Management of Patients with Cardiovascular Implantable Electronic Devices Undergoing Radiation Therapy: A National Survey of Canadian Multidisciplinary Radiation Oncology Professionals.

Purpose: This study aimed to characterize contemporary management of Canadian patients with cardiovascular implantable electronic devices (CIEDs) undergoing radiation therapy (RT) in light of updated American Association of Physicists in Medicine guidelines. Methods and Materials: A 22-question web-based survey was distributed to members of the Canadian Association of Radiation Oncology, Canadian Organization of Medical Physicists, and Canadian Association of Medical Radiation Technologists from January to February 2020. Respondent demographics, knowledge, and management practices were elicited. Statistical comparisons by respondent demographics were performed using χ2 and Fisher exact tests. Results: In total, 155 surveys were completed by 54 radiation oncologists, 26 medical physicists, and 75 radiation therapists in academic (51%) and community (49%) practices across all provinces. The majority of respondents (77%) had managed >10 patients with CIEDs in their career. Most respondents (70%) reported using risk-stratified institutional management protocols. Respondents used manufacturer recommendations, rather than American Association of Physicists in Medicine or institutionally recommended dose limits, when the manufacturer limit was 0 Gy (44%), 0 to 2 Gy (45%), or >2 Gy (34%). The majority of respondents (86%) reported institutional policies to refer to a cardiologist for CIED evaluation both before and after completion of RT. Cumulative dose to CIED, pacing dependence, and neutron production were considered during risk stratification by 86%, 74%, and 50% of participants, respectively. Dose and energy thresholds for high-risk management were not known by 45% and 52% of respondents, with radiation oncologists and radiation therapists significantly less likely to report thresholds than medical physicists (P < .001). Although 59% of respondents felt comfortable managing patients with CIEDs, community respondents were less likely to feel comfortable than academic respondents (P = .037). Conclusions: The management of Canadian patients with CIEDs undergoing RT is characterized by variability and uncertainty. National consensus guidelines may have a role in improving provider knowledge and confidence in caring for this growing population.

Spine Stereotactic Body Radiotherapy for Prostate Cancer Metastases and the Impact of Hormone Sensitivity Status on Local Control.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is used to deliver ablative dose of radiation to spinal metastases. OBJECTIVE: To report the first dedicated series of spine SBRT specific to prostate cancer (PCa) metastases with outcomes reported according to hormone sensitivity status. METHODS: A prospective database was reviewed identifying patients with PCa treated with spine SBRT. This included those with hormone-sensitive PCa (HSPC) and castrate-resistant PCa (CRPC). The primary end point was MRI-based local control (LC). RESULTS: A total of 183 spine segments in 93 patients were identified; 146 segments had no prior radiation and 37 had been previously radiated; 27 segments were postoperative. The median follow-up was 31 months. At the time of SBRT, 50 patients had HSPC and the remaining 43 had CRPC. The most common fractionation scheme was 24-28 Gy in 2 SBRT fractions (76%). LC rates at 1 and 2 years were 99% and 95% and 94% and 78% for the HSPC and CRPC cohorts, respectively. For patients treated with de novo SBRT, a higher risk of local failure was observed in patients with CRPC (P = .0425). The 1-year and 2-year overall survival rates were significantly longer at 98% and 95% in the HSPC cohort compared with 79% and 65% in the CRPC cohort (P = .0005). The cumulative risk of vertebral compression fracture at 2 years was 10%. CONCLUSION: Favorable LC rates were observed after spine SBRT for PCa metastases; strategies to improve long-term LC in patients with CRPC require further investigation.

Predicting response to radiotherapy of intracranial metastases with hyperpolarized [Formula: see text]C MRI.

BACKGROUND: Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a significant fraction of patients. Local progression after SRS can often only be detected with increased volume of enhancement on serial MRI scans which may lag true progression by weeks or months. METHODS: Patients with intracranial metastases (N = 11) were scanned using hyperpolarized [Formula: see text]C MRI prior to treatment with stereotactic radiosurgery (SRS). The status of each lesion was then recorded at six months post-treatment follow-up (or at the time of death). RESULTS: The positive predictive value of [Formula: see text]C-lactate signal, measured pre-treatment, for prediction of progression of intracranial metastases at six months post-treatment with SRS was 0.8 [Formula: see text], and the AUC from an ROC analysis was 0.77 [Formula: see text]. The distribution of [Formula: see text]C-lactate z-scores was different for intracranial metastases from different primary cancer types (F = 2.46, [Formula: see text]). CONCLUSIONS: Hyperpolarized [Formula: see text]C imaging has potential as a method for improving outcomes for patients with intracranial metastases, by identifying patients at high risk of treatment failure with SRS and considering other therapeutic options such as surgery.

