Facility development for a combined cancer therapy
The system for local hyperthermia of cancers was simulated. This system is based on independently phased dipoles with frequency 150 MHz. The electromagnetic field distributions are calculated in cut of tissue-equivalent phantom. It was shown that the electromagnetic field can be focused in desirable...
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Національний науковий центр «Харківський фізико-технічний інститут» НАН України
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Fadeev, A.M. Ivanov, S.M. Perelstein, E.A. Polozov, S.M. Tkachev, S.I. 2016-11-15T11:41:34Z 2016-11-15T11:41:34Z 2012 Facility development for a combined cancer therapy / A.M. Fadeev, S.M. Ivanov, E.A. Perelstein, S.M. Polozov, S.I. Tkachev // Вопросы атомной науки и техники. — 2012. — № 3. — С. 191-194. — Бібліогр.: 11 назв. — рос. 1562-6016 PACS: 87.50, 87.54.Br. https://nasplib.isofts.kiev.ua/handle/123456789/108745 The system for local hyperthermia of cancers was simulated. This system is based on independently phased dipoles with frequency 150 MHz. The electromagnetic field distributions are calculated in cut of tissue-equivalent phantom. It was shown that the electromagnetic field can be focused in desirable volume by means of independent vary of amplitude and phase of each dipole. The advantages of combined therapy are discussed for common using of hyperthermia with chemotherapy, radiation therapy or surgery. Проведено моделирование работы системы для локальной гипертермии онкологических заболеваний на основе системы независимо фазируемых дипольных излучателей, работающих на частоте 150 МГц. Получены картины распределения электрических полей в сечении облучаемого образца (тканеэквивалентного фантома). Показана возможность фокусировки электромагнитного поля в необходимом объеме за счет независимого изменения фазы и амплитуды излучения каждого из диполей. Рассмотрены перспективы комбинированного использования гипертермии и химической или лучевой терапии и хирургии. Проведено моделювання роботи системи для локальної гіпертермії онкологічних захворювань на основі системи незалежно фазіруємих дипольних випромінювачів, що працюють на частоті 150 МГц. Отримано картини розподілу електричних полів у перерізі опромінюваного зразка (тканееквівалентного фантома). Показана можливість фокусування електромагнітного поля в необхідному об’ємі за рахунок незалежної зміни фази і амплітуди випромінювання кожного з диполів. Розглянуто перспективи комбінованого використання гіпертермії та хімічної або променевої терапії та хірургії. en Національний науковий центр «Харківський фізико-технічний інститут» НАН України Вопросы атомной науки и техники Применение ускоренных пучков: детекторы и детектирование ядерных излучений Facility development for a combined cancer therapy Разработка установок для комбинированной терапии онкологических заболеваний Розробка установок для комбінованої терапії онкологічних захворювань Article published earlier |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| title |
Facility development for a combined cancer therapy |
| spellingShingle |
Facility development for a combined cancer therapy Fadeev, A.M. Ivanov, S.M. Perelstein, E.A. Polozov, S.M. Tkachev, S.I. Применение ускоренных пучков: детекторы и детектирование ядерных излучений |
| title_short |
Facility development for a combined cancer therapy |
| title_full |
Facility development for a combined cancer therapy |
| title_fullStr |
Facility development for a combined cancer therapy |
| title_full_unstemmed |
Facility development for a combined cancer therapy |
| title_sort |
facility development for a combined cancer therapy |
| author |
Fadeev, A.M. Ivanov, S.M. Perelstein, E.A. Polozov, S.M. Tkachev, S.I. |
| author_facet |
Fadeev, A.M. Ivanov, S.M. Perelstein, E.A. Polozov, S.M. Tkachev, S.I. |
| topic |
Применение ускоренных пучков: детекторы и детектирование ядерных излучений |
| topic_facet |
Применение ускоренных пучков: детекторы и детектирование ядерных излучений |
| publishDate |
2012 |
| language |
English |
| container_title |
Вопросы атомной науки и техники |
| publisher |
Національний науковий центр «Харківський фізико-технічний інститут» НАН України |
| format |
Article |
| title_alt |
Разработка установок для комбинированной терапии онкологических заболеваний Розробка установок для комбінованої терапії онкологічних захворювань |
| description |
The system for local hyperthermia of cancers was simulated. This system is based on independently phased dipoles with frequency 150 MHz. The electromagnetic field distributions are calculated in cut of tissue-equivalent phantom. It was shown that the electromagnetic field can be focused in desirable volume by means of independent vary of amplitude and phase of each dipole. The advantages of combined therapy are discussed for common using of hyperthermia with chemotherapy, radiation therapy or surgery.
