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Introduction: Stereotactic ablative radiotherapy (SABR) can achieve good local control for metastatic adrenal lesions. Magnetic resonance (MR)-guidance with daily on-table plan adaptation can augment the delivery of SABR with greater dose certainty. The goal of this study was to quantify the potential clinical benefit MR-guided daily-adaptive adrenal SABR using the normal tissue complication probability (NTCP) framework. Methods: Patients treated with adrenal MR-guided SABR at a single institution were retrospectively reviewed. Lyman-Kutcher-Burman NTCP models were used to calculate the NTCP of upper abdominal organs-at-risk (OARs) at simulation and both before and after daily on-table plan adaptation. Differences in OAR NTCPs were assessed using signed-rank tests. Potential predictors of the benefits of adaptation were assessed by linear regression. Results: Fifty-two adrenal MR-guided SABR courses were analyzed. The baseline simulation plan underestimated the absolute stomach NTCP by 10.0% on average (95% confidence interval: 4.7–15.2%, p < 0.001). Daily on-table adaptation lowered absolute NTCP by 8.7% (4.2–13.2%, p < 0.001). The most significant predictor of the benefits of adaptation was lesion laterality (p = 0.018), with left-sided lesions benefitting more (13.3% [6.3–20.4%], p < 0.001) than right-sided lesions (2.1% [−1.6–5.7%], p = 0.25). Sensitivity analyses did not change the statistical significance of the findings. Conclusion: NTCP analysis revealed that patients with left adrenal tumors were more likely to benefit from MR-guided daily on-table adaptive SABR using current dose/fractionation regimens due to reductions in predicted gastric toxicity. Right-sided adrenal lesions may be considered for dose escalation due to low predicted NTCP.

Background and Purpose: Magnetic resonance-guided radiotherapy (MRgRT) with real-time intra-fraction tumor motion monitoring allows for high precision Stereotactic Ablative Radiotherapy (SABR). This study aimed to investigate the clinical feasibility, patient satisfaction and delivery accuracy of single-fraction MR-guided SABR in a single day (one-stop-shop, OSS). Methods and Materials: Ten patients with small lung tumors eligible for single fraction treatments were included. The OSS procedure consisted of consultation, treatment simulation, treatment planning and delivery. Following SABR delivery, patients completed a reported experience measure (PREM) questionnaire. Prescribed doses ranged 28–34 Gy. Median GTV was 2.2 cm3 (range 1.3–22.9 cm3). A gating boundary of 3 mm, and PTV margin of 5 mm around the GTV, were used with auto-beam delivery control. Accuracy of SABR delivery was studied by analyzing delivered MR-cines reconstructed from machine log files. Results: All 10 patients completed the OSS procedure in a single day, and all reported satisfaction with the process. Median time for the treatment planning step and the whole procedure were 2.8 h and 6.6 h, respectively. With optimization of the procedure, treatment could be completed in half a day. During beam-on, the 3 mm tracking boundary encompassed between 78.0 and 100 % of the GTV across all patients, with corresponding PTV values being 94.4–100 % (5th-95th percentiles). On average, system-latency for triggering a beam-off event comprised 5.3 % of the delivery time. Latency reduced GTV coverage by an average of −0.3 %. Duty-cycles during treatment delivery ranged from 26.1 to 64.7 %. Conclusions: An OSS procedure with MR-guided SABR for lung cancer led to good patient satisfaction. Gated treatment delivery was highly accurate with little impact of system-latency.

BACKGROUND AND PURPOSE: We studied the benefits of using stereotactic MR-guided adaptive radiation therapy (SMART) for delivery of SABR in peripherally located lung tumors.METHODS AND MATERIALS: Twenty-three patients (25 peripheral lung tumors) underwent SMART in 3-8 fractions on an MR Linac or Cobalt-60 system. Before each fraction, a breath-hold MR scan was acquired, followed by on-table plan adaptation based on the anatomy-of-the-day. Breath-hold gated delivery was performed under continuous MR-guidance using an in-room monitor. Benefits of on-table adaptation were studied by comparing 112 «predicted» plans, which are the baseline plans recalculated on the anatomy-of-the-day, with the on-table reoptimized plans.RESULTS: The full SMART procedure took a median of 48 and 62 minutes on the MR Linac and Cobalt-60 system, respectively. Median SMART-PTVs were 9.5 cm3 (range, 3.1-55.6). In 14 patients who had undergone a free-breathing 4DCT, SMART-PTVs measured 53.7% (range, 31.9-75.0) of PTVs that would have been generated using a motion-encompassing internal target volume approach. On-table adaptation improved prescription dose coverage of the PTV from a median of 92.1% in predicted plans, to 95.0% in reoptimized ones, thereby increasing the proportion of fractions delivering ≥100 Gy (BED10Gy) to 95% of PTV, from 90.2% to 100.0%.CONCLUSION: Delivery of gated breath-hold SABR using MR-guidance resulted in significantly smaller target volumes than would have been the case with an ITV-based approach. Although on-table adaptation ensured delivery of ablative doses in all fractions, the dosimetric benefits were modest, suggesting that daily online plan adaptation may not benefit most patients with peripheral lung tumors.