Management of recurrent or progressive spinal metastases: reirradiation techniques and surgical principles.

With the growing incidence of new cases and the increasing prevalence of patients living longer with spine metastasis, a methodological approach to the management of patients with recurrent or progressive disease is increasing in relevance and importance in clinical practice. As a result, disease management has evolved in these patients using advanced surgical and radiotherapy technologies. Five key goals in the management of patients with spine metastases include providing pain relief, controlling metastatic disease at the treated site, improving neurologic deficits, maintaining or improving functional status, and minimizing further mechanical instability. The focus of this review is on advanced reirradiation techniques, given that the majority of patients will be treated with upfront conventional radiotherapy and further treatment on progression is often limited by the cumulative tolerance of nearby organs at risk. This review will also discuss novel surgical approaches such as separation surgery, minimally invasive percutaneous instrumentation, and laser interstitial thermal therapy, which is increasingly being coupled with spine reirradiation to maximize outcomes in this patient population. Lastly, given the complexities of managing recurrent spinal disease, this review emphasizes the importance of multidisciplinary care from neurosurgery, radiation oncology, medical oncology, neuro-oncology, rehabilitation medicine, and palliative care.

Mature Imaging-Based Outcomes Supporting Local Control for Complex Reirradiation Salvage Spine Stereotactic Body Radiotherapy.

BACKGROUND: Upon progression after upfront radiotherapy to spinal metastases, low-dose re-irradiation conventional external beam radiation (cEBRT) provides limited clinical benefit. Spine stereotactic body radiotherapy (SBRT) allows for dose escalation in the salvage setting with the potential for improved local control. OBJECTIVE: To report mature clinical and imaging-based outcomes for salvage SBRT. METHODS: A retrospective review was undertaken of consecutive patients with spinal metastases treated with re-irradiation spine SBRT having failed either cEBRT (n = 60 with 1 prior course and n = 17 with 2 or more prior cEBRT courses), or prior SBRT (n = 6) to the same spinal segment. The primary outcome was local failure (LF), and secondary outcomes included overall survival (OS) and the rate of vertebral compression fracture (VCF). RESULTS: A total of 43 patients with 83 spinal segments treated with salvage SBRT were reviewed. The crude risk of LF was 18%, and actuarial LF rates at 6, 12, and 24 mo were 7%, 14%, and 19%, respectively. The presence of extensive paraspinal disease (hazard ratio [HR] = 7.1, 95% CI 1.5-34) significantly predicted for LF. The median OS was 13.2 (95% CI 6.1-16.3) mo, and the presence of neurological deficits (HR = 4.7, 95% CI 1.8-12.1) and brain metastases (HR = 2.6, 95% CI 1.1-6.3) were significant prognostic factors. The crude risk of VCF was 4%, and radiation myelopathy was not observed. CONCLUSION: These data support the safety and efficacy of spinal re-irradiation with SBRT including patients with prior SBRT and multiple courses of prior cEBRT.

Impact of Biopsy Compliance on Outcomes for Patients on Active Surveillance for Prostate Cancer.