Проведено моделирование работы системы для локальной гипертермии онкологических заболеваний на основе системы независимо фазируемых дипольных излучателей, работающих на частоте 150 МГц. Получены картины распределения электрических полей в сечении облучаемого образца (тканеэквивалентного фантома). Показана возможность фокусировки электромагнитного поля в необходимом объеме за счет независимого изменения фазы и амплитуды излучения каждого из диполей. Рассмотрены перспективы комбинированного использования гипертермии и химической или лучевой терапии и хирургии.
Проведено моделювання роботи системи для локальної гіпертермії онкологічних захворювань на основі системи незалежно фазіруємих дипольних випромінювачів, що працюють на частоті 150 МГц. Отримано картини розподілу електричних полів у перерізі опромінюваного зразка (тканееквівалентного фантома). Показана можливість фокусування електромагнітного поля в необхідному об’ємі за рахунок незалежної зміни фази і амплітуди випромінювання кожного з диполів. Розглянуто перспективи комбінованого використання гіпертермії та хімічної або променевої терапії та хірургії.
|
| issn |
1562-6016 |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/108745 |
| citation_txt |
Facility development for a combined cancer therapy / A.M. Fadeev, S.M. Ivanov, E.A. Perelstein, S.M. Polozov, S.I. Tkachev // Вопросы атомной науки и техники. — 2012. — № 3. — С. 191-194. — Бібліогр.: 11 назв. — рос. |
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ISSN 1562-6016. ВАНТ. 2012. №3(79) 191
FACILITY DEVELOPMENT FOR A COMBINED CANCER THERAPY
A.M. Fadeev1, S.M. Ivanov3, E.A. Perelstein2, S.M. Polozov1, S.I. Tkachev3
1National Research Nuclear University MEPhI, Moscow, Russia;
2JINR, Dubna, Russia;
3N.N. Blokhin Russian Oncological Scientific Center, Moscow, Russia
E-mail: smpolozov@mephi.ru
The system for local hyperthermia of cancers was simulated. This system is based on independently phased di-
poles with frequency 150 MHz. The electromagnetic field distributions are calculated in cut of tissue-equivalent
phantom. It was shown that the electromagnetic field can be focused in desirable volume by means of independent
vary of amplitude and phase of each dipole. The advantages of combined therapy are discussed for common using of
hyperthermia with chemotherapy, radiation therapy or surgery.
PACS: 87.50, 87.54.Br.
1. INTRODUCTION
Surgery, chemical therapy and radiation (gamma,
electron or hadron) are three classical methods of the
cancer treatment. They are used independently and in
combination one another. But all tree methods have
some limitation and negative after effects for patients.
The decrease of such negative effects is one of main
direction of contemporary oncology.
So called hyperthermia (ancient Greek ὑπερ- − «ex-
cessively» and θέρμη − «heat») is one of possible meth-
ods to decrease negative after effects. The hyperthermia
is kind of thermotherapy based on increasing tempera-
ture of body, body part or organ prone to pathological
process. It was shown that combined chemical therapy
and hyperthermia is very perspective because the medi-
cal preparation dose can be 2-3 times reduced [1-4].
