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We evaluated a cohort of patients with cardiac angiosarcomas (CA) who developed brain metastases (BM) to define outcomes and intracranial hemorrhage (IH) risk.We reviewed 26 consecutive patients with BM treated between 1988 and 2020 identified from a departmental CA (n=103) database. Causes of death were recorded, and a terminal hemorrhage (TH) was defined as an IH that caused death or prompted a transfer to hospice.The prevalence of BM was 25% (n=26/103). A total of 23 patients (88%) had IH, including 21 (81%) at initial BM diagnosis, of which 18 (86%) required hospitalization. The median platelet count at the time of IH was 235k (interquartile range, 108 to 338k).Nearly all patients died of disease (n=23, 88%) and most patients died from TH (n=13, 57%). TH occurred at BM presentation in 6 (46%) patients, whereas 3 (23%) had TH from known but untreated lesions, 2 (15%) had continued uncontrolled IH during radiation therapy, and 2 (15%) from new BM. Platelet count50k was not associated with TH (P=0.25).Subsequent IH occurred in 9 patients (35%), and importantly, no patients who completed radiation therapy (n=10) for BM died from TH.Patients with CA frequently develop BM, and the risk of IH is high, resulting in an alarming rate of TH despite normal platelet counts. Therefore, early diagnosis and intervention are warranted. We recommend surveillance brain imaging, and importantly, once BM is detected, prompt local therapy is warranted to try and mitigate the risk of TH.

Background To determine if proton radiotherapy (PT), compared to intensity-modulated radiotherapy (IMRT), delayed time to cognitive failure in patients with newly diagnosed glioblastoma (GBM). Methods Eligible patients were randomized unblinded to PT vs IMRT. The primary endpoint was time to cognitive failure. Secondary endpoints included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported outcomes (PROs). Results A total of 90 patients were enrolled and 67 were evaluable with median follow-up of 48.7 months (range 7.1-66.7). There was no significant difference in time to cognitive failure between treatment arms (HR, 0.88; 95% CI, 0.45-1.75; P = .74). PT was associated with a lower rate of fatigue (24% vs 58%, P = .05), but otherwise, there were no significant differences in PROs at 6 months. There was no difference in PFS (HR, 0.74; 95% CI, 0.44-1.23; P = .24) or OS (HR, 0.86; 95% CI, 0.49-1.50; P = .60). However, PT significantly reduced the radiation dose for nearly all structures analyzed. The average number of grade 2 or higher toxicities was significantly higher in patients who received IMRT (mean 1.15, range 0-6) compared to PT (mean 0.35, range 0-3; P = .02). Conclusions In this signal-seeking phase II trial, PT was not associated with a delay in time to cognitive failure but did reduce toxicity and patient-reported fatigue. Larger randomized trials are needed to determine the potential of PT such as dose escalation for GBM and cognitive preservation in patients with lower-grade gliomas with a longer survival time.

There is a critical need for effective treatments for leptomeningeal disease (LMD). We conducted a single-arm, first-in-human phase I/Ib study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in melanoma patients with LMD. The primary endpoints were determination of safety and the recommended IT nivolumab dose. The secondary objective was overall survival (OS). Patients were treated with IT nivolumab alone in cycle 1; IV nivolumab 240 mg was included in subsequent cycles, which were administered every two weeks. The dose escalation portion evaluated 5, 10, 20, and 50 mg of IT nivolumab. Twenty-five patients were enrolled and treated (twenty-one previously treated with anti-PD1): 2 with 5 mg, 3 with 10 mg, 14 with 20 mg, and 6 with 50 mg of IT nivolumab. There were no dose-limiting toxicities at any dose level; 10 patients experienced grade 1 or 2 toxicities, possibly related to IT nivolumab. The recommended IT dose of nivolumab was 50 mg (with IV nivolumab 240 mg) every 2 weeks. The median OS was 4.9 months, with 44% and 26% OS rates at 26 and 52 weeks, respectively. Concurrent IT and IV nivolumab is safe, feasible and appears to have a preliminary efficacy signal in patients with melanoma LMD, including in patients with previous anti-PD1 therapy.

Highlights • GTVs on the 60 kV and 140 kV from DECT, and the T1c and T2 from MRI were compared. • Delineation was the most consistent using T1c (no interobserver difference in DSC). • T1c MRI provided higher interobserver agreement for skull base tumors. • 60 kV DECT provided higher interobserver agreement for non-skull base tumors., In treatment planning, multiple imaging modalities can be employed to improve the accuracy of tumor delineation but this can be costly. This study aimed to compare the interobserver consistency of using dual energy computed tomography (DECT) versus magnetic resonance imaging (MRI) for delineating tumors in the head and neck cancer (HNC) re-irradiation scenario. Twenty-three patients with recurrent HNC and had planning DECT and MRI were identified. Contoured tumor volumes by seven radiation oncologists were compared. Overall, T1c MRI performed the best with median DSC of 0.58 (0–0.91) for T1c. T1c MRI provided higher interobserver agreement for skull base sites and 60 kV DECT provided higher interobserver agreement for non-skull base sites.

