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Citation: Wolny-Rokicka E. Noninvasive Methods for Treatment of Brain Metastases. Austin Oncol. 2016; 1(3):
1011.
Austin Oncol - Volume 1 Issue 3 - 2016
Submit your Manuscript | www.austinpublishinggroup.com
Wolny-Rokicka. © All rights are reserved
Austin Oncology
Open Access
Abstract
Brain metatases occur in 20-40% of patients with cancer. Median survival
of patients who develop brain metastases is relatively short - 4 months.
Treatment methods such as Whole Brain Radio Therapy (WBRT), Surgery (S)
or Radiosurgery (SRS) prolong survival for 3 to 5 months. Treatment options in
brain metastases are as follows: symptomatic tratment, surgery, radiotherapy,
chemiotherapy and combination of those. Symptomatic treatment of edema
and anticonvulsive therapy are used if necessery and depends on neurological
patients status. Surgery has been used for single brain metstasis in patients with
good performance status. WBRT alone is a treatment of choice for patients with
multiple brain metastases, with single brain metastasis not sutable to surgery
or radiosurgery, especially those with an active and disseminated systemic
disease. SRS is an external irradiation technique to deliver a relatively large
radiation dose in a single fraction to an intracranial small target volume.
Chemotherapy alone (CT) is not used unless in clinical trials. Which method
to use depends on profile of prognosis factors such as:performance status,
patients age,number and volume of metastases.
Keywords: Brain metastases; Radiotherapy; Radiosurgery
popular is glikokortykosteroid. Its mechanism anti oedema is not
cleare, although it is probably the action by restoring the continuity of
broken capillaries that have been damaged by vasoactive substances
secreted by tumor [6]. Most patients start treatment at a dose of 4
to 8 mg dexamethasone daily with a noticeable improvement in
neurological status [7,8]. Patients with symptoms such as headache,
sleepiness may start treatment with higher doses of dexamethasone
(16 mg daily). Patients with small metastatic disease without
neurological symptoms do not require treatment with steroids.
During brain radiotherapy is used protectively glucocorticosteroids
in patients who reveal the acute symptoms of increased swelling of the
brain. This results in reducing symptoms and clinical improvement in
75% of patients after just 24 hours after treatment anti-edematous [9].
Consuming of drugs depend on degree of clinical symptoms to reduce
side effects in patients who had irradiated brain. After radiotherapy
can be reduce doses towards decreasing the risk of occurrence of side
effect.
The another group of drugs to reducing brain oedema are osmotic
diuretics - mannitol and glycerol; loop diuretics, which include
furosemide by rapidly effective diuretic. Anticonvulsant drugs used
to control seizures. These drugs (eg, phenytoin, carbamazepine,
phenobarbital) through interactions with corticosteroids reduce
its activity in the Central Nervous System (CNS), which should be
considered when dosing medications.
Surgery
Surgical treatment is used for single metastatic lesions in the
brain, taking into account the clinical condition of the patient and
tumor localization.The use of intraoperative ultrasonography and
magnetic resonance imaging (neuronavigation) allows during
surgery more quickly and accurately identify tumor [10]. In locations
in centers of speech particularly important is intraoperative mapping.
Introduction
Brain metastasis is a common manifestation of disseminated
malignancy [1,2]. In adults, lung, (36-40%), breast cancer (15-25%)
and skin melanoma (5-20%) are the most common sources of brain
metastases. Less frequent are colon, rectal, kidney, prostate, testicular,
ovarian cancer and sarcoma. Cerebral lesion are mainly located in
hemispheres (80%), in cerebellum (15%), in the brain stem (5%),
being very rare in the basal ganglia, the pineal gland or hypophysis.