Some types of cancer cells can be made more sensitive
to the radiation using hyperthermia also. Developing
and adoption of treatment methods when intensification
chemotherapy effect takes place, in clinical practice is a
primary target. The thermal effect lead to lysosome ac-
tivation, tissue breathing and protein synthesis inhibi-
tion, tissues pH decreasing, kariokynetic cycle modifi-
cation, trans membrane transfer improvement, sensitiza-
tion tumor cells to chemotherapy and growing up im-
munity. The temperature when volume blood flow in
healthy tissues decreases as a result of progress dis-
seminated intravascular clotting is the limit of the ther-
motherapy usage. The hyperthermia is conventionally
devisable into three temperature ranges:
- 43…44°С – direct destruction of tumor;
- 40…42°С – sensitization tumor cells to chemo-
therapy or radiotherapy;
- 38…40°С – tumor size increasing is possible.
Indeed, patient's heating to 44°С can lead to a num-
ber of pathological changes and progress of fatal com-
plication. That’s why the temperature 44°С during local
hyperthermia is not reached yet. The heating mode
41.5…42.1°С during 60…120 min are more often ap-
plied. There are several types of hyperthermia and re-
spectively several frequencies range:
- Overall hyperthermia (10…15 MHz);
- Regional hyperthermia (40…100 MHz);
- Local, distant, intracavitary hyperthermia
(100…200 MHz, 433 MHz, 915 MHz, 2.5…3 GHz);
- Combined hyperthermia (overall + local);
- Extra high frequency (EHF) therapy
(30…300 GHz).
Several heat-transfer materials (water, air) are used
for overall hyperthermia in practice medicine. In that
case the greatest temperature is reached on the body's
surface that leads to a burn.
2. HYPERTHERMIA COMBINED
WITH RADIOTHERAPY
There are a lot of works, where the synergism of hy-
perthermia and radiation effect on cancer’s growth is
shown. It is assumed that modification effect of hyper-
thermia on radiation’s effect consists of next points [5]:
1. Radiation’s sensitivity increasing;
2. Decreasing of cell’s ability to regenerate sublethal
and potential lethal damage;
3. Selective influence to cells which are in radiore-
sistance phase of kariokynetic cycle.
Blood flow increases with hyperthermia which leads
to tissues saturation growth by oxygen and, conse-
quently, to higher sensitivity of cancer to the radiother-
apy. Radiosensitization’s effect of hyperthermia is de-
pended of sequence of heating and radiation application:
the greatest effect is reached at their simultaneous appli-
cation. If radiotherapy precedes hyperthermia, regenera-
tion of radiation damages will take place at interaction
with thermal damage. If hyperthermia precedes radio-
therapy, regeneration of thermal damage will takes
place at interaction with radiation damage. The correla-
tion between this phenomenon and value of unprepared
filamentous DNA rupture was shown [6].
3. HYPERTHERMIA COMBINED
WITH CHEMOTHERAPY
Hyperthermia and anticarcinogenic chemotherapeu-
tic medicine can acts independently, can supplement
each other and perfectly cooperate. The major mecha-
nisms which provide anticarcinogenic chemotherapeutic
medicine’s effect are the raised concentration of drug in
a tumor. The concentration raise is a result of increasing
blood supply and permeability of membranes, and also
an increasing endocellular medicinal metabolism and
reaction acceleration.
There are four groups of chemical compounds which
antineoplastic effect in the conditions of a hyperthermia
is studied [7]. Drugs with linear cytotoxicity increasing
versus of the temperature rise make the first group: al-
kylating agent (thiophosphamide), bifunctional alkylates
(nitrosourea), mitomycin, cisplatin. A limit cytotoxicity
ISSN 1562-6016. ВАНТ. 2012. №3(79) 192
is proportional to the temperature for second group
drugs. The accurate synergism of hyperthermia and
chemotherapy appears for the temperature higher than
42…43ºC. For example it is observed for adriamycin,
bleomycin and actinomycin D. Third group consists of
drugs which become cytotoxic only at high temperature
(cystamine, amphotericin B). Drugs which have the
constant cytotoxicity at temperature 37…45ºC (meth-
otrexate, fluorouracil, vincristine, and vinblastine) can
be placed to the forth group.
