization followed this idea
Scientific Basis - 2
Later (2005), K.L. Leung and coll. of the Lawrence Berkeley National Laboratory (LBNL) (CA,
USA) proposed to employ a portable ion tube accelerator extremely light and compact (few kilos,
20-30 cm), being operated at a much lower energy (~ 150 keV). This device is designed to
produce 3He ions in a plasma chamber and then extract a 3He ion beam. It accelerates the beam
down a thin hollow tube to hit a deuteron-bearing target. However, they did not demonstrate
the feasibility of this device, and no prototype has been made. Actually the reaction cross
section at 150 keV 3He is depressed by 20 times with respect to maximum and the required
proton intensity looks difficult to obtain.
To my knowledge, both teams at Sandia and Berkeley have no further
plans to develop this device.
Why suggest again this method?
-We have today cheaper and lighter compact accelerator that may render
easier and cheaper the hospital usage of this device
-Potential medical application look today more fashionable (IORT for breast
cancer)
-The Sandia study has not exhausted in detail all the medical possible
applications and the related configuration of the aiming system
-Other non-medical application look possible (rad-hard microchip
assessment,…) that have not been considered
-We can easily reproduce, with the AN2000 for test purposes, the nuclear
reaction that give rise to the intermediate energy protons (17 MeV)
The cross section of 2H(3He,p)4He (EXFOR)
NO gamma and neutron background for 3He with E < 1 MeV
Doses in H2O in f(r) from a p(17 MeV) point-like source
3He
current = 1 mA
Dose on tissue
Metal matrices such as Ti, Zr, Er, Sc, maintain stable H or 2H
concentration. D in Ti may reach a stoichiometry of TiD2
( c= 1.16·1023 cm-3).
The cs of 2H(3He,p)4He has a broad peak at 650 keV, high
s=825 mbarn. To consider the energy loss in the target and
maximize the yield, the impinging3He should have ~ 800 keV.
Total Integrated cs over its full range of 1.9 in TiD2 is
Is=∫dz · s(E(z)) · exp(-mz) = 6.7·10-19 cm3.
N=number of incident 3He atoms= Qtot/e = 6.25·1012 · Q(mC)
Y=Yield= N ·c ·Is = 4.85 · 107 · Q(mC)
The average dose (every p looses between 13.6 and 17.4 MeV
on a sphere of 3.1 mm) is ~ 1 Gy · Q(mC).
Isodose Curves in H2O
for a 2 mm focus
2 mm
5 mm
Irradiation in H2O from far
Goals and Schedule
1)Development of an experimental setup to evaluate the nuclear reaction 2H(3He, p)4He. We will employ a
3He beam of LNL vdg AN2000. The setup includes detectors for measuring the energy spectrum and the
angular distribution of the ions, both 3He and p (1st year, Padova, LNL)
2) Acquisition of a deuterated target, like, for example, TiD2 and development of the 3He needle-like aiming
system that includes the target by the end tip. Feasibility study of a multiple needle aimimg system. (1st year,
Padova)
3) Evaluation of the effectiveness of the needle and the alignment of 3He with it . Measurement of the emitted
protons intensity and shape. Evaluation of dose and damage on phantoms to a high precision, by applying
micro-dosimetric methods. (1st-2nd year, Padova, LNL, Pavia)
4) Theoretical assessment of the therapeutic adequacy of the produced protons for local radio-therapy as for
energy (17 MeV), intensity and emission shape, by doing numeric simulations and tests on phantoms at the
AN2000 setup. The assessment will also be based on a bibliographic research and the experience of medical
staff (2nd year, Pavia, LNL, Padova)
5) We will “conceptually” design, but not realize, a compact device to be employed in hospital environment.
The design will include ion source, accelerator, the steering system to convey the He-3 ions, and the aiming
system. It will also include assessment of industrial feasibility, cost, and radio-protection issues related to
hospital usage. (2nd year, Padova, LNL, LNL-Gruppo Macchine?)
