Response of treatment-naive brain metastases to stereotactic radiosurgery.

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.

Nivolumab and ipilimumab with concurrent stereotactic radiosurgery for intracranial metastases from non-small cell lung cancer: analysis of the safety cohort for non-randomized, open-label, phase I/II trial.

BACKGROUND: Up to 20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), for which the current standard of care is radiation therapy with or without surgery. There are no prospective data on the safety of stereotactic radiosurgery (SRS) concurrent with immune checkpoint inhibitor therapy for BM. This is the safety cohort of the phase I/II investigator-initiated trial of SRS with nivolumab and ipilimumab for patients with BM from NSCLC. PATIENTS AND METHODS: This single-institution study included patients with NSCLC with active BM amenable to SRS. Brain SRS and systemic therapy with nivolumab and ipilimumab were delivered concurrently (within 7 days). The endpoints were safety and 4-month intracranial progression-free survival (PFS). RESULTS: Thirteen patients were enrolled in the safety cohort, 10 of whom were evaluable for dose-limiting toxicities (DLTs). Median follow-up was 23 months (range 9.7-24.3 months). The median interval between systemic therapy and radiation therapy was 3 days. Only one patient had a DLT; hence, predefined stopping criteria were not met. In addition to the patient with DLT, three patients had treatment-related grade ≥3 adverse events, including elevated liver function tests, fatigue, nausea, adrenal insufficiency, and myocarditis. One patient had a confirmed influenza infection 7 months after initiation of protocol treatment (outside the DLT assessment window), leading to pneumonia and subsequent death from hemophagocytic lymphohistiocytosis. The estimated 4-month intracranial PFS rate was 70.7%. CONCLUSION: Concurrent brain SRS with nivolumab/ipilimumab was safe for patients with active NSCLC BM. Preliminary analyses of treatment efficacy were encouraging for intracranial treatment response.

Deep Learning for Detecting Brain Metastases on MRI: A Systematic Review and Meta-Analysis.

Since manual detection of brain metastases (BMs) is time consuming, studies have been conducted to automate this process using deep learning. The purpose of this study was to conduct a systematic review and meta-analysis of the performance of deep learning models that use magnetic resonance imaging (MRI) to detect BMs in cancer patients. A systematic search of MEDLINE, EMBASE, and Web of Science was conducted until 30 September 2022. Inclusion criteria were: patients with BMs; deep learning using MRI images was applied to detect the BMs; sufficient data were present in terms of detective performance; original research articles. Exclusion criteria were: reviews, letters, guidelines, editorials, or errata; case reports or series with less than 20 patients; studies with overlapping cohorts; insufficient data in terms of detective performance; machine learning was used to detect BMs; articles not written in English. Quality Assessment of Diagnostic Accuracy Studies-2 and Checklist for Artificial Intelligence in Medical Imaging was used to assess the quality. Finally, 24 eligible studies were identified for the quantitative analysis. The pooled proportion of patient-wise and lesion-wise detectability was 89%. Articles should adhere to the checklists more strictly. Deep learning algorithms effectively detect BMs. Pooled analysis of false positive rates could not be estimated due to reporting differences.

Comparison of setup accuracy and efficiency between the Klarity system and BodyFIX system for spine stereotactic body radiation therapy.

BACKGROUND: Spine stereotactic body radiation therapy (SBRT) uses highly conformal dose distributions and sharp dose gradients to cover targets in proximity to the spinal cord or cauda equina, which requires precise patient positioning and immobilization to deliver safe treatments. AIMS: Given some limitations with the BodyFIX system in our practice, we sought to evaluate the accuracy and efficiency of the Klarity SBRT patient immobilization system in comparison to the BodyFIX system. METHODS: Twenty-three patients with 26 metastatic spinal lesions (78 fractions) were enrolled in this prospective observational study with one of two systems - BodyFIX (n = 11) or Klarity (n = 12). All patients were initially set up to external marks and positioned to match bony anatomy on ExacTrac images. Table corrections given by ExacTrac during setup and intrafractional monitoring and deviations from pre- and posttreatment CBCT images were analyzed. RESULTS: For initial setup accuracy, the Klarity system showed larger differences between initial skin mark alignment and the first bony alignment on ExacTrac than BodyFIX, especially in the vertical (mean [SD] of 5.7 mm [4.1 mm] for Klarity vs. 1.9 mm [1.7 mm] for BodyFIX, p-value < 0.01) and lateral (5.4 mm [5.1 mm] for Klarity vs. 3.2 mm [3.2 mm] for BodyFIX, p-value 0.02) directions. For set-up stability, no significant differences (all p-values > 0.05) were observed in the maximum magnitude of positional deviations between the two systems. For setup efficiency, Klarity system achieved desired bony alignment with similar number of setup images and similar setup time (14.4 min vs. 15.8 min, p-value = 0.41). For geometric uncertainty, systematic and random errors were found to be slightly less with Klarity than with BodyFIX based on an analytical calculation. CONCLUSION: With image-guided correction of initial alignment by external marks, the Klarity system can provide accurate and efficient patient immobilization. It can be a promising alternative to the BodyFIX system for spine SBRT while providing potential workflow benefits depending on one's practice environment.

