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SRS, SRT CNS Tumours

Stereotactic techniques, including SRS, SRT, and SBRT, utilize 3D coordinate systems to precisely target tumors for radiation therapy, minimizing damage to surrounding healthy tissue. These methods are particularly effective for CNS tumors and involve high-dose radiation delivered in single or multiple sessions, enhancing treatment efficacy while addressing challenges like the blood-brain barrier. Advancements in imaging and planning systems have improved the accuracy and safety of these procedures, which are essential for treating various tumor types effectively.

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SRS, SRT, SBRT for CNS tumours Moderator Prof. Rakesh Kapoor Dr. Namrata Das 4th semester, Junior Resident Department of Radiotherapy
Definition Stereotaxis: Greek word stereo (3-D approach)+taxis (tactile - touch), i.e. ordered in 3-dimensions Concept: Stereotaxy is a minimally-invasive form of surgical intervention which makes use of three-dimensional coordinate system to: • locate small targets inside the body • to perform on them some action such as ablation (removal), biopsy, injection, stimulation, implantation, radiosurgery etc.
Stereotactic Biopsy/ injection/stimulation Stereotactic Radiosurgery/ Radiotherapy
Stereotactic irradiation Stereotactic irradiation refers to irradiation technique that: • uses computer calculated 3-dimensional coordinates • to deliver a prescribed dose of ionizing radiation, using multiple non- coplanar photon radiation beams (LINAC) or radiation from multiple Co-60 source (Gamma knife) with extreme precision • To stereotactically localized lesions, primarily in the brain Stereotactic techniques were initially attempted in the CNS but now are used for other sites in the body
Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) are techniques to administer precisely directed, high- dose radiation that tightly conforms to an intracranial target to create a desired radiobiological response while minimizing dose to the normal tissue. Stereotactic body radiotherapy (SBRT) is a radiation technique that utilizes precisely targeted radiation to a tumour in a single or limited sessions in extracranial sites while minimizing dose to normal tissue. Definition
Stereotactic radiosurgery (SRS) • intracranial lesion is stereotactically defined using a rigid frame (type of EBRT, not a surgery) • high dose per fraction is delivered (type of usually more than 10 Gy) • usually treated in a single session (single day discharge) • can be up to 4 fractions but fractionated SRS (fSRS) a more accurate term • 4 Rs of radiobiology do not apply Stereotactic radiotherapy (SRT) Delivering dose in multiple fractions (more than or equal to 5) to sterotactically localized target using relocatable frames Stereotactic Radiosurgery (SRS) Stereotactic Radiotherapy (SRT) Stereotactic Body Radiotherapy (SBRT) CRANIAL SITE SPINE, EXTRA-CRANIAL SITE
Radiobiological basis of SRS/SRT • Vascular mediated mechanism for SRS/SBRT • Radio-immunology of ablative radiation • Opposite of traditional radiotherapy by conventional fractionation which treats broad areas of normal and diseased tissue to uniform doses • Ablative doses to only the diseased tissue in a single (or limited) treatment sparing the normal healthy tissue
Low dose, fractionated radiotherapy: • Cell death from radiation induced DNA damage • Radiosensitive, oxygenated cells preferentially killed, allowing reperfusion and reoxygenation of hypoxic cells High dose radiotherapy: • Tumour cell death secondary to ischemia • Endothelial cell death leads to tumour starvation Vascular mediated mechanism for SRS/SBRT
HIGH DOSE PER FRACTION Endothelial cell ASM (Acid sphingomyelinase) translocated to outer leaflet of cell membrane Sphingomyelin hydrolysed to ceramide Window of radiation doses for ceramide mediated death starts at 8-10 Gy and peaks at 10-25 Gy
• Intact immune system necessary for efficient tumour control • Multiple retrospective studies have shown poor clinical outcome in immunocompromised patients after radiation Radio-immunology of ablative radiation Proposed mechanism of immunological response following high dose per fraction radiation Studies suggest that RT can generate an autologous in situ tumour vaccine and induce anti-tumoral immunity that contributes to higher local control rates when ablative RT doses given Basis for newer studies combining SABR/SRS with immunotherapy
Radio-immunology of ablative radiation
Rationale for Fractionated SRS and single SRS approaches Orange: Target lesion Red: 100% isodose Light blue: 80% isodose impinging on brainstem • BED2 for single fraction (15 Gy/#) plan is higher (84Gy) versus fractionated (5 Gy/5#) • Treating in 5 fractions yields similar tumour control (BED10 = 37.5 in both) • Treating in a single session with 12 Gy yields same normal tissue toxicity but with lower tumour control BRAINSTEM
SRS SRT Target ≤ 3cm lesions lesions >3cm Safety margins Treatment volume same as target volume Treatment volume larger than target volume No. of fractions 1-5 (usually single) More than or equal to 6 (fractionated) Immobilization device Uses a rigid stereotactic head or body frame Uses a repositionable stereotactic mask or body mold Optimal dose Very high dose delivered during one treatment session Moderate “fractions” of the complete high dose delivered over multiple treatment sessions Differences between SRS and SRT
Rationale of SRS/SRT in CNS tumours • CNS tumour treatment pose unique problems: • chemo/ immuno therapy → blood brain barrier • invasive brain surgery → high Risk • non-invasive radiotherapy → too non-specific • Stereotactic irradiation was introduced in 1952 by a neurosurgeon using pre-existing stereotactic neurosurgery frames to decrease the morbidity of open procedures “The tools used by the surgeon must be adapted to the task – and where the human brain is concerned they cannot be too refined.” -Professor Lars Leksell (1907-1986)