Are more common than primary brain tumors [3]. Frequency of
disclosure is the result: a more effective treatment of the primary
tumor, more effective systemic treatment of disseminated disease
(clinical or subclinical), the existence of blood - brain barrier for the
majority of cytostatic drugs and the introduction of new imaging
techniques. Most patients who develop brain metastases have short
time survival. The treatment is used: steroids, surgery, radiation
therapy and symptomatic treatment. The choice of treatment depends
on the age, general condition of the patient, the number and location
of metastatic lesions and the severity of the underlying disease [4].
The last decade has created new possibilities for the treatment of
metastatic tumors such as radiosurgery and radiochemotherapy
combination treatment with radiation [5].
Treatment Options
Treatment options for brain metastases are: symptomatic and
specific therapy directed at the area of the tumor or tumors. To the
first treatment should antioedematous and anticonvulsants. Causal
treatment includes: surgical resection with or without radiotherapy
of the whole brain (WBRT), an independent method of WBRT,
radiosurgery (SRS), SRS + WBRT, chemotherapy.
Symptomatic treatment
Using antiedematous drugs is it routine methods. The most
Review Article
Noninvasive Methods for Treatment of Brain Metastases
Wolny-Rokicka E*
Radiotherapy Department, Regional Clinical Hospital in
Zielona Gora ul.Zyty, University of Zielona Gora, Poland
*Corresponding author: Edyta Wolny-Rokicka,
Radiotherapy Department, Regional Clinical Hospital in
Zielona Gora Zyty, University of Zielona Gora, Poland
Received: August 29, 2016; Accepted: October 05,
2016; Published: October 07, 2016
Austin Oncol 1(3): id1011 (2016) - Page - 02
Wolny-Rokicka E Austin Publishing Group
Submit your Manuscript | www.austinpublishinggroup.com
For decreasing of neurological deficit is used mapping. Mapping
involves electrical stimulation of the cortex during a treatment of a
patient who is woke up under the control of a local anesthetic [11].
It was also shown the benefit of combining surgery with radiation
therapy (median survival 9-10 months in compare to WBRT as a
independently treatment: 3-6 months) [12,13,14].
Chemotherapy
Chemotherapy can be used in patients with sensitive chemistry
tumors (eg. small cell lung cancer, breast cancer, germ cell tumors,
gestational trophoblastic disease) and can be an alternative to
radiotherapy. Indications and methods of administration of
chemotherapy in such cases are selected according to the rules for the
corresponding primary tumors.
The response rate after applying alone chemotherapy in small
cell lung cancer by Grossi et al. ranged from 21% to 76% [15] and
breast cancer by Boogerd et al. from 35% to 60% [16]. That authors
suggested that cytostatic treatment should be a first in patients with
metastasis and radiotherapy should be used in resistance cases.
Radiotherapy - treatment technique
Whole brain radiotherapy (WBRT): The value of radiation
therapy as a treatment of brain metastases were first described by
Chao et al., 1954. [17] and the Chu Hilaris in 1961 [18]. They used
standard fractionation to total doses from 3000 to 4000r in 3 - 4
weeks. They noticed a benefit in improving the clinical condition and
decreased neurological symptoms in 60 to 80% patients and prolong
median overvival survival from 6,6 - 8,2 months. Authors as: Hindo
et al [19], Shehata et al [20] showed that using high total doses in few
fractionated doses is effective as same as standard schema.
WBRT is the treatment of choice for patients who are not
candidates for surgery or radiosurgery, especially those with an active
disease [12]. The method consists in whole brain irradiation with two
coaxialopposedlateralbeams.Forpatients,treatmentplanningbegins
with preparing a thermoplastic mask (orfit mask). Is planned to be a
homogeneous distribution of the set doses of ionizing radiation in
the volume of the entire brain. With the help of the histogram (DVH
- Dose Volume Histogram) is check the dose distribution in areas of
interest. The used doses are in range 10 Gy in one fraction to 40 Gy in
20 fraction. The most used schemas are 20 Gy in 5 fractions and 30 Gy
in 10 fractions. All schemas have comparison result [21,22]. During
teleradiotherapy an external beam of high-energy X-rays is generated
by a linear accelerator to irradiate and destroy the tumor.