Dosimetric analysis of MR-LINAC treatment plans for salvage spine SBRT re-irradiation.

PURPOSE: We investigated the feasibility of thoracic spine stereotactic body radiotherapy (SBRT) using the Elekta Unity magnetic resonance-guided linear accelerator (MRL) in patients who received prior radiotherapy. We hypothesized that Monaco treatment plans can improve the gross tumor volume minimum dose (GTVmin) with spinal cord preservation and maintain consistent plan quality during daily adaptation. METHODS: Pinnacle clinical plans for 10 patients who underwent thoracic spine SBRT (after prior radiotherapy) were regenerated in the Monaco treatment planning system for the Elekta Unity MRL using 9 and 13 intensity-modulated radiotherapy (IMRT) beams. Monaco adapt-to-position (ATP) and adapt-to-shape (ATS) workflow plans were generated using magnetic resonance imaging with a simulated daily positional setup deviation, and these adaptive plans were compared with Monaco reference plans. Plan quality measures included target coverage, Paddick conformity index, gradient index, homogeneity index, spinal cord D0.01cc , esophagus D0.01cc , lung V10, and skin D0.01cc . RESULTS: GTVmin values from the Monaco 9-beam and 13-beam plans were significantly higher than those from Pinnacle plans (p < 0.01) with similar spinal cord dose. Spinal cord D0.01cc , esophagus D0.01cc , and lung V10 did not statistically differ among the three plans. The electron-return effect did not induce remarkable dose effects around the lungs or skin. While in the ATP workflow, a large increase in GTVmin was observed at the cost of a 10%-50% increase in spinal cord D0.01cc , in the ATS workflow, the spinal cord dose increase was maintained within 3% of the reference plan. CONCLUSION: These findings show that MRL plans for thoracic spine SBRT are safe and feasible, allowing tumor dose escalation with spinal cord preservation and consistent daily plan adaptation using the ATS workflow. Careful plan review of hot spots and lung dose is necessary for safe MRL-based treatment.

Automation of radiation treatment planning for rectal cancer.

PURPOSE: To develop an automated workflow for rectal cancer three-dimensional conformal radiotherapy (3DCRT) treatment planning that combines deep learning (DL) aperture predictions and forward-planning algorithms. METHODS: We designed an algorithm to automate the clinical workflow for 3DCRT planning with field aperture creations and field-in-field (FIF) planning. DL models (DeepLabV3+ architecture) were trained, validated, and tested on 555 patients to automatically generate aperture shapes for primary (posterior-anterior [PA] and opposed laterals) and boost fields. Network inputs were digitally reconstructed radiographs, gross tumor volume (GTV), and nodal GTV. A physician scored each aperture for 20 patients on a 5-point scale (>3 is acceptable). A planning algorithm was then developed to create a homogeneous dose using a combination of wedges and subfields. The algorithm iteratively identifies a hotspot volume, creates a subfield, calculates dose, and optimizes beam weight all without user intervention. The algorithm was tested on 20 patients using clinical apertures with varying wedge angles and definitions of hotspots, and the resulting plans were scored by a physician. The end-to-end workflow was tested and scored by a physician on another 39 patients. RESULTS: The predicted apertures had Dice scores of 0.95, 0.94, and 0.90 for PA, laterals, and boost fields, respectively. Overall, 100%, 95%, and 87.5% of the PA, laterals, and boost apertures were scored as clinically acceptable, respectively. At least one auto-plan was clinically acceptable for all patients. Wedged and non-wedged plans were clinically acceptable for 85% and 50% of patients, respectively. The hotspot dose percentage was reduced from 121% (σ = 14%) to 109% (σ = 5%) of prescription dose for all plans. The integrated end-to-end workflow of automatically generated apertures and optimized FIF planning gave clinically acceptable plans for 38/39 (97%) of patients. CONCLUSION: We have successfully automated the clinical workflow for generating radiotherapy plans for rectal cancer for our institution.

