Mr. Tan was 45 when he was diagnosed with stage II nasopharyngeal cancer. It took him a while to accept the diagnosis as he had been in perfectly health before this. After explanation about the curability of his condition and the possible side effects from treatment, he agreed to 7 weeks of radiation therapy. The few weeks while he was on radiation were tough. He had a severe sore throat and ulcers developed in his mouth that made eating painful.

He persevered. He completed his treatment and the mouth ulcers disappeared 1 month after therapy and he was able to eat normally again. It is now 8 years since he completed radiotherapy and he is considered cured from his cancer. In the last few months however, Mr. Tan found that he choked whenever he swallowed water. What are the possible causes:

	A.	Recurrence of his cancer
	B.	Development of a new cancer in the radiation field
	C.	Radiation related damage to nerves and muscles involved in swallowing
	D.	Manifestation of bulbar palsy due to stroke either related or unrelated to his treatment
	E.	All of the above need to be considered and carefully excluded.

You guessed it right the correct answer is ‘E’. His doctor excluded any recurrence after detailed ENT examination and a CT scan. He was told that his trouble with swallowing is due to damage to nerves and incoordination of his pharyngeal muscles that help swallowing. Using special swallowing methods taught to him by a speech therapist, he no longer coughs when he swallows water.

It has been estimated that 50–60% of patients diagnosed with cancer will require radiotherapy (RT) at some point in the course of their disease evolution. Like any other methods of cancer treatment, the decision to use RT, whether to cure or to palliate symptoms, should be made only after weighing the benefit against the possible side effects of treatment.

The side effects of RT can be broadly divided into early and late. Early side effects (like the mucositis and mouth ulcers Mr. Tan experienced) occur during radiation and usually recover within 1 month following radiation. Late side effects (like Mr. Tan’s swallowing difficulty) on the other hand, develop gradually over months to years after radiation is completed, and tend to be permanent once they develop.

It is easy to understand why side effects are experienced during treatment, but why should a patient develop late side effects only many months after radiation has been completed? There are many theories as to why late reactions occur, but the most widely accepted theory currently is that certain chemicals are released from our body in response to radiation.

These chemicals are intended to heal damages inflicted by radiation. In most individuals, these chemicals are turned off after healing occurs so no late reactions are seen. Unfortunately, in a small minority, these chemicals are perpetually released even after the healing is completed. After many months, this leads to scarring of the organs and blood vessels, leading to the late side effects that we see. Another type of late toxicity stems from irreversible damage from acute side effects leading to failure of repair mechanisms. This is known as consequential late side effects.

The specific late side effects that occur would depend on the site treated. Clinical manifestations differ between each vital organ. For example clinical hepatitis may not be evident when treating part of the liver beyond the tolerance dose as the rest of the liver is still functioning normally. On the contrary, treating a small segment of the spinal cord beyond tolerance will lead to neurological damage such as paraplegia. The table below lists some of these side effects.

Area Treated	Late Side Effect
General	Skin fibrosis, atrophy, necrosis, non-healing ulcers, telangiectasia, alopecia
Abdomen	Injury to liver, kidneys, bowel
Brain	Hypopituitarism, memory & intellectual impairment
Breast	Breast swelling, hardening or contraction, lymphedema, pneumonitis, injury to ribs, nerves or heart
Chest	Pneumonitis, heart and spinal cord injury, swallowing difficulty
Head and Neck	Xerostomia, dental decay, hearing loss, difficulty swallowing, injury to bone and organs (eg. eye, voice box, spinal cord)
Pelvis	Rectal bleeding, anal narrowing, impotence, vaginal dryness/narrowing, premature menopause, sterility, lymphedema
Others	Radiation induced cancers (very rare)

In general, no more than 5% of treated patients experience late side effects and they tend to be of mild grade. Nevertheless, radiation oncologists take these side effects seriously and take precautions to minimise the chances of this happening. Treatment planning is conducted with full knowledge of tolerance doses of the normal tissue within the treatment volume.

This is determined by using TD5/5 (Tolerance Dose 5/5), ie 5% incidence of long-term adverse reactions in 5 years with a given dose. With modern treatment planning methods and state-of-the-art treatment machines such as inverse planning, IMRT and stereotactic radiosurgery, we are able to better limit the dose to normal tissues and vital organs without compromising the therapeutic dose to the target organ.

Another determinant is the dose of radiation per treatment. In general the risk of long-term adverse reaction is lower with smaller fraction sizes. In the event that late side effects do unfortunately occur, specific treatments may be available, depending on the type and severity of complications. This may be in the form of physiotherapy, medication such as pentoxifylline and tocopherol, hyperbaric oxygen therapy and, albeit rarely, surgery.

At present, doctors are still unable to predict who are the ones who will or will not develop late side effects of RT. It is therefore important to discuss the available treatment options, weigh the benefits and the potential side effects of treatment with before deciding on any treatment.

 

Dr Soong Yoke Lim
Registrar
Radiation Oncology
National Cancer Centre, Singapore

Dr Michael Wang
Associate Consultant
Radiation Oncology
National Cancer Centre, Singapore