A total of 30 consecutive patients with primary brain tumors were enrolled, following written informed consent being obtained, between March 2009 and June 2010 at the Department of Radiation Oncology, Martin Luther University Halle-Wittenberg [Halle (Saale), Germany]. Patient characteristics and treatment details are presented in Table I. The patients were requested to complete the Core Questionnaire C30 and the module questionnaire BN20, from the European Organization for Research and Treatment of Cancer (EORTC). The study was approved by the Ethics Review Committee of the Medical Faculty, Martin Luther University Halle-Wittenberg.

The following inclusion criteria were applied: Sufficient compliance, understanding of patient information describing the HRQOL study and the existence of a brain tumor without previously administered radiotherapy. Patients who had received prior irradiation or had insufficient cognitive skills to complete the HRQOL questionnaire, as assessed by the treating radiation oncologist, were excluded. The present study was longitudinal, consisting of five questionnaires completed during a 12-month period: Prior to (t0), at the end of radiotherapy (t1) and 3 months (t2), 6 months (t3) and 12 months (t4) following the end of radiotherapy. Questionnaires were distributed to patients at t0 and t1 in the Department of Radiation Oncology, Martin Luther University Halle-Wittenberg. At subsequent time points, the questionnaires were posted with a pre-stamped envelope. Other information regarding the patients and their therapy was extracted from medical records and anamnesis.

For evaluation of QOL, the EORTC QLQ-C30 questionnaire version 3.0 (8) and the QLQ-BN20 questionnaire (9) were used. The BN20 was developed specifically for patients with primary brain tumors by the EORTC Quality of Life Group (9). The two questionnaires had previously been validated by the EORTC (8,10). The QLQ-C30 consisted of 30 questions associated with functions and symptoms. Each question may be answered using 4 grades: 1, not at all; 2, low; 3, moderate; and 4, high. There were two questions concerning global QOL scored from 1 (very poor) to 7 (excellent). According to the EORTC C30 scoring manual (11), the answers may be transformed into scales ranging from 0 to 100. There are five functional scales (physical, role, cognitive, emotional and social functioning), nine symptom scales (fatigue, nausea and emesis, pain, dyspnea, sleep disturbance, loss of appetite, constipation, diarrhea and financial difficulties) and one scale for global QOL. The QLQ-BN20 consisted of 20 questions; the responses may be transformed into 11 symptom scales (future uncertainty, visual disorder, motor dysfunction, communication deficit, headaches, seizures, drowsiness, alopecia, itchy skin, weakness of legs and bladder control). For the functional scales and global QOL, high scores represent a good functioning and QOL. For the symptom scales, high scores indicate the presence of severe symptoms.

Adverse events were also objectively assessed at t1, using checklists based on the CTCAE (version 3) (12). The symptoms of alopecia, nausea, headache and fatigue were evaluated. According to CTCAE, symptoms are classified as grades 1–5: Grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life-threatening or disabling adverse event; and grade 5, mortality associated with adverse event. The symptom of alopecia was classified from 0 to 2 as an exception, as this toxicity cannot be severe or life-threatening. The objective adverse events assessed using the CTCAE checklists could be subsequently compared with the subjective responses from the QOL questionnaires.

The following five groups were formed: All patients (n=30); malignant (n=14); benign (n=16); glioblastoma multiforme (GBM; n=10); meningioma (n=11). GMB and meningioma were the two largest subgroups (full patient characteristics are presented in Table I). Data at each time point were compared to t0 (prior to radiotherapy). The mean, median and standard deviation values were calculated. Statistical evaluation was performed using the non-parametric Mann-Whitney U test and STATISTICA version 10 software (StatSoft, Inc., Tulsa, OK, USA). Based on the multiple comparisons, P<0.01 were considered to indicate a significant difference. Additionally, changes in clinical significance over time were considered, according to Osoba et al (13). This study defined which magnitude of change in HRQOL scores, assessed using EORTC questionnaires, corresponds to a change, noticed by the patient as significant. According to Osoba et al (13), a deviation in an individual score by 5–10 points indicated a slight change, by 10–20 points indicated a moderate change, and by >20 points represented a high clinical relevance.

The median age was 64.6 years (range, 25.9–80.4 years). A total of 14 patients exhibited a malignant brain tumor and 16 had a benign tumor. A total of nine patients also received chemotherapy (temozolomide) during and subsequent to radiotherapy. Detailed treatment characteristics are presented in Table I. During the 12-month follow-up period, eight patients succumbed: Of those, two patients succumbed after 3 months (t2), three patients after 6 months (t3) and additional three patients after the 12-month period (t4). The causes of mortalities were not analyzed; however, it was expected that in patients with malignant brain tumors, including glioblastoma, the mortalities were predominantly tumor-associated. All patient and treatment characteristics are summarized in Table I.