Purpose: As patients with centrally located lung tumors are at increased risk of toxicity with stereotactic ablative radiation therapy (SABR), we performed stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for such patients. We retrospectively analyzed the benefits of daily on-table plan adaptation. Methods and Materials: Twenty-five patients with central lung tumors underwent a total of 182 fractions of video-assisted, respiration-gated SMART on the MRIdian (ViewRay, Inc). Risk-adapted fractionation was used to deliver 60 Gy in 8 fractions (n = 20) or 55 Gy in 5 fractions (n = 5). For each fraction, daily MR-guided setup and on-table plan reoptimization, based on planning target volume (PTV) coverage and organ-at-risk (OAR) constraints, was performed. Gated breath-hold delivery was performed under continuous MR guidance. Benefits of daily plan reoptimization were studied by comparing 168 “predicted” plans, which are the calculated baseline plans on the anatomy of the day, with the reoptimized treatment plans. Results: The reoptimized plan was chosen for treatment in 92% of fractions. On-table plan adaptation improved PTV coverage in 61% of fractions by achieving superior coverage by the prescription dose (V 100% ) and a higher median dose (D 50% ). Mean increase in PTV V 100% was 4.6% (P

Background Adaptive magnetic resonance imaging‐guided radiation therapy (MRgRT) can escalate dose to tumors while minimizing dose to normal tissue. We evaluated outcomes of inoperable pancreatic cancer patients treated using MRgRT with and without dose escalation. Methods We reviewed 44 patients with inoperable pancreatic cancer treated with MRgRT. Treatments included conventional fractionation, hypofractionation, and stereotactic body radiation therapy. Patients were stratified into high‐dose (biologically effective dose [BED10] >70) and standard‐dose groups (BED10 ≤70). Overall survival (OS), freedom from local failure (FFLF) and freedom from distant failure (FFDF) were evaluated using Kaplan‐Meier method. Cox regression was performed to identify predictors of OS. Acute gastrointestinal (GI) toxicity was assessed for 6 weeks after completion of RT. Results Median follow‐up was 17 months. High‐dose patients (n = 24, 55%) had statistically significant improvement in 2‐year OS (49% vs 30%, P = 0.03) and trended towards significance for 2‐year FFLF (77% vs 57%, P = 0.15) compared to standard‐dose patients (n = 20, 45%). FFDF at 18 months in high‐dose vs standard‐dose groups was 24% vs 48%, respectively (P = 0.92). High‐dose radiation (HR: 0.44; 95% confidence interval [CI]: 0.21‐0.94; P = 0.03) and duration of induction chemotherapy (HR: 0.84; 95% CI: 0.72‐0.98; P = 0.03) were significantly correlated with OS on univariate analysis but neither factor was independently predictive on multivariate analysis. Grade 3+ GI toxicity occurred in three patients in the standard‐dose group and did not occur in the high‐dose group. Conclusions Patients treated with dose‐escalated MRgRT demonstrated improved OS. Prospective evaluation of high‐dose RT regimens with standardized treatment parameters in inoperable pancreatic cancer patients is warranted.

Background and purpose MR-guided radiation therapy (MRgRT) with daily plan adaptation is a novel but time- and resource-intensive treatment for locally advanced pancreatic cancer (LAPC). We analyzed the benefit in target coverage and organ-at-risk (OAR) sparing of daily plan adaptation in 36 consecutive LAPC patients treated with MRgRT to 40 Gy in 5 fractions. Materials and methods Adaptive planning was assessed for 180 fractions by comparing non-adapted plans with re-optimized plans using (a) GTV coverage and OAR high-doses, and (b) compliance with institutional objectives for GTV coverage and high-dose OAR constraints. Using these criteria, plan adaptation for each fraction was characterized as “not needed”, “beneficial”, or “no benefit”. Decision-tree analysis was performed to identify subgroups most likely or not to benefit from routine plan adaptation. Results The percentage of plans fulfilling institutional constraints increased from 43.9% (non-adapted plans) to 83.3% after online plan adaptation, with significant improvements in GTV coverage and lower V33Gy OAR doses. Adaptive re-optimization was found to be “not needed” in 80 fractions (44.4%), “beneficial” in 95 fractions (52.8%) and of “no benefit” in 5 fractions (2.8%). Decision-tree analysis identified a grouping based on distance from tumor to OAR of ≤3 mm and GTV size, respectively, to be the major determinants for the benefit of daily plan adaptation. Conclusion MRgRT with daily plan adaptation for LAPC was of benefit in approximately half of fractions, improving target coverage and OAR sparing. Plan adaptation appeared to be relevant mainly in cases where the GTV to adjacent OAR distance was ≤3 mm.

Background: Since publication of the QUARTZ trial, the clinical value of whole brain radiotherapy (WBRT) for brain metastases is a matter of debate due to significant side effects. In order to avoid these side effects and to improve local tumor control, stereotactic radiosurgery (SRS) is an attractive treatment option. We have initiated a randomized trial (NCT02353000) to investigate whether quality of life is better preserved after SRS alone than after WBRT in patients with newly diagnosed multiple brain metastases. Methods: Patients with 4 up to 10 brain metastases (BM) were randomized between the standard arm WBRT (total dose 20 Gy in 5 fractions) or SRS (single fraction or 3 fractions). Primary endpoint was difference in quality of life (QOL) at three months after radiotherapy compared to baseline (EQ5D5L EUROQOL score). Findings: The study was prematurely closed due to poor accrual. A total of 29 patients (13%) were randomized between July 2016 and May 2018, of which 15 patients have been treated with SRS and 14 patients with WBRT. The median number of lesions per patient was 6 (range, 4-9) and the median total treatment volume was 13.0 cc 3 (range, 1.8-25.9 cc 3 ). QOL at three months decreased in the SRS group with 0.1 (SD=0.2), compared to 0.2 (SD=0.2) in the WBRT group (p=0.23).The actuarial one year survival was 57% (SRS) and 31% (WBRT) (p=0.52). The actuarial one year brain salvage free survival was 50% (SRS) and 78% (WBRT) (p=0.22). Interpretation: In patients with 4 up to 10 BM, SRS alone resulted in one-year survival in 57% of patients while maintaining quality of life. Due to premature closure of the trial, no statistical significant differences could be determined between SRS alone and WBRT in the investigated endpoints. Trial Registration: NCT02353000 Funding Statement: Varian Medical Systems, the Dutch technology Foundation STW, and Kankeronderzoekfonds Limburg. Declaration of Interests: No competing interests to declare. Ethics Approval Statement: All patients willing to participate gave written informed consent. The study protocol was approved by the medical ethical committee of the Maastricht University Medical Center, The Netherlands.