Tumour volume: As size increases, normal tissue radiation increases RTOG dose escalation study of cerebral metastasis, recommended marginal doses were: • 24 Gy: <2Gy • 18 Gy: 2 to 3 cm • 15 Gy: 3 to 4 cm • Not recommended for lesions more than 4 cm Proximity to cranial nerves: Cranial nerves II and VIII most sensitive and SRS avoided if dose > 10 Gy delivered Rationale of SRS/SRT in CNS tumours
Location of lesion: Fractionated RT preferred for treatment of lesions in deep gray matter or brainstem Neurocognitive function: • SRS preferred over whole brain RT for focal intracranial lesions – less NCF decline • There is inevitable spillage of radiation in SRS too. Therefore for larger lesions or patients who undergo multiple rounds of SRS, higher risk of NCF decline Rationale of SRS/SRT in CNS tumours
Key Requirements for optimal stereotactic irradiation Requirement Rationale Small target/treatment volume Reducing the volume of normal and target tissue improves tolerance Sharply defined target Sharply defined targets can be treated with little or no extra margin of surrounding normal tissue and/or without unintentional underdosage of the target (marginal miss) Accurate radiation delivery No margin of normal tissue needed for set up error and/or reduced chance of underdosing target High conformality Reduces the treatment volume to match the target volume Sensitive structures excluded from target Dose-limiting structures )optic chiasm, spinal cord etc.) should be able to be defined and excluded from the target volume to limit the risk of radiation injury
History Discovery of X Rays (1895), Radioactivity (1896) - Clinical use of ionizing radiation to cure cancer Advances in neurosurgery and the invention of stereotactic frames Lars Leskell and the invention of Radiosurgery
(a) Elekta gamma knife with converging beams in original U model helmet (b) Original Leskell Gamma unit First Linear Accelerator based SRS
Physics of Radiosurgery “SRS is a single fraction radiation therapy procedure for treating intracranial lesions using a combination of a stereotactic apparatus and narrow multiple beams delivered through noncoplanar isocentric arcs.” -Faiz M Khan, The Physics of Radiation Therapy Principle: • Precisely locate the target stereo tactically using special frames • Hold the target still • Accurately aim the radiation beam • Shape the radiation beam to the target • Deliver a radiation dose that damages abnormal cells yet sparing normal cells
Major advances in stereotactic localization, noninvasive neuroimaging, and radiation physics made it possible to selectively irradiate a sharply defined target, largely sparing the surrounding normal tissue. This approach, called stereotactic radiosurgery (SRS), is achieved by focusing multiple radiation beams on the tumor tissue from different directions
Characteristics Characteristics of stereotactic irradiation are as follows : • High doses of the order of 10-15 Gy are delivered to target volume to achieve better tumor control • High degree of dose conformity • PTVs are small & range from 1-35cm3 so that • Less irradiation of normal tissue • Less morbidity • With requirement for • positional accuracy +/- 1mm • dose delivery accuracy +/- 5%
Different machines for delivering SRS/SRT 1. Gamma knife, Rotating Gamma Systen (RGS): Co-60 gamma rays 2. Cyberknife
3. Modified Linear Accelerator/ Tomotherapy 4. Charged particles Different machines for delivering SRS/SRT
SRS Techniques Leskell Gamma Knife Radiosurgery • 1st Gamma unit was developed in 1968 by Leksell at Karolinska institute, Stockholm. • Gamma radiation from Cobalt-60 Source • Targeting precision of within 0.2 mm • Multiple targets can be easily treated in one session
COMPONENTS: • A radiation unit with an upper hemispherical shield (central body) • Lower half of hemisphere has a shielding door • An operating table & sliding cradle • A control unit • Planning system Leskell Gamma Knife Radiosurgery
• Source: Perfexion model: 192 Cobalt 60 sources distributed in 8 sectors • Dimension: 2 cm height, 1 mm diameter • Housed in hemisphere called Central body • Shield: 18000 kgs surrounding the hemispherical array of Co60 sources Leskell Gamma Knife Radiosurgery
Leskell Gamma Knife Radiosurgery • Collimation helmets: 4, 8, 16 mm diameter • Depth helmet: Confirms the position of head ring on patients head
Treatment components • Position stabilization (attachment of a frame or frameless) • Imaging for localization (CT, MRI, angiography, PET etc.) • Computer assisted tumour localization (i.e., “image guidance”) • Treatment planning – number of isocentres, number, placement and length of arcs or angles, number of beams, beam size and weight etc. • Isodose distributions, dosage prescription and calculation • Simulation of prescribed arcs or fixed portals • Radiation treatment delivery
SRS/SRT team •Radiation Oncologist •Neurosurgeon •Medical Physicist •Neuro-Radiologist •Neuro-Anesthesiologist •Neuro-Oncology Nurse •Radiation Therapy Technologist
Frame Fixation SRS frames Leksell frame in Gamma Knife BRW (Brown-Roberts-Wells) & CRW (Cosman-Roberts-Wells) in X-Knife Relocatable frames for fractionated stereotactic irradiation (SRT) GTC (Gill-Thomas-Cosman) • helps us in defining the images in a coordinate • system - fiducial points: accurate positioning of the patient at the time of • treatment
Frame Fixation To check whether frame will cover area of interest 60 year old F, pituitary adenoma