At t0 (prior to radiotherapy) and t1 (subsequent to radiotherapy), all questionnaires were completed (100% response rate). In the whole group, the response rate among surviving patients was 78.6% at t2 (3 months), 81.5% at t3 (6 months) and 63,6% at t4 (12 months) which is predominantly >70% response rate, the level which is typically aimed at achieving, and acceptable, considering the palliative situation among the malignant brain tumor patients. The poorest response rate was achieved after 12 months in the malignant group (50%). At all time points, there were higher response rates from the benign and meningioma groups, compared with the malignant and GBM groups. The response rates for all surveys are presented in Table II. The results were generated from the proportion of questionnaires returned by patients who were alive each of the time points.

There were no statistically significant changes recorded in global QOL for any of the subgroups observed. However, there was an increase of mean global QOL between t0 and t4, as indicated in Fig. 1, which was of a clinically significant extent, according to the definitions by Osoba et al (13) (t0=49; t4=65). Similar results were identified in the following groups: Benign (t0=55; t4=66); meningioma (t0=54; t4=72); malignant (t0=42; t4=61); GBM (t0=42; t4=67). Therefore, the results indicated that there was a moderate increase in the mean global QOL for all participating groups. Compared with the groups receiving palliative therapy (malignant and GBM), the global QOL was higher in the groups receiving curative therapy (benign and meningioma) during duration of the present study (Fig. 2).

At the end of radiotherapy (t1), patients experienced significantly higher mean levels of fatigue (t0=29; t1=54; P=0.002), appetite loss (t0=11; t1=24; P=0.008) and alopecia (t0=9; t1=31; P=0.006) compared with the beginning of radiotherapy. At 3 months after radiotherapy (t2), there was a significant increase in reports of itchy skin (t0=4; t2=26; P=0.006). At the end of radiotherapy (t1), patients exhibited increased levels of itchy skin, however, this was not identified as significant (t0=4; t1=19). Fig. 3 presents an overview of the surveyed symptoms scales for all patients.

The objective evaluation of the side effects using CTCAE following radiotherapy (t1) indicated certain types of therapy-associated side effects in 93.3% of the participants. The main issues that patients identified were fatigue and alopecia. In addition, 80% of patients demonstrated alopecia grade 1 (thinned or fragmentary). The results indicated that 90% of patients suffered from fatigue; of those, 56.7% had mild fatigue and 13.3% had severe fatigue. Overall, only two patients (6.7%) were asymptomatic following radiotherapy at t1. There were specific differences between the subgroups. All patients in the GBM group exhibited alopecia grade 1; by contrast only 73% of patients with meningioma exhibited alopecia grade 1 and 27% reported no alopecia. There were higher grades of fatigue observed in the groups with palliative therapy (7.2% grade 0; 50% grade 1; 21.4% grade 2; 21.4% grade 3; 0% grade 4) in comparison with the groups receiving curative therapy (12.5% grade 0; 62.5% grade 1; 18.7% grade 2; 6.3% grade 3; 0% grade 4). Only a small number of patients exhibited nausea (23.3%) or headaches (36,7%). The distribution of objective toxicity grades is presented in Fig. 4.

Patients with benign brain tumors demonstrated stable functional scales over time, revealing constant or improved values after radiotherapy in the five types of function measured using the EORTC QLQ-C30 questionnaire. However, in patients with malignant tumors, the functional scales became poorer from t1 (end of radiotherapy) and recovered slightly up until t4 (after 12 months). The cognitive function decreased in the GBM group 12 months following radiotherapy (t0=85; t4=58). Patients in the meningioma group exhibited more stable cognitive functioning (t0=88; t4=88). There was an increase in future uncertainty in the GBM group after 12 months (t0=39; t4=58), whereas future uncertainty continuously decreased in the meningioma group (t0=28; t4=17). Patients with meningioma experienced increased levels of alopecia during the study period, as compared with patients with GBM (Fig. 5).

An additional distinction identified was associated with financial difficulties (Fig. 6): Patients in the meningioma and benign groups exhibited less financial difficulties, compared with patients in the GBM and malignant groups. In addition, financial difficulties decreased at t4 (12 months following radiotherapy) in the groups receiving curative therapy, and markedly increased in groups with palliative therapy.