Background This secondary image analysis of a randomized trial of proton radiotherapy (PT) vs. photon intensity modulated radiotherapy (IMRT) compares tumor progression based on clinical radiological assessment vs. Response Assessment in Neuro-Oncology (RANO). Methods Eligible patients were enrolled in the randomized trial and had MR imaging at baseline and follow-up beyond 12 weeks from completion of radiotherapy. ‘Clinical progression’ was based on a clinical radiology report of progression and/or change in treatment for progression. Results Of 90 enrolled patients, 66 were evaluable. Median clinical progression-free survival (PFS) was 10.8 (Range: 9.4-14.7) months; 10.8 months IMRT vs. 11.2 months PT (p=0.14). Median RANO PFS was 8.2 (Range: 6.9, 12): 8.9 months IMRT vs. 6.6 months PT (p=0.24). RANO PFS was significantly shorter than clinical PFS overall (p=0.001) and for both the IMRT (p=0.01) and PT (p=0.04) groups. There were 31 (46.3%) discrepant cases of which 17 had RANO progression more than a month prior to clinical progression, and 14 had progression by RANO but not clinical criteria. Conclusion Based on this secondary analysis of a trial of PT vs. IMRT for GBM, while no difference in PFS was noted relative to treatment technique, RANO criteria identified progression more often and earlier than clinical assessment. This highlights the disconnect between measures of tumor response in clinical trials versus clinical practice. With growing efforts to utilize real-world data and personalized treatment with timely adaptation, there is a growing need to improve the consistency of determining tumor progression within clinical trials and clinical practice.

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.

OBJECTIVEThe objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors.METHODSFrom 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15–20 Gy) prescribed to the 50% isodose line (range 43%–55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21–27 Gy) prescribed to the 50% isodose line (range 45%–50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory–Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS.RESULTSSeven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0–34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p < 0.001); MDASI-HN pain scores (n = 13) decreased from 5.02 ± 1.68 to 2.02 ± 1.54 (p < 0.01); scheduled FED (n = 19) decreased from 62.4 ± 102.1 to 27.9 ± 45.5 mcg/hr (p < 0.01); PRN OMED (n = 19) decreased from 43.9 ± 77.5 to 10.9 ± 20.8 mg/day (p = 0.02); and frequency of any PRN analgesic use (n = 19) decreased from 0.49 ± 0.55 to 1.33 ± 0.90 per day (p = 0.08). At 6 months after GKRS, 9 (56%) of 16 patients reported being pain free (NRS score 0), with 6 (67%) of the 9 being both pain free and not requiring analgesic medications. One patient treated early in our experience developed a temporary increase in trigeminal pain 3–4 days after GKRS requiring hospitalization. All subsequently treated patients were given a single dose of intravenous steroids immediately after GKRS followed by a 2–3-week oral steroid taper. No further cases of increased or new pain after treatment were observed after this intervention.CONCLUSIONSGKRS for palliation of trigeminal pain secondary to recurrent malignant skull base tumors demonstrated a significant decrease in patient-reported pain and opioid requirement. Additional patients and a longer follow-up duration are needed to assess durability of symptom relief and local control.

Background To test the hypothesis that intraventricular ADC values can be used to determine the presence of neoplastic leptomeningeal disease (LMD). Materials and methods ADC values were measured at multiple sites in the ventricular system in 32 patients with cytologically-proven LMD and 40 control subjects. Multiple linear regression analysis was used to determine the mean difference of ADCs between the LMD and control groups after adjusting for ventricle size and tumor type. Receiver operating characteristics (ROC) analysis was performed and optimal ADC value cut-off point for predicting the presence of LMD. ADC was compared to T1 enhancement and FLAIR signal hyperintensity for determining the presence of LMD. Results After adjusting for ventricular volume and tumor type, the mid body of lateral ventricles showed no significant difference in ventricular volume and a significant difference in ADC values between the control and LMD groups (p > 0.05). In the mid-body of the right lateral ventricle the AUC was 0.69 (95% CI 0.57–0.81) with an optimal ADC cut off point of 3.22 × 10− 9 m2/s (sensitivity, specificity; 0.72, 0.68). In the mid-body of left lateral ventricle the AUC was 0.7 (95% CI 0.58–0.82) with an optimal cut-off point of 3.23 × 10− 9 m2/s (0.81, 0.62). Using an average value of HU measurements in the lateral ventricles the AUC was 0.73 (95% CI 0.61–0.84) with an optimal cut off point was 3.11 × 10− 9 m2/s (0.78, 0.65). Compared to the T1 post-contrast series, ADC was predictive of the presence of LMD in the mid-body of the left lateral ventricle (p = 0.036). Conclusion Complex interactions affect ADC measurements in patients with LMD. ADC values in the lateral ventricles may provide non-invasive clues to the presence of LMD.

