Side effects of radiation in head and neck cancer

SIDE EFFECTS OF RADIATION IN HEAD AND NECK CANCERS

ANAGHA S PACHATINTERNMSc RADIATION PHYSICS

introduction• Radiation therapy is an integral part of the treatment of patients inflicted with cancer.

• It is estimated that over 60% of patients with cancer will have radiotherapy as part of their total course of treatment .

• Radiation therapy affects both tumor cells and uninvolved normal cells; the former to the benefit and the later to the detriment of patients.

• With the goal of achieving uncomplicated local regional control of cancer, balancing between the two is both an art and a science of radiation oncology

• From a historical point of view, the first formal attempt to address the goal, namely normal tissue tolerance to radiation, was carried out by Rubin and Cassarett. This was purely empirical.

• In 1991, investigators pooled their clinical experience, judgment, and information regarding partial organ tolerance doses and produced the “Emami paper”.

• During the 1990s and 2000s, a large number of studies related dose–volume data to clinical outcomes. The QUANTEC review was an attempt to refine the guidelines based on the available 3D dose/volume/outcome data

Effects of radiation on cells• Radiation damage cell by two methods

DIRECT ACTION

Exposure to ionizing radiation causes direct DNA damage through linear energy transfer

INDIRECT ACTION

indirect damage by radiolytic cleavage of water, yielding hydroxyl radicals capable of abstracting hydrogen from the backbone of DNA to cause double-stranded breaks

Deterministic Effects• Deterministic effects are characterized by:

A threshold dose below which no effect is seen Worsening of the effect as dose increases over the threshold Always occurring once the threshold dose is reached Different effects, tissues and people have different threshold doses for deterministic effects

• All early effects, and most normal tissue late effects are deterministic.

•Stochastic Effects Stochastic effects account for the remaining late effects:

They have no threshold dose They increase in likelihood as dose increase Their severity is not dose related There is no dose above which stochastic effects are certain to occur

• Stochastic effects include radiation carcinogenesis and hereditary effects

Head and neck cancers

Normal tissue tolerance dose as per QUANTEC

• Parotid glands mean <25Gy(both glands) or mean <20Gy (one gland)

• Submandibular glands mean <35Gy• Larynx mean<44 Gy, v30<27% max 63 -66 Gy• Mandible max 70 GY if not possible V75<1cc• Oral cavity non oral cavity cancer mean<30Gy avoid hotspots >60Gy

oral cavity cancer mean<30 Gy V55<icc max 65Gy• Esophagus V45<33%• Pharyngeal constrictor mean<50Gy• Thyroid V26<20%

Radiation Side Effects• Acute Side Effects• Acute reactions that can occur during irradiation are

predictable toxicities,

• depend on the dose and schedule of radiation therapy used

• Such effects include mucositis, odynophagia, dysphagia, hoarseness, xerostomia, dermatitis, and weight loss.

• These effects occur to some degree in the majority of patients, but they are self-limited in duration.

Dermatitis

• Radiation damage to stem cells in basal layers of the skin can give rise to a sunburn-like desquamation.

• These effects can occur as early as 2 weeks after the start of radiotherapy.

• This side effect can be minimized through appropriate skin care, avoidance of exposure to potential chemical irritants, limitation of direct sun exposure, and avoiding application of lotions, ointments, or fragrances to the head and neck region

• IMRT typically worsens skin reaction because of the multiple target beams, but this effect can be reduced by specifying the skin as an avoidance structure and by treating the lower neck with an anterior beam rather than including it in the IMRT plan

Xerostomia—• The severity of xerostomia resulting from RT for HNC depends on the volume of salivary tissue irradiated.• Temporary loss of saliva is significant after about 10 Gy is delivered to the salivary glands,• administration of doses significantly higher than 26 Gy can cause permanent loss of function.• Alteration in taste can also occur, • decreased oral intake may contribute to reduced saliva production.• Prevention of this side effect can be performed by reducing salivary gland dosage in formal planning.

Mucositis• Radiation-induced loss of stem cells in the basal layer interferes with the replacement of cells in the superficial mucosal layers when they are lost through normal physiologic sloughing.

• The subsequent denuding of the epithelium results in mucositis, which can be painful and can interfere with food intake and nutrition.

• Mucositis usually develops 2 to 3 weeks after the start of RT.