6) We will compare the device to other existing solutions, and offer a final recommendation on its actual
usage and development by a manufacturer.(2nd year, Padova, LNL, Pavia)
Costi (Consumo)
Padova
-lavorazioni meccaniche esterne per ago deuterato
-preparazione bersaglio di TiD2
-materiali meccanici
LNL
-adattamento linea microfascio e camera di scattering
-rivelatore per protoni ad energia intermedia e adattamento readout
-contributo bottiglia 3He (intiera 35000 € )
Hypodermic Needle (PD)
Setup adjustment and test at the AN2000 (LNL, PD)
50 nA
3He
p(17 MeV)
(800 keV)
Scattering chamber
Microbeam (0°)
or chamber at (60°)
-Scattering chamber adjustment for in-air irradiation with needle,
including flange, detector and goniometer
-Study of the effectiveness of the needle with deuterated tip
Conceptual Design of a portable system, for
hospital usage (LNL-gruppo Macchine)
Are these protons (17 MeV, range= 3mm)
really useful in Medicine? (LNL, PD, PV)
The radiation cannot penetrate too much. Lets examine three
cases to see potential uses and shortcomings
Brachitherapy (f.e. prostate cancer)
Surface irradiation (skin cancer, skin melanoma)
Intra-Operative Radiotherapy (IORT, f.e. breast cancer)
1)Configuration for brachytherapy-like application
Portable
Accelerator
(not on scale)
800 KeV He-3
Transport system
Patient
body
Needle
(1.0-2.0 x 50 mm)
irradiation area
(range=3.1 mm)
TiD2 target
17 MeV protons
1bis) Multiple Needles Brachytheraphy
800 KeV He-3
Vacuum pipe
Patient
body
2)Intra Operative Radio Therapy (IORT)
800 KeV He-3
800 KeV He-3
Needle
(1.0-2.0 x 50 mm)
irradiation area
(range=3.1 mm)
TiD2 target
Patient
body
Patient
body
17 MeV protons
irradiation area
(range=3.1 mm)
17 MeV protons
2bis )Large Field IORT
Thin Deuterated target (5-10 mm)
Thick Metallic support
800 KeV He-3
Conformal irradiation
screen sector
Patient
body
R=3.1mm
10-20 mm
Field=10-20 mm
irradiation area
1-2 mm
HDR temporary brachytherapy instead involves placing very tiny plastic catheters into the
prostate gland, and then giving a series of radiation treatments through these catheters. The
catheters are then easily pulled out, and no radioactive material is left in the prostate gland.
Radioactive iridium seed into the catheters one by one.So one is able to control the radiation
dose in different regions of the prostate. We can give the tumor a higher dose, and we can
ensure that the urine passage (urethra) and rectum will receive a lower dose.
Prostate Brachytherapy
HDR (High Dose Radiotherapy)
There is also the permanent seed implant
(125I, X~27keV, m-1~20mm) or
(103Pd, X~20keV, m-1~10mm
the seeds are placed in the prostate by
needles through the perineal skin (between
the scrotum and the rectum) under
anesthesia in an operating room
environment.
p17MeV range too small and
needles connection stiff
Non-melanoma skin cancer
The most common forms of non-melanoma skin cancer are called basal cell carcinoma and
squamous cell carcinoma, reflecting the different types of skin cell from which the disease can
develop.
Treatment usually needs only to remove the cancer that is visible, as most non-melanoma skin
cancers are unlikely to spread to other parts of the body. In some cases one type of treatment is
all that is needed.
Topical therapy (creams), PDT (Photodynamic Therapy) are often used.
Surgery is successful for most types of non-melanoma skin cancer. There are a variety of
different procedures, which doctors will select depending on the type and extent of the cancer.
Doctors use radiotherapy as a
treatment for non-melanoma skin
cancers that cover a large area. or
are in areas of the body that are
difficult to operate on. It is also an
alternative for people who may find
surgery difficult to cope with, such as
elderly people or those in poor health.
Malignant melanoma
Surgery can certainly remove the
original melanoma tumor and any
affected lymph nodes. However, the
spread of the melanoma, whether it is
to the rest of the lymph nodes with
Stage 3, and other organs for Stage
4, means more aggressive treatment
with chemotherapy, radiotherapy
and/or immunotherapies is needed.
