Clinical Oncology SC015: Advancing Technologies In Radiation Oncology Flashcards
Principles of RT
Ionising radiation (電離輻射):
1. β rays
2. γ rays
3. High energy X rays (Photons (光子))
4. Charged particles (帶電粒子) (e.g. C-11, Protons)
Tumour control is NOT achieved by direct cell kill but by producing **secondary electrons (carry high energy)
—> **double-strand DNA breaks in nuclei
—> irreversible + permanent + fatal damage to tumour cell
—> cell death
Radiation falls off following **inverse-square law but **never drops to zero (theoretically go indefinitely, only drop to background level)
- Unit: ***Gray (Gy)
Most important background radiation:
- From universe
Goals of RT
Duplicating chromosomes (S phase in cell cycle) are more vulnerable to radiation
- unwinding —> double strands become single strand —> weak covalent bond —> more susceptible to radiation effect
RT:
1. Preferentially destroys tumour cells (actively proliferating esp. fasting growing tumour cells) but normal tissue cells also suffer (though to lesser extent)
—> Eradicate tumour cells while minimising damage to surrounding normal tissues
Other fast growing cells:
- Hair follicles —> Alopecia
- GI mucosa —> N+V, Diarrhoea
- Bone marrow —> BM suppression
- Preferentially treat malignant tumours but also treat **benign tumours / lesions as well
- **Meningioma
- **Acoustic (vestibular) schwannoma
- Trigeminal neuralgia
- Cavernous haemangioma
- **AVM (by stereotactic radiosurgery)
- Keloid scar
- Aneurymsal bone cyst
- Vertebral haemangioma
- Heterotopic ossifications
- **Graves’ ophthalmopathy
- Orbital pseudotumour / idiopathic orbital inflammation
- Pterygium
- Pigmented villonodular synovitis
- **Pleomorphic adenoma (recurrent)
- ***Pituitary adenoma (recurrent)
- Gynaecomastia after hormonal therapy for prostate cancer
***Therapeutic ratio
Effect (on normal + tumour cells) (Y-axis) vs Radiation dose (X-axis):
- Sigmoidal curve (contain an exponential phase)
- Tumour cell curve ↑ much earlier than Normal cell curve (∵ more susceptible to radiation)
—> separate wider when ↑ dose (**↑ tumour cell killing)
—> ↑ up to a point of maximum **therapeutic ratio (widest margin: max tumour cell killing with minimal normal cell damage)
—> just before plateau phase / turning point of tumour cell curve
—> further ↑ dose —> narrow the gap (∵ normal cell curve now exponential phase —> now also susceptible to radiation —> necrosis i.e. ***↑ SE)
- Fully makes use of difference of cell **killing and **regeneration capacities of tumour cells + normal cells to achieve the ***maximum therapeutic ratio
Implications:
1. Cannot just rely on RT as sole modality for treatment
—> need ***other modalities to widen therapeutic ratio
- More advanced radiation techniques can wide therapeutic ratio
Linear accelerator
3 components:
1. Electron gun (Cathode emit electron —> accelerated by electromagnetic field —> up to 1000x original speed —> hit tungsten —> emit X-ray)
2. Gantry
3. Couch
RT planning (電療設計 / 放射治療設計)
Purposes:
1. Pre-planning
- Clinical evaluation + Staging (TNM for solid tumours, Ann-Arbor for haematological malignancies)
- **Intent: **Radical / Curative vs ***Palliative
- Choice of treatment: Surgery, RT, Chemo, Targeted, Immunotherapy, Combination
- RT planning (after deciding on using RT)
- Patient immobilisation (e.g. by thermoplastic cast) —> ↓ collateral damage
- ***Image acquisition of tumour (e.g. CXR, CT, MRI, PET)
—> Contouring of radiation field
—> Shielding of important structures (e.g. neurostructures: brainstem, cerebellum, spinal cord) (otherwise paralysis / death) - Choice of ***technique + beam modification
- ***Calculation of dose distribution
2-dimensional RT
Old technique: Narrow therapeutic ratio
Prone to radiate other unnecessary structures:
1. Temporal lobe —> Temporal necrosis (may require steroid / surgery to resect)
2. Brainstem
3. Optic nerve, chiasm, lenses
4. Parotid glands —> Xerostomia
5. Jaw / Mandible / TMJ joint —> Osteonecrosis of jaw, Trismus, Neck fibrosis
6. Molar
7. Tongue
8. Spinal cord
Intensity Modulated RT (IMRT (強度調適放射治療))
- Makes use of **multiple beams directed to tumour at **different angles (e.g. 9 fields)
-
**Intensity of radiation dose in each beam can be further modified
—> create a **dose gradient to the tumour + surrounding normal structures (i.e. higher dose to tumour + lower dose to normal structures) - PET/CT + MRI co-registration (overlap 2 images) for tumour contouring
—> MRI for drawing accurately exact tumour location
—> Computer to calculate radiation dose based on CT scan - PET/CT for diagnosis of subtle synchronous tumour
***2D RT vs IMRT
2D RT:
- Based on films
- **Less detailed localisation of tumour + normal structures
- **Planning time shorter
- Easy set-up
- Shorter delivery time
