Radiotherapy: Adverse effects and Complications

Dev Tripathi

09/07/2015

History

Background… • Ionising radiations like X rays, electrons,

protons, alpha particles

• The effects of radiation result mainly from DNA damage either directly or through generation of free radicals from water molecules

Background

• Radiotherapy delivered to around half of cancer patients , is a vital part of curative treatment in around 40% patients

• More curative/contributive towards cure than chemotherapy, much lower acute mortality

• Late effects can be severe but usually well understood and have long history

Severity of reaction depends on

• Total Dose and dose per fraction

• Size of the field

• Total duration of treatment

• Tissue sensitivity

‘4 Rs’ of Radiotherapy- Repair, Repopulation, Redistribution, Re-oxygenation

Severity of reaction depends on

• Co-Morbidities-

Inflammatory Bowel Disease

Connective Tissue Diseases (Scleroderma, SLE)

DNA repair disorders (Ataxia Telangiectasia,

Fanconi Syndrome)

• Concurrent chemotherapy

Classification

• Acute vs. Late Acute effects within days to weeks. More prominent in

fast dividing/rapidly regenerating tissues (Skin, GI tract)

Late effects over months to years in both types

May be very important in slow responding tissue e.g.

Spinal Cord, Kidneys, Lungs

• System/Tissue involved Skin, Mucosa, GI tract, CNS, Kidneys, Lungs etc.

Acute and Late SEs

General Principles- Acute

• Resuscitate

• Rehydrate

• Replace electrolytes

• Reduce Transit

• Keep clean

• Control Pain

General Principles- Late

• Supportive Care

• SALT

• Physiotherapy

• Palliative care referral

• Nutritional Support

• Other specialists, eg. Chest Physicians, Endocrinologists

• Late Effects Clinic

System/Tissue Involved

• Skin

• Oral mucosa

• GI tract

• Lung

• Neuro

• Renal

• Heart

• Liver

Skin

RTOG Grade

Definition

0 No change over baseline

1 Follicular, faint or dull erythema/ epilation/dry desquamation/ decreased sweating

2 Tender or bright erythema, patchy moist desquamation/ moderate oedema

3 Confluent, moist desquamation other than skin folds, pitting oedema

4 Ulceration, haemorrhage, necrosis

Skin

• Significant in

Breast

Vulva

Head and Neck

Rectum/Anus

Skin Cancers

• Less common with MV radiotherapy

• Visible by 2nd or 3rd week of radiotherapy

Management

• Avoid direct sunlight

• Gentle Washing with non perfumed soaps and shampoos, lukewarm water

• Use plenty of moisturiser- water based, non perfumed

• Dry shaving- electric razor

Management

• Specific treatment for desquamation: Hydrocortisone for itch, Flamazine to prevent infections

• Simple, non adhesive dressings

• Treat infection, analgesia (WHO pain ladder-nonopioids e.g. Paracetamol, then mild opioids e.g. Codeine, then strong opioids such as Morphine)

Oral Mucositis

WHO Grade

Definition

0 No change over baseline

1 Soreness with erythema

2 Erythema, ulcers, can eat solids

3 Ulcers, liquid diet only

4 Alimentation not possible

Oral Mucositis

• Common with Head and Neck RT

• Starts within 12-14 days

• Often mistaken for oral thrush by junior ward staff

• Can last for several weeks post RT completion

Management

• Careful Oral Hygiene- Soft tooth brush, gentle toothpaste, alcohol free mouthwash

• Saline mouthwash

• Pharmacological management- Difflam mouthwash and spray , Bioxtra mouthwash, toothpaste and gel

Management

• Soluble Aspirin mouthwash- 300 mg tds in lukewarm water

• Alcohol free Oramorph topically, analgesia according to pain control ladder

• Treat infections- Fluconazole, Acyclovir, Oral antibiotics, Chlorhexidine mouthwash