Diagnostic Imaging • CT or MRI can be used MRI (preferred) • Requires MRI compatible localization box. • scans directly in axial, saggital, coronal or oblique planes • Better imaging of soft tissue tumors. • Can assess neural invasion Angiography for AVM
Image Transfer Networking - Local area networking (LAN) PACS - to Gamma plan - to X-plan • Magneto Optical disc • DAC tape • Film scanner • CT, MR film
Depth Helmet • The Depth Helmet provides quantitative quality assurance for relocatable head rings (GTC). • Checks that head ring has not moved b/w CT scanning & treatment delivery. • confirms that head rings have been accurately repositioned on patient prior to each SRT treatment. • A Depth Probe with millimeter scale passed into the guide tubes on the helmet to measure distance from the hole to the patient's head with millimeter accuracy. • This measurement data provides a permanent and precise record of positional accuracy for every treatment
Depth Helmet
Treatment Planning • Defining isocenter • Dose prescription • Plan Evaluation • QA & Set up
Treatment Planning Target vol. is encompassed by 70% to 90% isodose while using single isocenter. Entire treatment volume encompassed by 50% isodose curve while using multiple isocenters • For better dose conformity • For reduced dose to normal tissue
Treatment Planning • Delineation of target and critical structures • Prescription of dose: 12 Gy at 50 % isodose Safety Limits Cochlea 7.4 Gy Brainstem 12 Gy Optic Pathway 8 Gy CN VII < 14 Gy CN VIII < 12 Gy
Treatment Planning Techniques of plan evaluation • Display of isodose lines over target volume • Display of 3-D dose shells • Display of DVHs Radiation oncologists approve the plan
Set up and Treatment
Linear Accelerator Based Radiosurgery 4 or 6MV LINACS with tight mechanical and electrical tolerances, are modified for radio surgery • A remotely controlled motorized couch • Tertiary collimation that brings collimator closer to the surface • to reduce geometric penumbra ( inversely proportional to SDD) Tertiary collimation is either : • Cone based • Micro MLC based
CONE BASED Highly collimated narrow beams defined by • 15 cm long circular cones made of Cerrobend Lead, encased in stainless steel. • The cones are mounted below X-ray jaws • A range of cones with dia. from 5mm to 40mm in steps of 2.5mm are used for SRS lesions
MICRO MLC BASED Used for small irregular field SRS/SRT - for greater conformity & efficiency than circular collimators • Computer controlled motorized leaves • Number of Leaves : 52 (26 pair) • Field Size (max): 10 cm x 10 cm • Leaf Width at Isocenter: 2.5 mm at isocenter
Cyber Knife Three key components: • Advanced light weight LINAC (High energy 6 MV beam) • Robotic arm pointing LINAC beam from wide variety of angles • Several X-ray cameras combined with powerful software to track patient position
• Uses complex system of cameras, motion tracking softwares, fibreoptic sensing technology & Infra red emitters • Records breathing movement with sequential X-ray images of implanted radio-opaque markers 3-4 mm long
Robot precisely follows moving tumour to deliver radiation to desired target
Advantages • Procedure painless, no anaesthesia, completed in 30-90 min, immediate recovery • Appropriate for many patients otherwise diagnosed as inoperable • No invasive head frame or other rigid immobilization device is required • The ability to perform radiosurgery (1-5 fractions) on targets throughout the body, not just the brain Disadvantages • More time consuming • Requires placement of fiducials
Clinical uses of SRS and SRT Arteriovenous malformations (AVM) Benign brain tumors • Acoustic neuromas • Meningiomas • Pineal & pituitary tumors Malignant brain tumors including Gliomas Astrocytomas Metastatic brain tumors Functional disorders Intractable Pain Trigeminal Neuralgia Psychiatric Diseases Parkinson’s Disease and Epilepsy
PGI Experience YEAR Meningio ma Schwanno ma AVM Pituitary adenoma Trigeminal Neuralgia Cavernous Lesion Glomus Lesion Jugular SOL Total 2016 67 65 52 38 15 12 8 2 271 2015 62 44 44 34 22 7 6 - 223
Site Dose Trigeminal neuralgia 80 – 90 Gy single shot at 7-8 mm anterior to emergence of nerve. Repeat GK if good response to first GK with at least 3 years Pituitary adenoma Non secretory: 12 – 17 Gy Secretory: 20 – 28 Gy Meningioma 10- 20 Gy Schwannoma Virgin Lesion: 11- 13 Gy Recurrent after 3 years if GK/EBRT: 10 – 12 Gy AVM 23 – 25 Gy at margins, assess response at 2 years Retreatment for residual lesion, <1cc: 22-24 Gy 3.5 – 8 cc: 19 – 32 Gy 8 – 13 cc: 18 – 20 Gy Metastasis > 20 mm: 22 – 25 Gy < 20 mm: 25 – 30 Gy Prior EBRT> 16 – 20 Gy Glial tumour Low grade: 15 – 17 Gy High grade: < 3 cm, unifocal: 7 – 10 Gy PGI Experience
SRS for brain metastasis Brain metastasis are the most common intracranial malignancy Indications: 1. Single brain metastasis: Accessible site: Surgery followed by WBRT/SRS Inaccessible site: SRS is an alternative but all studies are comparisons of WBRT followed by SRS boost versus surgery
SRS for brain metastasis 2. Multiple brain metastasis: 1) Limited number of tumours, all < 3 cm 2) High tumour burden or multiple large tumours
2. Dose: • < 2 cm: 22-25 Gy • > 2 cm: 25-30 Gy • Prior EBRT: 16-20 Gy 3. Local Control: 1 yr LC: 70-80% 4. Side effects: • Acute: nausea, dizziness, vomiting • Late: radiation necrosis, optic neuropathy SRS for brain metastasis
SRS for Pituitary adenoma Multiple treatment options available: medical therapy, microscopic or endoscopic trans-sphenoidal surgery, radiosurgery, radiation therapy, or observation. 1. Indication: Stereotactic radiosurgery (SRS) is usually indicated for: (1) incomplete surgical resections that leave residual tumor (2) tumor recurrence (3) cases in which medical therapy provides inadequate hormone control.
