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Side Effects and Complications from Brain Irradiation

Read the review article on side effects/complications of brain radiation here , here, here, here  and here; and radiosurgery here. There are different types of brain injury (here) and standard doses (here). There are standards as to the proper dose of brain radiation from the NCCN go here. Safe doses are described for the brain, brainstem, optic nerve and spinal cord.

There is evidence that even low doses of brain radiation can effect memory (see outcome data from RTOG 0214 trial here and here) and so there is interest in a new technique to try to spare the area of brain stem cells (go here , here, here, here).

RTOG has a trial combining memantine (Namenda) with brain radiation to try to lower the risk of creating memory problems (see RTOG 0614)

see MRI brain pictures after treatment here

brain_lateral_adam.jpg (5050 bytes)

brain_pet_radiation_necrosis.jpg (8972 bytes)

CNS radiation necrosis: The patient above had a history of a solitary brain metastasis from non-small cell lung cancer. The lesion had been resected and the patient had received radiation therapy to the area. A follow-up MR exam revealed a ring enhancing region in the left parietal-temporal area on post-gadolinium enhanced images (white arrows). A FDG PET exam revealed no tracer uptake consistent with post-surgical and post radiation change.


(Also note that chemotherapy may affect the brain, go here).

(See the side effects listed below from the RTOG.)  Radiation kills cancer cells by damaging the division of rapidly dividing cells. Since adult brain cells no longer divide (with some exceptions) it is in fact relatively safe to expose the brain to radiation. The 'safe' dose to the brain (6000cGy) in much higher than for other organs of the body (go here.) Picture of radiation necrosis of the brain here.

There is some concern that after treating the whole brain (particularly if combined with chemotherapy) the patient may develop memory problems. This had resulted in some controversy concerning the use of preventative (or prophylactic) radiation used in small cell lung cancer patients (go here.)

There is more risk of brain complications when the dose per fraction is high, e.g. radiosurgery (go here.) Patients with MS may be at higher risk for radiation complications (go here).

neurotoxicity_bactchelor.jpg (35094 bytes)

Neurotoxicity. Cranial fluid-attenuated inversion recovery magnetic resonance images from a 67-year-old patient with primary CNS lymphoma 1 year after achieving a complete response to whole-brain radiation therapy. The patient developed memory failure, gait ataxia, and incontinence in the postradiation setting. There is increased signal throughout the cerebral white matter, cortical atrophy, and ventricular enlargement.
In general, the dose commonly used to treat brain metastases (300cGy X10) is thought to have very little long term risks.  In  patients with primary brain tumors where the doses are higher there is some risk of brain injury when the doses approach or exceed 6000cGy.

The picture on the left is from a patient who had high dose whole brain irradiation combined with chemotherapy.

There are specific parts of the brain that are more sensitive (e.g. the optic chiasm in patients with pituitary tumors,) and there are higher risks in patients who are also treated with chemotherapy (e.g. brain lymphoma.The short term side effects of brain radiation are usually mild: some fatigue, skin irritation and later hair loss. Some patients have hearing problems if  the radiation causes swelling in the ear canal or fluid behind the ear drums. Some patients develop increased brain pressure or edema and need to be on increased doses of Decadron. Hair loss (alopecia) usually takes 2 or 3 weeks to develop and the hair usually grows back in a few months if the dose is not too high (see study below.)

 
Permanent alopecia after cranial irradiation: Dose–response relationship
Lawenda BD, IJROBP 2004; 60: 879-887

One of the troubling complications resulting from cranial irradiation is permanent alopecia. The psychological effects of being diagnosed with cancer and the subsequent treatments are tremendous burdens on our patients. Hair loss is one of the most stressful side effects for patients undergoing oncologic treatment with either chemotherapy or cranial irradiation.

Temporary alopecia is a dose-dependent treatment effect that occurs in humans approximately 2–3 weeks after radiation exposure and usually resolves within 2–3 months after completion of radiotherapy (RT).. Doses as low as 2 Gy in a single fraction have been shown to cause temporary alopecia.. The historical data from the atomic bomb survivors in Hiroshima indicated that epilation was noted with estimated doses of only 0.75 Gy. The doses reported to cause permanent hair loss vary widely. A recently published analysis documented that a dose of 36 Gy (2 Gy/fraction, 5 d/wk) was reported to cause permanent alopecia in a range of 0–80% of patients (median risk, 5%) and that a dose of 45 Gy resulted in a risk of 5–100% (median, 15%) of permanent alopecia.. International Commission on Radiological Protection Publication 85 has stated that permanent epilation occurs at 7 Gy (single fraction).. In this paper, we present a dose–response relationship analysis for alopecia persisting at least 12 months after completion of a course of fractionated cranial irradiation.

The D50, the follicle dose at which 50% of the patients developed permanent alopecia, was estimated to be 43 Gy. No statistically significant difference was found in the D50 between patients who received radiosensitizing chemotherapy agents (i.e., cisplatin, temozolomide, and carboplatin) vs. those who received agents that were not radiosensitizing . Radiation dose–response relationship for permanent alopecia; 95% confidence interval of dose D50 see graph.

Typical Side Effects (Consent Form) from the RTOG

RADIATION THERAPY ONCOLOGY GROUP/RTOG 0420

A PHASE II STUDY OF RADIATION THERAPY PLUS LOW DOSE TEMOZOLOMIDE FOLLOWED BY TEMOZOLOMIDE PLUS IRINOTECAN FOR GLIOBLASTOMA MULTIFORME

Risks Associated with Radiation Therapy

Common (more than 10 out of 100 patients

Temporary partial hair loss with some areas of permanent hair loss
Headache
Fatigue Sleepiness
Dry mouth
Altered sense of taste
Scalp redness or soreness

Uncommon (more than 1 but less than 10 patients out of 100)

Hearing loss, Dryness of the ear canal and redness of the external ear if in radiated area

Rare (less than 1 out of 100 patients)

Eye injury resulting in blindness
Mental slowness, behavioral changes
Severe damage to normal brain tissue that may require additional surgery
Brain swelling in the area receiving the radiation therapy
Seizure

Typical Side Effects (Consent Form) from the RTOG (RADIATION THERAPY ONCOLOGY GROUP.RTOG 0320)

Risks Associated with Whole Brain Radiation Therapy:

(Both temozolomide and gefitinib could make the radiation side effects worse.)

Likely

• Scalp redness or soreness
• Hair loss
• Dry mouth or altered taste
• Fatigue, sleepiness
• Muffled hearing (temporary)
Less Likely
• Fever, chills, heavy sweating
• Upset stomach, nausea and/or vomiting
• Loss of appetite, taste changes
• Headaches, seizure, weakness
Rare, But Serious
• Permanent hair loss
• Hearing loss
• Eye injury resulting in blindness
• Mental slowness, behavioral changes

  •  Severe damage to normal brain tissue that may require additional surgery

Risks of Radiosurgery:

Likely
• Pin site soreness for a day or two
Less Likely
• Brain swelling, which may cause any prior or existing neurologic symptoms to get worse
• Muffled hearing (temporary)
Rare, But Serious
• Radiation necrosis, which can cause brain swelling months later