4. RADIOTHERAPY AND COMBINED
THERAPY IN RUSSIAN ONCOLOGICAL
SCIENTIFIC CENTER
Combined therapy using the radiotherapy with the
hyperthermia Thermo Radio Therapy, TRT) in RORC is
spent since 1980. TRT was carried out more than 1000
patients at present.
The improved results of TRT in comparison with
conventional radiotherapy (RT) are presented in Ta-
ble 1. The frequency of full regresses of localizations
listed above is higher after TRT. Result’s analysis
shows that the five-year survival rate after TRT is
higher than after radiotherapy (Table 2).
Table 1
Frequency of full regression after radiotherapy
or thermoradiotherapy courses
Tumor’s localization TRT, % RT, % Statistic
error
Prostate cancer 94±2.3 69±8.2
Soft tissue sarcoma 45±5.2 14±5.1
Regional metastasis of
neck epidermoid cancer 57±6 12±7.8
Epidermoid anal channel
cancer 100 60±21.9
Extraabdomenal des-
moids cancer 33±7 0
Relapse rectum cancer 24±6.3 5±4.9
p<0.05
The TRT treatment program is realized in RORC.
Such program allows to sufficient and authoritative re-
duce of the regional cancer recrudescence and metasta-
ses comparatively to the surgery or independently radio-
therapy. As an example, the rectum cancer recrudes-
cence was observed for 0.9±0.6 % (2 form 220 patients)
and metastases for 5 % (11 from 220 patients) compara-
tively with 16.2±1.9 % (64 form 395) for surgery and
9.6±2.1 % (26 from 272) for surgery and before RT.
Table 2
Five-years survival rate after radiotherapy
or thermoradiotherapy courses
Tumor’s localization TRT, % RT, % Statistic
error
Prostate cancer 68±4.5 53±8.0
Soft tissue sarcoma 46±5.2 35±7.0
Regional metastasis of
neck epidermoid cancer 24±4.2 9±4.6
Epidermoid anal channel
cancer 69±6.8 30±12.7
Extraabdomenal des-
moids cancer 40±5.7 6±4.5
p<0.05
Relapse rectum cancer 68±4.5 53±8.0 p<0.01
Indeed, the efficiency of TRT was shown for a num-
ber of cancer types in RORC. The local heating with
41…45ºC temperature regime and 60 minutes duration is
improved the RT results because of the cancer cells dam-
age and radio sensitization. Cancer treatment effect grows
versus temperature and procedure time increasing.
5. HYPERTHERMIA FACILITIES
AND FREQUENCY RANGE CHOICE
Facilities for overall and regional hyperthermia are
manufacturing by some companies since 1980’s [8-10].
Federal state unitary enterprise "Research & production
corporation "Istok" is the main manufacturer in Russia.
The local hyperthermia became more useful as whole
body hyperthermia at present. The local hyperthermia
allows to focus the radiation in the local volume placed
deep inside into human body and to prevent of other
tissues or organs heating.
Microwaves application is more perspective in com-
parison with optical and infrared waves because they
having higher penetrating capacity in the human body
perspective in the field of a hyperthermia. The RF fre-
quency range (100…200 MHz) is optimal because the
wavelength in human body will approximately equal to
the body’s size. Dielectric properties of biological tis-
sues at 150 MHz are shown in Table 3 [11].
Table 3
Dielectric properties of biological tissues
in 150 MHz range
ε ρ, g/cm3 σ, S/m
Muscle 62.8 1.047 0.72
Bone 14.6 1.99 0.068
Skin 63.5 1.125 0.53
Blood 72.2 1.058 1.25
Tumor 74 1.047 0.89
Fat 5.84 0.95 0.037
The blood is the most conductive tissue but blood in-
travascular clotting can not be a serious problem due to
the blood flow. Dielectric properties of cancer are com-
parable with muscle’s one (they have same density,
similar values of conductivity and relative permittivity).
It’s should be taken into account at planning of the hy-
perthermia procedure in order to decrease damage ef-
fects on healthy tissues. Fat and bones have a less con-
ductivity in comparison with muscle and tumor.