BACKGROUND AND PURPOSE: During thyroidectomy incomplete resection of the thyroid gland may occur. This complicates the imaging surveillance of these patients as residual thyroid needs to be distinguished from local recurrence. Therefore, the purpose of this study was to determine if multiphasic multi-detector computed tomography (4D-MDCT) can differentiate residual nonmalignant thyroid tissue and recurrent thyroid carcinoma after thyroidectomy. MATERIALS AND METHODS: In this retrospective study, Hounsfield unit values on multiphasic multidetector CT in precontrast, arterial (25 seconds), venous (55 seconds), and delayed (85 seconds) phases were compared in 29 lesions of recurrent thyroid cancer, 29 with normal thyroid, and 29 with diseased thyroid (thyroiditis/multinodular thyroid). The comparison of Hounsfield unit values among lesion types by phase was performed using ANOVA. The performance of Hounsfield unit values to predict recurrence was evaluated by logistic regression and receiver operating characteristic analysis. RESULTS: All 3 tissue types had near-parallel enhancement characteristics, with a wash-in–washout pattern. Statistically different Hounsfield unit density was noted between the recurrence (lowest Hounsfield unit), diseased (intermediate Hounsfield unit), and normal (highest Hounsfield unit) thyroid groups throughout all 4 phases (P

Purpose/objective(s) Cardiac angiosarcomas (CA) often develop early distant disease with risk of brain metastases (BM) and have recognized hemorrhagic risk. However, limited data exists characterizing this presentation. Therefore, we evaluated a cohort of patients with CA who developed BM to better define outcomes and intracranial hemorrhage (IH) risk. Materials/methods We reviewed 26 consecutive patients with BM treated between 1988 and 2020 identified from a departmental CA (n = 103) database. Institutional practice has shifted over the decades to include a CT head at diagnosis but with infrequent serial imaging. Causes of death were recorded, and a terminal hemorrhage (TH) was defined as an IH that caused death during hospitalization or prompted transfer to hospice. Results The prevalence of BM was 25% (n = 26/103) among patients with CA at a median age of 37 years (IQR 26-50). All primary tumors involved the right heart (atrium: n = 20, 77%), and 20 patients (77%) presented with metastases at initial diagnosis, of which only 4 had BM. The median time between initial CA diagnosis to BM was 11 m (IQR 3-18) resulting in a 6-m BM free survival of 65%. There was a median of 3 lesions (IQR 1-7), and a majority had 1-4 (n = 15, 58%). The median follow-up from the time of BM was short at 2 m (IQR 1-6.5) due to a high rate of TH. Nearly all patients died of disease (n = 23, 88%). The 6-m OS from the time of BM was 21%, and most patients died from TH (n = 13, 57%). TH occurred at BM presentation in 6 (46%) patients, whereas 3 (23%) had TH from known and untreated lesions, 2 (15%) had continued uncontrolled IH during RT, and 2 (15%) from new BM. The only factor associated with TH as the cause of death was platelet count as a continuous variable (median 162 vs 360k, P = 0.02; platelet count Conclusion Patients with CA frequently develop BM, and the risk of IH is high resulting in an alarming rate of TH despite normal platelet counts. Therefore, early diagnosis and intervention is warranted. We recommend incorporating MRI brain imaging into the standard q2-3 month staging evaluation. And importantly, once BM are detected, prompt local therapy is recommended to try and mitigate the risk of TH.

