Background
Methods
Literature search
Study selection
Assessment of included studies
Results
Selected studies
First author, year Study design Modality (dose) | Participants (n), median (range) | Histology (n) | Primary endpoint | HRQoL questionnaire Scales | HRQoL after SRSb | Comments |
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Studies using brain cancer–specific HRQoL questionnaires | ||||||
Skeie, 2017 [33] Single-arm study Gamma knife (mean 22.7; 15–25 Gy) | 97 patients with 1–6 BM Age 64 (32–86) Female (51) Mean BM volume 6.3 cm3 (0.072–25.2) KPS 80 (60–100)a | Lung (45) Colorectal (17) Skin (12) Other (23) | Health-related quality of life | FACT-Br All 8 scales | Group level: stable HRQoL after SRS up to 12 months, except for general HRQoL. Individual level: less or stable additional concerns (brain cancer subscale) for 64%, 60%, 66%, 72%, and 60% of the patients at respectively 1, 3, 6, 9, and 12 months (based on MCIDs; cutoff point unclear). | Prior treatment with the following: WBRT (n = 9), surgery (n = 6), surgery and WBRT (n = 5). Follow-up questionnaires sent by mail. |
Bragstad, 2017 [32] Single-arm study Gamma knife (mean 40.4; 16–25 Gy) | 44 patients with 1–5 BM Age 62.8 (42–82) Female (19) KPS 100 (5); 90 (14); 80 (9); 70 (10); < 70 (6) Steroid use at GKRS (34) | NSCLC (39) SCLC (5) | Health-related quality of life | FACT-Br All 8 scales | Group level: stable HRQoL up to 12 months after SRS Individual level: at 1 month (n = 39), 23 patients had less, 6 had stable, and 9 had more additional concerns (brain cancer subscale). | Only patients with primary lung cancer included. Prior treatment with the following: surgery, WBRT, or surgery and WBRT (number of patients not reported). Reasons for dropout not reported. Follow-up questionnaires sent by mail. |
Chang, 2007 [34] Single-arm study (pilot) Linear accelerator (median 20; 15–24 Gy) | 15 patients with 1–3 BM Age 64.9 (31.5–77) Female (10) Total BM volume 1.76 cm3 (0.16–19.98) KPS 90 (70–100)a | NSCLC (8) Melanoma (4) Renal cell (3) | Cognitive functioning | FACT-Br One preselected total score; FACT-Brain score | Individual level: 11 patients with stable and 2 patients with declined HRQoL scores 1 month after SRS (based on the RCI). For 4 out of 5 long-term survivors (patients with an evaluation ≥ 200 days after SRS) scores remained relatively stable up to their last evaluation after SRS (± 8.5 months); a decline was observed in a patient who was hospitalized because of edema. | Measurement of pretreatment HRQoL after SRS in an unknown number of patients. Reasons for dropout not reported. No report of mean HRQoL scores at all time points. |
Kirkpatrick, 2015 [35] Single-arm study (randomized per lesion) Linear accelerator (15–24 Gy) | 49 patients with 1–3 BM Age 61 (26–87) Female (33) KPS 90 (70–100)a Chemotherapy before SRS (28) Chemotherapy after SRS (43) | NSCLC (25) Melanoma (8) Breast (6) Other (10) | Local recurrence | FACT-Br All 8 scales | Group level: stable HRQoL 3 months after SRS (n = 24). | Reasons for dropout not reported. Poor compliance with HRQoL assessment. Randomized per lesion to a 1- or 3-mm margin expansion group. |
Habets, 2016 [36] Single-arm study Linear accelerator (18–24 Gy) | 97 patients with 1–4 BM Mean age 63 (33–82) Female (51) Total BM volume 7.8 cm3 (0.12–63.9) KPS 80 (60–100) Chemotherapy < 3 months of SRS (13) Use of corticosteroids (85) Use of anti-epileptic drugs (21) | NSCLC (48) Renal (12) Melanoma (9) Other (28) | Cognitive functioning | EORTC-QLQ-C30 All 9 scales and 6 single items EORTC-QLQ-BN20 All 4 scales and 7 single items | Group level: worse scores on physical functioning, nausea, appetite loss, and (more bothered by) hair loss over 6 months’ time after SRS. Other aspects of HRQoL were stable over time. | No report of mean HRQoL scores at follow-up. Patients treated with WBRT during the study were no longer followed (n = 13). BM with volumes > 13 cm3 or near the brainstem were treated in 3 fractions of 8 Gy; other BM were treated in 1 fraction of 18–21 Gy. |