Cognitive and Imaging Differences After Proton and Photon Whole Brain Irradiation in a Preclinical Model.

PURPOSE: Compared with photon cranial radiation therapy (X-CRT), proton cranial radiation therapy (P-CRT) offers potential advantages in limiting radiation-induced sequalae in the treatment of pediatric brain tumors. This study aims to identify cognitive, functional magnetic resonance and positron emission tomography imaging markers and molecular differences between the radiation modalities. METHODS AND MATERIALS: Juvenile rats received a single faction of 10 Gy (relative biological effectiveness-weighted dose) delivered with 6 MV X-CRT or at the midspread out Bragg peak of a 100 MeV P-CRT beam. At 3, 6, and 12 months post-CRT, executive function was measured using 5-choice serial reaction time task. At ∼12 months post-CRT, animals were imaged with 18F-Flurodeoxy-glucose positron emission tomography imaging followed by functional ex vivo magnetic resonance imaging and stained for markers of neuroinflammation. RESULTS: Irradiated animals had cognitive impairment with a higher number of omissions and lower incorrect and premature responses compared with sham (P ≤ .05). The accuracy of the animals' X-CRT was less than that of sham (P ≤ .001). No significant difference in rates of cognitive change were found between the radiation modalities. At 12 months post-CRT, glucose metabolism was significantly higher than sham in X-CRT (P = .04) but not P-CRT. Using diffusion tensor imaging, P-CRT brains were found to have higher white matter volume and fiber lengths compared with sham (P < .03). Only X-CRT animals had higher apparent diffusion coefficient values compared with sham (P = .04). P-CRT animals had more connectomic changes compared with X-CRT. Correlative analysis identified several imaging features with cognitive performance. Furthermore, microgliosis (P < .05), astrogliosis (P < .01), and myelin thinning (P <.05) were observed in both radiation modalities, with X-CRT showing slightly more inflammation. CONCLUSIONS: Both P-CRT and X-CRT lead to neurocognitive changes compared with sham. Although no significant difference was observed in neuroinflammation between the irradiated groups, differences were found in late-term glucose metabolism and brain connectome. Our results indicate that despite relative biological effectiveness weighting of the proton dose there are still differential effects which warrants further investigation.

Clinical implementation of automated treatment planning for whole-brain radiotherapy.

The purpose of the study was to develop and clinically deploy an automated, deep learning-based approach to treatment planning for whole-brain radiotherapy (WBRT). We collected CT images and radiotherapy treatment plans to automate a beam aperture definition from 520 patients who received WBRT. These patients were split into training (n = 312), cross-validation (n = 104), and test (n = 104) sets which were used to train and evaluate a deep learning model. The DeepLabV3+ architecture was trained to automatically define the beam apertures on lateral-opposed fields using digitally reconstructed radiographs (DRRs). For the beam aperture evaluation, 1st quantitative analysis was completed using a test set before clinical deployment and 2nd quantitative analysis was conducted 90 days after clinical deployment. The mean surface distance and the Hausdorff distances were compared in the anterior-inferior edge between the clinically used and the predicted fields. Clinically used plans and deep-learning generated plans were evaluated by various dose-volume histogram metrics of brain, cribriform plate, and lens. The 1st quantitative analysis showed that the average mean surface distance and Hausdorff distance were 7.1 mm (±3.8 mm) and 11.2 mm (±5.2 mm), respectively, in the anterior-inferior edge of the field. The retrospective dosimetric comparison showed that brain dose coverage (D99%, D95%, D1%) of the automatically generated plans was 29.7, 30.3, and 32.5 Gy, respectively, and the average dose of both lenses was up to 19.0% lower when compared to the clinically used plans. Following the clinical deployment, the 2nd quantitative analysis showed that the average mean surface distance and Hausdorff distance between the predicted and clinically used fields were 2.6 mm (±3.2 mm) and 4.5 mm (±5.6 mm), respectively. In conclusion, the automated patient-specific treatment planning solution for WBRT was implemented in our clinic. The predicted fields appeared consistent with clinically used fields and the predicted plans were dosimetrically comparable.

Early and Midtreatment Mortality in Palliative Radiotherapy: Emphasizing Patient Selection in High-Quality End-of-Life Care.

