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J Radiosurg SBRT. 2012; 1(4): 281–286.
PMCID: PMC5658862

Quality of life after gamma knife radiosurgery for benign lesions: a prospective study


This study was initiated to evaluate the impact of intracranial radiosurgery for non-malignant indications on a patient’s quality of life (QOL).The study sample includes a total of 31 patients treated with single-fraction Gamma Knife radiosurgery (GKRS) for a non-malignant indication. Patients were treated at the Cleveland Clinic from 2005 through 2007 and all underwent pretreatment evaluation including screening for depression and anxiety, serum hemoglobin, hematocrit, calcium, albumin and thyroid stimulating hormone. Each patient was followed prospectively for eight weeks after treatment using a validated tool to assess fatigue and a separate questionnaire assessing quality of life. Dose and volume of GKRS were based on institutional practice and indication. The 13 question Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) was used to assess fatigue. Six additional questions assessing QOL outcomes not measured by the FACIT-F were added. Patients completed the questionnaire prior to GKRS and weekly for eight weeks. Questionnaires were scored using the FACIT scoring guidelines with a maximum score of 52. The additional questions were scored similarly with higher scores correlating with better QOL. The indications for treatment were arteriovenous malformation (5), schwannoma (12), trigeminal neuralgia (7), meningioma (4), pituitary adenoma (2), and glomus tumor (1). Median radiosurgery dose was 15 Gy (range 12-82 Gy). Doses for trigeminal neuralgia were prescribed to the 100% isodose line (IDL) while other lesions were treated to approximately the 50% IDL. Median volume of tissue treated was 2.5 cc (range 0.132-15.4 cc). Analysis of the 31 patients and 227 person-weeks of follow-up shows that GKRS does not adversely impact fatigue and QOL during the first 8 weeks after treatment. Mean FACIT-F score was 43 at baseline and 41, 43, 45, 43, 46, 44, 45, 47 at weeks 1-8 respectively after GKRS. In addition, questions assessing patients’ quality of life, and ability to work and exercise showed no decline after GKRS. Mean baseline score for these questions was 13 and 18, 19, 19, 19, 20, 19, 19 and 21 at weeks 1-8 after GK. This analysis of a prospective data set indicates that Gamma Knife radiosurgery does not adversely impact levels of fatigue or quality of life during the first 8 weeks after treatment for benign indications.

Keywords: Gamma Knife, radiosurgery, fatigue, prospective, benign, radiation


Although radiation related fatigue has been described for several decades, its impact on patients’ quality of life and functional status is now receiving increased attention. Fatigue is often cited as a potential side effect of fractionated radiotherapy during initial consultation with patients. Prospective studies of breast and prostate cancer patients do show a potential relationship.(1,2,3) While cancer related fatigue has been well described, the biologic mechanism of fatigue and radiation is not well understood.(4) Some propose a cytokine based mechanism or more simply, the effects of a daily commute to the treatment center.(5) Recent reports have increased our knowledge about fatigue and quality of life as they relate to patients receiving single fraction radiosurgery.

In an effort to further describe the effects of radiation therapy on fatigue and quality of life in this population, we prospectively studied patients undergoing Gamma Knife radiosurgery for a benign intracranial indication. The current series constitutes only one of a few studies with patients having a non-malignant indication for single-fraction radiosurgery and followed prospectively for its impact on fatigue and quality of life.


An IRB-approved questionnaire study was utilized for this study. Eligible patients were identified at initial consultation by the treating physician. Each participant was counseled on the details of the study and informed consent to participate was obtained. Demographic information was obtained from the chart and confirmed. All participants were ≥ 18 years of age, were able to participate in an English language interview, and had a benign indication for single fraction radiosurgery utilizing the Gamma Knife system.

A diagnosis of malignancy, administration of cytotoxic chemotherapy within 60 months of the treatment date, or previous cranial stereotactic radiosurgery excluded patients from participation in this study. In addition, patients taking oral steroids, having a diagnosis or undergoing treatment for hypothyroidism, chronic fatigue syndrome, severe depression, sleep apnea, narcolepsy or other conditions relating to symptoms of fatigue were excluded.