Purpose/Objective(s) In the setting of head and neck (HN) re-irradiation (reRT), the goal is to adequately cover disease with as small a volume as appropriate to minimize normal tissue toxicity without compromising local control. However, it can be a challenge to gauge the extent microscopic disease beyond the gross tumor to be included in the reRT volume. Here, we aim to determine the patterns of failure after HN reRT. Materials/Methods Patients treated with curative intent intensity modulated radiation therapy (IMRT) or proton reRT from September 1999 – June 2015 were evaluated. A total of 148 patients with inoperable tumors received definitive reRT (intact) and 61 who underwent salvage surgery received post-operative reRT (postop). Those who had locoregional recurrence (LRR) and intact imaging data were analyzed. Using deformable imaging registration, diagnostic images at time of recurrence were overlaid on reRT treatment plans. The site of recurrence was delineated and evaluated by at least 2 radiation oncologists/radiologist with HN expertise. The patterns of failure were classified into five types based on spatial and dosimetric criteria: A (central high dose, or “in-field”), B (peripheral high dose), C (central elective dose), D (peripheral elective dose), and E (extraneous dose, or “out-of-field”). For patients who had multiple sites of recurrences, each site was classified independently. The kappa statistic was used to assess the inter-observer agreement on failure classification. Results Of the 209 patients treated, 67 developed LRR. This represented 44 of 148 (30%) intact patients (median dose 66 Gy) and 23 of 61 (38%) postop patients (median dose 60 Gy). Of these, 41 (61%) had imaging data for analysis, representing 47 sites of failures. Median time to failure was 21 weeks (range: 4 – 220 weeks). Patterns of failure among intact reRT were as follows: 13 Type A (39%), 6 Type B (18%), 1 Type C (3%), and 13 Type E (39%). The majority (79%) of failures were either in the high dose field or completely out of field. Interobserver agreement was 0.92. Patterns of failure among postop reRT were as follows: 4 type A (17%), 5 type B (22%), 5 type C (22%) and 5 type D (22%). The majority (56%) of recurrences were within 1 cm of the reconstructive flap bed, 40% recurred in the same primary subsite, and 17% recurred in the 1st echelon nodal level. Interobserver agreement was 0.68. Conclusion In patients who recurred after reRT, the majority was either within the central high-dose region, or completely outside the high-dose region suggesting poor disease biology. Biologic dose-escalation and or the addition of systemic therapies may offer improved disease control.

Neoplastic leptomeningeal disease (LMD) represents infiltration of the leptomeninges by tumor cells. Knowledge of the frequencies of locations of LMD on MRI may assist in early detection, help elucidate the process of leptomeningeal spread of cancer and understand how LMD affects the central nervous system. Our goal was to identify intracranial sites of neoplastic LMD predilection on MRI in patients with cytologically-proven LMD. The presence of FLAIR signal hyperintensity and T1-weighted post-contrast enhancement in the sulci of the supratentorial compartment and cerebellum and enhancement of the cranial nerves (CNs), basal cisterns, pituitary stalk, and ependymal surface of the lateral ventricles, as well as the presence of parenchymal metastasis were recorded. Within each imaging sequence, sites were ordered by prevalence and compared using McNemar's test. The study included 270 patients. Positive MRI findings were present in 185/270 (68.5%) patients. FLAIR signal hyperintensity was significantly more common (p≤0.003) in the cerebellum (n=96) and occipital lobe (n=92) relative to the other lobes. Leptomeningeal enhancement was also significantly more common (p≤0.009) in the cerebellum (n=82) and occipital lobe (n=67) relative to the other lobes. Enhancement was most commonly found involving CN VII/VIII and the ependymal surface of the lateral ventricles compared to other sites. Parenchymal metastases were present in 110 (40.1%) of the patients. In conclusion, neoplastic LMD predominantly involves the cerebellum and occipital lobes, CN VII/VIII, and the ependymal lining of the lateral ventricles. Parenchymal metastases are frequently present in patients with neoplastic LMD.

9519 Background: MM pts with LMD have a dismal prognosis, with median overall survival (OS) < 3 months, no approved therapies and extremely limited clinical trial options. We previously reported initial safety findings from an open label, single arm, single center phase I/IB trial (NCT03025256), in which IT and IV N were well tolerated, without any CNS-specific or unexpected toxicity. Here we report an update on safety and maximum tolerated dose (MTD) for all patients enrolled, and efficacy for the completed dose cohorts. Methods: MM patients aged >18 with evidence of LMD by MRI and/or CSF cytology, ECOG PS ≤2 were treated with IT and IV N. Dexamethasone ≤4mg/daily and concurrent BRAF/MEK inhibitor(i) treatment was allowed. For cycle 1, IT N was administered via intraventricular reservoir on day (D)1. For subsequent cycles (every 14 days), pts received IT N on D1, followed by IV N 240 mg on D2. IT N doses evaluated were 5, 10, 20 mg and 50 mg. Blood and CSF were collected at multiple time points for translational research. The primary objectives of this first-in-human study were to determine the safety and MTD of IT N given with IV N in MM pts with LMD. Bayesian mTPI methodology was used to define the MTD. Results: To date, 23 pts have been treated: two at 5, three at 10, fourteen at 20 mg and four at 50 mg IT N. Median age at LMD diagnosis was 42 (28-73); 12 pts are male. All pts had radiographic evidence of LMD and neurological symptoms; 14 pts had positive CSF cytology at baseline. 21 pts received prior therapies for their metastatic melanoma: anti-PD1 (n = 19), BRAFi/MEKi (n = 14), chemo (n = 2), IT IL2 (n = 4) other (n = 2). 19 pts had prior XRT, including whole brain RT (n = 7). Two pts were treatment-naïve. The median number of IT N doses was five (1- 66). The combination regimen was well tolerated by all evaluable pts (n=23), with only five pts (22%) experiencing gr 3 AEs, and no reported gr 4 or 5 toxicities. Nausea (30%), diarrhea (26%), and rash (22%) were the most common AEs. Eight pts (23%) experienced AEs after IT N administration, all gr 1. Initial efficacy analysis included only pts (n=19) treated with first three dose levels (5-20mg). Median follow-up for these pts is 4.5 months (mos) (1.1, 31.5 mos) and median OS is 63 % at 3 mos, 42 % at 6 mos and 30% at 12 mos. Conclusions: The trial demonstrates the feasibility and safety of IT administration of modern immunotherapy for MM pts with LMD. No unexpected systemic or neurological toxicity was observed with 20mg IT N. 2 additional patients are required to complete the 50mg IT N cohort. OS rates at 6 and 12 mos are encouraging and support further evaluation of IT administration of immunotherapy agents for pts with MM and LMD. Final presentation will include results of LMD for all dose cohorts, composite response assessment and comparative analysis of longitudinal CSF samples to assess immunologic effects. Clinical trial information: NCT03025256.

