Radiotherapy

How many cancer patients are cured with radiotherapy as part of their management plan?

40%

Early complications of radiotherapy

80% general fatigue (most common) - tends to peak in 2nd week - improves about 4 weeks after completing treatment - persists chronically in 30% - keep active! Skin: - erythema - dry and moist desquamation (if moist, keep very clean to avoid superinfection) - skin tanning - temporary hair loss in treatment field (regrows within weeks of completing treatment) - sweat/sebaceous gland dysfunction - heals from outer margins by about 3 weeks - when skin needs to be irradiated, the technique is altered to produce a brisk skin reaction - topical aloe vera claimed as good prophylaxis GI tract: - loss of taste - salivary dysfunction - oral mucositis (head and neck treatments, may be complicated by yeast or bacterial superinfection) - dysphagia (thoracic treatments) - diarrhoea (abdo and pelvic treatments) - N+V (stomach, liver, brain treatments) Bone marrow: - cytopenias (often due to large areas being irradiated) Lungs: - pneumonitis Cystitis (pelvic treatments)

What is external beam radiotherapy therapy (EBRT)?

Administered using a linear accelerator Usually uses high-energy X-rays, which penetrate deep into body tissue while relatively sparing the skin (can also be used to treat skin tumours) From lecture (probably won't bother learning): - To produce a megavoltage x-ray beam, it is necessary to have a waveguide (evacuated tube) in which the electron stream can be accelerated onto a transmission target using the energy of a radio-frequency wave - Target composed of Tungsten and is cooled by a flow of water

Complications of radiotherapy

Apart from fatigue, toxicity depends on the anatomical location of the radiotherapy fields Toxicity divided into early and late: - Early toxicity: generally reversible but must be managed appropriately to avoid unnecessary gaps in treatment, begins about 2 weeks into treatment but symptoms tend to peak at 2-4 weeks after completion of treatment - Late toxicity: occurs at least 6 months after treatment and may present after many years, often irreversible Rapidly proliferating tissues (e.g. skin, mucosa, bone marrow) most sensitive

Internal radiation therapy

Brachytherapy (more detail on next card) Systemic radiation therapy: systemically administered radioisotopes target tumour cells Radioactive I(131) can be taken orally to treat thyrotoxicosis and thyroid cancers

Common cancers curable with regimens that include radiotherapy (don't learn this)

Breast carcinoma Locally advanced lung carcinomas (NSCLC and SCLC) Seminomas Endometrial Locally advanced uterine cervix Several CNS tumours Soft tissue sarcomas Rectal and anal carcinomas Lymphomas (Hodgkin and non-Hodgkin) Advanced head and neck Bladder carcinomas Paediatric: Wilms tumour, medulloblastomas, neuroblastoma, Eqing's sarcoma, rhabdomyosarcoma

General uses of radiotherapy

Curative setting: radical radiotherapy can be offered as the sole treatment for some cancers (AKA radical radiotherapy) Used with surgery, neoadjuvantly (e.g. to shrink tumours) or adjuvantly (e.g. decrease the risk of local or regional tumour recurrence) Patients medically unfit for surgery Anatomically unresectable cancers Palliative radiotherapy: - reduce or eliminate pain from bone metastases - palliate brain metastases - spinal cord compression - compressive symptoms from visceral metastases (e.g. airway or GI obstruction) - uncontrolled bleeding - e.g. haemoptysis or haematuria - may take 3 weeks before therapeutic effect

Stereotactic radiotherapy (SRT)

Form of EBRT Multiple radiation beams converge on the tumour, delivering high-dose radiation to the tumour but little to surrounding tissues - good for targeting small lesions with great precision e.g. intracranially Stereotactic radiosurgery (e.g. gamma knife): SRT delivered in 1 session Stereotactic body radiation therapy (e.g. CyberKnife®): high-dose radiation delivered using robotic guidance

Intensity-modulated radiotherapy (IMRT)

Form of EBRT Uses multiple beams with a non-uniform dose across the field, which can create steep dose gradients - increases sparing of normal tissues - higher and potentially more effective doses could be used without the risk of increased toxicity - however, a greater volume of tissue receives a lower dose (suggested that it might increase risk of secondary cancer) Particularly useful for head and neck cancers because of the high number of important normal tissue structures within close proximity to the tumour Reduction in side-effects

Image-guided radiotherapy (IGRT)

Forms of EBRT Allows positional correction if required by taking into account tumour motion - involves determining the position of the tumour everyday before giving radiotherapy and then altering the settings/treatment positioning if the tumour has moved Essential for IMRT because steep dose gradients carry a risk of the target being given too low a dose and normal tissue being overdosed 3D conformal radiation therapy: CT or MRI used to target tumours 4D radiation therapy: computer-assisted tracking or gating of CT images of moving targets (for tumours susceptible to movement e.g. lung, liver, pancreas, breast) - e.g. can obtain a series of scans at different phases of respiratory cycle In some cases e.g. prostate cancer, implanting radio-opaque seeds allows the target to be identified using treatment X-rays

How is radiotherapy given?