Melanoma does not respond to
Radiotherapy in a predictable way.
For this reason it is rarely used for
treating primary melanoma but it is
very occasionally used when surgery
is not suitable.
Radiotherapy is also used more to
prevent the cancer's spread rather
than provide a cure. High energy Xrays target a specific area to destroy
the cancer cells.
There are also indications that radiosensibilizer chemicals may boost the
effectiveness of radiotherapy in
curing bthis kind of cancer
Malignant skin Melanoma
(3 mm range are enough?)
Malignant Melanoma -2
how much surgical removal of a margin of normal tissue is
recommended for melanomas?
Thickness
Less than 1mm
Between 1mm-2mm
Between 2mm-4mm
Greater than 4mm
Suggested Margins
1cm, the Veronesi (WHO) study has now been widely accepted
1-2cm, other authorities feel 2 cm is required
2cm, some authorities say 2-3cm
3cm (anything greater is likely of no additional value)
If requirement of at least 1 cm removal means that also the
radiotherapy should penetrate that much, PROTEL is ineffective,
but ….
Intra-operative RadioTherapy
Usually e- linac
(6-12 MV)
Max dose relase 10-12 mm
(for e- linac)
Breast Cancer. Electron linac (LIAC)
SORDINA spa, Saonara, GIO-MARCO spa (agente)
Therapy Effectiveness Conclusion
PROTEL Vs Brachytherapy
Confined released Dosed
-rigidity of needles usage due
to Beam alignment
-Shorter range (3 mm) than
brachy X-rays (10-20 mm)
Is this really bad?
PROTEL Vs IORT or surface application
Confined released Dose
-Shorter range (3 mm) than
IORT e- or Xrays (10 mm).
Is this really bad?
Other Applications possible
cheap high energy protons…
For example: rad-hard microchip assessment
Others??
Conclusion
The nuclear reaction base of PROTEL has been considered for radiotherapy since the
nineties. In spite of this, no exhaustive assessment of its therapeutic interest has been
carried out. The advantages are of course the dose confinement typical of protons and
the reduced cost. After 13 years since the first proposal, accelerators are even cheaper
and lighter and PROTEL seems adequate to become a portable tool for surgery room
and even for doctor’s office.
Among the medical indications are the prostate, skin and breast cancers, where local
radiotherapy (either brachytherapy like and IORT) are already indicated.
The most weak facet of this method is the range of protons (3 mm in tissue) that might
be too small for some of this applications. Other issues are the fragility of the vacuum
window in the needle tip and of course the requirement of a perfect beam alignment that
might spoil the PROTEL flexibility.
Cheap 17 MeV Protons with limited intensity might find also non-medical application, like
in the rad-hard microchips assessment.
The LNL AN2000 vdg accelerator may easily offer now the 3He ions for provisional tests.
For all these reasons, a feasibility study, employing also the AN2000, and addressing
therapeutic possibilities and issues looks advisable.
Depth in Tissue
Non malignant skin cancer
Skin reaction during topical therapy for superficial skin cancer. Note the
selective response as only skin cancer and precancerous cells are reacting.
PDT (Photodynamic Therapy) applies a chemical (photosensitizer) that
sensitizes your skin to light. Cancerous skin treated with this photosensitizer is
then exposed to various light sources
Test in water. Setup
Needles insertion
Brachytherapy is a minimally invasive
procedure where the doctor implants
tiny permanent radioactive seeds
(about the size of a grain of rice) into
the prostate where they irradiate the
cancer from inside the gland. The
implanted seeds are small enough that
they will not be felt by the patient.
Depending on your circumstances,
either
(125I, X~27keV, m-1~20mm) or
(103Pd, X~20keV, m-1~10mm ) will be
used. Brachytherapy is also referred to
as interstitial radiation therapy or seed
implant therapy.
Before the seeds are implanted, the patient receives anesthesia. Needles containing
the seeds are then inserted through the skin of the perineum (the area between the
scrotum and anus) using ultrasound guidance. The seeds remain in the prostate,
where the radioactive material gives off localized radiation for a number of months to
destroy the prostate cancer.