- Mainly for **palliative treatment, occasional for **early-staged disease with simple set-up (e.g. T1N0 glottic cancer, T1N0 NPC, cervical / uterine cancer)
- SE esp. chronic SE more severe
IMRT:
- Based on CT images
- **Detailed localisation
- **Planning time much longer (computer planning)
- Complicated set-up
- Longer delivery RT
- Mainly for ***radical treatment aiming to give an escalated radical dose
- SE esp. chronic SE less severe
- ?More radiation-induced secondary malignancies (risk: 1 in 10,000 ∵ RT delivered at multiple angle)
Image-guided RT (IGRT (影像導航放射治療))
- Even immobilised by thermoplastic cast, patients / tumours can still move 1-2 mm in all directions
- Also set up error of 1-2 mm as well
- ***Real-time imaging before each treatment can provide important information on patient + tumour location
—> Detect + Correct set-up error / discrepancies before Rx - Monitor body contour during course of RT
Indications:
- Tumours with **undetectable organ motions during treatment / sites with **dramatic change of body contour during RT
—> **Prostate cancer (position varies depending on bladder + rectum)
—> **H+N cancer (esp. neck LN +ve tumour) which shrink rapidly during RT / ChemoRT
Limitations:
- Cannot manage large discrepancies
—> e.g. severe weight loss —> have to re-plan everything again (e.g. CT contouring, thermoplastic cast, dose calculation again)
Components:
1. Linear accelerator (Mega voltage)
2. Cone-beam CT (Kilo voltage)
Cyberknife (數碼導航刀)
- Linear accelerator equipped with a ***robotic arm —> able to rotate at every angle
- ***Long RT delivery time ∵ small gantry size (3-5 cm) —> small area of irradiation
- Currently only available in private sector
Indication:
- ***Small tumours (<3 cm) close to normal critical structures (e.g. spinal cord compression, brain metastasis / tumours close to brainstem / optic nerve / chiasm / spinal cord)
Stereotactic radiosurgery (SRS (立體定向放射外科手術))
Types:
1. **X-knife
2. **Gamma-knife
—> Multiple X-ray / Gamma rays (Very high dose) from ***different angles converging to the tumour
- Delivered in (**one fraction only **18-20 Gy (Very high dose) (or few fractions only: Stereotactic (Fractionated) RT (SRT))
- ***Very complicated set-up for immobilisation (if irradiate wrong position —> can be serious consequences)
—> past: stereotactic head frame to fixed head
—> current: frameless head frame - ***Long RT delivery time
Indications (small tumour + important structures nearby):
1. Brain metastases (max. 3, <3 cm each)
2. Meningioma
3. Acoustic neuroma (Vestibular schwannoma)
4. Cavernous haemangioma
5. Glomus jugulare
6. AVM
Charged-particle therapy (帶電粒子治療)
Overcome inherent limitations of X-ray (Photons)
- Inverse square law: ↑ tissue depth —> ↓ radiation intensity
Charged-particle:
- Characteristic peak of max dose deposition at a certain depth (Radiation intensity ↑ sharply then ↓ sharply) (***Bragg peak) for each type of charged particle
—> align to location of tumour
—> allow very high radiation dose while sparing unnecessary organs
Types of Charged-particle therapy:
1. Proton (most commonly used)
2. Carbon ion
3. Neon
The machine (Cyclotron) that produces proton takes a lot of space (~half of a football pitch!)
Proton therapy (質子治療)
- ***Hydrogen ion carrying 1+ charge
Indications:
- Best for **small tumours close to critical structures where a **rapid dose fall-off is essential to avoid radiation-induced permanent damage
—> orbits / optic nerve / chiasm / pituitary
—> spinal cord
—> brainstem
Examples:
- Orbital tumours (e.g. Uveal melanoma (need to protect fovea / macula))
- Ependymomas of spinal cord
- Paediatric brain tumours (protect developing brain)
- Prostate cancer
Brachytherapy (短距治療)
Brachy: within a short distance
- Delivery of RT by placing radioactive sources (e.g. I-125, Iridium-192 etc.) (β + **γ emissions) in **close proximity to tumours e.g. prostate cancer, cervical cancer, uterine cancer, rectum / anus, recurrent NPC etc.
Types:
1. Interstitial brachytherapy
- ***neck nodal recurrences in NPC / H+N cancer
- lip cancer
- breast cancer
- Intracavitary brachytherapy
- **uterine cavity / vagina for cervical cancer —> spare skin / muscles
- **nostrils for NPC
- breast cancer - Endoluminal brachytherapy (e.g. lung, rectal cancer)
Intra-cavitary partial organ irradiation
- Traditionally, when RT is needed for breast cancer, usually the whole breast is
irradiated - Recently found that majority (>90%) of local recurrence is in the ***vicinity of original site of tumour for stage I cancer
- Irradiation of partial breast (only irradiate on close proximity sites) may provide similar cure rate but better cosmetic outcome compared with whole-breast RT
- Single catheter balloon intracavitary brachytherapy
- Multi-catheter balloon intracavitary brachytherapy
—> Load catheter into surgical cavity
—> Inflate balloon to fit surgical cavity