PurposeTo study inter-fractional organ changes during MR-guided stereotactic ablative radiotherapy (SABR) for adrenal metastases and to evaluate the dosimetric advantages of online plan adaptation.Methods and MaterialsSeventeen patients underwent a total of 84 fractions of video-assisted, respiration-gated MR-guided adaptive radiotherapy to deliver either 50 Gy (5 fractions), 60 Gy (8 fractions) or 24 Gy (3 fractions). An MR scan was repeated prior to each fraction, followed by rigid co-registration to the GTV on the pre-treatment MR scan. Contour deformation, PTV (GTV+3mm) expansion and online plan re-optimization were then performed. Re-optimized plans were compared to baseline treatment plans recalculated on the anatomy-of-the-day (‘predicted plans').Inter-fractional changes in OARs were quantified according to OAR volume changes within a 3 cm distance from PTV surface, centre of mass (COM) displacements and the Dice Similarity Coefficient (DSC). Plan quality evaluation was based on target coverage (GTV and PTV), and also high dose sparing of all OARs (V36Gy, V33Gy and V25Gy).ResultsSubstantial COM displacements were observed for stomach, bowel and duodenum of 17, 27 and 36 mm, respectively. Maximum volume changes for the stomach, bowel and duodenum within 3 cm of PTV were 23.8, 20.5 and 20.9 cc, respectively. DSC values for OARs ranged from 0.0 to 0.9 for all fractions.Baseline plans recalculated on anatomy-of-the-day revealed underdosage of target volumes, and variable OAR sparing, leading to a failure to meet institutional constraints in a third of fractions. Online re-optimization improved target coverage in 63% of fractions, and reduced the number of fractions not meeting the V95% objective for GTV and PTV. Re-optimized plans exhibited significantly better sparing of OAR.ConclusionsSignificant inter-fractional changes in OARs positions were observed despite breath-hold SABR delivery under MR-guidance. Online re-optimization of treatment plans led to significant improvements in target coverage and OAR sparing.

BACKGROUND Delay in cancer care may adversely affect emotional distress, treatment outcome and survival. Optimal timings in multidisciplinary glioblastoma care are a matter of debate and clear national guidelines only exist for time to neurosurgery. We evaluated the between-hospital variation in timings to neurosurgery and adjuvant radiotherapy and chemotherapy in newly diagnosed glioblastoma patients in the Netherlands. MATERIAL AND METHODS Data were obtained from the nation-wide Dutch Brain Tumor Registry between 2014 and 2018. All adult patients with glioblastoma were included, covering all 18 neurosurgical hospitals, 28 radiotherapy hospitals, and 33 oncology hospitals. Long time-to-surgery (TTS) was defined as >3 weeks from the date of first brain tumor diagnosis to surgery, long time-to-radiotherapy (TTR) as either >4 or >6 weeks after surgery, and long time-to-chemotherapy (TTC) as either >4 or >6 weeks after completion of radiotherapy. Between-hospital variation in standardized rate of long timings was analyzed in funnel plots after case-mix correction. RESULTS A total of 4203 patients were included. Median TTS was 20 days and 52.4% of patients underwent surgery within 3 weeks. Median TTR was 20 days and 24.6% of patients started radiotherapy within 4 weeks and 84.2% within 6 weeks after surgery. Median TTC was 28 days and 62.6% of patients received chemotherapy within 4 weeks and 91.8% within 6 weeks after radiotherapy. After case-mix correction, three (16.7%) neurosurgical hospitals had significantly more patients with longer than expected TTS. Three (10.7%) and one (3.6%) radiotherapy hospitals had significantly more patients with longer than expected TTR for >4 and >6 weeks, respectively. In seven (21.2%) chemotherapy hospitals, significantly less patients with TTC >4 weeks were observed than expected. In four (12.1%) chemotherapy hospitals, significantly more patients with TTC >4 weeks were observed than expected. CONCLUSION Between-hospital variation in timings to multidisciplinary treatment was observed in glioblastoma care in the Netherlands. A substantial percentage of patients experienced timings longer than anticipated.