BACKGROUND: Palliative radiotherapy (RT) is effective, but some patients die during treatment or too soon afterward to experience benefit. This study investigates end-of-life RT patterns to inform shared decision-making and facilitate treatment consistent with palliative goals. MATERIALS AND METHODS: All patients who died ≤6 months after initiating palliative RT at an academic cancer center between 2015 and 2018 were identified. Associations with time-to-death, early mortality (≤30 days), and midtreatment mortality were analyzed. RESULTS: In total, 1,620 patients died ≤6 months from palliative RT initiation, including 574 (34%) deaths at ≤30 days and 222 (14%) midtreatment. Median survival was 43 days from RT start (95% CI, 41-45) and varied by site (P<.001), ranging from 36 (head and neck) to 53 days (dermal/soft tissue). On multivariable analysis, earlier time-to-death was associated with osseous (hazard ratio [HR], 1.33; P<.001) and head and neck (HR, 1.45; P<.001) sites, multiple RT courses ≤6 months (HR, 1.65; P<.001), and multisite treatments (HR, 1.40; P=.008), whereas stereotactic technique (HR, 0.77; P<.001) and more recent treatment year (HR, 0.82; P<.001) were associated with longer survival. No difference in time to death was noted among patients prescribed conventional RT in 1 to 10 versus >10 fractions (median, 40 vs 47 days; P=.272), although the latter entailed longer courses. The 30-day mortality group included 335 (58%) inpatients, who were 27% more likely to die midtreatment (P=.031). On multivariable analysis, midtreatment mortality among these inpatients was associated with thoracic (odds ratio [OR], 2.95; P=.002) and central nervous system (CNS; OR, 2.44; P=.002) indications, >5-fraction courses (OR, 3.27; P<.001), and performance status of 3 to 4 (OR, 1.63; P=.050). Conversely, palliative/supportive care consultation was associated with decreased midtreatment mortality (OR, 0.60; P=.045). CONCLUSIONS: Earlier referrals and hypofractionated courses (≤5-10 treatments) should be routinely considered for palliative RT indications, given the short life expectancies of patients at this stage in their disease course. Providers should exercise caution for emergent thoracic and CNS indications among inpatients with poor prognoses due to high midtreatment mortality.

Our Experience Leading a Large Medical Physics Practice During the COVID-19 Pandemic.

PURPOSE: To provide a series of suggestions for other Medical Physics practices to follow in order to provide effective radiation therapy treatments during the COVID-19 pandemic. METHODS AND MATERIALS: We reviewed our entire Radiation Oncology infrastructure to identify a series of workflows and policy changes that we implemented during the pandemic that yielded more effective practices during this time. RESULTS: We identified a structured list of several suggestions that can help other Medical Physics practices overcome the challenges involved in delivering high quality radiotherapy services during this pandemic. CONCLUSIONS: Our facility encompasses 4 smaller Houston Area Locations (HALs), a main campus with 8 distinct services based on treatment site (ie. Thoracic, Head and Neck, Breast, Gastrointestinal, Gynecology, Genitourinary, Hematologic Malignancies, Melanoma and Sarcoma and Central Nervous System/Pediatrics), a Proton Center facility, an MR-Linac, a Gamma Knife clinic and an array of brachytherapy services. Due to the scope of our services, we have gained experience in dealing with the rapidly changing pandemic effects on our clinical practice. Our paper provides a resource to other Medical Physics practices in search of workflows that have been resilient during these challenging times.

Phase 1 study of spinal cord constraint relaxation with single session spine stereotactic radiosurgery in the primary management of patients with inoperable, previously irradiated metastatic epidural spinal cord compression.