Key Clinical Message Methotrexate‐induced leukoencephalopathy is to be considered as a potential etiology in any patient presenting with stroke‐like symptoms after receiving methotrexate. One of our cases suggests that the method of administration of the methotrexate can be IV or intrathecal and still results in leukoencephalopathy.

Summary Background After brain metastasis resection, whole brain radiotherapy decreases local recurrence, but might cause cognitive decline. We did this study to determine if stereotactic radiosurgery (SRS) to the surgical cavity improved time to local recurrence compared with that for surgical resection alone. Methods In this randomised, controlled, phase 3 trial, we recruited patients at a single tertiary cancer centre in the USA. Eligible patients were older than 3 years, had a Karnofsky Performance Score of 70 or higher, were able to have an MRI scan, and had a complete resection of one to three brain metastases (with a maximum diameter of the resection cavity ≤4 cm). Patients were randomly assigned (1:1) with a block size of four to either SRS of the resection cavity (within 30 days of surgery) or observation. Patients were stratified by histology of the primary tumour, metastatic tumour size, and number of metastases. The primary endpoint was time to local recurrence in the resection cavity, assessed by blinded central review of brain MRI scans by the study neuroradiologist in the modified intention-to-treat population that analysed patients by randomised allocation but excluded patients found ineligible after randomisation. Participants and other members of the treatment team (excluding the neuroradiologist) were not masked to treatment allocation. The trial is registered with ClinicalTrials.gov, number NCT00950001, and is closed to new participants. Findings Between Aug 13, 2009, and Feb 16, 2016, 132 patients were randomly assigned to the observation group (n=68) or SRS group (n=64), with 128 patients available for analysis; four patients were ineligible (three from the SRS group and one from the observation group). Median follow-up was 11·1 months (IQR 4·8–20·4). 12-month freedom from local recurrence was 43% (95% CI 31–59) in the observation group and 72% (60–87) in the SRS group (hazard ratio 0·46 [95% CI 0·24–0·88]; p=0·015). There were no adverse events or treatment-related deaths in either group. Interpretation SRS of the surgical cavity in patients who have had complete resection of one, two, or three brain metastases significantly lowers local recurrence compared with that noted for observation alone. Thus, the use of SRS after brain metastasis resection could be an alternative to whole-brain radiotherapy. Funding National Institutes of Health.

PURPOSE To compare tumor progression based on clinical radiological assessment and on Response Assessment in Neuro-Oncology (RANO) criteria between GBM patients treated with proton radiotherapy (PT) vs. photon intensity modulated radiotherapy (IMRT). METHODS Eligible patients were enrolled on the described prospective phase II trial and had MR imaging at baseline and follow-up beyond 12 weeks from treatment completion. ‘Clinical’ progression was based on a radiology report of progression in combination with changes in treatment due to suspected disease progression. A single blinded observer applied RANO criteria to determine the RANO-based tumor progression. RESULTS Of 90 enrolled patients, 66 were evaluable, with median follow-up of 19.8 (Range: 3.2–65.1) months; median of 22.6 months for PT (n=25) vs. 18.9 months for IMRT (n=41). Median time to progression (TTP) was 7.9 months based on clinical progression criteria (8.1 months IMRT, 6.3 months PT) and 7.2 months (7.3 months IMRT, 5.7 months PT) by RANO criteria (p=ns for all). Median ‘clinical’ progression-free survival (PFS) was 8.7 (Range: 6.4–11.1) months; 8.9 months IMRT vs. 8.7 months PT (p=0.065). Median RANO PFS was 8.3 (range, 5.8–11.6) months: 8.3 months IMRT vs. 6.9 months PT (p=0.226). There were 14 discrepant cases: 3 had progression based on ‘clinical’ but not RANO criteria, and 11 had progression based on RANO but not ‘clinical’ criteria. CONCLUSION Based on this secondary analysis of a randomized trial of PT vs. IMRT for GBM, there was no difference in tumor progression relative to treatment technique used. There was no statistical difference in PFS noted between clinical and RANO-based assessments, but RANO criteria identified progression more often than clinical assessment, and TTP was shortened with the use of RANO criteria alone. Further development of tumor assessment tools that improve consistency and accuracy of determining tumor progression are needed to guide therapeutic trials in GBM.