Given as either external or internal radiotherapy The dose of radiation is defined as the irradiation absorbed by each kilogram of tissue expressed as Grays (Gy) - 1 Gy = 1 J/kg of tissue - the dose is usually given in a number of daily fractions with the total dose determined by tumour sensitivity and normal tissue tolerance - each treatment session/fraction takes about 10-20 minutes, including time spent ensuring the patient is correctly positioned on the treatment couch Cells start to recover within 6 hours - if fractions are too close together then normal tissues would suffer excessive toxicity, however too far apart and sublethal damage to cancerous tissue could be repaired Patients receiving multiple fractions are usually reviewed at least weekly by a doctor, to help manage treatment-related S/Es Shorter treatments of lower dose often used for palliative radiotherapy (low doses of can provide tumour control for a short time (months) with minimal S/Es)

Radiotherapy target delineation

Gross tumour volume (GTV) = what you can see on imaging or clinically Clinical tumour volume (CTV) = area encompassing the area where the cancer has spread microscopically Planned target volume (PTV) = takes into account patient movement and targeting errors Treated volume

Brachytherapy

Interstitial: inserted directly into tumour e.g. prostate, head and neck Intracavitary e.g. endometrium, oesophagus Temporary brachytherapy implant: radiation source placed within or near the tumour target and later removed Permanent brachytherapy implant: low-dose rate (i.e. long half-life) radiation source placed within or near the tumour target

Brachytherapy in prostate cancer

Iodine seed brachytherapy Advantages - single visit intra-operative - rapid return to normal activity - can optimise dose (very high radiation dose 145Gy, low irradiated volume, no concerns regarding movement or fractionation) - <1% risk of incontinence and rectal damage - 70% potency rates Disadvantages - not suitable for all patients e.g. those with very large prostates - main S/E urethritis up to 9-12 months - proctitis 5% - stricture 5-10% - PSA falls slowly and can go up and down (psychologically difficult to deal with)

Challenges in achieving optimal dose in treatment of breast cancer

Large pendulous breasts Pectus excavatum Normal tissue tolerance of: heart, spinal cord

Planning radiotherapy

Multidisciplinary team Most EBRT planned uses CT imaging to locate the tumour and provide information on the patient's shape and tissue density - correlation with diagnostic imaging essential (best diagnostic imaging for many tumours is MRI) For some sites (e.g. the brain), computerised image fusion is used with the planning CT scan to improve the accuracy of tumour localisation PET-CT can help radiotherapy planning for lung cancers and lymphomas Modern techniques can align treatment more closely to the tumour (3D conformal radiotherapy) - allows sparing of more healthy tissue and less toxicity Position and immobilisation important for accurate delivery - supine position more common Can improve localisation of target volume using surgical clips at resection site Take into account: previous radiotherapy, tolerance of surrounding normal tissue

Can radiotherapy ever be given during pregnancy?

NO

Management of some early complications of radiotherapy

Oral mucositis: - dental check-up before therapy in head and neck cancers - avoid smoking, alcohol, spicy food - antiseptic mouthwash - aspirin gargle and other soluble analgesics helpful N+V: - 1st line = metoclopramide or domperidone - 2nd line = ondansetron Diarrhoea: - maintain good hydration - avoid high-fibre bulking agents - loperamide

Indications for IMRT in breast cancer

Pectus excavatum Bilateral breast cancer Tricky anatomy i.e. medial tumours

Common cancers curable at early stage with radiotherapy alone (maybe learn this?)

Prostate Head and neck Non-small cell lung carcinoma Hodgkin lymphomas Uterine cervix carcinomas

Radioprotectors

Protect against radiation injury when given prior to radiation exposure Potentially improve outcomes of radiotherapy by allowing higher doses of radiation and/or reduced damage to normal tissues E.g. amifostine, palifermin, superoxide dismutase

Different types of beam arrangement

Single field Opposing fields Complex beam arrangements

Late complications of radiotherapy

Specific to tissues involved Usually occur if normal tissue tolerance is exceeded Neck: - fibrosis and decreased movement Jaw muscles: - fibrosis impairing mastication Lymphatic system: - lymphoedema - intermittent erysipelas Skin: - telangiectases - ulceration - bone osteoradionecrosis Salivary function: - loss of salivary flow with xerostomia - oral and gingival tissue atrophy and telangiectases Central nervous system: - transverse myelitis and Lhermitte's symptom (electric shock-like sensation in upper limbs on neck flexion) - full transverse myelitis with Brown-Séquard syndrome - somnolence (brain treatment) - brachial plexopathy (numb, weak, painful arm after axillary treatment) - reduced IQ (brain treatment in children <6yo) GI: - benign strictures (bowel, oesophagus) - fistulae - radiation proctitis GU: - urinary frequency (small fibrosed bladder) - reduced fertility (consider pre-treatment sperm or ova storage) - vaginal stenosis - dyspareunia - erectile dysfunction Endocrine: - panhypopituitarism - hypothyroidism (50% for head and neck cancers) Eye: - cataracts - dry eye syndrome - retinitis Ears: - otitis - sensorineural hearing loss Delayed wound healing Increased risks of cardiovascular events and stroke Risk of second cancers increases over the decades after treatment and depends on the treated volume and dose

Proton beam therapy

Uses protons rather than photons to deliver the radiation dose - allows the dose to be deposited at a specific depth but not before or beyond it(allows improved target coverage, with reduced doses to the normal tissue beyond) Expected to reduce the risks of late effects e.g. second cancers and cardiovascular risk (important for children and young adults) but currently no evidence for this Current indications in adults = spinal and base of skull tumours In the UK, patients suitable for proton beam therapy can now be referred abroad under the NHS Proton Overseas Programme

How radiotherapy works

X-rays deliver energy through waves called photons, which are produced by accelerating a stream of electrons and colliding them with a metal target. High-energy photons produce secondary electrons in human tissue, which cause DNA damage which, if not repaired, is fatal at cell division. Direct OR indirect interaction with cell DNA