Quality indicators in neuro-oncology: Review of the literature and development of a new quality indicator set for glioma care through a two-round Delphi survey.

BACKGROUND: Quality Indicators (QIs) are important tools to assess the quality and variability of oncological care. However, their application in neuro-oncology is limited so far. The objective of this study was to develop a set of QIs for glioma, covering process and outcome indicators. METHODS: A systematic review was conducted to identify both QIs in the field of adult glioma care, and guidelines or recommendations that could be translated into QIs. Also reports from national and international healthcare agencies and scientific associations ("grey literature") were taken into account. After conversion of these recommendations into QIs, merging with existing QIs found in the literature and rationalization, a two-round Delphi survey was conducted to gain consensus on relevance for the proposed QIs. RESULTS: In total 240 recommendations and 30 QIs were retrieved from the literature. After conversion, merging and rationalization, 147 QIs were evaluated in the Delphi survey and eventually consensus was gained on 47 QIs in the following 7 domains: Diagnosis and Imaging, Surgery, Pathology, Radio/Chemotherapy, Recurrence, Supportive Treatments (Epilepsy, Thromboembolism, Steroid Use and Rehabilitation) and Survival. CONCLUSION: This study defined a set of 47 QIs for assessing quality of care in adult glioma patients, distributed amongst 7 crucial phases in the patient's care trajectory. These QIs are readily applicable for use in diverse health care systems, depending on the availability of population-based health care data enabling (inter)national benchmarking.

Survival impact of incidental subventricular zone irradiation in IDH-wildtype glioblastoma.

BACKGROUND AND PURPOSE: The subventricular zone (SVZ) is an important niche for neural stem cells but probably also for brain tumor propagating cells, including the glioblastoma stem cell. The SVZ may become a target for radiation therapy in glioblastoma patients. However, reports studying the effect of irradiation of the SVZ on glioblastoma patient survival show conflicting results. We studied the correlation between incidental SVZ radiation dose and survival in a cohort of isocitrate dehydrogenase-wildtype (IDHwt) glioblastoma patients with inclusion of important survival prognosticators. PATIENTS AND METHODS: In this retrospective analysis, only adult patients with supratentorial IDHwt glioblastoma were included who were treated with temozolomide-based chemoradiotherapy after surgery. The SVZ was contoured on the radiotherapy planning imaging. Cox proportional regression overall survival (OS) analysis was used to study the correlation between SVZ dose and survival. Age, Karnofsky Performance Score, extent of resection and O6-methylguanine-methyl-DNA-transferase gene promoter (MGMTp) methylation were used as covariates in multivariate analysis. RESULTS: In total, 137 patients were included. Median OS was 13.3 months. The MGMTp methylation was present in 40% of cases. Ipsilateral SVZ (iSVZ) mean dose was 44.4 Gy and 27.2 Gy for the contralateral SVZ (cSVZ). Univariate survival analysis showed an inverse relationship between cSVZ mean dose and OS (HR 1.029 (1.003-1.057); p= .032). However, there was no correlation between cSVZ mean dose and OS in multivariate analysis. iSVZ dose did not correlate with survival. CONCLUSION: In this cohort of 137 IDHwt glioblastoma patients, iSVZ did not correlate with OS. Higher cSVZ dose was inversely correlated with OS in univariate survival analysis but lost its significance in multivariate analysis, including MGMTp-methylation. Hence, the correlation between SVZ radiation and glioblastoma patient survival remains unclear. Carefully designed prospective studies are needed to provide unequivocal results on this controversial topic.

Local relapse after breast-conserving therapy for ductal carcinoma in situ: a European single-center experience and external validation of the Memorial Sloan-Kettering Cancer Center DCIS nomogram.

PURPOSE: Adjuvant treatments after breast-conserving surgery (BCS) for ductal carcinoma in situ to prevent local relapse are considered standard of care. However, patient selection to prevent increased morbidity without proven survival benefit remains a challenge. To predict the risk of ipsilateral breast tumor relapse (IBTR) after BCS, the Memorial Sloan-Kettering Cancer Center (MSKCC) developed a nomogram. The aim of this study was to develop our own prediction model for IBTR and to provide an external validation of the MSKCC nomogram. METHODS: From 1973 to 2010, 467 patients were treated with BCS for ductal carcinoma in situ at the University Hospital Leuven. Clinicopathologic and treatment parameters of all patients were used to create a multivariable model. The predictive value of the model was evaluated using the concordance index (C-index) and concordance probability estimate (CPE). Multiple imputation was used to account for missing data to allow the MSKCC model to be tested on 467 patients. RESULTS: Median follow-up was 7.2 years, with 48 women who developed an IBTR. Omission of adjuvant endocrine therapy, younger age, and positive or close surgical margins were significantly associated with an increased risk of IBTR. The bootstrap-corrected C-index for 10-year prediction by our own model was 0.63 and the CPE was 0.61. The C-index and CPE for the 10-year relapse probabilities predicted by the MSKCC nomogram were 0.66 and 0.61, respectively. CONCLUSIONS: Despite the small number of events, the need for multiple imputation, and few patients without radiation, the MSKCC nomogram performance was somewhat better than our model. This shows that the MSKCC nomogram is externally valid. The MSKCC nomogram allows users to integrate the information from 10 different variables to provide a more precise risk stratification than the use of conventional single variables or hazard ratios.