Purpose The aim of this study was to evaluate outcomes of patients who received reirradiation for small skull base tumors utilizing either intensity modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT), and proton radiotherapy (PRT). Methods Patients who received IMRT, SBRT or PRT reirradiation for recurrent or new small skull base tumors ( Results Of the 75 patients eligible, 30 (40%) received SBRT, 30 (40%) received IMRT, and 15 (20%) received PRT. The median retreatment volume was 28 cc. The median reirradiation dose was 66 Gy in 33 fractions for IMRT/PRT, and 45 Gy in 5 fractions for SBRT. The median time to reirradiation was 41 months. With a median follow-up of 24 months, the LC, RC, DC, PFS, and OS rates were 84%, 79%, 82%, 60%, and 87% at 1 year, and 75%, 72%, 80%, 49%, and 74% at 2 years. There was no difference in OS between radiation modalities. The 1- and 2-year late Grade 3 toxicity rates were 3% and 11% respectively.. Conclusions Reirradiation of small skull base tumors utilizing IMRT, PRT, or SBRT provided good local tumor control and low rates of Grade 3 late toxicity. A prospective clinical trial is needed to guide selection of radiation treatment modalities.

Leptomeningeal disease (LMD), the presence of metastasis in the subarachnoid space, has devastating implications if left untreated. The gold standard for LMD diagnosis is cytologic analysis of cerebrospinal fluid (CSF); MRI is also used to evaluate suspected LMD. The purpose of this study was to compare the appearance of LMD in the spinal canal onIn twenty-one patients with cytologically-proven spinal LMD, findings onAt diagnosis of LMD, abnormal

The histiocytoses are a rare group of varied but related disorders characterized by abnormal tissue proliferation of macrophages and dendritic cells within tissues. The purpose of this article was to review the imaging findings in patients presenting with CNS and with head and neck manifestations of these disorders. Histiocytoses include but are not limited to Rosai-Dorfman disease, Erdheim Chester disease, Langerhans cell histiocytosis, histiocytic sarcoma, and juvenile xanthogranuloma. A review of the literature was performed to determine the sites of disease involvement. This article includes the demographics, histopathologic criteria for diagnosis, and imaging features of these histiocytoses, and describes the manifestations in locations known to harbor disease: intraaxial and extra-axial intracranial regions, the calvaria, skull base, hypothalamopituitary axis, orbits, paranasal sinuses, spine, and the head and neck region. Histiocytoses have variable imaging appearances in the CNS and in the head and neck region, and radiologists should be aware of the spectrum of findings to avoid mistaking them for other disease processes. Learning Objective To understand the general pathophysiology, clinical presentation, and typical imaging characteristics of the most common histiocytoses; comprehend the morphologic and immunohistochemical characteristics of these histiocytoses and the hallmark findings on pathology; and be able to differentiate between these disorders based on their most common presentations.

Although the survival of most melanoma patients diagnosed with leptomeningeal disease (LMD) is short, some patients can have better outcomes and prolonged survival. A large retrospective cohort of patients was analyzed to identify features associated with survival with LMD from melanoma. Clinical characteristics, treatments and survival were collected for melanoma patients diagnosed with LMD from 1999 to 2015. The Kaplan–Meier method was used to estimate overall survival (OS) and Cox proportional hazards regression was used to test statistical significance of associations with survival. Multivariate analysis was performed using Cox proportional regression modeling. 178 melanoma patients with LMD were identified. Median age at LMD diagnosis was 51 years. Most (n = 153) patients received at least one treatment for LMD, including radiation (n = 98), chemotherapy (n = 89), targeted therapy (n = 60), immunotherapy (n = 12), or intrathecal (IT) therapy (n = 64). Median OS from LMD diagnosis was 3.5 months. One-, two-, and five-year OS rates were 22%, 14%, and 9%, respectively. Factors significantly associated with OS on multivariate analysis included Eastern Cooperative Oncology Group [ECOG] performance status > 0 (HR 2.1, P