Stereotactic radiotherapy: The concept of stereotactic developed
in the early twentieth century and was then examined by Horsley’a
and Clark in experimental animals [23].
Only Ernest Spiegl introduced this technique in 1947 for
neurosurgery [24] and in 1951 Leksell combined the principles of
location stereotactic of ionizing radiation and called this method
“Radiosurgery” (SRS) [25]. Initially, Leksell envisioned the
development of this method in neurology - ablation selective areas of
the brain to treat Parkinson’s disease and chronic pain [26]. However,
the increase in clinical experience increased use and efficacy of
treatment in primary and secondary brain tumors.
Stereotactic radiosurgery is used most frequently in the treatment
of solitary brain metastases. The treatment’s effects of solitary brain
metastases are comparable to surgical treatment. This method is based
on the strict immobilization of the patient, precise determination of
the boundaries of the tumor and using a computer system to the
treatment planning and delivery of a high dose of radiation in a
well-defined area of the tumor as much as possible sparing healthy
tissue. Treatment planning is based on the fusion of a series of CT
images and MRI in order to precisely determine the volume of
tumor [27]. The stereotactic technique employs an external system
of coordinates (usually a stereotactic frame) ensuring maximum
precision for the tumor site. The techniques of radiosurgery: static
technique (the so-called. conformal radiotherapy CRT) and a
dynamic technique (radiosurgery based on the modulation of dose
intensity, IMRS - Intensity Modulated Radiosurgery). In CRT - the
shape of the radiation beam exposure is constant (static field), while
in the dynamic technique- shape of the radiation beam is changed in
time of exposure by using a multileaf collimator (dynamic field) [28].
For radiosurgery dose administered once it is most often depending
on the diameter of a tumor. The most used doses are 12-24 Gy [29].
Well-defined tumor volume is irradiation as a once (SRS) or in
some cases, the treatment may be divided into several sessions or
fractions, and the treatment is then called Fractionated Stereotactic
Radiotherapy (SRF). In SRS a biological effect is three time greater
than the same dose fractionated radiotherapy [30]. Rapid decrease in
dose outside the area of interest, reduces the risk of damage to normal
nerve tissue in the vicinity of the tumor and critical organs, which in
radiosurgery are usually: lenses, eyeballs, a cross between the optic
nerves and brain stem (Figure 1).
In modern radiosurgery systems, such as the CyberKnife, the
tumor can be located without using a stereotactic frame, the reference
system being the patient’s anatomical structures (the so-called
Figure 1: Profile of CT scan: transverse, frontal and sagittal. Metastases and
critical organs. Plan of treatment and isodose distribution.
Figure 2: Eclipse system, VMAT technique. Two metastases.
Austin Oncol 1(3): id1011 (2016) - Page - 03
Wolny-Rokicka E Austin Publishing Group
Submit your Manuscript | www.austinpublishinggroup.com
“internal coordinate system”) (Figure 3).
Volumetric Modulated Arc Therapy (VMAT): RapidArc or
volumetric modulated arc therapy (VMAT) is a dynamic technique
performed by using a multileaf collimator a variable dose rate
and a gantry rotation around the patient. It combines the arc and
IMRT techniques and is characterized by a relatively shorter single
radiotherapy treatment session compared with other available
methods (Figure 2).
Summary
The use of methods depend on many prognostic factors as:
performans status, age, numbers and volume of tumors. Surgery and
SRS are terapeutic methods used in patients with favorable prognostic
factors. Whereas the radiotherapy is a treatment method should pay
attention to neurological deficits u.e defects of the association that are
related to quality of life.
References
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13.	Pirotte B. The use of MRI and PET imaging in neuro-oncology. Perspectives
in Central Nervous System Malignancies. Conference, Czech Republic,
Prague. 2005.
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A randomized trial to asses the efficacy of surgery in addition to radiotherapy
in patients with a single cerebral metastasis. Cancer 1996; 78: 1470-1476.