SRS for Pituitary adenoma Study Mean Dose Tumour control Hormonal control Visual field defects Induced hypopituitaris m Zhang et al n=79 31.3 Gy 92% 96% One None Izawa et al n=56 23.8 Gy 93.6% 30.3% cure 80.3% imp. One None 2. Dose: - functioning: 12 – 17 Gy - non-functioning: 13 - 15 Gy 3. Results:
4. Side effects: - hypothalamic, hypopituitarism - Cranial neuropathy
SRS for glial tumours 1. Indications: • unresectable LGG such as pilocytic astrocytoma, selected oligodendrogliomas • salvage therapy in patients with recurrent or residual glial tumors. 2. Dose: Due to the possibility of adverse radiation effects (ARE) after repeated fractionated radiation therapy, SRS is often used to boost the tumor radiobiological effect for smaller-volume recurrent or progressive tumors.
SRS for vestibular schwannoma Vestibular schwannomas (more commonly referred to as acoustic neuromas) are tumors arising from the Schwann cells of the eighth cranial nerve. These tumors are commonly slow-growing, but growth can be variable. 1. Dose (PGI): • Virgin lesion: 11-13 Gy • Recurrence after 3 years of GK/EBRT: 10-12 Gy 2. Results: Kondziolka D et al (2003) treated 157 patients (40 undergone previous surgery): Median follow up : 9.1 years Decrease in tumor size : 114 (73%) No change : 40 (25.5%) Increase in size : 3 (1.9%) Normal facial nerve function : 95%
3. Side effects: - Hearing loss - Facial, trigeminal neuropathy SRS for vestibular schwannoma
SRS for AVM 1. Indications: • small- to medium-sized AVMs less than 3–3.5 cm in diameter • AVMs located in deep or eloquent brain regions 2. Dose: 16 to 25 Gy and obliteration rates tend to improve at doses greater than 17 Gy
SRS for AVM 3. Results: Obliteration rates depend on a multitude of factors relating to AVM characteristics and treatment parameters, and they vary widely from 50% to 90% in reported studies 4. Side effects: hemiparesis (48.9% of all symptomatic patients), headache (16.3%), seizures (12.1%), sensory dysfunction (7.1%), and ataxia (3.5%)
SRS for Trigeminal Neuralgia 1. Indication: Microvascular decompression was the gold standard but since the 1970s, SRS has gained popularity 2. Dose:60 to 90 Gy to 4 mm isocenter 3. Results: 58% were free of pain at a median follow-up of 18 months, and another 36% had significant improvement (>50%) in their pain HISTORY: (1951) First time SRS was used by Dr. Leksell for treating two patients with trigeminal neuralgia using 280 kV X rays
SRS for Trigeminal Neuralgia It is postulated that TN results from a combination of central demyelination of the nerve root entry zone (REZ) and the subsequent, reinforced electrical excitability of the nerve
SBRT for Spinal Tumours 1. Indication: The most common and ideal indications for spine SBRT are in patients with no prior history of radiation, oligometastatic disease, limited or no epidural disease and no spinal instability.
2. Dose - not standardized - 24 Gy in 3 fractions SBRT for Spinal Tumours
SBRT for Spinal Tumours 3.Results: De novo metastasis, Guckenberger et al (2014) treated 387 spinal metastases across 8 institutions with a median dose of 24 Gy in 3 fxs. Median overall survival was noted to be 19.5 months, and 1- yr and 2-yr local control rates were 89.9% and 83.9% 4. Side effects: Vertebral Compression fracture Radial plexopathy
SRS Complications ACUTE: Severe acute reaction: Rare: 835 consecutive patients: 18 had a neurological event within 7 days of treatment (e.g. new focal deficit or seizure), three died Immediate side effects: Two weeks after SRS, approximately one third patients had mild dizziness, nausea headache
SRS Complications LATE: 1. Radiation Necrosis: With greater use of SRS, the incidence of radiation necrosis is increasing. Radiation necrosis develops in 7–24% of patients undergoing SRS. Bevacizumab has emerged as the best supported agent in the management of radiation necrosis.
SRS Complications and Management LATE: 2. Optic neuropathy RON can develop as early as 3 months post radiation, but can take years to develop. The peak incidence is 1–1.5 years.
Role of re-irradiation with SRS • Re-irradiation of brain metastasis in NSCLC with SRS in currently being tried on a case to case basis. • Balermpas et al. reported on 31 patients with 32 recurrent brain metastases: - Median interval was 12 months - Sequence was WBRT + SRS + SRS - One year survival and local control was 62% and 80%
Conclusion • With the advancement in equipment and better understanding of radiobiology of high dose per fraction radiation, the role of SRS and SRT is increasing • Both the techniques require meticulous treatment planning and execution • Local control in oligometastatic patients have increased by it • Recent interest has been shown in ultra-fast dose rate radiotherapy (excess of 40 Gy/s) – FLASH radiotherapy
Thank you

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SRS, SRT CNS Tumours

  • 1.
    SRS, SRT, SBRTfor CNS tumours Moderator Prof. Rakesh Kapoor Dr. Namrata Das 4th semester, Junior Resident Department of Radiotherapy
  • 2.