INTRODUCTION We evaluated outcomes of patients with newly diagnosed MBM treated with concurrent immune checkpoint inhibition (ICI) and stereotactic radiosurgery (SRS) (concurrentTx), defined as treatment delivery within 30 days of each other. METHODS Screening of 2,617 melanoma patients who received ICI (anti-CTLA4/anti-PD1/both) between 2011-2019 identified 151 pts who received concurrentTx for MBM. Among these, 51 had newly-diagnosed MBM and received no prior ICI or SRS, and were included in the current study. Overall survival (OS) and distant brain failure (DBF) were estimated using the Kaplan-Meier method. Incidence of radiation necrosis (RN) was captured. RESULTS Median follow up from treatment initiation (either ICI or SRS, whichever occurred first) was 37 months. Median OS was 30 months. Median interval between ICI/SRS was 12 days (range: 1-29). Twenty-two patients received ICI first and 29 received SRS first, without differences in OS (p=0.22), DBF (p=0.91), or development of RN (p=0.86). However, the interval between ICI and SRS was significant. Patients who received concurrentTx 1-11 days apart (n=25, “early”) experienced a significant improvement in OS and DBF compared to 12-29 days apart (n=26, “delayed”) (p=0.01, HR 2.8; 95%CI 1.3-6.2 for OS and p=0.02, HR 2.5; 95%CI 1.2-5.6 for DBF). OS and DBF at 36 months were 67% vs. 26% and 60% vs. 27%, respectively, for the early vs. delayed groups. Time to concurrentTx as a continuous variable was significantly associated with DBF (p=0.02), but not OS (p=0.06). Although not significant, more patients developed RN in the early (26.0%) versus delayed (3.8%) group (p=0.07). No additional patient or treatment differences were identified. CONCLUSIONS Early concurrentTx was associated with prolonged OS and improved DBF in newly diagnosed MBM patients who did not receive prior CNS-directed therapy. This finding suggests therapeutic synergism related to combined early treatment and should be validated in a prospective clinical trial.

2531 Background: Nivolumab (nivo) and ipilimumab (ipi) were found in the recent phase III CheckMate 227 trial to have an overall survival benefit over chemotherapy for advanced non-small cell lung cancer (NSCLC). However, patients (pts) with untreated brain metastasis (mets) were excluded from that trial. Because 30% of NSCLC pts develop brain mets, we tested nivo/ipi with concurrent stereotactic radiosurgery (SRS) for NSCLC pts with active brain mets. Methods: We report the safety data from the phase I portion of an ongoing phase I/II single-institution trial in which one treatment group was given SRS with nivo (3 mg/kg) every 2 weeks (wks) plus ipi (1 mg/kg) every 6 wks x 4 cycles, followed by maintenance nivo (480 mg) every 4 wks until disease progression, unacceptable toxicity, or withdrawal of consent. Brain SRS was delivered within 7 days of initiation of nivo/ipi. The primary endpoints were safety and 4-month (mo) intracranial progression-free survival (PFS). Dose-limiting toxicity (DLT) was defined as > 15% intracranial toxicity (>G3 hypophysitis / neurologic toxicity) or > 30% extracranial toxicity (>G3 non-dermatologic non-lab toxicity or >G4 dermatologic / lab toxicity), refractory to medical management, assessed at 8 wks after treatment initiation. Target accrual for phase I was 10 evaluable pts, with enrollment suspended after every 5 pts for DLT assessment. Results: Since June 15, 2018, 13 pts were enrolled and 10 were evaluable for DLT. The median follow-up time was 6.8 mo (range 1.2‒18). As of January 6, 2020, only 1 pt had DLT-defined toxicity and thus the predefined stopping criteria were not met. This pt had G3 seizure right after SRS that resolved within a week, and then had increased but asymptomatic CNS edema 4 wks later. Aside from DLTs, 3 pts (25%) developed treatment-related G3 (elevated liver function tests, fatigue, nausea, adrenal insufficiency, and myocarditis) or G4 events (pneumonitis/acute respiratory distress syndrome in 1 pt with confirmed influenza at 7 mos after treatment initiation). This pt subsequently died of hemophagocytic lymphohistiocytosis (considered possibly related to the study drugs). Median intracranial PFS time was 9.7 mo, and the 4-mo intracranial PFS rate was 75%. Extracranial objective response rate was 33% in the 12 evaluable pts with a median response duration of 9.1 mo. Conclusions: Concurrent SRS withnivo/ipi was safe for pts with active NSCLC brain mets. Preliminary analyses of efficacy were encouraging for durable intracranial and extracranial response. Clinical trial information: NCT02696993 .