van der Meer, 2018 [37] Single-arm study Linear accelerator (18–24 Gy) | 55 patients with 1–4 BM Mean age 63, SD 9 Female (30) Total BM volume 7.3 cm3 (0.12–63.9) KPS 80 (interquartile range 80–90) Chemotherapy (6) Use of corticosteroids (48) Use of anti-epileptic drugs (12) | NSCLC (27) Renal (11) Melanoma (4) Other (13) | Cognitive functioning | EORTC-QLQ-C30 6 preselected scales; global health status, physical, emotional, role, cognitive functioning, and fatigue EORTC-QLQ-BN20 2 preselected scales; motor dysfunction and communication deficits | Individual level, scale: at 3 months, on 4 out of 8 HRQoL scales, most patients had stable scores; on 3 scales, most patients had a decline in scores; and on 1 scale, most patients had improved scores. At 6 months, on 7 HRQoL scales, most patients had stable scores; and on 1 scale, most patients had worse scores (based on an increase or decrease of ≥ 10 points). Individual level, patient: after 3 and 6 months, 22% and 21% of patients reported a decline on at least one HRQoL scale (other scales declined as well or remained stable), 12% and 18% an improvement on at least one HRQoL scale, 64% and 58% both a decline as an improvement, and 2% and 3% had stable scores on all HRQoL scales, respectively (based on an increase or decrease of ≥ 10 points). | No report of mean HRQoL scores at all time points. Patients treated with WBRT during the study were no longer followed (number of patients not reported). BM with volumes > 13 cm3 or near the brainstem were treated in 3 fractions of 8 Gy; other BM were treated in 1 fraction of 18–21 Gy. |
Studies using generic HRQoL questionnaires | ||||||
Miller, 2017 [38] Single-arm Gamma knife (median 22; 20–24 Gy) | 67 patients Mean age 59, SD 11 Female (37) KPS 80 (70–90) Chemotherapy in past month (67) | NSCLC (30) Breast (14) Melanoma (9) Other (14) | Time to health state (EQ-5D index) failure | EQ-5D All 5 dimensions | Group level: worse scores on all dimensions at patients’ last follow-up (analyzed on the basis of 122 treatments) Individual level: overall health state failure in 28% and improvement in 24% of treatments (MCID of 0.1) and self-perceived health state failure in 50% and improvement in 41% of treatments (MCID of 10). | Limited patient characteristics (mostly per treatment). Prior treatment with the following: WBRT (n = 41) and resection (n = 21). Reasons for dropout not reported. Measurement of pretreatment HRQoL after SRS in an unknown number of patients. Mean HRQoL scores only reported at last follow-up. Only HRQoL data at a patients’ last follow-up was analyzed. HRQoL data analyzed per treatment. |
Kotecha, 2017 [39] Single-arm study Gamma knife (15–24 Gy) | 59 patients with 1–11 BM Baseline characteristics of the 27 patients with HRQoL assessment not reported | NA | Intracranial recurrence patterns after multiple SRS courses | EQ-5D All 5 dimensions | Group level: longitudinal overall health state remained relatively stable over time. Worse scores on mobility, self-care, usual activities, overall health state, and self-perceived health state at patients’ last follow-up (data abstracted from a table). Individual level: at patients’ last follow-up, most patients declined (48%, 54%) or improved (45%, 45%) on overall health state and self-perceived health state, respectively, based on the MCIDs (data abstracted from a table). At 1 year, most patients were free from HRQoL failure (overall health state 77%; self-perceived health state 69%). | patients who underwent a minimum of 3 SRS courses for BM were included. Prior treatment with the following: WBRT (n = 19). Reasons for dropout not reported. Mean HRQoL scores only reported at last follow-up. Only HRQoL data at a patients’ last follow-up was analyzed. |
Randolph, 2017 [40] Single-arm study Gamma knife (median 20; 10–24 Gy) | 114 patients with 1–4 BM Baseline characteristics of the 39 patients with HRQoL assessment not reported | NA | Local control Distant control Overall survival | SQLI Total score | Group level: significant decline in HRQoL scores 6 and 12 months after SRS compared with baseline No significant difference between 6 and 12 months after SRS. | Subgroup of geriatric patients (age ≥ 70). Previous treatments not reported. Reasons for dropout not reported. |
Characteristics of studies
HRQoL assessments
HRQoL instrument | Description | Scales/items | Used by |
---|---|---|---|