BACKGROUND: Patients with previously irradiated metastatic epidural spinal cord compression (MESCC) who are not surgical candidates are at high risk of neurologic deterioration due to disease in the setting of limited treatment options. We seek to establish the feasibility of using salvage spine stereotactic radiosurgery (SSRS) allowing for spinal cord dose constraint relaxation as the primary management of MESCC in inoperable patients monitoring for radiation related toxicity and radiographic local control (LC). METHODS: Inoperable patients with previously irradiated MESCC were enrolled on this prospective Phase 1 single institution protocol. Single fraction SSRS was delivered to a prescription dose of 18 Gy. Spinal cord constraint relaxation was performed incrementally from an initial allowable Dmax cohort of 8 Gy to 14 Gy in the final planned cohort. Patients were monitored every 3 months with follow-up visits and MRI scans. RESULTS: The trial was closed early due to slow accrual. From 2011 to 2014, 11 patients were enrolled of which 9 patients received SSRS. Five patients were in the 8 Gy cord Dmax cohort and 4 in the 10 Gy cord Dmax cohort.The median overall survival (OS) was 11.9 months (95% CI 7.1, 22 months). Of the 9 patients treated with SSRS, 1 died prior to post-SSRS evaluation. Of the remaining 8 patients, 5 experienced a local failure. Three of the five were treated with surgery while two received systemic therapy. Two of the five failures ultimately resulted in loss of neurologic function. The median LC was 9.1 months (95%CI 4.8, 20.1 months). With a median clinical follow-up of 6.8 months, there were no cases of RM. CONCLUSIONS: Despite the limited life expectancy in this high-risk cohort of patients, strategies to optimize LC are necessary to prevent neurologic deterioration. Larger prospective trials exploring optimal dose/fractionation and cord constraints are required.

Feasibility of spinal stereotactic body radiotherapy in Elekta Unity® MR-Linac.

The Elekta Unity MR-Linac (MRL) is expected to benefit spine stereotactic body radiotherapy (SBRT) due to the improved soft tissue contrast available with onboard MR imaging. However, the irradiation geometry and beam configuration of the MRL deviates from the conventional linear accelerator (Linac). The purpose of the study was to investigate the feasibility of spine SBRT on the MRL. Treatment plans were generated for lumbar and thoracic spines. Target and spinal cord doses were measured with two cylindrical ion chambers inserted into an anthropomorphic spine phantom. Our study indicated that the Monaco treatment planning system (TPS) could generate clinical treatment plans for the MRL that were of comparable quality to the RayStation TPS with a conventional Linac. For both Linacs the planned dose within the gross tumor volume agreed with measurements within ±3%. For the spinal cord, while the measured doses from the TrueBeam were 1.8% higher for the lumbar spine plan and 6.9% higher for thoracic spine plan, the measured doses from MRL were 0.6% lower for the lumbar spine plan and 3.9% higher for the thoracic spine plan. In conclusion, the feasibility of spine SBRT in Elekta Unity MRL has been demonstrated, however, more effort is needed for such as optimizing the online plan adaptation method.

MetNet: Computer-aided segmentation of brain metastases in post-contrast T1-weighted magnetic resonance imaging.

PURPOSE: Brain metastases are manually contoured during stereotactic radiosurgery (SRS) treatment planning, which is time-consuming, potentially challenging, and laborious. The purpose of this study was to develop and investigate a 2-stage deep learning (DL) approach (MetNet) for brain metastasis segmentation in pre-treatment magnetic resonance imaging (MRI). MATERIALS AND METHODS: We retrospectively analyzed postcontrast 3D T1-weighted spoiled gradient echo MRIs from 934 patients who underwent SRS between August 2009 and August 2018. Neuroradiologists manually identified brain metastases in the MRIs. The treating radiation oncologist or physicist contoured the brain metastases. We constructed a 2-stage DL ensemble consisting of detection and segmentation models to segment the brain metastases on the MRIs. We evaluated the performance of MetNet by computing sensitivity, positive predictive value (PPV), and Dice similarity coefficient (DSC) with respect to metastasis size, as well as free-response receiver operating characteristics. RESULTS: The 934 patients (mean [±standard deviation] age 59 ± 13 years, 474 women) were randomly split into 80% training and 20% testing groups (748:186). For patients with metastases 1-52 mm (n = 766), 648 (85%) were detected and segmented with a mean segmentation DSC of 81% ± 15%. Patient-averaged sensitivity was 88% ± 19%, PPV was 58% ± 25%, and DSC was 85% ± 13% with 3 ± 3 false positives (FPs) per patient. When considering only metastases ≥6 mm, patient-averaged sensitivity was 99% ± 5%, PPV was 67% ± 28%, and DSC was 87% ± 13% with 1 ± 2 FPs per patient. CONCLUSION: MetNet can segment brain metastases across a broad range of metastasis sizes with high sensitivity, low FPs, and high segmentation accuracy in postcontrast T1-weighted MRI, potentially aiding treatment planning for SRS.

Low risk of radiation myelopathy with relaxed spinal cord dose constraints in de novo, single fraction spine stereotactic radiosurgery.