Pre-treatment screening included assessment of baseline anxiety and depression as well as routine laboratory values. The Hospital Anxiety and Depression Scale (HADS), a validated, self-reported 14 item questionnaire used to detect anxiety and depression, was administered at the time of enrollment. (6) If a patient was found to have symptoms consistent with anxiety or depressive state, additional evaluation was recommended, but this did not preclude enrollment in the study.

Laboratory values were also obtained at the time of enrollment. This evaluation included a thyroid stimulating hormone (TSH), serum albumin, hemoglobin, hematocrit, and serum calcium. Patients with abnormal values (TSH >5.5 uU/ml, albumin <2.5 g/dl, hemoglobin <11 g/dl, hematocrit <35%, or uncorrected calcium <8.5 mg/dl) were excluded from the study. If recent values were obtained by an outside physician, these results were substituted for study purposes. Funding for laboratory tests for this study was provided by the Cleveland Clinic Rose Ella Burkhardt Brain and Neuro-oncology Center.

The selection of an instrument to assess fatigue and quality of life in this cohort of patients was based upon several criteria.(7) First, validation of the questionnaire in the both the general population as well as in patients receiving radiation therapy was desired. The assessment tool also had to be easily administered across a variety of formats including telephone and e-mail. We chose to use the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) questionnaire, which includes 13 questions that assess fatigue and ability to perform usual activities. Six additional questions were developed to further characterize the impact of treatment and side effects on work, exercise, and enjoyment of life.

Each FACIT-F questionnaire was scored from 0-52 by a physician investigator (VVT and STC). Higher scores reflected less fatigue and a score <37 has previously been shown to represent a significant amount of fatigue.(8) The additional questions were tallied similarly with a higher score indicating a higher quality of life. Since there were two questions that could only be answered after treatment, the maximum score was 16 at baseline and 24 for weeks 1-8 for these additional questions.

Patient preparation, imaging, planning, treatment and discharge were performed based upon disease type and institutional guidelines. Thirty of 31 patients received a single dose of 10 mg Decadron IV prior to treatment and three patients treated for an arterio-venous malformation were given 8 mg Decadron daily, tapered one week after treatment. In general, lesions were treated to the 50% isodose line (IDL) with the exception of trigeminal neuralgia which was treated to approximately the 100% IDL. Additional treatment details regarding total dose, volume of treatment and location were obtained from the institutional database for each patient. The trial schema is depicted in Figure 1.

Figure 1
Schema of trial

Patients were followed weekly for a total of eight weeks and asked to complete the same 19 item questionnaire in Figure 2. The method of study completion was either telephone interview or e-mail, based on patient preference at the time of enrollment. All correspondence and data were collected by two physician investigators.

Questionnaire Utilized for Study

A total of 60 subjects were anticipated to be enrolled with an assumed attrition rate of 10%. However due to information from an interim analysis and slow trial accrual, enrollment was stopped after 31 patients had completed the eight week follow up for the study. Repeated measures analysis of variance was used to determine if there was a significant change in the FACIT-F and Gamma Knife specific questionnaire scores from baseline and over the course of the eight week follow up period. Data was maintained on a password protected database within the Cleveland Clinic and access was limited to designated study personnel.


There were a total of 31 evaluable patients enrolled on the study. The median age was 60 years (range: 25-90) with 18 men (58%) and 13 women (42%). Twelve patients (38%) had schwannoma, seven (23%) had trigeminal neuralgia, five(16%) were diagnosed with an arteriovenous malformation, four (13%) had meningioma, two (7%) had pituitary adenoma, and one (3%) had a glomus tumor. The patient characteristics are summarized in Table 1.

Table I
Patient characteristics

The median travel distance was 60 miles (range: 10-1240). Body mass index (BMI) ranged from 21.3 to 34.6 with a median value of 26.9. Screening laboratory values are reported in Table 2.