PURPOSE: Active surveillance for prostate cancer relies on regular prostate specific antigen tests and surveillance biopsies. Compliance rates with biopsies vary but the subsequent impact on oncologic outcomes is not known. The objective of this study was to determine whether noncompliance with the confirmatory biopsy negatively impacts prostate cancer specific outcomes. MATERIALS AND METHODS: A retrospective analysis was performed on a prospective single-arm cohort of men enrolled in active surveillance for prostate cancer between 1995 and 2018 with a median followup of 9.1 years. A total of 1,275 patients were enrolled and 1,043 had a minimum of 3 years of followup and were included in the analysis. Patients were stratified by compliance with a confirmatory biopsy within 24 months of enrollment in active surveillance. The primary outcome was recurrence-free survival. Secondary outcomes included metastatic-free survival and cause specific survival. RESULTS: A total of 1,275 patients were enrolled, and 1,043 had a minimum of 3 years of followup and were included in the analysis, of whom 425 were treated for localized prostate cancer. Patients noncompliant with the confirmatory biopsy had higher rates of recurrence after treatment (19% vs 12%, HR 1.64, 95% CI 1.19-2.26, p=0.003) and metastases (7% vs 2%, HR 3.56, 95% CI 1.8-7.0, p=0.0003) even after accounting for age, prostate specific antigen and Grade Group. Cause specific survival was not significantly different between the 2 groups. The results were consistent even in the subset of patients with Grade Group 1 disease at study entry. CONCLUSIONS: Noncompliance with a confirmatory biopsy compromises the control of prostate cancer in men followed on active surveillance. Patients and physicians should be aware of the importance of adhering to protocol for men on active surveillance.

Perfusion imaging of colorectal liver metastases treated with bevacizumab and stereotactic body radiotherapy.

Stereotactic body radiotherapy (SBRT) and bevacizumab are used in the treatment of colorectal liver metastases. This study prospectively evaluated changes in perfusion of liver metastases in seven patients treated with both bevacizumab and SBRT. Functional imaging using dynamic contrast-enhanced CT perfusion and contrast-enhanced ultrasound were performed at baseline, after bevacizumab, and after SBRT. After bevacizumab, a significant decrease was found in permeability (-28%, p < .05) and blood volume (-47%, p < .05), while SBRT led to a significant reduction in permeability (-22%, p < .05) and blood flow (-37%, p < .05). This study demonstrates that changes in perfusion can be detected after bevacizumab and SBRT.

Differentiating radiation necrosis from tumor progression in brain metastases treated with stereotactic radiotherapy: utility of intravoxel incoherent motion perfusion MRI and correlation with histopathology.

Radiation necrosis is a serious potential adverse event of stereotactic radiosurgery that cannot be reliably differentiated from recurrent tumor using conventional imaging techniques. Intravoxel incoherent motion (IVIM) is a magnetic resonance imaging (MRI) based method that uses a diffusion-weighted sequence to estimate quantitative perfusion and diffusion parameters. This study evaluated the IVIM-derived apparent diffusion coefficient (ADC) and perfusion fraction (f), and compared the results to the gold standard histopathological-defined outcomes of radiation necrosis or recurrent tumor. Nine patients with ten lesions were included in this study; all lesions exhibited radiographic progression after stereotactic radiosurgery for brain metastases that subsequently underwent surgical resection due to uncertainty regarding the presence of radiation necrosis versus recurrent tumor. Pre-surgical IVIM was performed to obtain f and ADC values and the results were compared to histopathology. Five lesions exhibited pathological radiation necrosis and five had predominantly recurrent tumor. The IVIM perfusion fraction reliably differentiated tumor recurrence from radiation necrosis (fmean = 10.1 ± 0.7 vs. 8.3 ± 1.2, p = 0.02; cutoff value of 9.0 yielding a sensitivity/specificity of 100%/80%) while the ADC did not distinguish between the two (ADCmean = 1.1 ± 0.2 vs. 1.2 ± 0.4, p = 0.6). IVIM shows promise in differentiating recurrent tumor from radiation necrosis for brain metastases treated with radiosurgery, but needs to be validated in a larger cohort.

Long-term tracking of bone marrow progenitor cells following intracoronary injection post-myocardial infarction in swine using MRI.