Functional Assessment of Cancer Therapy-Brain (FACT-Br) | The FACT-Br was developed for patients with primary brain tumors. Questions are answered on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). The FACT-Br consists of 5 subscales, 2 total scales, and 1 index. The FACT-General is a summary of general HRQoL and can be used in diverse patient groups. The FACT-Br combines the FACT-G with a disease-specific subscale score for patients with a brain tumor. The TOI is assumed to be more responsive to change after treatment than a total HRQoL score. Higher scores on each (sub)scale indicate better health-related quality of life [41‐43]. The FACT-Br has high validity and reliability coefficients [42] and is a valid measure for use in patients with brain metastases [43]. | • Five subscales o Physical well-being o Social/family well-being o Emotional well-being o Functional well-being o Brain cancer subscale (additional concerns specific for patients with brain tumors) • Two total scales o FACT-General (FACT-G; physical + social + emotional + functional well-being) o FACT-Brain (FACT-BR; FACT-G + brain cancer subscale) • One index o Trial Outcome Index (TOI; physical + functional well-being + brain cancer subscale) | Chang, 2007 [34] Kirkpatrick, 2015 [35] Skeie, 2017 [33] Bragstad, 2017 [32] |
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) | The EORTC QLQ-C30 consists of 5 functional scales, 3 symptom scales, 1 global health/quality of life scale and 6 single items. All of the scales and single-item measures range in scores from 0 to 100, with higher scores reflecting more severe symptoms. In case of functional scales, higher scores reflect better functioning. The EORTC QLQ-C30 is a reliable and valid measure of the quality of life of patients with cancer [44]. | • Five functional scales o Physical functioning o Role functioning o Cognitive functioning o Emotional functioning o Social functioning • Three symptom scales o Fatigue o Pain o Nausea and vomiting • One global quality of life scale • Six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) | Habets, 2016 [36] van der Meer, 2018 [37] |
EORTC-QLQ Brain Cancer Module (EORTC-QLQ-BN20) | The EORTC-QLQ-BN20 was developed for brain cancer patients and is designed to complement the QLQ-C30. It consists of 20 items and four subscales. All items and scale scores are linearly transformed to a 0–100 scale, with higher scores reflecting more severe symptoms. The BN20 has adequate psychometric properties for use in assessing the HRQoL of brain cancer patients in international studies [45, 46]. | • Four subscales o Future uncertainty o Motor dysfunction o Visual disorder o Communication deficit • Seven single items (headaches, hair loss, weakness of legs, seizures, itchy skin, bladder control, drowsiness) | Habets, 2016 [36] van der Meer, 2018 [37] |
Spitzer Quality of Life Index (SQLI) | The Spitzer Quality of Life Index was developed for use by physicians to assess the relative benefits and risks of various treatments for serious illness. It consists of 5 questions concerning HRQoL according to five factors. For each item, a score of 0, 1, or 2 is obtained; the maximum score is 10. Lower scores reflect better performance. The SQLI has convergent discriminant and content validity among cancer patients [47]. | • One index consisting of 5 factors o Activity o Support o Daily living o Outlook o Health | Randolph, 2017 [40] |
EuroQol 5 Dimensions questionnaire (EQ-5D) | The EQ-5D was developed as standardized measure of health state, applicable to a wide range of patient populations. It consists of 5 items representing 5 dimensions. Each item is answered on a 3-point scale; 1 no problems, 2 some problems, and 3 extreme problems. The index score overall health state consists of all 5 items and ranges between 0 (dead) and 1 (best possible health). Self-perceived health state is measured on a 20-cm vertical scale with endpoints 0 (worst imaginable health) and 100 (best imaginable health) [48‐50]. | • Five subscales/dimensions o Mobility o Self-care o Usual activities o Pain/discomfort o Anxiety/depression • One index o Overall health state (all 5 subscales) • One vertical visual analogue scale o Self-perceived health state | Kotecha, 2017 [39] Miller, 2017 [38] |