BACKGROUND Over the past years, increasing worldwide attention towards centralization of complex cancer care has been pursued as higher volume centers have shown improved outcomes. Changes in distribution of care and the impact on travel distance in glioblastoma patients have not been determined yet. In this study, we determine trends in distribution of glioblastoma care in the Netherlands over the last three decades and assess whether the observed trends affected travel distance for individual patients. MATERIAL AND METHODS Data were obtained from the Dutch Brain Tumor Registry from 1989 to 2018. All glioblastoma patients (≥18 years) were included for analysis. Patients, neurosurgical centers and radiotherapy centers were geocoded. Data were analyzed in six time intervals of 5 years. High volume hospitals were defined as >50 cases per year. Travel distance was examined in two categories, ≤60km and >60km respectively. Trend analyses for proportions were used to analyze hospital volume changes and travel distances. RESULTS A total of 16.477 glioblastoma patients were registered, with an annual increase from 203 patients in 1989 to 917 patients in 2018. Neurosurgical centers increased from 16 to 17 and for radiotherapy from 19 to 22 centers between 1989–1993 and 2014–2018. Mean neurosurgical- and radiotherapy center volumes increased from 12 to 39 (P=0.025) and 7 to 27 (P=0.025) patients per hospital per year from 1989–1993 to 2014–2018. High volume neurosurgical centers were observed since 2004, and an increased number of patients were treated in these centers, 27.8%, 52.6% and 64.1% in the time periods 2004–2008, 2009–2013, and 2014–2018 (P60km to the neurosurgical center reduced from 15.8% to 13.2% (P=0.033). Travel distance >60km to the radiotherapy center did not reduce significantly (10.4% to 8.8%, P=0.601). CONCLUSION An increasing number of glioblastoma patients were differentially treated in high volume neurosurgery and radiotherapy centers. The observation that this did not translate into increased travel distances, indicates accessible specialized Neuro-Oncology care for glioblastoma patients in The Netherlands.

Introduction: Commonly used clinical models for survival prediction after stereotactic radiosurgery (SRS) for brain metastases (BMs) are limited by the lack of individual risk scores and disproportionate prognostic groups. In this study, two nomograms were developed to overcome these limitations.Methods: 495 patients with BMs of NSCLC treated with SRS for a limited number of BMs in four Dutch radiation oncology centers were identified and divided in a training cohort (n = 214, patients treated in one hospital) and an external validation cohort n = 281, patients treated in three other hospitals). Using the training cohort, nomograms were developed for prediction of early death (12 months) with prognostic factors for survival. Accuracy of prediction was defined as the area under the curve (AUC) by receiver operating characteristics analysis for prediction of early death and long term survival. The accuracy of the nomograms was also tested in the external validation cohort.Results: Prognostic factors for survival were: WHO performance status, presence of extracranial metastases, age, GTV largest BM, and gender. Number of brain metastases and primary tumor control were not prognostic factors for survival. In the external validation cohort, the nomogram predicted early death statistically significantly better (p Conclusion: The nomograms predicted early death and long-term survival more accurately than commonly used prognostic scores after SRS for a limited number of BMs of NSCLC. Moreover these nomograms enable individualized probability assessment and are easy into use in routine clinical practice. (C) 2017 Elsevier B.V. All rights reserved.

Purpose Magnetic resonance (MR)-guided SABR was performed for patients with lung tumors in whom treatment delivery was challenging owing to tumor location, motion, or pulmonary comorbidity. Because stereotactic MR-guided adaptive radiation therapy (SMART) is a novel approach, we studied clinical outcomes in these high-risk lung tumors. Methods and Materials Fifty consecutive patients (54 lung tumors) underwent SMART between 2016 and 2018 for either a primary lung cancer (29 patients) or for lung metastases (21 patients). Eligible patients had risk factors that could predispose them to toxicity, including a central tumor location (n = 30), previous thoracic radiation therapy (n = 17), and interstitial lung disease (n = 7). A daily 17-second breath-hold MR scan was acquired in treatment position, and on-table plan adaptation was performed using the anatomy of the day. Gated SABR was delivered during repeated breath-holds under continuous MR guidance. Results All but 1 patient completed the planned SMART schedule. With daily plan adaptation, a biologically effective dose ≥100 Gy to 95% of the planning target volume was delivered in 50 tumors (93%). Median follow-up was 21.7 months (95% confidence interval, 19.9-28.1). Local control and overall and disease-free survival rates at 12 months were 95.6%, 88.0%, and 63.6%, respectively. Local failures developed in 4 patients: in 2 after reirradiation for a recurrent lung cancer and in 2 patients with a colorectal metastasis. Overall rates of any grade ≥2 and ≥3 toxicity were 30% and 8%, respectively. Commonest toxicities were grade ≥2 radiation pneumonitis (12%) and chest wall pain (8%). No grade 4 or 5 toxicities were observed. Conclusions Use of MR-guided SABR resulted in low rates of high-grade toxicity and encouraging early local control in a cohort of high-risk lung tumors. Additional studies are needed to identify patients who are most likely to benefit from the SMART approach.

OBJECTIVES: Stage I non-small cell lung cancer (NSCLC) can be treated with either Stereotactic Body Radiotherapy (SBRT) or Video Assisted Thoracic Surgery (VATS) resection. To support decision making, not only the impact on survival needs to be taken into account, but also on quality of life, costs and cost-effectiveness. Therefore, we performed a cost-effectiveness analysis comparing SBRT to VATS resection with respect to quality adjusted life years (QALY) lived and costs in operable stage I NSCLC.MATERIALS AND METHODS: Patient level and aggregate data from eight Dutch databases were used to estimate costs, health utilities, recurrence free and overall survival. Propensity score matching was used to minimize selection bias in these studies. A microsimulation model predicting lifetime outcomes after treatment in stage I NSCLC patients was used for the cost-effectiveness analysis. Model outcomes for the two treatments were overall survival, QALYs, and total costs. We used a Dutch health care perspective with 1.5 % discounting for health effects, and 4 % discounting for costs, using 2018 cost data. The impact of model parameter uncertainty was assessed with deterministic and probabilistic sensitivity analyses.RESULTS: Patients receiving either VATS resection or SBRT were estimated to live 5.81 and 5.86 discounted QALYs, respectively. Average discounted lifetime costs in the VATS group were €29,269 versus €21,175 for SBRT. Difference in 90-day excess mortality between SBRT and VATS resection was the main driver for the difference in QALYs. SBRT was dominant in at least 74 % of the probabilistic simulations.CONCLUSION: Using a microsimulation model to combine available evidence on survival, costs, and health utilities in a cost-effectiveness analysis for stage I NSCLC led to the conclusion that SBRT dominates VATS resection in the majority of simulations.