• Maintain nutrition- Regular weight checks, Dietary review, PEG feed

Radiation Pneumonitis

• Lung Cancer

• Breast Cancer

• Lymphomas

• Oesophageal Cancers

• Clinically evident radiation Pneumonitis

in 5-15% patients receiving thoracic RT

• 60% patients will have asymptomatic radiological changes

Radiation Pneumonitis- Risk Factors

• V20- Volume of normal lung getting >20 Gy- risk high if >35%

• Concurrent chemotherapy

• Pre existing COPD, Pulmonary Fibrosis- FEV1 >40% predicted or 1L, TLCO >50%

• Connective tissue diseases

• Heavy smoking history

Symptoms

• Usually acute phase occurs a few weeks after completion of radiotherapy (4-12 weeks)

• Symptoms typically include

Cough

Dyspnoea (exertional or at rest)

Low grade fever

Chest discomfort and pleuritic pain

Hypoxia

• Over time, may progress to irreversible fibrosis

Investigations

• CXR- Often non-specific. Airspace opacities common. Pleural effusions or atelectasis may be seen. Changes often do not follow anatomical boundaries- might have straight edges

• HRCT- The two most common findings are ground-glass opacities and airspace consolidation

• PFTs- Reduced Lung Volumes, Reduced Transfer Factor

Treatment

• Steroids, example- Prednisolone 40 mgs for 3-4 weeks, then taper slowly over several weeks

• Antibiotics, might help if there is an element of coexisting infection

• Supplemental Oxygen for Hypoxia

• Symptomatic treatment- home oxygen, pulmonary rehab for Lung Fibrosis

GI toxicities

• GI tract vulnerable as contains many rapidly proliferating cells

• GI tract irradiation may result in- Oesophagitis- retosternal burning, dysphagia,

odynophagia. Onset usually after 20 Gy

Nausea and Vomiting- release of serotonin by cell death

in GI mucosa

Diarrhoea

Proctitis- diarrhoea, tenesmus, urgency, bleeding

Management

• Oesophagitis Analgesia for pain control

Barrier- Mucilage, Alginates- Gaviscon

Local Anaesthetic- Oxtecaine/Antacid

Proton Pump Inhibitors

Soft, Bland food, dietary supplementation

Treat Infections, eg Candida

Management

• Diarrhoea Rehydrate, correct electrolyte abnormalities

Rule out infection (C.Diff toxin, stool culture & viral testing)

Exclude other causes- laxatives, PPI, other meds

Exclude overflow diarrhoea

Symptomatic Relief- Loperamide, Codeine

Rectal steroids- (Colifoam/Predfoam)

Management

• Nausea and Vomiting

May be caused by RT to the GI tract or Brain

General principles-

Rehydrate: may need intravenous fluids.

Correct electrolytes

Antiemetics- 5HT3 antagonists, Domeperidone, Cyclizine

May benefit from steroids (Dexamethasone 4-8 mg daily)

Neurological Toxicity

• Acute Whole brain radiotherapy- during or shortly after

finishing RT

Caused by cerebral oedema secondary to disrupted

blood brain barrier

Symptoms- Headaches, drowsiness, seizures, worsening

neurological deficits

Managed by starting steroids (or increasing steroid dose)

Example Dexamethasone 4mg-8 mg PO BD

Neurological Toxicity

• Subacute Somnolence syndrome- occurs 1-6 months after finishing

RT (typically 6 weeks)

Features- somnolence, headaches, irritability

Treatment with steroids: may reduce duration. Usually

settles over weeks to months

Finally… • Newer radiation techniques (IMRT, IGRT)

• Much more conformal, possible to reduce doses to surrounding tissues and organs at risk

• Reduced acute and late toxicities

BUT- low dose “splash” to a higher volume-

long term effects unknown

To Summarise…

• Radiotherapy is a vital component of cancer treatments

• Acute and long term toxicities common but usually mild, self limiting and manageable

• General principles to manage acute toxicities

• We are always available to offer advise and help

Thank you for listening