Breathing adapted radiation therapy in comparison with prone position to reduce the doses to the heart, left anterior descending coronary artery, and contralateral breast in whole breast radiation therapy.

PURPOSE: To compare 3 different treatment positions in whole breast radiation therapy in terms of target volume coverage and doses to the organs at risk (OAR). METHODS AND MATERIALS: Thirty-four breast cancer (BC) patients (17 right-sided and 17 left-sided) were included in this dosimetric planning study. They all underwent a computed tomography (CT) scan in standard supine position in free-breathing (FB), supine position with gating in deep inspiratory breath hold (DIBH)(G), and prone position (P). Three-dimensional treatment plans were made for all 3 CTs. Target coverage and OAR sparing were evaluated. RESULTS: Breast volumes varied between 209 and 2814 cm(3). The target coverage, expressed as the mean volume of the breast receiving at least 95% of the prescription dose, was similar for the 3 treatment positions. The mean lung dose and the volume of the lungs receiving >20 Gy were significantly lower in P (1.7 Gy; 2.3%) compared with G (3.4 Gy; 5.6%; P < .0001) and FB (4 Gy; 7.3%; P < .0001). The volume of the contralateral breast receiving >5 Gy was significantly lower in G (P = .001) or FB (P = .004) versus prone. The supine position with gating in DIBH significantly reduced the volume of the heart receiving >30 Gy (V30(heart)), the mean heart (D(heart)), and mean left anterior descending coronary artery (LAD) dose (D(LAD)) for left-sided BC patients (V30(heart) 0.9%, D(heart) 1.6 Gy, DLAD 22.4 Gy) with respect to FB (V30(heart) 4.3%, D(heart) 3.5 Gy, DLAD 30.9 Gy)(V30(heart) and mean D(heart): P ≤ .0001; mean D(LAD): P = .008) and P (V30(heart) 7.9%, D(heart) 5.4 Gy, D(LAD) 36.4 Gy)(V30(heart) and mean D(heart): P = .0004; mean D(LAD): P = .01). CONCLUSIONS: The coverage of the planning target volume breast was equal for the 3 treatment positions. The lowest doses to the lungs were achieved in prone. The heart, LAD, and contralateral breast were best spared in the supine position with gating in DIBH.

Subclinical cardiotoxicity detected by strain rate imaging up to 14 months after breast radiation therapy.

PURPOSE: Strain rate imaging (SRI) is a new echocardiographic modality that enables accurate measurement of regional myocardial function. We investigated the role of SRI and troponin I (TnI) in the detection of subclinical radiation therapy (RT)-induced cardiotoxicity in breast cancer patients. METHODS AND MATERIALS: This study prospectively included 75 women (51 left-sided and 24 right-sided) receiving adjuvant RT to the breast/chest wall and regional lymph nodes. Sequential echocardiographs with SRI were obtained before RT, immediately after RT, and 8 and 14 months after RT. TnI levels were measured on the first and last day of RT. RESULTS: Mean heart and left ventricle (LV) doses were both 9 ± 4 Gy for the left-sided patients and 4 ± 4 Gy and 1 ± 0.4 Gy, respectively, for the right-sided patients. A decrease in strain was observed at all post-RT time points for left-sided patients (-17.5% ± 1.9% immediately after RT, -16.6% ± 1.4% at 8 months, and -17.7% ± 1.9% at 14 months vs -19.4% ± 2.4% before RT, P<.01) but not for right-sided patients. When we considered left-sided patients only, the highest mean dose was given to the anterior left ventricular (LV) wall (25 ± 14 Gy) and the lowest to the inferior LV wall (3 ± 3 Gy). Strain of the anterior wall was reduced after RT (-16.6% ± 2.3% immediately after RT, -16% ± 2.6% at 8 months, and -16.8% ± 3% at 14 months vs -19% ± 3.5% before RT, P<.05), whereas strain of the inferior wall showed no significant change. No changes were observed with conventional echocardiography. Furthermore, mean TnI levels for the left-sided patients were significantly elevated after RT compared with before RT, whereas TnI levels of the right-sided patients remained unaffected. CONCLUSIONS: In contrast to conventional echocardiography, SRI detected a regional, subclinical decline in cardiac function up to 14 months after breast RT. It remains to be determined whether these changes are related to clinical outcome. In the meantime, we encourage the use of radiation techniques that minimize the exposure of the anterior LV wall in left-sided patients.