Background and purpose This work evaluates the accuracy of deformable dose accumulation for organs at risk (OAR) in MR-guided prostate SBRT using an anthropomorphic deformable phantom. Materials and methods Six MR-guided prostate SBRT treatment courses were simulated using volumetric OAR (bladder and rectum) information derived from actual patient data. Deformed OAR contours, geometrical landmarks and GafChromic EBT3 film strips (1.25 × 2.0 cm2) placed at the surface of the OARs were used to validate DIR-based dose accumulation in MRgRT. Two DIR methods were applied: an intensity-based deformation (IB-D) applied to the whole image, and a contour-based deformation (CB-D), resulting in a separate deformation and dose accumulation for each OAR. Dosimetric accuracy was evaluated by quantifying the dose differences, and performing a gamma-index analysis between measured and DIR-derived accumulated dose for both OARs. Geometrical accuracy was assessed by measuring the Dice similarity coefficient (DSC), Hausdorff distance (HDD) and residual distance error (RDE) for all markers at each fraction. Results CB-D resulted in an average dose deviation from film measurements for rectum and bladder surfaces of 0.6% and 0.3%, respectively. IB-D led to worse results resulting in an overall average dose accumulation inaccuracy of 7.2% and 2.5% for rectum and bladder. CB-D also showed a higher geometrical accuracy than IB-D with significantly higher DSC values and lower RDE and HDD deviations. Conclusion Empirical validation of dose accumulation in MR-guided SBRT for prostate cancer obtained a good agreement with reference film measurements when using a contour-based DIR approach.

Highlights • The use of MRgRT in clinical practice requires thorough preparation. • MRgRT combining with daily plan adaptation indicates adjusting existing workflows. • Clinical implementation of adaptive MRgRT requires a multidisciplinary approach. • Role and responsibilities of RTT will expand with growing clinical experience., The latest development in radiation oncology departments towards high precision and adaptive radiation therapy is the clinical introduction of magnetic resonance image guided radiation therapy (MRgRT). Early 2016, patient treatment using MRgRT was started at Amsterdam UMC, location VU University Medical Center. Introducing this novel technique in clinical practice requires thorough preparation with regard to important topics, such as MR-safety and training, equipping the treatment vault and console room, development of MRgRT workflow and logistical issues. Certainly when MRgRT is combined with daily plan adaptation, this indicates adjusting existing workflows and protocols. The MRgRT workflow requires a multidisciplinary process, and while each discipline has had its own tasks and responsibilities, with growing clinical experience there has been a shift towards RTT responsibilities. In this overview we discuss preclinical training and preparation for the implementation of (adaptive) MRgRT, with a particular focus on the perspective of RTTs. Although the reviewed logistics are partly the result of the decision to perform daily plan re-optimization, our experience can be extrapolated to implementation of alternative approaches for MRgRT.

In this case presentation, we describe the challenges of performing magnetic resonance-guided radiation therapy (MRgRT) with plan adaptation in a patient with advanced endometriosis, in whom several prior therapeutic attempts were unsuccessful and extensive pelvic irradiation was regarded as being too toxic. Treatment was delivered in two sessions, first for the seemingly only active right ovary, and at a later stage for the left ovary. Some logistical problems were encountered during the preparation of the first treatment, which were subsequently optimized for the second treatment by using transvaginal ultrasound to determine the optimum time point for simulation and delivery. Using breath-hold gated delivery and plan adaptation, radiation dose to the bowel could be minimized, resulting in good tolerance of treatment. Because of the need to simulate and deliver in a brief optimal time span for visibility of the follicles in the ovaries, a single fraction dose of 8 Gy was used in our patient. Hormonal outcome after her second treatment is still pending. In conclusion, MRgRT with plan adaptation is feasible for the occasional patient with refractory endometriosis. Simulation and delivery needs to be synchronized with the menstrual cycle, ensuring that the Graafian follicles allow the ovaries to be visible on magnetic resonance imaging (MRI). Because the ovaries are only visible on T2-weighted MRI for a very brief period of time, we suggest that it is preferable to use single fraction radiotherapy with a brief interval between simulation imaging and delivery.

Purpose: As patients with centrally located lung tumors are at increased risk of toxicity with stereotactic ablative radiation therapy (SABR), we performed stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for such patients. We retrospectively analyzed the benefits of daily on-table plan adaptation. Methods and Materials: Twenty-five patients with central lung tumors underwent a total of 182 fractions of video-assisted, respiration-gated SMART on the MRIdian (ViewRay, Inc). Risk-adapted fractionation was used to deliver 60 Gy in 8 fractions (n = 20) or 55 Gy in 5 fractions (n = 5). For each fraction, daily MR-guided setup and on-table plan reoptimization, based on planning target volume (PTV) coverage and organ-at-risk (OAR) constraints, was performed. Gated breath-hold delivery was performed under continuous MR guidance. Benefits of daily plan reoptimization were studied by comparing 168 “predicted” plans, which are the calculated baseline plans on the anatomy of the day, with the reoptimized treatment plans. Results: The reoptimized plan was chosen for treatment in 92% of fractions. On-table plan adaptation improved PTV coverage in 61% of fractions by achieving superior coverage by the prescription dose (V 100% ) and a higher median dose (D 50% ). Mean increase in PTV V 100% was 4.6% (P

