Intensity-modulated proton therapy decreases dose to organs at risk in low-grade glioma patients: results of a multicentric in silico ROCOCO trial.

BACKGROUND AND PURPOSE: Patients with low-grade glioma (LGG) have a prolonged survival expectancy due to better discriminative tumor classification and multimodal treatment. Consequently, long-term treatment toxicity gains importance. Contemporary radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), tomotherapy (TOMO) and intensity-modulated proton therapy (IMPT) enable high-dose irradiation of the target but they differ regarding delivered dose to organs at risk (OARs). The aim of this comparative in silico study was to determine these dosimetric differences in delivered doses. MATERIAL AND METHODS: Imaging datasets of 25 LGG patients having undergone postoperative radiotherapy were included. For each of these patients, in silico treatment plans to a total dose of 50.4 Gy to the target volume were generated for the four treatment modalities investigated (i.e., IMRT, VMAT, TOMO, IMPT). Resulting treatment plans were analyzed regarding dose to target and surrounding OARs comparing IMRT, TOMO and IMPT to VMAT. RESULTS: In total, 100 treatment plans (four per patient) were analyzed. Compared to VMAT, the IMPT mean dose (Dmean) for nine out of 10 (90%) OARs was statistically significantly (p < .02) reduced, for TOMO this was true in 3/10 (30%) patients and for 1/10 (10%) patients for IMRT. IMPT was the prime modality reducing dose to the OARs followed by TOMO. DISCUSSION: The low dose volume to the majority of OARs was significantly reduced when using IMPT compared to VMAT. Whether this will lead to a significant reduction in neurocognitive decline and improved quality of life is to be determined in carefully designed future clinical trials.

Survival after whole brain radiotherapy for brain metastases from lung cancer and breast cancer is poor in 6325 Dutch patients treated between 2000 and 2014.

BACKGROUND: Whole brain radiotherapy (WBRT) is considered standard of care for patients with multiple brain metastases or unfit for radical treatment modalities. Recent studies raised discussion about the expected survival after WBRT. Therefore, we analysed survival after WBRT for brain metastases 'in daily practice' in a large nationwide multicentre retrospective cohort. METHODS: Between 2000 and 2014, 6325 patients had WBRT (20 Gy in 4 Gy fractions) for brain metastases from non-small cell lung cancer (NSCLC; 4363 patients) or breast cancer (BC; 1962 patients); patients were treated in 15 out of 21 Dutch radiotherapy centres. Survival was calculated by the Kaplan-Meier method from the first day of WBRT until death as recorded in local hospital data registration or the Dutch Municipal Personal Records Database. FINDINGS: The median survival was 2.7 months for NSCLC and 3.7 months for BC patients (p < .001). For NSCLC patients aged <50, 50-60, 60-70 and >70 years, survival was 4.0, 3.0, 2.8 and 2.1 months, respectively (p < .001). For BC patients, survival was 4.5, 3.8, 3.2 and 2.9 months, respectively (p = .047). In multivariable analyses, higher age was related to poorer survival with hazard ratios (HR) for patients aged 50-60, 60-70 and >70 years being 1.05, 1.19 and 1.34, respectively. Primary BC (HR: 0.83) and female sex (HR: 0.85) were related to better survival (p < .001). INTERPRETATION: The survival of patients after WBRT for brain metastases from NSCLC treated in Dutch 'common radiotherapy practice' is poor, in breast cancer and younger patients it is disappointingly little better. These results are in line with the results presented in the QUARTZ trial and we advocate a much more restrictive use of WBRT. In patients with a more favourable prognosis the optimal treatment strategy remains to be determined. Prospective randomized trials and individualized prognostic models are needed to identify these patients and to tailor treatment.

Cone-beam CT-based adaptive planning improves permanent prostate brachytherapy dosimetry: An analysis of 1266 patients.

PURPOSE: To evaluate adaptive planning for permanent prostate brachytherapy and to identify the prostate regions that needed adaptation. METHODS AND MATERIALS: After the implantation of stranded seeds, using real-time intraoperative planning, a transrectal ultrasound (TRUS)-scan was obtained and contoured. The positions of seeds were determined on a C-arm cone-beam computed tomography (CBCT)-scan. The CBCT-scan was registered to the TRUS-scan using fiducial gold markers. If dose coverage on the combined image-dataset was inadequate, an intraoperative adaptation was performed by placing remedial seeds. CBCT-based intraoperative dosimetry was analyzed for the prostate (D90, V100, and V150) and the urethra (D30). The effects of the adaptive dosimetry procedure for Day 30 were separately assessed. RESULTS: We analyzed 1266 patients. In 17.4% of the procedures, an adaptation was performed. Without the dose contribution of the adaptation Day 30 V100 would be < 95% for half of this group. On Day 0, the increase due to the adaptation was 11.8 ± 7.2% (1SD) for D90 and 9.0 ± 6.4% for V100. On Day 30, we observed an increase in D90 of 12.3 ± 6.0% and in V100 of 4.2 ± 4.3%. For the total group, a D90 of 119.6 ± 9.1% and V100 of 97.7 ± 2.5% was achieved. Most remedial seeds were placed anteriorly near the base of the prostate. CONCLUSION: CBCT-based adaptive planning enables identification of implants needing adaptation and improves prostate dose coverage. Adaptations were predominantly performed near the anterior base of the prostate.

Therapeutic management of brain metastasis.

This review focuses on the management of brain metastases. The four main modes of therapy are discussed: whole brain radiation therapy (WBRT), surgery, radiosurgery, and chemotherapy. Young patients with limited extracranial disease may benefit from surgical resection of a single brain metastasis, and from radiosurgery (or stereotactic radiotherapy) if two to four brain metastases are present. Whether WBRT after surgery or radiosurgery is beneficial is uncertain. Therefore, two approaches can be justified in patients with a good prognosis: WBRT after surgery or radiosurgery, or alternatively, observation with MRI follow-up after surgery or radiosurgery. A hyperfractionated radiation scheme is then to be preferred to limit late toxicity of WBRT. Patients with extensive extracranial tumour activity or impaired quality of life may benefit from radiosurgery (one to four brain metastases), or from shorter WBRT schedules. We propose a decision tree on the various ways to treat brain metastasis.