    Definition Stereotaxis: Greek word stereo(3-D approach)+taxis (tactile - touch), i.e. ordered in 3-dimensions Concept: Stereotaxy is a minimally-invasive form of surgical intervention which makes use of three-dimensional coordinate system to: • locate small targets inside the body • to perform on them some action such as ablation (removal), biopsy, injection, stimulation, implantation, radiosurgery etc.
  • 3.
  • 4.
    Stereotactic irradiation Stereotactic irradiationrefers to irradiation technique that: • uses computer calculated 3-dimensional coordinates • to deliver a prescribed dose of ionizing radiation, using multiple non- coplanar photon radiation beams (LINAC) or radiation from multiple Co-60 source (Gamma knife) with extreme precision • To stereotactically localized lesions, primarily in the brain Stereotactic techniques were initially attempted in the CNS but now are used for other sites in the body
  • 5.
    Stereotactic radiosurgery (SRS)and stereotactic radiotherapy (SRT) are techniques to administer precisely directed, high- dose radiation that tightly conforms to an intracranial target to create a desired radiobiological response while minimizing dose to the normal tissue. Stereotactic body radiotherapy (SBRT) is a radiation technique that utilizes precisely targeted radiation to a tumour in a single or limited sessions in extracranial sites while minimizing dose to normal tissue. Definition
  • 6.
    Stereotactic radiosurgery (SRS) •intracranial lesion is stereotactically defined using a rigid frame (type of EBRT, not a surgery) • high dose per fraction is delivered (type of usually more than 10 Gy) • usually treated in a single session (single day discharge) • can be up to 4 fractions but fractionated SRS (fSRS) a more accurate term • 4 Rs of radiobiology do not apply Stereotactic radiotherapy (SRT) Delivering dose in multiple fractions (more than or equal to 5) to sterotactically localized target using relocatable frames Stereotactic Radiosurgery (SRS) Stereotactic Radiotherapy (SRT) Stereotactic Body Radiotherapy (SBRT) CRANIAL SITE SPINE, EXTRA-CRANIAL SITE
  • 7.
    Radiobiological basis ofSRS/SRT • Vascular mediated mechanism for SRS/SBRT • Radio-immunology of ablative radiation • Opposite of traditional radiotherapy by conventional fractionation which treats broad areas of normal and diseased tissue to uniform doses • Ablative doses to only the diseased tissue in a single (or limited) treatment sparing the normal healthy tissue
  • 8.
    Low dose, fractionatedradiotherapy: • Cell death from radiation induced DNA damage • Radiosensitive, oxygenated cells preferentially killed, allowing reperfusion and reoxygenation of hypoxic cells High dose radiotherapy: • Tumour cell death secondary to ischemia • Endothelial cell death leads to tumour starvation Vascular mediated mechanism for SRS/SBRT
  • 9.
    HIGH DOSE PER FRACTION Endothelialcell ASM (Acid sphingomyelinase) translocated to outer leaflet of cell membrane Sphingomyelin hydrolysed to ceramide Window of radiation doses for ceramide mediated death starts at 8-10 Gy and peaks at 10-25 Gy
  • 10.
    • Intact immunesystem necessary for efficient tumour control • Multiple retrospective studies have shown poor clinical outcome in immunocompromised patients after radiation Radio-immunology of ablative radiation Proposed mechanism of immunological response following high dose per fraction radiation Studies suggest that RT can generate an autologous in situ tumour vaccine and induce anti-tumoral immunity that contributes to higher local control rates when ablative RT doses given Basis for newer studies combining SABR/SRS with immunotherapy
  • 11.
  • 12.
    Rationale for FractionatedSRS and single SRS approaches Orange: Target lesion Red: 100% isodose Light blue: 80% isodose impinging on brainstem • BED2 for single fraction (15 Gy/#) plan is higher (84Gy) versus fractionated (5 Gy/5#) • Treating in 5 fractions yields similar tumour control (BED10 = 37.5 in both) • Treating in a single session with 12 Gy yields same normal tissue toxicity but with lower tumour control BRAINSTEM
  • 13.
    SRS SRT Target ≤3cm lesions lesions >3cm Safety margins Treatment volume same as target volume Treatment volume larger than target volume No. of fractions 1-5 (usually single) More than or equal to 6 (fractionated) Immobilization device Uses a rigid stereotactic head or body frame Uses a repositionable stereotactic mask or body mold Optimal dose Very high dose delivered during one treatment session Moderate “fractions” of the complete high dose delivered over multiple treatment sessions Differences between SRS and SRT
  • 14.
    Rationale of SRS/SRTin CNS tumours • CNS tumour treatment pose unique problems: • chemo/ immuno therapy → blood brain barrier • invasive brain surgery → high Risk • non-invasive radiotherapy → too non-specific • Stereotactic irradiation was introduced in 1952 by a neurosurgeon using pre-existing stereotactic neurosurgery frames to decrease the morbidity of open procedures “The tools used by the surgeon must be adapted to the task – and where the human brain is concerned they cannot be too refined.” -Professor Lars Leksell (1907-1986)
  • 15.
    Tumour volume: Assize increases, normal tissue radiation increases RTOG dose escalation study of cerebral metastasis, recommended marginal doses were: • 24 Gy: <2Gy • 18 Gy: 2 to 3 cm • 15 Gy: 3 to 4 cm • Not recommended for lesions more than 4 cm Proximity to cranial nerves: Cranial nerves II and VIII most sensitive and SRS avoided if dose > 10 Gy delivered Rationale of SRS/SRT in CNS tumours
  • 16.