15.	Grossi F, Scolaro T, Tixi L, Loprevite M, Ardizzoni A. The role of systemic
chemotherapy in the treatment of brain metastases from small – cell lung
cancer. Crit Rev Oncol Hematol. 2001; 37: 61-67.
16.	Boogerd W, Dalesio O, Bais EM, van der Sande JJ. Response of brain
metastases from breast cancer to systemic chemotherapy. Cancer. 1992; 69:
972-980.
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metastases. Cancer. 1954; 7: 682-689.
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Figure 3: Cyber Knife technique. System planning Multi Plan. Two metastasis
Dc 15Gy, 291statical radiation beams.

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Austin Oncology

  • 1. Citation: Wolny-Rokicka E. Noninvasive Methods for Treatment of Brain Metastases. Austin Oncol. 2016; 1(3): 1011. Austin Oncol - Volume 1 Issue 3 - 2016 Submit your Manuscript | www.austinpublishinggroup.com Wolny-Rokicka. © All rights are reserved Austin Oncology Open Access Abstract Brain metatases occur in 20-40% of patients with cancer. Median survival of patients who develop brain metastases is relatively short - 4 months. Treatment methods such as Whole Brain Radio Therapy (WBRT), Surgery (S) or Radiosurgery (SRS) prolong survival for 3 to 5 months. Treatment options in brain metastases are as follows: symptomatic tratment, surgery, radiotherapy, chemiotherapy and combination of those. Symptomatic treatment of edema and anticonvulsive therapy are used if necessery and depends on neurological patients status. Surgery has been used for single brain metstasis in patients with good performance status. WBRT alone is a treatment of choice for patients with multiple brain metastases, with single brain metastasis not sutable to surgery or radiosurgery, especially those with an active and disseminated systemic disease. SRS is an external irradiation technique to deliver a relatively large radiation dose in a single fraction to an intracranial small target volume. Chemotherapy alone (CT) is not used unless in clinical trials. Which method to use depends on profile of prognosis factors such as:performance status, patients age,number and volume of metastases. Keywords: Brain metastases; Radiotherapy; Radiosurgery popular is glikokortykosteroid. Its mechanism anti oedema is not cleare, although it is probably the action by restoring the continuity of broken capillaries that have been damaged by vasoactive substances secreted by tumor [6]. Most patients start treatment at a dose of 4 to 8 mg dexamethasone daily with a noticeable improvement in neurological status [7,8]. Patients with symptoms such as headache, sleepiness may start treatment with higher doses of dexamethasone (16 mg daily). Patients with small metastatic disease without neurological symptoms do not require treatment with steroids. During brain radiotherapy is used protectively glucocorticosteroids in patients who reveal the acute symptoms of increased swelling of the brain. This results in reducing symptoms and clinical improvement in 75% of patients after just 24 hours after treatment anti-edematous [9]. Consuming of drugs depend on degree of clinical symptoms to reduce side effects in patients who had irradiated brain. After radiotherapy can be reduce doses towards decreasing the risk of occurrence of side effect. The another group of drugs to reducing brain oedema are osmotic diuretics - mannitol and glycerol; loop diuretics, which include furosemide by rapidly effective diuretic. Anticonvulsant drugs used to control seizures. These drugs (eg, phenytoin, carbamazepine, phenobarbital) through interactions with corticosteroids reduce its activity in the Central Nervous System (CNS), which should be considered when dosing medications. Surgery Surgical treatment is used for single metastatic lesions in the brain, taking into account the clinical condition of the patient and tumor localization.The use of intraoperative ultrasonography and magnetic resonance imaging (neuronavigation) allows during surgery more quickly and accurately identify tumor [10]. In locations in centers of speech particularly important is intraoperative mapping. Introduction Brain metastasis is a common manifestation of disseminated malignancy [1,2]. In adults, lung, (36-40%), breast cancer (15-25%) and skin melanoma (5-20%) are the most common sources of brain metastases. Less