BACKGROUND AND PURPOSE: Spine stereotactic radiosurgery (SSRS) offers high rates of local control in a critical anatomic area by delivering precise, ablative doses of radiation for treatment of spine metastases. However, the dose tolerance of the spinal cord (SC) after SSRS with relation to radiation myelopathy (RM) is not well-described. MATERIALS AND METHODS: We reviewed patients who underwent single fraction, de novo SSRS from 2012-2017 and received >12 Gy Dmax to the SC, defined using MRI-CT fusion without PRV expansion. The standard SC constraint was D0.01cc ≤ 12 Gy. Local control was estimated with the Kaplan-Meier method. Bayesian analysis was used to compute posterior probabilities for RM. RESULTS: A total of 146 SSRS treatments among 132 patients were included. The median SC Dmax was 12.6 Gy (range, 12.1-17.1 Gy). The SC Dmax was >12 and <13 Gy for 109 (75%) treatments, ≥13 and <14 Gy for 28 (19%) treatments, and ≥14 Gy for 9 (6%) treatments. The 1-year local control rate was 94%. With a median follow-up time of 42 months, there were zero (0) RM events observed. Assuming a prior 4.3% risk of RM, the true rate of RM for SC Dmax of ≤14 Gy was computed as <1% with 98% probability. CONCLUSION: In one of the largest series of patients treated with single fraction, de novo SSRS, there were no cases of RM observed with a median follow-up of 42 months. These data support safe relaxation of MRI-defined SC dose up to D0.01cc ≤ 12 Gy, which corresponds to <1% risk of RM.

Use of uniform shots for robust planning of mask-based treatment in Gamma Knife Icon.

PURPOSE: To verify whether Icon automatic correction is robust in preserving plan quality. MATERIALS/METHODS: An end-to-end phantom was used to verify Icon's correction accuracy qualitatively. For quantitative assessment, two plans, a composite- and a uniform-shot-only, were created for an elliptical- (E) and a sausage-shaped (S) lesion inside a PseudoPatient head phantom with a film insert. The phantom was irradiated in the planned and three other positions under each plan: 14° pitch (B); 14° rotation + 8° pitch (C); 95° rotation + 4-cm shift (D). RESULTS: Icon accurately corrects the locations of the shots. For the uniform-shot plans: all gamma index passing rates were >97%, and the differences between the planned and the delivery doses (minimum, maximum, and mean) were all ≤0.1 Gy. For the composite-shot plans, however, the dose differences increased as the phantom was shifted through positions B-D, with a gamma index passing rate of 61% for lesion-E in position D, and 92%, 79%, and 45% for lesion-S in positions B, C, and D, respectively. CONCLUSIONS: Plans using only uniform shots are more robust to deviations in treatment position. The tolerance for such deviations may be lower for plans using composite shots.

Computer-aided Detection of Brain Metastases in T1-weighted MRI for Stereotactic Radiosurgery Using Deep Learning Single-Shot Detectors.

Background Brain metastases are manually identified during stereotactic radiosurgery (SRS) treatment planning, which is time consuming and potentially challenging. Purpose To develop and investigate deep learning (DL) methods for detecting brain metastasis with MRI to aid in treatment planning for SRS. Materials and Methods In this retrospective study, contrast material-enhanced three-dimensional T1-weighted gradient-echo MRI scans from patients who underwent gamma knife SRS from January 2011 to August 2018 were analyzed. Brain metastases were manually identified and contoured by neuroradiologists and treating radiation oncologists. DL single-shot detector (SSD) algorithms were constructed and trained to map axial MRI slices to a set of bounding box predictions encompassing metastases and associated detection confidences. Performances of different DL SSDs were compared for per-lesion metastasis-based detection sensitivity and positive predictive value (PPV) at a 50% confidence threshold. For the highest-performing model, detection performance was analyzed by using free-response receiver operating characteristic analysis. Results Two hundred sixty-six patients (mean age, 60 years ± 14 [standard deviation]; 148 women) were randomly split into 80% training and 20% testing groups (212 and 54 patients, respectively). For the testing group, sensitivity of the highest-performing (baseline) SSD was 81% (95% confidence interval [CI]: 80%, 82%; 190 of 234) and PPV was 36% (95% CI: 35%, 37%; 190 of 530). For metastases measuring at least 6 mm, sensitivity was 98% (95% CI: 97%, 99%; 130 of 132) and PPV was 36% (95% CI: 35%, 37%; 130 of 366). Other models (SSD with a ResNet50 backbone, SSD with focal loss, and RetinaNet) yielded lower sensitivities of 73% (95% CI: 72%, 74%; 171 of 234), 77% (95% CI: 76%, 78%; 180 of 234), and 79% (95% CI: 77%, 81%; 184 of 234), respectively, and lower PPVs of 29% (95% CI: 28%, 30%; 171 of 581), 26% (95% CI: 26%, 26%; 180 of 681), and 13% (95% CI: 12%, 14%; 184 of 1412). Conclusion Deep-learning single-shot detector models detected nearly all brain metastases that were 6 mm or larger with limited false-positive findings using postcontrast T1-weighted MRI. © RSNA, 2020 See also the editorial by Kikinis and Wells in this issue.