    Location of lesion:Fractionated RT preferred for treatment of lesions in deep gray matter or brainstem Neurocognitive function: • SRS preferred over whole brain RT for focal intracranial lesions – less NCF decline • There is inevitable spillage of radiation in SRS too. Therefore for larger lesions or patients who undergo multiple rounds of SRS, higher risk of NCF decline Rationale of SRS/SRT in CNS tumours
  • 17.
    Key Requirements foroptimal stereotactic irradiation Requirement Rationale Small target/treatment volume Reducing the volume of normal and target tissue improves tolerance Sharply defined target Sharply defined targets can be treated with little or no extra margin of surrounding normal tissue and/or without unintentional underdosage of the target (marginal miss) Accurate radiation delivery No margin of normal tissue needed for set up error and/or reduced chance of underdosing target High conformality Reduces the treatment volume to match the target volume Sensitive structures excluded from target Dose-limiting structures )optic chiasm, spinal cord etc.) should be able to be defined and excluded from the target volume to limit the risk of radiation injury
  • 18.
    History Discovery of XRays (1895), Radioactivity (1896) - Clinical use of ionizing radiation to cure cancer Advances in neurosurgery and the invention of stereotactic frames Lars Leskell and the invention of Radiosurgery
  • 19.
    (a) Elekta gammaknife with converging beams in original U model helmet (b) Original Leskell Gamma unit First Linear Accelerator based SRS
  • 20.
    Physics of Radiosurgery “SRSis a single fraction radiation therapy procedure for treating intracranial lesions using a combination of a stereotactic apparatus and narrow multiple beams delivered through noncoplanar isocentric arcs.” -Faiz M Khan, The Physics of Radiation Therapy Principle: • Precisely locate the target stereo tactically using special frames • Hold the target still • Accurately aim the radiation beam • Shape the radiation beam to the target • Deliver a radiation dose that damages abnormal cells yet sparing normal cells
  • 21.
    Major advances instereotactic localization, noninvasive neuroimaging, and radiation physics made it possible to selectively irradiate a sharply defined target, largely sparing the surrounding normal tissue. This approach, called stereotactic radiosurgery (SRS), is achieved by focusing multiple radiation beams on the tumor tissue from different directions
  • 22.
    Characteristics Characteristics of stereotacticirradiation are as follows : • High doses of the order of 10-15 Gy are delivered to target volume to achieve better tumor control • High degree of dose conformity • PTVs are small & range from 1-35cm3 so that • Less irradiation of normal tissue • Less morbidity • With requirement for • positional accuracy +/- 1mm • dose delivery accuracy +/- 5%
  • 23.
    Different machines fordelivering SRS/SRT 1. Gamma knife, Rotating Gamma Systen (RGS): Co-60 gamma rays 2. Cyberknife
  • 24.
    3. Modified LinearAccelerator/ Tomotherapy 4. Charged particles Different machines for delivering SRS/SRT
  • 25.
    SRS Techniques Leskell GammaKnife Radiosurgery • 1st Gamma unit was developed in 1968 by Leksell at Karolinska institute, Stockholm. • Gamma radiation from Cobalt-60 Source • Targeting precision of within 0.2 mm • Multiple targets can be easily treated in one session
  • 26.
    COMPONENTS: • A radiationunit with an upper hemispherical shield (central body) • Lower half of hemisphere has a shielding door • An operating table & sliding cradle • A control unit • Planning system Leskell Gamma Knife Radiosurgery
  • 27.
    • Source: Perfexion model:192 Cobalt 60 sources distributed in 8 sectors • Dimension: 2 cm height, 1 mm diameter • Housed in hemisphere called Central body • Shield: 18000 kgs surrounding the hemispherical array of Co60 sources Leskell Gamma Knife Radiosurgery
  • 28.
    Leskell Gamma KnifeRadiosurgery • Collimation helmets: 4, 8, 16 mm diameter • Depth helmet: Confirms the position of head ring on patients head
  • 29.
    Treatment components • Positionstabilization (attachment of a frame or frameless) • Imaging for localization (CT, MRI, angiography, PET etc.) • Computer assisted tumour localization (i.e., “image guidance”) • Treatment planning – number of isocentres, number, placement and length of arcs or angles, number of beams, beam size and weight etc. • Isodose distributions, dosage prescription and calculation • Simulation of prescribed arcs or fixed portals • Radiation treatment delivery
  • 31.
    SRS/SRT team •Radiation Oncologist •Neurosurgeon •MedicalPhysicist •Neuro-Radiologist •Neuro-Anesthesiologist •Neuro-Oncology Nurse •Radiation Therapy Technologist
  • 32.
    Frame Fixation SRS frames Leksellframe in Gamma Knife BRW (Brown-Roberts-Wells) & CRW (Cosman-Roberts-Wells) in X-Knife Relocatable frames for fractionated stereotactic irradiation (SRT) GTC (Gill-Thomas-Cosman) • helps us in defining the images in a coordinate • system - fiducial points: accurate positioning of the patient at the time of • treatment
  • 33.
    Frame Fixation To checkwhether frame will cover area of interest 60 year old F, pituitary adenoma
  • 34.
    Diagnostic Imaging • CTor MRI can be used MRI (preferred) • Requires MRI compatible localization box. • scans directly in axial, saggital, coronal or oblique planes • Better imaging of soft tissue tumors. • Can assess neural invasion Angiography for AVM
  • 35.
    Image Transfer Networking - Localarea networking (LAN) PACS - to Gamma plan - to X-plan • Magneto Optical disc • DAC tape • Film scanner • CT, MR film
  • 36.