Now some USA, Germany and Netherlands compa-
nies are offer a number of local hyperthermia facilities
but its price is very high (up to 8 MEuro).
6. DIPOLE SYSTEM FOR LOCAL
HYPERTHERMIA
The antenna grid consisting of number independently
phased dipoles is proposed for local hyperthermia of can-
cers. The operating frequency is chosen equal to
150 MHz in R&D. The dipoles proposed are modification
of well-known half-wave dipoles. The grid will consists
of an array of such dipoles and hold on the cylindrical
surface with diameter equal to 40 cm. Dipoles fed inde-
pendently by coax cable (for instance low loss cable as
RG213) from amplifiers at frequency 150 MHz. Inde-
ISSN 1562-6016. ВАНТ. 2012. №3(79) 193
pendent feeding is necessary to focus electromagnetic
fields in local region. The focusing can be done by inde-
pendently operation phase and amplitude choice for each
dipole in the grid. The tissue-equivalent phantom and
heating dipoles grid are shown in Fig.1.
Fig.1. Tissue-equivalent phantom and dipoles grid
Distributions of EM field in transverse (a) and longitu-
dinal (b) cuts of heating model are presented in Fig.2.
a
b
Fig.2. Electric field distributions in cuts of heating
model: a – transverse cut; b – longitudinal cut
It is clear, that the electric field maximum is located
in the center of the tumor. It was reached by means of
an especial choice of phase and amplitude values of the
RF field in each dipole as it was noted above. The elec-
tric field distribution versus time (or RF field phase) is
shown in Fig.3. The transversal size of heated spot
(where electric field decreases in 2 times) is equal
~7…8 cm, and the longitudinal size is equal
~10…12 cm. In other words, heating volume is a vol-
ume of cylinder with a radius ~4 cm and length ~10 cm.
The specific absorption rate (SAR) can be calculated
if the electric field distribution in phantom is known.
SAR is the measure of the rate energy which is absorb-
ing in the body when in is irradiating by RF electro-
magnetic field. It is defined as the power absorbed per
mass of tissue. SAR can be calculated f as:
2
ESAR σ
ρ
=
ur
[W/kg], (1)
where σ is the electrical conductivity; E is the RMS
electric field; ρ is the phantom density.
Also we can calculate the rate of temperature in-
creasing in the tissue, if specific heat ci is known:
i
dTSAR c
dt
= . (2)
Eq. (2) is rewritten taking no account the blood flow.
SAR is equal 235.5 W/kg with RMS supply power of
each dipole equal 60 W. This implies that some minutes
will necessary to heat tumor to 8 K (the tumor heat ca-
pacity is equal to 3560 J kg-1 K-1). At the same time the
temperature of healthy tissues will increases no more
then 2.5 K.
Fig.3. Electric field distribution versus time
(or RF field phase)
7. RF POWER FEEDING SCHEME
As it was noted above, the RF power supply should
be independed for each dipole. The RF power system
schematic layout is shown in Fig.4: 1 – driving genera-
tor with input signal’s frequency range 100…300 MHz
and input impedance 50 Ohm; 2 – 8-out power splitter
(for example Mini-circuits ZBSC-8-82+); 3 – voltage-
controlled phase shifter (Mini-circuits JSPHS-150) with
frequency range 100…150 MHz, phase range 180°,
control voltage 0…12 V; 4 – solid state amplifier (Mit-
subishi RA60H1317M1A-101) with frequency range
135…175 MHz, output power – 60 W, supply voltage –
12.5 V, control GAP-pin voltage 12.5 V; 5 – RF di-
pole’s grid.
The operating principle of such layout is the follow-
ing. The signal from driving generator has the constant
frequency and splits into 8 channels. Then by means of
controlled 8 phase shifters and 8 solid state amplifiers
ISSN 1562-6016. ВАНТ. 2012. №3(79) 194
we can adjust phase and amplitude of every signal. Due
to these adjustments electric field focusing in the desire
region is available.