frequent are colon, rectal, kidney, prostate, testicular, ovarian cancer and sarcoma. Cerebral lesion are mainly located in hemispheres (80%), in cerebellum (15%), in the brain stem (5%), being very rare in the basal ganglia, the pineal gland or hypophysis. Are more common than primary brain tumors [3]. Frequency of disclosure is the result: a more effective treatment of the primary tumor, more effective systemic treatment of disseminated disease (clinical or subclinical), the existence of blood - brain barrier for the majority of cytostatic drugs and the introduction of new imaging techniques. Most patients who develop brain metastases have short time survival. The treatment is used: steroids, surgery, radiation therapy and symptomatic treatment. The choice of treatment depends on the age, general condition of the patient, the number and location of metastatic lesions and the severity of the underlying disease [4]. The last decade has created new possibilities for the treatment of metastatic tumors such as radiosurgery and radiochemotherapy combination treatment with radiation [5]. Treatment Options Treatment options for brain metastases are: symptomatic and specific therapy directed at the area of the tumor or tumors. To the first treatment should antioedematous and anticonvulsants. Causal treatment includes: surgical resection with or without radiotherapy of the whole brain (WBRT), an independent method of WBRT, radiosurgery (SRS), SRS + WBRT, chemotherapy. Symptomatic treatment Using antiedematous drugs is it routine methods. The most Review Article Noninvasive Methods for Treatment of Brain Metastases Wolny-Rokicka E* Radiotherapy Department, Regional Clinical Hospital in Zielona Gora ul.Zyty, University of Zielona Gora, Poland *Corresponding author: Edyta Wolny-Rokicka, Radiotherapy Department, Regional Clinical Hospital in Zielona Gora Zyty, University of Zielona Gora, Poland Received: August 29, 2016; Accepted: October 05, 2016; Published: October 07, 2016
  • 2. Austin Oncol 1(3): id1011 (2016) - Page - 02 Wolny-Rokicka E Austin Publishing Group Submit your Manuscript | www.austinpublishinggroup.com For decreasing of neurological deficit is used mapping. Mapping involves electrical stimulation of the cortex during a treatment of a patient who is woke up under the control of a local anesthetic [11]. It was also shown the benefit of combining surgery with radiation therapy (median survival 9-10 months in compare to WBRT as a independently treatment: 3-6 months) [12,13,14]. Chemotherapy Chemotherapy can be used in patients with sensitive chemistry tumors (eg. small cell lung cancer, breast cancer, germ cell tumors, gestational trophoblastic disease) and can be an alternative to radiotherapy. Indications and methods of administration of chemotherapy in such cases are selected according to the rules for the corresponding primary tumors. The response rate after applying alone chemotherapy in small cell lung cancer by Grossi et al. ranged from 21% to 76% [15] and breast cancer by Boogerd et al. from 35% to 60% [16]. That authors suggested that cytostatic treatment should be a first in patients with metastasis and radiotherapy should be used in resistance cases. Radiotherapy - treatment technique Whole brain radiotherapy (WBRT): The value of radiation therapy as a treatment of brain metastases were first described by Chao et al., 1954. [17] and the Chu Hilaris in 1961 [18]. They used standard fractionation to total doses from 3000 to 4000r in 3 - 4 weeks. They noticed a benefit in improving the clinical condition and decreased neurological symptoms in 60 to 80% patients and prolong median overvival survival from 6,6 - 8,2 months. Authors as: Hindo et al [19], Shehata et al [20] showed that using high total doses in few fractionated doses is effective as same as standard schema. WBRT is the treatment of choice for patients who are not candidates for surgery or radiosurgery, especially those with an active disease [12]. The method consists in whole brain irradiation with two coaxialopposedlateralbeams.Forpatients,treatmentplanningbegins with preparing a thermoplastic mask (orfit mask). Is planned to be a homogeneous distribution of the set doses of ionizing radiation in the volume of the entire brain. With the help of the histogram (DVH - Dose Volume Histogram) is check the dose distribution