    Depth Helmet • TheDepth Helmet provides quantitative quality assurance for relocatable head rings (GTC). • Checks that head ring has not moved b/w CT scanning & treatment delivery. • confirms that head rings have been accurately repositioned on patient prior to each SRT treatment. • A Depth Probe with millimeter scale passed into the guide tubes on the helmet to measure distance from the hole to the patient's head with millimeter accuracy. • This measurement data provides a permanent and precise record of positional accuracy for every treatment
  • 37.
  • 38.
    Treatment Planning • Definingisocenter • Dose prescription • Plan Evaluation • QA & Set up
  • 39.
    Treatment Planning Target vol.is encompassed by 70% to 90% isodose while using single isocenter. Entire treatment volume encompassed by 50% isodose curve while using multiple isocenters • For better dose conformity • For reduced dose to normal tissue
  • 40.
    Treatment Planning • Delineationof target and critical structures • Prescription of dose: 12 Gy at 50 % isodose Safety Limits Cochlea 7.4 Gy Brainstem 12 Gy Optic Pathway 8 Gy CN VII < 14 Gy CN VIII < 12 Gy
  • 41.
    Treatment Planning Techniques ofplan evaluation • Display of isodose lines over target volume • Display of 3-D dose shells • Display of DVHs Radiation oncologists approve the plan
  • 42.
    Set up andTreatment
  • 45.
    Linear Accelerator Based Radiosurgery 4or 6MV LINACS with tight mechanical and electrical tolerances, are modified for radio surgery • A remotely controlled motorized couch • Tertiary collimation that brings collimator closer to the surface • to reduce geometric penumbra ( inversely proportional to SDD) Tertiary collimation is either : • Cone based • Micro MLC based
  • 46.
    CONE BASED Highly collimatednarrow beams defined by • 15 cm long circular cones made of Cerrobend Lead, encased in stainless steel. • The cones are mounted below X-ray jaws • A range of cones with dia. from 5mm to 40mm in steps of 2.5mm are used for SRS lesions
  • 47.
    MICRO MLC BASED Usedfor small irregular field SRS/SRT - for greater conformity & efficiency than circular collimators • Computer controlled motorized leaves • Number of Leaves : 52 (26 pair) • Field Size (max): 10 cm x 10 cm • Leaf Width at Isocenter: 2.5 mm at isocenter
  • 48.
    Cyber Knife Three keycomponents: • Advanced light weight LINAC (High energy 6 MV beam) • Robotic arm pointing LINAC beam from wide variety of angles • Several X-ray cameras combined with powerful software to track patient position
  • 49.
    • Uses complexsystem of cameras, motion tracking softwares, fibreoptic sensing technology & Infra red emitters • Records breathing movement with sequential X-ray images of implanted radio-opaque markers 3-4 mm long
  • 50.
    Robot precisely followsmoving tumour to deliver radiation to desired target
  • 51.
    Advantages • Procedure painless,no anaesthesia, completed in 30-90 min, immediate recovery • Appropriate for many patients otherwise diagnosed as inoperable • No invasive head frame or other rigid immobilization device is required • The ability to perform radiosurgery (1-5 fractions) on targets throughout the body, not just the brain Disadvantages • More time consuming • Requires placement of fiducials
  • 52.
    Clinical uses ofSRS and SRT Arteriovenous malformations (AVM) Benign brain tumors • Acoustic neuromas • Meningiomas • Pineal & pituitary tumors Malignant brain tumors including Gliomas Astrocytomas Metastatic brain tumors Functional disorders Intractable Pain Trigeminal Neuralgia Psychiatric Diseases Parkinson’s Disease and Epilepsy
  • 53.
    PGI Experience YEAR Meningio ma Schwanno ma AVMPituitary adenoma Trigeminal Neuralgia Cavernous Lesion Glomus Lesion Jugular SOL Total 2016 67 65 52 38 15 12 8 2 271 2015 62 44 44 34 22 7 6 - 223
  • 54.
    Site Dose Trigeminal neuralgia80 – 90 Gy single shot at 7-8 mm anterior to emergence of nerve. Repeat GK if good response to first GK with at least 3 years Pituitary adenoma Non secretory: 12 – 17 Gy Secretory: 20 – 28 Gy Meningioma 10- 20 Gy Schwannoma Virgin Lesion: 11- 13 Gy Recurrent after 3 years if GK/EBRT: 10 – 12 Gy AVM 23 – 25 Gy at margins, assess response at 2 years Retreatment for residual lesion, <1cc: 22-24 Gy 3.5 – 8 cc: 19 – 32 Gy 8 – 13 cc: 18 – 20 Gy Metastasis > 20 mm: 22 – 25 Gy < 20 mm: 25 – 30 Gy Prior EBRT> 16 – 20 Gy Glial tumour Low grade: 15 – 17 Gy High grade: < 3 cm, unifocal: 7 – 10 Gy PGI Experience
  • 55.
    SRS for brainmetastasis Brain metastasis are the most common intracranial malignancy Indications: 1. Single brain metastasis: Accessible site: Surgery followed by WBRT/SRS Inaccessible site: SRS is an alternative but all studies are comparisons of WBRT followed by SRS boost versus surgery
  • 56.
    SRS for brainmetastasis 2. Multiple brain metastasis: 1) Limited number of tumours, all < 3 cm 2) High tumour burden or multiple large tumours
  • 57.
    2. Dose: • <2 cm: 22-25 Gy • > 2 cm: 25-30 Gy • Prior EBRT: 16-20 Gy 3. Local Control: 1 yr LC: 70-80% 4. Side effects: • Acute: nausea, dizziness, vomiting • Late: radiation necrosis, optic neuropathy SRS for brain metastasis
  • 58.