Introduction: Stereotactic ablative radiotherapy is a guideline-recommended treatment for early stage non–small-cell lung cancer. We report on incidence and salvage of local recurrences (LR) and second primary lung cancers (SPLC) in a large series of patients with long-term follow-up, to generate data for evidence-based follow-up regimens. Methods: We excluded all patients with double tumors, TNM-stages other than T1-T2N0M0, biologically effective dose less than 100 Gy 10 and previous treatment for the index tumor from our institutional database. LR was defined as recurrence in/adjacent to the planning target volume. A diagnosis of SPLC was determined using criteria described by Martini et al. Results: The 855 patients included had a median follow-up of 52 months. Forty-six patients developed LR after a median of 22 months (range 7–87 months). Actuarial local control rates at 3 and 5 years were 92.4% and 90.9%, respectively. Fifty-four percent had isolated LR and 13% had LR in combination with regional recurrences. Ten patients underwent radical salvage treatment; surgery ( N = 6), high-dose radiotherapy ( N = 3), or chemoradiation ( N = 1). Median overall survival following LR was 13 months, but it was 36 months in patients who underwent radical salvage. A SPLC was diagnosed in 79 patients, after a median interval of 34 months. Actuarial cumulative incidences of SPLC at 3 and 5 years were 11.7% and 16.7%, respectively. Radical salvage for SPLC was performed in 63 patients (80%). Conclusions: Both the timing of LR and persistent risk of SPLC serve as rationale for long-term follow-up using computed tomography scans in patients fit enough to undergo any radical treatment.

Purpose: A prognostic model for 5-year overall survival (OS), consisting of recursive partitioning analysis (RPA) and a nomogram, was developed for patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). Methods and Materials: A primary dataset of 703 ES-NSCLC SABR patients was randomly divided into a training (67%) and an internal validation (33%) dataset. In the former group, 21 unique parameters consisting of patient, treatment, and tumor factors were entered into an RPA model to predict OS. Univariate and multivariate models were constructed for RPA-selected factors to evaluate their relationship with OS. A nomogram for OS was constructed based on factors significant in multivariate modeling and validated with calibration plots. Both the RPA and the nomogram were externally validated in independent surgical (n = 193) and SABR (n = 543) datasets. Results: RPA identified 2 distinct risk classes based on tumor diameter, age, World Health Organization performance status (PS) and Charlson comorbidity index. This RPA had moderate discrimination in SABR datasets (c-index range: 0.52-0.60) but was of limited value in the surgical validation cohort. The nomogram predicting OS included smoking history in addition to RPA-identified factors. In contrast to RPA, validation of the nomogram performed well in internal validation (r(2) = 0.97) and external SABR (r(2) = 0.79) and surgical cohorts (r(2) = 0.91). Conclusions: The Amsterdam prognostic model is the first externally validated prognostication tool for OS in ES-NSCLC treated with SABR available to individualize patient decision making. The nomogram retained strong performance across surgical and SABR external validation datasets. RPA performance was poor in surgical patients, suggesting that 2 different distinct patient populations are being treated with these 2 effective modalities. (C) 2015 Elsevier Inc. All rights reserved.

BACKGROUND The practice of treating a solitary pulmonary nodule (SPN) suspicious for stage I non-small cell lung cancer (NSCLC) with stereotactic ablative radiotherapy (SABR) in the absence of pathology is growing. In the absence of randomized evidence, the appropriate prior probability threshold of lung cancer of when such a strategy is warranted can be informed using decision analysis. METHODS A decision tree and Markov model were constructed to evaluate the relative merits of surveillance, a PET scan-directed SABR strategy (without pathology), or a PET scan-biopsy-SABR strategy, when faced with an SPN at different prior probabilities for lung cancer. Diagnostic characteristics, as well as disease, treatment, and toxicity parameters, were extracted from the literature. Deterministic analysis and probabilistic sensitivity analyses were performed to inform the appropriate lung cancer prior probability threshold between treatment strategies. RESULTS In the reference case analysis, the prior probability threshold between surveillance and PET scan-biopsy-SABR was 17.0%; between PET scan-directed SABR and PET scan-biopsy-SABR, the threshold was 85.0%. The latter finding was confirmed on probabilistic sensitivity analysis (85.2%; 95% CI, 80.0% to 87.2%). This predicted lung cancer prior probability threshold was most sensitive to the diagnostic sensitivity of transthoracic biopsy (range, 77.2% to 94.0%) and the detection rate of false negatives on CT scan surveillance (range, 82.4% to 92.3%). CONCLUSIONS This model suggests that if there are concerns about morbidity related to biopsy for an SPN, a PET scan-directed SABR strategy is warranted when the prior probability of lung cancer exceeds a point estimate of 85%.

New guidelines recommend the use of CT surveillance after a curative treatment for lung cancer as survivors have a 3-6% risk per person year of developing a second primary lung cancer. Our analysis of 107 patients with second primary lung cancer treated by stereotactic ablative radiotherapy showed a comparable 3 years overall survival (60%) and local control rate (89%) as for an initial lung cancer. Toxicity was uncommon, despite the fact that 73% of patients had undergone a prior (bi)lobectomy. Our findings indicate that CT surveillance is also appropriate in patients who may be unfit, or unwilling, to undergo surgery.

This report describes clinical trends in the use of stereotactic lung radiotherapy in a large single-institution program over the last 10 years. Changes in patient, tumor, and treatment characteristics are highlighted.