Spine stereotactic radiosurgery for metastatic thyroid cancer: a single-institution experience.

OBJECTIVE: Patients with metastatic thyroid cancer have prolonged survival compared to those with other primary tumors. The spine is the most common site of osseous involvement in cases of metastatic thyroid cancer. As a result, obtaining durable local control (LC) in the spine is crucial. This study aimed to evaluate the efficacy of spine stereotactic radiosurgery (SSRS) in patients with metastatic thyroid cancer. METHODS: Information on patients with metastatic thyroid cancer treated with SSRS for spinal metastases was retrospectively evaluated. SSRS was delivered with a simultaneous integrated boost technique using single- or multiple-fraction treatments. LC, defined as stable or reduced disease volume, was evaluated by examining posttreatment MRI, CT, and PET studies. RESULTS: A total of 133 lesions were treated in 67 patients. The median follow-up duration was 31 months. Dose regimens for SSRS included 18 Gy in 1 fraction, 27 Gy in 3 fractions, and 30 Gy in 5 fractions. The histology distribution was 36% follicular, 33% papillary, 15% medullary, 13% Hurthle cell, and 3% anaplastic. The 1-, 2-, and 5-year LC rates were 96%, 89%, and 82%, respectively. The median overall survival (OS) was 43 months, with 1-, 2-, and 5-year survival rates of 86%, 74%, and 44%, respectively. There was no correlation between the absolute biological equivalent dose (BED) and OS or LC. Patients with effective LC had a trend toward improved OS when compared to patients who had local failure: 68 versus 28 months (p = 0.07). In terms of toxicity, 5 vertebral compression fractures (2.8%) occurred, and only 1 case (0.6%) of greater than or equal to grade 3 toxicity (esophageal stenosis) was reported. CONCLUSIONS: SSRS is a safe and effective treatment option with excellent LC and minimal toxicity for patients with metastatic thyroid cancer. No association with increased radiation dose or BED was found, suggesting that such patients can be effectively treated with reduced dose regimens.

Low incidence of late failure and toxicity after spine stereotactic radiosurgery: Secondary analysis of phase I/II trials with long-term follow-up.

BACKGROUND AND PURPOSE: To characterize local control and late toxicity in long-term survivors prospectively-treated with spine stereotactic radiosurgery (SSRS). MATERIALS AND METHODS: From 2002 to 2011, 228 patients were prospectively-treated on protocol for metastatic disease of 261 vertebral sites. A subset of 52 patients surviving >4 years following treatment were collectively treated for 58 sites (encompassing 69 vertebrae) and underwent secondary analysis. Of all sites, 9% received prior radiation, and 16% encompassed multiple contiguous vertebrae. Radiation prescriptions were most commonly 24 Gy in 1 and 27 Gy in 3 fractions. Outcomes were evaluated via Kaplan-Meier, and associations analyzed via logistic regression. RESULTS: Median follow-up was 6.7 years (range: 49-142 months). Five-year local control by site was 91%, with late failures (>2 years) occurring in 3%. Overall and Grade ≥3 late toxicities (>2 years) were observed in 5% and 2% of sites. The last known neurologic event (grade 2 radiculopathy) was noted 2.1 years post-treatment, while the last documented fracture occurred at 4.1 years. No Grade ≥3 events were witnessed after 3.1 years post-SSRS, and no toxicities were noted after 4.1 years through end of follow-up. Re-irradiation, number of segments treated per site (1 vs. 2-3), and fractionation (1 vs. 3-5) were not associated with failure or toxicity. CONCLUSION: SSRS maintains excellent disease control and a favorable late toxicity profile even among long-term survivors, with very few failures or toxicities after 2 years in this prospectively-treated population. Overall, these data support the durable control and long-term safety of SSRS with extended follow-up.

Intensity Modulated Radiation Therapy Versus Volumetric Arc Radiation Therapy in the Treatment of Glioblastoma-Does Clinical Benefit Follow Dosimetric Advantage?