Magnetic resonance imaging (MRI) can track progenitor cells following direct intramyocardial injection. However, in the vast majority of post-myocardial infarction (MI) clinical trials, cells are delivered by the intracoronary (IC) route, which results in far greater dispersion within the myocardium. Therefore, we assessed whether the more diffuse distribution of cells following IC delivery could be imaged longitudinally with MRI. In 11 pigs (7 active, 4 controls), MI was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Seven (0) days [median (interquartile range)] following MI, bone marrow progenitor cells (BMCs) were colabeled with an iron-fluorophore and a cell viability marker and delivered to the left anterior descending coronary artery distal to an inflated over-the-wire percutaneous transluminal coronary angioplasty balloon. T2*-weighted images were used to assess the location of the magnetically labeled cells over a 6-wk period post-MI. Immediately following cell delivery, hypointensity characteristic of the magnetic label was observed in the infarct border rather than within the infarct itself. At 6 wk, the cell signal hypointensity persisted, albeit with significantly decreased intensity. BMC delivery resulted in significant improvement in infarct volume and ejection fraction (EF): infarct volume in cell-treated animals decreased from 7.1 +/- 1.5 to 4.9 +/- 1.0 ml (P < 0.01); infarct volume in controls was virtually unchanged at 4.64 +/- 2.1 to 4.39 +/- 2.1 ml (P = 0.7). EF in cell-treated animals went from 30.4 +/- 5.2% preinjection to 34.5 +/- 2.5% 6 wk postinjection (P = 0.013); EF in control animals went from 34.3 +/- 4.7 to 31.9 +/- 6.8% (P = 0.5). Immunohistochemical analysis revealed intracellular colocalization of the iron fluorophore and cell viability dye with the labeled cells continuing to express the same surface markers as at baseline. MRI can track the persistence and distribution of magnetically labeled BMCs over a 6-wk period following IC delivery. Signal hypointensity declines with time, particularly in the first week following delivery. These cells maintain their original phenotype during this time course. Delivery of these cells appears safe and results in improvement in infarct size and left ventricular ejection fraction.

Multicontrast late gadolinium enhancement imaging enables viability and wall motion assessment in a single acquisition with reduced scan times.

PURPOSE: To determine the accuracy of multicontrast late enhancement imaging (MCLE) in the assessment of myocardial viability and wall motion compared to the conventional wall motion and viability cardiac magnetic resonance imaging (MRI) pulse sequences. MATERIALS AND METHODS: Forty-one patients with suspected myocardial infarction were studied. Patients underwent assessment of cardiac function with cine steady-state free-precession (SSFP), followed by late gadolinium enhancement (LGE) imaging using inversion recovery gradient echo scanning (IR-GRE) sequence and MCLE. MCLE was compared to cine SSFP in the assessment of wall motion, ejection fraction (EF), left ventricular (LV) mass, LV end-diastolic volume (EDV), and to IR-GRE for measuring infarct size. RESULTS: MCLE, IR-GRE, and SSFP imaging demonstrated excellent agreement in the assessment of EF, LV infarct size, and LV mass (r > 0.95, P < 0.001 for all measures), as well as in the assessment of wall motion (kappa statistic 0.75). CONCLUSION: MCLE provided coregistered images for the assessment of viability and wall motion without loss of accuracy in the assessment of quantitative cardiac parameters. MCLE provides accurate quantitative cardiac assessment with reduced scan times compared to the conventional sequences and thus may be used as an alternative to conventional cine SSFP and IR-GRE imaging.

Reproducible classification of infarct heterogeneity using fuzzy clustering on multicontrast delayed enhancement magnetic resonance images.

Delayed enhancement MRI (DE-MRI) can be used to identify myocardial infarct (MI). Classification of MI into the infarct core and heterogeneous periphery (called the gray zone) on conventional inversion-recovery gradient echo (IR-GRE) DE-MRI images has been related to inducibility for ventricular tachycardia. However, this classification is sensitive to image noise, depends on the signal intensity characteristics in a remote region of myocardium, and requires manual contours of the endocardial border. Image analysis and fuzzy clustering techniques were developed to analyze images acquired using a multicontrast delayed enhancement (MCDE) sequence in order characterize the infarct zones. The MCDE analysis is automated and uses data fitting of signal intensities acquired at multiple inversion times. In a study of 15 patients with chronic MI, the gray zones derived from IR-GRE and MCDE images were comparable. The variability in the gray zone size associated with random noise and operator input was significantly reduced using the MCDE-based analysis compared to the IR-GRE-based analysis. In summary, the MCDE approach yields a more reproducible measure of the infarct core and gray zones on any given data set.

Free-breathing, nongated real-time delayed enhancement MRI of myocardial infarcts: a comparison with conventional delayed enhancement.