BACKGROUND: Previous studies reported that meningioma patients have impaired health-related quality of life (HRQoL) and cognitive function up to 5 years after intervention. We aimed to assess the long-term disease burden of meningioma patients. METHODS: In this multicenter cross-sectional study, intracranial meningioma patients at a median of 9.9 years after anti-tumor therapy were included. HRQoL was measured with the SF-36 and EORTC QLQ-BN20, anxiety and depression with the Hospital Anxiety and Depression Scale (11/21 points is indicative for probable anxiety or depression), and objective cognitive functioning on six domains (z-score< -1.5 is defined as a clinically relevant deficit). Generalized linear models were used to compare meningioma patients with healthy controls, corrected for age, sex, educational level and comorbidities, and one-sample t-tests to compare meningioma patients with data of newly diagnosed glioblastoma. Patient recruitment and data collection is still in progress. RESULTS: 164 meningioma patients were included (mean age:63.9 years, WHO grade I:91.7%, surgery:89.2%, radiotherapy:14.6%). Compared with 110 controls, meningioma patients had worse HRQoL scores on 4/10 SF-36 scales/component scores: role limitations due to physical problems and emotional problems, social functioning, and the mental component score (range mean difference: 4.4–13.8, all p0.05), and better on all other items/scales. More patients suffered from probable anxiety (14.3%) and depression (7.5%) than controls (anxiety: 3.7%, p=0.015; depression: 7.5%, p=0.011). Clinically relevant cognitive deficits were found in executive function (10.9%), verbal memory (19.4%), working memory (13.4%), attention (10.3%), information processing (25.0%) and psychomotor speed (14.4%). CONCLUSION: Almost 10 years after the last anti-tumor treatment, meningioma disease burden is still significant. A considerable number of patients have impaired HRQoL, suffer from cognitive deficits and report high levels of anxiety and depression.

Purpose To compare lesional stereotactic radiosurgery to whole brain (WBRT) radiotherapy with simultaneous in-field boost for brain metastases in terms of overall survival. Methods A retrospective review was performed on two institutional databases of 500 patients diagnosed with brain metastatic disease who received either stereotactic radiosurgery (SRS, n =381) or whole brain with simultaneous in-field boost radiotherapy (SIB, n =119), between 2002 and 2011. Propensity-score matching was utilized to obtain two groups with similar known prognostic factor characteristics. Kaplan–Meier and univariable/multivariable Cox modeling were conducted to assess the treatment impact on overall survival (OS). Results Propensity-score matching created a matched cohort of 178 patients (89 SRS/SIB) with similar baseline characteristics. Multivariable analysis demonstrated that presence/absence of systemic metastases, patient age, tumor volume, and presence/absence of active primary were found to be more predictive of OS than treatment assignment ( p =0.38). SIB was associated with reduced intracranial failure likely due to the WBRT component of the treatment (HR 0.36, p Conclusions Adjusting for other predictive factors, treatment with either SRS or SIB did not result in any statistically significant difference in OS; however, observed intracranial failure was different due to the use of WBRT in the SIB cohort.

Background Video-assisted thoracoscopic surgery (VATS) lobectomy and stereotactic ablative radiotherapy (SABR) are both used for early-stage non-small-cell lung cancer. We carried out a propensity score-matched analysis to compare locoregional control (LRC). Patients and methods VATS lobectomy data from six hospitals were retrospectively accessed; SABR data were obtained from a single institution database. Patients were matched using propensity scores based on cTNM stage, age, gender, Charlson comorbidity score, lung function and performance score. Eighty-six VATS and 527 SABR patients were matched blinded to outcome (1:1 ratio, caliper distance 0.025). Locoregional failure was defined as recurrence in/adjacent to the planning target volume/surgical margins, ipsilateral hilum or mediastinum. Recurrences were either biopsy-confirmed or had to be PET-positive and reviewed by a tumor board. Results The matched cohort consisted of 64 SABR and 64 VATS patients with the median follow-up of 30 and 16 months, respectively. Post-SABR LRC rates were superior at 1 and 3 years (96.8% and 93.3% versus 86.9% and 82.6%, respectively, P = 0.04). Distant recurrences and overall survival (OS) were not significantly different. Conclusion This retrospective analysis found a superior LRC after SABR compared with VATS lobectomy, but OS did not differ. Our findings support the need to compare both treatments in a randomized, controlled trial.

The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed. Electronic supplementary material The online version of this article (doi:10.1186/s13014-016-0740-5) contains supplementary material, which is available to authorized users.

Objectives Patients with severe chronic obstructive pulmonary disease (COPD) have a high risk of lung cancer and of postsurgical complications. We studied outcomes after stereotactic body radiotherapy (SBRT) in patients with severe COPD, as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, and performed a systematic review of the literature on outcomes after SBRT or surgery in these patients. Methods A single-institution cohort of 176 patients with COPD GOLD III-IV and Stage I non–small-cell lung cancer (NSCLC) treated with SBRT was evaluated. A systematic review identified studies reporting outcomes after SBRT or surgery for Stage I NSCLC in patients with GOLD III-IV or a predicted postoperative forced expiratory volume in 1 second (FEV1) of ≤40%. Results In the single-institution cohort, median follow-up was 21 months and median overall survival (OS) was 32 months. Actuarial 3-year local control was 89%, and 1- and 3-year OS were 79% and 47%, respectively. COPD severity correlated with OS ( p = 0.01). The systematic review identified four other studies (two surgical, two SBRT, n = 196 patients). SBRT studies were published more recently and included older patients than surgical studies. Mean 30-day mortality was 0% post-SBRT and 10% after surgery. Local or locoregional control was high (≥89%) after both treatments. Post-SBRT, actuarial OS was 79–95% at 1 year and 43–70% at 3 years. Postsurgical actuarial OS was 45–86% at 1 year and 31–66% at 3 years. Conclusions SBRT and surgery differ in risk of 30-day mortality in patients with severe COPD. Despite the negative selection of SBRT patients, survival at 1 and 3 years is comparable between the two treatments.