    SRS for Pituitaryadenoma Multiple treatment options available: medical therapy, microscopic or endoscopic trans-sphenoidal surgery, radiosurgery, radiation therapy, or observation. 1. Indication: Stereotactic radiosurgery (SRS) is usually indicated for: (1) incomplete surgical resections that leave residual tumor (2) tumor recurrence (3) cases in which medical therapy provides inadequate hormone control.
  • 59.
    SRS for Pituitaryadenoma Study Mean Dose Tumour control Hormonal control Visual field defects Induced hypopituitaris m Zhang et al n=79 31.3 Gy 92% 96% One None Izawa et al n=56 23.8 Gy 93.6% 30.3% cure 80.3% imp. One None 2. Dose: - functioning: 12 – 17 Gy - non-functioning: 13 - 15 Gy 3. Results:
  • 60.
    4. Side effects: -hypothalamic, hypopituitarism - Cranial neuropathy
  • 61.
    SRS for glialtumours 1. Indications: • unresectable LGG such as pilocytic astrocytoma, selected oligodendrogliomas • salvage therapy in patients with recurrent or residual glial tumors. 2. Dose: Due to the possibility of adverse radiation effects (ARE) after repeated fractionated radiation therapy, SRS is often used to boost the tumor radiobiological effect for smaller-volume recurrent or progressive tumors.
  • 62.
    SRS for vestibularschwannoma Vestibular schwannomas (more commonly referred to as acoustic neuromas) are tumors arising from the Schwann cells of the eighth cranial nerve. These tumors are commonly slow-growing, but growth can be variable. 1. Dose (PGI): • Virgin lesion: 11-13 Gy • Recurrence after 3 years of GK/EBRT: 10-12 Gy 2. Results: Kondziolka D et al (2003) treated 157 patients (40 undergone previous surgery): Median follow up : 9.1 years Decrease in tumor size : 114 (73%) No change : 40 (25.5%) Increase in size : 3 (1.9%) Normal facial nerve function : 95%
  • 63.
    3. Side effects: -Hearing loss - Facial, trigeminal neuropathy SRS for vestibular schwannoma
  • 64.
    SRS for AVM 1.Indications: • small- to medium-sized AVMs less than 3–3.5 cm in diameter • AVMs located in deep or eloquent brain regions 2. Dose: 16 to 25 Gy and obliteration rates tend to improve at doses greater than 17 Gy
  • 65.
    SRS for AVM 3.Results: Obliteration rates depend on a multitude of factors relating to AVM characteristics and treatment parameters, and they vary widely from 50% to 90% in reported studies 4. Side effects: hemiparesis (48.9% of all symptomatic patients), headache (16.3%), seizures (12.1%), sensory dysfunction (7.1%), and ataxia (3.5%)
  • 66.
    SRS for TrigeminalNeuralgia 1. Indication: Microvascular decompression was the gold standard but since the 1970s, SRS has gained popularity 2. Dose:60 to 90 Gy to 4 mm isocenter 3. Results: 58% were free of pain at a median follow-up of 18 months, and another 36% had significant improvement (>50%) in their pain HISTORY: (1951) First time SRS was used by Dr. Leksell for treating two patients with trigeminal neuralgia using 280 kV X rays
  • 67.
    SRS for TrigeminalNeuralgia It is postulated that TN results from a combination of central demyelination of the nerve root entry zone (REZ) and the subsequent, reinforced electrical excitability of the nerve
  • 68.
    SBRT for SpinalTumours 1. Indication: The most common and ideal indications for spine SBRT are in patients with no prior history of radiation, oligometastatic disease, limited or no epidural disease and no spinal instability.
  • 69.
    2. Dose - notstandardized - 24 Gy in 3 fractions SBRT for Spinal Tumours
  • 70.
    SBRT for SpinalTumours 3.Results: De novo metastasis, Guckenberger et al (2014) treated 387 spinal metastases across 8 institutions with a median dose of 24 Gy in 3 fxs. Median overall survival was noted to be 19.5 months, and 1- yr and 2-yr local control rates were 89.9% and 83.9% 4. Side effects: Vertebral Compression fracture Radial plexopathy
  • 72.
    SRS Complications ACUTE: Severe acutereaction: Rare: 835 consecutive patients: 18 had a neurological event within 7 days of treatment (e.g. new focal deficit or seizure), three died Immediate side effects: Two weeks after SRS, approximately one third patients had mild dizziness, nausea headache
  • 73.
    SRS Complications LATE: 1. RadiationNecrosis: With greater use of SRS, the incidence of radiation necrosis is increasing. Radiation necrosis develops in 7–24% of patients undergoing SRS. Bevacizumab has emerged as the best supported agent in the management of radiation necrosis.
  • 74.
    SRS Complications andManagement LATE: 2. Optic neuropathy RON can develop as early as 3 months post radiation, but can take years to develop. The peak incidence is 1–1.5 years.
  • 75.
    Role of re-irradiationwith SRS • Re-irradiation of brain metastasis in NSCLC with SRS in currently being tried on a case to case basis. • Balermpas et al. reported on 31 patients with 32 recurrent brain metastases: - Median interval was 12 months - Sequence was WBRT + SRS + SRS - One year survival and local control was 62% and 80%
  • 76.
    Conclusion • With theadvancement in equipment and better understanding of radiobiology of high dose per fraction radiation, the role of SRS and SRT is increasing • Both the techniques require meticulous treatment planning and execution • Local control in oligometastatic patients have increased by it • Recent interest has been shown in ultra-fast dose rate radiotherapy (excess of 40 Gy/s) – FLASH radiotherapy
  • 77.