PURPOSE: Volumetric modulated arc therapy (VMAT) has been shown by multiple planning studies to hold dosimetric advantages over intensity modulated radiation therapy (IMRT) in the management of brain tumors, including glioblastoma (GBM). Although promising, the clinical impact of these findings has not been fully elucidated. METHODS AND MATERIALS: We retrospectively reviewed consecutive patients with a pathologic-confirmed diagnosis of GBM who were treated between 2014 and 2015, a period that encompassed the transition from IMRT to VMAT at a single institution. After surgery, radiation with VMAT consisted of 2 to 3 coplanar arcs with or without an additional noncoplanar arc or IMRT with 5 to 6 gantry angles with concurrent and adjuvant temozolomide. Actuarial analyses were performed using the Kaplan Meier method. RESULTS: A total of 88 patients treated with IMRT (n = 45) and VMAT (n = 43) were identified. Patients were similar in terms of age, sex, performance status, extent of resection, and the high dose target volume. At a median follow-up time of 27 months (range, .7-32.3 months), the overall survival, freedom from progression, and freedom from new or worsening toxicity rates were not different between the 2 treatment groups (log-rank: P = .33; .87; and .23, respectively). There was no difference in incidences of alopecia, erythema, nausea, worsening or new onset fatigue, or headache during radiation, or temozolomide dose reduction for thrombocytopenia or neutropenia (all P > .05). Patterns of failure were different with more out of field failures in the IMRT group (P = .02). The mean time of treatment (TOT) was significantly reduced by 29% (P < .01) with VMAT (mean TOT: 10.3 minutes) compared with IMRT (mean TOT: 14.6 minutes). CONCLUSIONS: For GBM, treatment with VMAT results in similar oncologic and toxicity outcomes compared with IMRT and may improve resource utilization by reducing TOT. VMAT should be considered a potential radiation modality for patients with GBM.

End-to-end testing of automatic plan optimization using RayStation scripting for hypofractionated multimetastatic brain stereotactic radiosurgery.

For external beam stereotactic radiosurgery of multiple brain metastatic lesions, it is difficult to select optimal treatment isocenters because the orientation and volume of each planning target volume (PTV) and its proximity to critical structures are unique for each patient. The RayStation treatment planning system offers Python-based scripting to optimize the placement of the treatment isocenter by comparing scenario-based plans. This can improve the plan quality by reducing the dose to the normal brain and increasing planning efficiency. The purpose of the current study was to compare the isocenter-optimized plans generated by RayStation with clinical plans created by the Pinnacle treatment planning system and to validate the RayStation treatment planning and delivery with end-to-end testing. Ten patient plans were automatically regenerated using the script in RayStation. For each patient, 4 plans with 4 different types of isocenters were generated: (1) 2 separate isocenters at the PTV centroids, (2) a single isocenter at the mid-point of 2 centroids, (3) a single isocenter at PTV1, and (4) a single isocenter at PTV2. The best plans were compared with paired Pinnacle plans using plan quality parameters, including normal brain volume excluding PTVs receiving 4 Gy (V4Gy), normal brain volume excluding PTVs receiving 12 Gy (V12Gy), maximum dose to the brainstem, homogeneity index, conformity indices, gradient index of each PTV, and monitor units per fraction. All plans were verified with a cylindrical quality assurance phantom, and end-to-end testing was performed with an anthropomorphic head phantom with a radiochromic film. The script was executed within 5-6 minutes to generate 4 scenario-based automatic plans. The homogeneity index and conformity indices showed small but statistically significant improvement with the RayStation plans. The gradient index (3.9 ± 0.9 for Pinnacle and 3.5 ± 0.6 for RayStation, p = 0.04) was also more favorable in the RayStation plans. V12Gy was significantly reduced by 13% and V4Gy was reduced by 5%. The total monitor units per fraction was significantly reduced by 20% for the RayStation plans. Plan optimization time using RayStation was reduced by 64%. The measured doses at each PTV centroid agreed within 3%, and all RayStation plans passed quality assurance verification tests. Scenario-based automatic plan generation using Python scripting helps identify an optimal treatment isocenter to reduce the dose to the normal brain and improve planning efficiency. RayStation plans provided better plan quality, especially lower doses to the normal brain, than Pinnacle plans. Thus, RayStation is a suitable planning modality for hypofractionated stereotactic radiosurgery for multiple brain metastases.