To report pooled overall survival and time to radiological intracranial progression results related to arc-based image-guided radiotherapy for dose-escalation of oligometastatic disease of the brain.Anonymized patient, tumor, and treatment data were pooled from the VU University medical center (VUmc) and the London Regional Cancer Program (LRCP) for patients treated with whole brain radiotherapy (20 Gy/5 VUmc, 30 Gy/10 LRCP) with simultaneous integrated boost (SIB) to individual intracranial lesions (40 Gy/5 VUmc, 35-60 Gy/10 LRCP) to perform survival/intracranial control outcome analyses.A total of 120 patients were treated by both the LRCP (n=70) and VUmc (n=50) between 2005 and 2010. Median lesional dose BED3,10 for the entire cohort of patients were 147 and 72 Gy, respectively. Median follow-up for the entire cohort of patients was 4.7 months with median follow-up of 5.2 months for living patients. On multivariable analysis, primary lung cancer (HR 2.044), presence of systemic metastatic disease (HR 1.937), and lower baseline WHO performance status (HR 1.742) were significant (p0.05) predictors of shorter overall survival. Cumulative brain metastases volume (HR 1.014, p=0.06) was of borderline significance on analysis of intracranial control.This pooled analysis has provided robust outcome data regarding the use of arc-based radiotherapy with SIB.

Introduction: The use of stereotactic ablative radiotherapy (SABR) in centrally located early-stage lung tumors has been associated with increased toxicity. We studied outcomes after delivery of risk-adapted SABR of central tumors. Methods: SABR was delivered in eight fractions of 7.5 Gy to 63 such patients between 2003 and 2009. Of these, 37 patients had a tumor at a central hilar location, whereas 26 patients had tumors abutting the pericardium or mediastinal structures. Survival outcomes were compared with patients with peripheral tumors treated during the same time period using fewer fractions of SABR. Results: Median follow-up was 35 months. Late grade III toxicity was limited to chest wall pain ( n = 2) and increased dyspnoea ( n = 2). No grade IV/V toxicity was observed, but grade V toxicity could not be excluded with certainty in nine patients who died of cardiopulmonary causes. Distant metastases were the predominant cause of death; cardiovascular deaths were not associated with a paracardial tumor location. No significant differences in outcomes were observed between these 63 patients and 445 other SABR patients treated for peripheral early-stage lung tumors. Three-year local control rates were 92.6% and 90.2% ( p = 0.9). Three-year overall survival rates were 64.3% and 51.1% with median survival rates of 47 and 36 months, in favor of the group of patients with central tumors ( p = 0.09). Conclusions: Use of risk-adapted SABR delivered in eight fractions of 7.5 Gy did not result in excess toxicity for centrally located early-stage lung tumors, and clinical outcomes were comparable with those seen for peripheral lesions.

Introduction Stereotactic body radiation therapy (SBRT) is entering routine clinical use for selected patients with early-stage non-small cell lung cancer. Post-SBRT radiological changes are commonly seen on follow-up computed tomography (CT) imaging and can cause diagnostic dilemmas. The aim of this study is to describe the incidence, radiological severity, and long-term morphology of these changes. Methods CT scans from patients treated between 2003 and June 2008 were eligible for evaluation if radiological follow-up had been performed at our center for at least 2 years, and there was no definite evidence of local recurrence. Timing, incidence, morphology, and severity of lung changes were determined. Results CT scans from 61 patients (68 lesions) with a median follow-up of 2.5 years were evaluated. Within 6 months, 54% of lesions were associated with additional radiological abnormalities, and this figure reached 99% after 36 months. Most changes were scored as mild to moderate, and although the median time to first observation was 17 weeks, 25% appeared ≥1 year post-SBRT. In 47% of lesions, the morphology or severity of changes continued to evolve more than 2 years posttreatment. Conclusions Mild-moderate radiological changes are common after lung SBRT. Some degree of late change is nearly universal, and it often continues to evolve more than 2 years post-SBRT. Clinicians should be aware of these radiological findings, which need to be distinguished from the uncommon cases of local failure post-SBRT.

Background Elderly patients with stage I NSCLC who undergo surgical resection are at high risk of treatment-related toxicity. Stereotactic body radiation therapy (SBRT) may provide an alternative treatment with a favorable toxicity profile. Methods A population-based registry in North-Holland was used to conduct a matched-pair analysis of overall survival (OS) after surgery versus SBRT for elderly patients (age ⩾75) who were diagnosed between 2005 and 2007. Patients were matched by age, stage, gender, and treatment year; co-morbidity data was not available. SBRT was delivered at two centers; 17 centers provided surgery. Results A total of 120 patients could be matched (60 surgery, 60 SBRT). Median age was 79years, 67% were male, and 64% had T1 disease. Median follow-up was 43months. Thirty-day mortality was 8.3% after surgery and 1.7% after SBRT. OS at one- and three-years was 75% and 60% after surgery, and 87% and 42% after SBRT, respectively (log-rank p =0.22). Limiting the analysis to SBRT patients with pathological confirmation of disease and their matches revealed no significant difference between groups. Conclusion Similar OS outcomes are achieved with surgery or SBRT for stage I NSCLC in elderly patients. Comorbidity data and outcomes from centralized surgical programs are needed for more robust conclusions.