Table II
Screening Laboratory Values

Radiosurgery dose ranged from a minimum of 12 Gy to 82 Gy in a single fraction with a median value of 15 Gy. Treatment volume of brain was 2.5 cc median with a range of 0.132 to 15.4 cc, as seen in Table 3.

Table III
Gamma Knife Treatment Data

Nineteen patients completed all of the follow up assessments. Six patients completed 7 weeks of follow up while three patients each completed 6 and 5 weeks, equalling to 227 person-weeks of follow-up.

Mean FACIT-F score was 43 at baseline and 41, 43, 45, 43, 46, 44, 45, 47 at weeks 1-8 respectively after Gamma Knife radiosurgery. Analysis of weekly FACITF data shows no significant difference in the scores over 8 weeks. Similarly, analysis of patient quality of life by the additional questions did not show a significant decline during the study period. Mean baseline score for these questions was 13 and 18, 19, 19, 19, 20, 19, 19 and 21 at weeks 1-8 after GK.


Gamma Knife radiosurgery has become an increasingly popular method of treating intracranial lesions. We hypothesized that, unlike fractionated radiation schemes, radiosurgery is less associated with fatigue after treatment. By excluding diagnoses and treatments that may be related to fatigue, such as cancer, chemotherapy, anemia, malnutrition, electrolyte abnormalities and hypothyroidism, this prospective study helps to clarify the impact that the procedure itself may have on patient’s quality of life. To our knowledge, this is the first prospective study focused only on the evaluation of fatigue in this patient population.

Other retrospective series have quantified the low rate of acute complications following Gamma Knife radiosurgery. (9) Several recent prospective studies have specifically evaluated QOL in patients with vestibular schwannoma, trigeminal neuralgia or arteriovenous malformation. Myrseth et al. published a prospective study of 91 patients using the Glasgow Benefit Inventory showing better quality of life in the Gamma Knife radiosurgery group versus microsurgery.(10) A second study by Di Maio et al. compared QOL outcomes in patients undergoing observation, radiation or surgery for vestibular schwannoma using the Short Form Health Survey. In this report, quality of life remained unchanged for patients in the radiation group through the follow-up period.(11) Improvement in QOL was also noted for trigeminal neuralgia after Gamma Knife radiosurgery in a prospective study from Iran that used the Short Form 36 questionnaire.(12) Two recent retrospective analyses reaffirmed the positive impact of Gamma Knife radiosurgery on QOL in the the trigeminal neuralgia population.(13,14)

Week #: __________
Patient #:__________Date:___________

Below is a list of statements that other people with your illness have said are important. By circling one (1) number per line, please indicate how true each statement has been for you during the past 7 days.

The findings of this study show that patients were generally highly functional at baseline and treatment with Gamma Knife did not result in an increase of fatigue or reduction in quality of life. Although the impact of BMI and distance to treatment center were not directly studied, these factors did not appear to have a significant impact on fatigue or QOL in the context of Gamma Knife treatment.

This study did have some limitations, most notably that we enrolled only slightly over 50% of the planned patients. Of the 31 patients enrolled, only 61% completed all of the weekly follow-up questionnaires. The early termination of the study was primarily due to slow accrual and an interim analysis showing a low likelihood of Gamma Knife radiosurgery increasing fatigue or reducing QOL in this patient population. Although the FACIT-F tool has been validated, the additional questions utilized to directly study other aspects of quality of life have not been formally validated in this patient population. Furthermore, there has been a suggestion that increased treatment volume is related to a higher rate of side effects and the volume was quite small for patients in this study. Despite these shortcomings, this study demonstrates that Gamma Knife radiosurgery does not contribute to fatigue for patients with benign intracranial conditions. We did not specifically study the use of radiosurgery for patients with malignant tumors. While we speculate that radiosurgery in itself does not produce fatigue in that patient population, we recognize that those patients receive higher prescription doses and hence a more formal evaluation of this hypothesis needs to be performed.

Figure 3
FACIT and GK Scores +/- 1 standard deviation for all patients




Suh, John MD, Consultant for Abbott Oncology


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