Adverse Effects of Radiation Dr Mohammed Malik Afroz

Radiation Induced Changes Fibrosis of musculature Masticatory inadequacy (chewing with less force) Impaired Deglutition (swallowing) Altered response to irritation, infection Trismus Capillary Fragility Increased Vascular Permeability Oral Incompetence (lips not closing) Tissue fragility and friability(crushed) Decreased repair potential Fear, Depression. Golden Period – 6 week period following RT

Adverse Effects Susceptibility to soft tissue necrosis Susceptibility to osteoradionecrosis Increased susceptibility to radiation caries Susceptibility to infection – candidiasis Salivary changes Ulcer - Hemorrhage

Late Effects Mucositis Osteoredionecrosis Radiation caries Xerostomia Dysphagia

Mucositis Etiology Multifactorial – habit related to dose of radiation Hyperfractionated radiotherapy show more side effects 6 months interval following radiation therapy complete ulcer healing.

Mechanism of Mucositis Development In 1998, Sonis proposed that mucositis is related to direct and indirect cytotoxocity, Radiation therapy has a direct cytotoxicity - local tissue cytokine and immune activity, and bacterial colonization of ulcerative lesion Chemotherapy causes Myelosuppression in which neutropenia and thrombocytopenia can influence mucositis indirectly through secondary infection and hemorrhage Another proposed mechanism involves the alteration of salivary immunoglobulins, proteins, electrolytes, and nonspecific host defense in saliva

Cryotherapy – use of ice chips Xerostomia – Pilocarpine Mucositis Mangement General Mouth Care Cryotherapy – use of ice chips Xerostomia – Pilocarpine Cytoprotective Agent – Amifostine Mucositis Pain Induced by Radiation Therapy: Prevalence, Severity, and Use of Self-Care Behaviors Wong P.C, Dodd M V, Miaskowski C, Journal of Pain and Symptom Management Vol. 32 No. 1 July 2006

Osteoradionecrosis Regaud 1920 – described osteoradionecrosis as side effect of radiation therapy Definition – as a condition in which devitalized, irradiated bone becomes exposed through a wound in the overlying skin or mucosa. Such a wound must not be caused by tumor recurrence, or by tumor necrosis during radiation therapy, and it must persist without healing for 3 to 6 months ORN clinical features – intolerable pain, fracture of bone, sequestration of devitalized bone and fistulas, which makes chewing impossible. Early stage ORN (< 2 years) after radiotherapy is seen with high radiation dose of more than 70 Gy and/or concomitant surgical and/or radiation trauma Late stage ORN is observed several years after radiotherapy and is related to trauma within the hypo vascular – hypo cellular hypoxic tissue

Facts regarding osteoradionecrosis General conditions and personal hygiene. it is rare when doses of less than 60Gy are used at 1,000 cGy or less per week (2) it is more likely to occur if brachytherapy is used instead of or in addition to external beam therapy (3) the mandible is affected far more frequently than is the maxilla or the other bones of the head and neck (4) dental extractions, surgery, or other types of trauma frequently precede (happen before) the onset of osteoradionecrosis (5) osteoradionecrosis is a problem of impaired wound healing, not an infection like osteomyelitis, although there may be secondary infection.

Management Of Osteoradionecrosis Oral/intravenous administration of antibiotics in combination with surgical procedures immediately after extraction. Particular care must be taken with extraction techniques, dental hygiene, fluoride devices for tooth protection, adequate healing time for teeth extracted before radiotherapy an exact pre-radiation planning and a careful post-surgical wound treatment. Hyper Baric Oxygen treatment has been used to promote revascularization of the irradiated tissues. This therapy alone seems to be ineffective in ORN because it is not able to revitalize dead bone hence surgical removal of devitalised bone followed by HBO is helpful.

Xerostomia Decrease in saliva usually seen after 2 weeks. Symptomatic Grading of Xerostomia Grade 0: no effect on speech and food intake. Grade 1: some effort required for speech and food intake but not requiring liquid for taking dry food. Grade 2: discomfort on speech and food intake requiring liquid for taking dry food. Grade 3: requiring liquid for regular conversation, presence of dried, coated oral mucosa. Does radiation dose to the salivary glands and oral cavity predict patient-rated xerostomia and sticky saliva in head and neck cancer patients treated with curative radiotherapy? Jellemaa A P, Doornaerta P, Slotmana B, Leemansb C, Johannes A., Langendijka,c Radiotherapy and Oncology 77 (2005) 164–171

XEROSTOMIA MANAGEMENT Pilocarpine – is the drug of choice The response of salivary glands to pilocarpine requires residual functional salivary gland tissue Other Methods – Frequent sipping of water Artificial salivary supplements (oral balance) Maintenance of oral hygiene Amifostine

Amifostine – Most Important Drug IV infusion prior to radiotherapy each time - doses 200 mg/m2 and 340 mg/m2 Has protective effect on the salivary glands due to high uptake and retention of amifostine and its metabolites in the salivary glands Adverse effects seen are – vomiting, allergic reaction, severe anaphylactic reaction which can be decreased by subcutaneous application In patients who undergo chemotherapy adverse effects are more. Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients Radesa D, Fehlauera F, Bajrovica A, Mahlmannb B, Richterb E, Albertia W Radiotherapy and Oncology 70 (2004) 261–264h

Radiation Caries Radiation caries Rampant form of dental decay. Highly destructive Evident within 3 months of radiation therapy. Etiology: changes in salivary gland & saliva composition. Reduced cleansing action of saliva debris accumulate.

Clinical features Seen on plaque forming surfaces & areas of exposed dentin Types: Type 1: widespread superficial lesion- buccal, occlusal, incisal, & palatal surfaces.- common

Type 2: involves cementum, & dentin in cervical region.- loss of crown. Type 3: dark pigmentation of entire crown, incisal edge markedly worn. Areas below contact pt affected last by caries Striking feature – rapid progression but rarely associated acute pain. Decrease in pulpal response- decrease in vascularity, fibrosis, & atrophy of pulp.

Management Oral hygiene instructions Education Avoidance of dietary sucrose Methods to control: Daily application of viscous topical 1% neutral NaF gel Combination of dental restorative procedures, oral hygiene, topical application- best result. Pt co-operation. Gross decay- extraction advised.

Hyperbaric Oxygen Therapy It was believed that ORN was a chronic infective osteomyelitis HBO has adjuvant(joint) role in the treatment of infection in this situation. The rationale for using HBO is that intermittent elevation of tissue oxygen tension stimulates collagen synthesis and fibroblastic proliferation. contra-indications to HBO are: Optic neuritis existing neoplasia.

Indications for HBO 1 Radiation necrosis of bone and soft tissues 2 Healing of hypoxic wounds 3 Compromised skin grafts and flaps 4 Chronic refractory osteomyelitis 5 Crush injuries and traumatic ischaemia 6 Diabetic ulcers 7 Carbon monoxide and cyanide poisoning

Hyperbaric Therapy Unit (HTU) Treatment with HBO is measured by the number of ‘DIVES’ in the chamber. A ‘DIVE’ consists of breathing 100% pure oxygen at 2 atm of pressure. The ‘DIVE’ lasts approximately 90 min including compression and decompression. Clinical Hyperbaric Unit (CHU) Hyperbaric Therapy Unit (HTU)

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