• The incidence of mucositis is variable, depending on the field, the total dose and duration of RT

Late Toxicities

• Radiation effects that occur months, years, or even decades after irradiation, called late effects. “Consequential late effects” result from the host's reaction to severe acute toxicity. Certain organs are more prone to late toxicity 

XerostomiaA dry mouth or xerostomia is one of the most common complications during and after radiotherapy for head and neck cancerRadiation-induced xerostomia consists in the chronic dryness of the mouth caused by parotid gland irradiation. Parotid glands produce approximately 60% of saliva while the rest is secreted by submandibular and accessory salivary glandssince irreparable damage is caused to the salivary glands, which are included in the radiation fields. Xerostomia not only significantly impairs the quality of life of potentially cured cancer patients, it may also lead to severe and long-term oral disorders

Xerostomia is a frustrating side effect that may lead to many other effects. It often improves with time, but it can be long-lasting or even permanent.The threshold dose for development of xerostomia was described before in the range of 10 to 25.8 gy• Regarding treatment, several strategies may minimize the incidence of xerostomia. When possible, sparing one parotid gland and, if possible, the submandibular glands can greatly diminish the incidence of xerostomia.

Osteoradionecrosis• The Osteoradionecrosis (ORN) of the jaw is a severe complication of RT for HNC.• Osteoradionecrosis (ORN) is a condition of nonvital bone in a site of radiation injury. ORN can be spontaneous, but it most commonly results from tissue injury. • Depending on the location and extent of the lesion, symptoms can include pain, bad breath, dysgeusia, trismus, difficulty with mastication, deglutition, and/or speech, fistula formation, pathologic fracture, and local, spreading, or systemic infection.

• mandible is the most commonly affected bone, because in the majority of patients undergoing treatment for HNC, a large part of it is inevitably exposed to high RT doses.•  It has been shown that increasing the external beam radiation dose above 50 Gray gives a significantly increased risk for developing osteoradionecrosis

Effects on hearing• Radiotherapy can result in cochlear damage, with sensorineural hearing loss (SNHL) occurring in about 25% of patients treated with doses approaching 60 Gy,

• SNHL has been considered infrequent at lower radiation therapy doses

• Data suggest that cochlear doses of 30 to 50 Gy can cause intermediate frequency SNHL,

• . Emerging data on adults treated for head and neck cancer also suggest that doses of >45 Gy impair hearing, particularly in the higher frequencies

Effects on eye• Radiotherapy can affect the retina, lens, conjunctiva, lacrimal apparatus, optic nerve, and lid.

• Patient may develop dry eye, cataract, orbital hypoplasia, ptosis, retinopathy, keratoconjunctivitis, optic neuropathy, lid epithelioma, and impairment of vision, following doses of 30 to 65 Gy.

• the higher dose ranges (>50 Gy) are associated with lid epitheliomas, keratoconjunctivitis, lacrimal duct atrophy, and severe dry eye.

• Retinitis and optic neuropathy may also occur following doses of 50 to 65 Gy, and even at lower total doses if the individual fraction size is >2 Gy .

• Cataracts are reported following lower doses of 10 to 18 Gy 

fibrosis

• A serious complication of RT in the treatment of cancer patients is the late-onset of fibrosis in normal tissues, including the neck, pharynx, esophagus, and temporomandibular joint.• Radiation-induced fibrosis (RIF) is similar to inflammation, wound healing, and fibrosis of any origin• .

• RIF can cause a wide range of clinical manifestations, including cutaneous induration, lymphedema, restrictions in joint motion, strictures and stenoses in hollow organs, and ulcerations.

• Specifically in the head and neck region it may cause trismus, which can progress over time.

• RIF in the esophagus and hypopharynx may lead to strictures, ulcerations, and fistula formation.

• Radiation fibrosis to the constrictor muscles may lead to chronic dysphagia. The best way to prevent this side effect is conformal planning to spare unnecessary radiation.

•  The risk of radiation-induced fibrosis is increased with higher radiation doses and larger treated volumes . The radiation dose that causes fibrosis can vary substantially in different tissues• ●Fibrosis in both connective and vascular tissues is generally associated with total radiation doses of 60 Gy or higher.

Thyroid Dysfunction • Hypothyroidism or hyperthyroidism can develop after radiotherapy.

• Hyperthyroidism is characterized by heat intolerance, weight loss, insomnia, increased appetite, diarrhea, moist skin,, nervousness, tremors, exophthalmus, and goiter. Thyroid enlargement, and more frequently, thyroid nodularity, can also develop.

• . Hypo- or hyperthyroidism results from fractionated radiation >20 Gy to the neck or cervical spine, or >7.5 Gy of TBI. Thyroid nodularity can occur after lower dose exposure

•RT-induced hypothyroidism develops at a median of 1.4 to 1.8 years after RT• It is more common in patients undergoing both neck surgery and RT than in those who have RT alone.

Vascular Complications

• Carotid artery rupture (also called carotid blowout syndrome) and oropharyngo cutaneous fistula are major complications associated with RT to the neck. These sequelae occur almost exclusively in patients who have received combined surgery and RT.

Conclusion •With the use of megavoltage radiation , careful radiotherapy planning and techniques with the aid of dedicated computers, better understanding of radiobiology , tolerance of normal tissues and organs and improvement of other surgical technology major complications occur less frequently in modern practice radiation therapy

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