PURPOSE: To compare a free-breathing, nongated, and black-blood real-time delayed enhancement (RT-DE) sequence to the conventional inversion recovery gradient echo (IR-GRE) sequence for delayed enhancement MRI. MATERIALS AND METHODS: Twenty-three patients with suspected myocardial infarct (MI) were examined using both the IR-GRE and RT-DE imaging sequences. The sensitivity and specificity of RT-DE for detecting MI, using IR-GRE as the gold standard, was determined. The contrast-to-noise ratios (CNR) between the two techniques were also compared. RESULTS: RT-DE had a high sensitivity and specificity (94% and 98%, respectively) for identifying MI. The total acquisition time to image the entire left ventricle was significantly shorter using RT-DE than IR-GRE (5.6+/-0.9 versus 11.5+/-1.9 min). RT-DE had a slightly lower infarct-myocardium CNR but a higher infarct-blood CNR than IR-GRE imaging. Compared with IR-GRE, RT-DE accurately measured total infarct sizes. CONCLUSION: RT-DE can be used for delayed enhancement imaging during free-breathing and without cardiac gating.

MRI evaluation of microvascular obstruction in experimental reperfused acute myocardial infarction using a T1 and T2 preparation pulse sequence.

PURPOSE: To investigate a T1 and T2 preparation pulse sequence to evaluate microvascular obstruction (MO) in a porcine model of reperfused acute myocardial infarction (AMI). MATERIALS AND METHODS: A total of 14 pigs with reperfused AMI underwent MRI examinations at baseline and three to four hours after reperfusion. MRI scans included a left ventricular functional study, T1 and T2 measurement on a 1.5T MRI system. At reperfusion, first-pass myocardial perfusion (FPMP) images were obtained after bolus injection of gadopentetate dimeglumine followed by an intravenous drip. Delayed contrast-enhanced MRI (DE-MRI) and T1 measurements were performed 30 and 45 minutes, respectively, after the bolus, during a constant infusion of gadopentetate dimeglumine. RESULTS: In 11 pigs MO was hypoenhanced in FPMP and DE-MRI. In later T1 preparation difference images postcontrast, MO was hyperenhanced while delayed hyperenhanced (DHE) regions appeared dark. MO areas on DE-MRI and T1 images were comparable. T1 reduction (%) postcontrast in MO was small compared to measurements from DHE regions (P < 0.0001) and similar to those from control segments (P = 0.66). Precontrast T1 and T2 values at reperfusion from MO and DHE regions were larger than in control regions. CONCLUSION: Using T1 preparation under a constant gadopentetate dimeglumine (Gd-DTPA) infusion, delayed imaging at 30 to 45 minutes demonstrates MO as a positive contrast with larger T1 values. Elevated T1 and T2 values in MO precontrast may also help to differentiate them from both control and DHE regions.

Real-time Fourier velocity encoding: an in vivo evaluation.

PURPOSE: To compare in vivo real-time Fourier velocity encoding (FVE), spectral-Doppler ultrasound, and phase-contrast (PC) magnetic-resonance (MR) imaging. MATERIALS AND METHODS: In vivo velocity spectra were measured in the suprarenal and infrarenal aorta and the hepatic segment of the inferior vena cava of eight normal volunteers using FVE, and compared to similar measurements using Doppler ultrasound and gated PC MR imaging. In vivo waveforms were compared qualitatively according to flow pattern appearance (number, shape, and position of velocity peaks) and quantitatively according to peak velocity. RESULTS: Good agreement was obtained between peak velocities measured in vitro using FVE and PC MR imaging (R(2) = 0.99, P = 2.10(-6), slope = 0.97 +/- 0.05). Qualitatively, the FVE and ultrasound measurements agreed closely in the majority of in vivo cases (excellent or good in 21/24 cases) while the PC MR method resolved fewer velocity peaks due to the inherent temporal averaging of cardiac-gated studies (excellent or good agreement with FVE in 13/24 cases). Quantitatively, the FVE measurement of peak velocity correlated strongly with both ultrasound (R(2) = 0.71, P = 2.10(-7), slope = 0.81 +/- 0.08) and PC MR (R(2) = 0.85, P = 2.10(-10), slope = 1.04 +/- 0.08). CONCLUSION: Real-time MR assessment of blood-flow velocity correlated well with spectral Doppler ultrasound. Such new methods may allow hemodynamic information to be acquired in vessels inaccessible to ultrasound or in patients for whom respiratory compensation is not possible.