in areas of interest. The used doses are in range 10 Gy in one fraction to 40 Gy in 20 fraction. The most used schemas are 20 Gy in 5 fractions and 30 Gy in 10 fractions. All schemas have comparison result [21,22]. During teleradiotherapy an external beam of high-energy X-rays is generated by a linear accelerator to irradiate and destroy the tumor. Stereotactic radiotherapy: The concept of stereotactic developed in the early twentieth century and was then examined by Horsley’a and Clark in experimental animals [23]. Only Ernest Spiegl introduced this technique in 1947 for neurosurgery [24] and in 1951 Leksell combined the principles of location stereotactic of ionizing radiation and called this method “Radiosurgery” (SRS) [25]. Initially, Leksell envisioned the development of this method in neurology - ablation selective areas of the brain to treat Parkinson’s disease and chronic pain [26]. However, the increase in clinical experience increased use and efficacy of treatment in primary and secondary brain tumors. Stereotactic radiosurgery is used most frequently in the treatment of solitary brain metastases. The treatment’s effects of solitary brain metastases are comparable to surgical treatment. This method is based on the strict immobilization of the patient, precise determination of the boundaries of the tumor and using a computer system to the treatment planning and delivery of a high dose of radiation in a well-defined area of the tumor as much as possible sparing healthy tissue. Treatment planning is based on the fusion of a series of CT images and MRI in order to precisely determine the volume of tumor [27]. The stereotactic technique employs an external system of coordinates (usually a stereotactic frame) ensuring maximum precision for the tumor site. The techniques of radiosurgery: static technique (the so-called. conformal radiotherapy CRT) and a dynamic technique (radiosurgery based on the modulation of dose intensity, IMRS - Intensity Modulated Radiosurgery). In CRT - the shape of the radiation beam exposure is constant (static field), while in the dynamic technique- shape of the radiation beam is changed in time of exposure by using a multileaf collimator (dynamic field) [28]. For radiosurgery dose administered once it is most often depending on the diameter of a tumor. The most used doses are 12-24 Gy [29]. Well-defined tumor volume is irradiation as a once (SRS) or in some cases, the treatment may be divided into several sessions or fractions, and the treatment is then called Fractionated Stereotactic Radiotherapy (SRF). In SRS a biological effect is three time greater than the same dose fractionated radiotherapy [30]. Rapid decrease in dose outside the area of interest, reduces the risk of damage to normal nerve tissue in the vicinity of the tumor and critical organs, which in radiosurgery are usually: lenses, eyeballs, a cross between the optic nerves and brain stem (Figure 1). In modern radiosurgery systems, such as the CyberKnife, the tumor can be located without using a stereotactic frame, the reference system being the patient’s anatomical structures (the so-called Figure 1: Profile of CT scan: transverse, frontal and sagittal. Metastases and critical organs. Plan of treatment and isodose distribution. Figure 2: Eclipse system, VMAT technique. Two metastases.
  • 3. Austin Oncol 1(3): id1011 (2016) - Page - 03 Wolny-Rokicka E Austin Publishing Group Submit your Manuscript | www.austinpublishinggroup.com “internal coordinate system”) (Figure 3). Volumetric Modulated Arc Therapy (VMAT): RapidArc or volumetric modulated arc therapy (VMAT) is a dynamic technique performed by using a multileaf collimator a variable dose rate and a gantry rotation around the patient. It combines the arc and IMRT techniques and is characterized by a relatively shorter single radiotherapy treatment session compared with other available methods (Figure 2). Summary The use of methods depend on many prognostic factors as: performans status, age, numbers and volume of tumors. Surgery and SRS are terapeutic methods used in patients with favorable prognostic factors. Whereas the radiotherapy is a treatment method should pay attention to neurological deficits u.e defects of the association that are related to quality of life. References 1. 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