Fig.4. RF power system schematic layout
Modern solid state amplifiers can derive the neces-
sary amplification and are simple and stable at opera-
tion. For example, solid state RF amplifier Mitsubishi
RA60H1317M with amplify frequency range of
135…175 MHz and supply voltage 12.5 V can be used
to provide the necessary RF power (to 60 W) and SAR
values. The control of RF power can be realized using
amplifier’s GAP channel which provide the turn on/off
of amplifier.
Indeed the 8 dipole antenna grid should be controlled
by 16 voltage signals (8 for amplifiers and 8 for phase
shifters). The low-voltage control system connected to
PS should be designed future.
CONCLUSIONS
Combined therapy using the hyperthermia with the
radiotherapy of the chemotherapy is very perspective
methods of the cancer treatment. The efficiency of com-
bined therapy is evaluated on practice. The local hyper-
thermia became more useful as whole body and regional
hyperthermia at present. The array of half wave dipoles
is proposed for local hyperthermia. It was shown that
the localization of heating in ~ 4×10 cm volume can be
realized using this scheme. It was calculated that some
minutes is necessary for tissue heating on 8 K (from
36.6 to 44°С) with 60 W of RF power in each dipole.
A number of problems should be solved before in-
troducing the facility in the clinical trials:
1. 3D-models of body should be done using MRI
and PET-CT scanning and correct tissue model should
be simulated. In other words, after determining of tumor
localization by means of scanning, it is necessary to
simulate the computer model in which all tissues will be
marked out. It is necessary because all tissues have per-
sonal dielectric properties. The thermodynamic problem
should be solved using 3D model of RF field.
2. Software for fast 3D simulation of electromag-
netic fields distribution should be developed. This soft-
ware should include the heating process simulation.
3. Correct and low traumatic methods of temperature
control are necessary.
REFERENCES
1. S.I. Tkachev, O.P. Trofimova, V.M. Ivanov //
Mammalogy (3). 2006, p.46 (in Russian).
2. S.I. Tkachev, et al. // Medical Radiology and Radia-
tion safety (53). 2008, №2, p.25 (in Russian).
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Статья поступила в редакцию 23.09.2011 г.
РАЗРАБОТКА УСТАНОВОК ДЛЯ КОМБИНИРОВАННОЙ ТЕРАПИИ ОНКОЛОГИЧЕСКИХ
ЗАБОЛЕВАНИЙ
А.М. Фадеев, С.М. Иванов, Е.А. Перельштейн, С.М. Полозов, С.И. Ткачев
Проведено моделирование работы системы для локальной гипертермии онкологических заболеваний на
основе системы независимо фазируемых дипольных излучателей, работающих на частоте 150 МГц. Получе-
ны картины распределения электрических полей в сечении облучаемого образца (тканеэквивалентного фан-
тома). Показана возможность фокусировки электромагнитного поля в необходимом объеме за счет незави-
симого изменения фазы и амплитуды излучения каждого из диполей. Рассмотрены перспективы комбиниро-
ванного использования гипертермии и химической или лучевой терапии и хирургии.
РОЗРОБКА УСТАНОВОК ДЛЯ КОМБІНОВАНОЇ ТЕРАПІЇ ОНКОЛОГІЧНИХ ЗАХВОРЮВАНЬ
О.М. Фадєєв, С.М. Іванов, Є.А. Перельштейн, С.М. Полозов, С.І. Ткачов
Проведено моделювання роботи системи для локальної гіпертермії онкологічних захворювань на основі
системи незалежно фазіруємих дипольних випромінювачів, що працюють на частоті 150 МГц. Отримано
картини розподілу електричних полів у перерізі опромінюваного зразка (тканееквівалентного фантома). По-
казана можливість фокусування електромагнітного поля в необхідному об’ємі за рахунок незалежної зміни
фази і амплітуди випромінювання кожного з диполів. Розглянуто перспективи комбінованого використання
гіпертермії та хімічної або променевої терапії та хірургії.
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