Background Removal of a pin during Gamma Knife stereotactic radiosurgery (GK-SRS) may be necessary to prevent collision and allow treatment. Objective To investigate outcomes after GK-SRS for treatment of brain metastases using a head frame immobilized to the skull with only 3 pins. Methods Between 2009 and 2014, we retrospectively reviewed the records of 1971 patients and identified 20 patients with multiple brain metastases treated with GK-SRS in which 1 anterior pin was removed immediately before treatment of a single posterior lesion. GK-SRS was also delivered to 116 other lesions in these 20 patients using the standard 4 pins during the same session, serving as an internal control for comparison. Endpoints included local control, dosimetric parameters, toxicity, and overall survival. Results The median number of lesions treated per session was 6 (range, 2-14). The lesions treated using 3 pins were located in the occipital lobe (n = 14) or the cerebellum (n = 6). Median follow-up was 12.3 months. There was 1 local failure involving a control lesion. Lesions treated using 3 pins had a lower prescription isodose line. GK-SRS of a lesion using 3 pins did not cause any clinical toxicities or increase in radiographic edema or hemorrhage. Conclusion Treating posteriorly located brain metastases with GK-SRS using only 3 pins provided excellent local control and no difference in treatment toxicity, which may make it a safe and reasonable option for lesions that may otherwise be difficult to treat.

10008 Background: MM pts with LMD have a dismal prognosis, with a median overall survival (OS) < 3 months and no approved therapies. IT administration of interleukin-2 (IL2) achieves survival in ~15% of MM LMD pts, but at cost of severe toxicities. Given the favorable clinical activity and safety of systemic anti-PD1, we hypothesized that IT N administration is safe and can achieve clinical benefit in pts with LMD. Methods: The primary objectives of this first-in-human study (NCT03025256) were to determine the safety and the maximum tolerated dose (MTD) of IT N given with IV N in MM pts with LMD. Eligible pts had MM, ECOG PS < / = 2, and evidence of LMD by MRI and/or CSF cytology. Dexamethasone < / = 4mg/daily was allowed. For cycle 1, IT N is administered via intraventricular reservoir on day (D) 1; Blood and CSF is collected at multiple time points for translational research. For subsequent cycles (every 14 days), pts receive IT N on D1, followed by IV N 240 mg on D2. IT N doses evaluated were 5, 10, and 20 mg. Bayesian mTPI methodology was used to define the MTD. The study was recently amended to allow for concurrent BRAF/MEK inhibitor(i) treatment. Results: To date, 15 pts have been treated: two at 5, three at 10, and 10 at 20 mg IT N. Median age at LMD diagnosis was 41.8 (30.9-73.2) years; 6 pts are male. All pts had radiographic evidence of LMD and neurological symptoms; 8 pts had positive CSF cytology. 12 pts received prior therapies for their MM: anti-PD1 (n = 11), BRAFi/MEKi (n = 9), chemo (n = 2), IT IL2 (n = 4) other (n = 2). 11 pts had prior XRT, including whole brain RT (n = 7). 1 pt was treatment-naïve. The median numbers of IT N doses was 4 (1-42). No grade (Gr) 4-5 AEs were attributed to IT N or IV N; only 4 events (Gr 1, n = 2; Gr2, n = 2) were possibly related to the IT N. With a median follow-up of 18.7 weeks (1-83.3 wks), the median OS is 46.1 weeks (0.1-83.3). Clinical response data, translational research endpoints, including changes in CSF cytokines and cfDNA, will be reported. Conclusions: The trial demonstrates the feasibility of prospective clinical trials in MM patients with LMD. The combination of IT/ IV N was safe and well-tolerated, with no unexpected systemic or neurological toxicity. Final presentation will include results of LMD composite response assessment, comparative analysis of longitudinal CSF/blood samples to assess immunologic effects. Finally, the interim OS of the patients is encouraging, and supports further evaluation of IT administration of immunotherapy agents for pts with MM and LMD. Clinical trial information: NCT03025256.

Objective The objective of this study was to compare multidetector computed tomography (MDCT) images with volume-rendered translucent display (VRTLD) series to plain radiographs for evaluating spinal surgical instrumentation after resection and reconstruction for spinal malignancies. Methods In 44 patients with tumor resection and spinal reconstruction, 17 with complications, 3 neuroradiologists evaluated plain radiographs, MDCT images alone, VRTLD images alone, and MDCT images with VRTLD images for identifying complications in 3 categories: subsidence/migration, construct fracture, and screw loosening. Each category was scored as 1 (complications), 2 (no complications), or 3 (not sure), and the minimum score was used for analyses. Clinical/surgical outcomes were the reference standard. Results Sensitivity, specificity, and accuracy (95% confidence interval), respectively, were as follows: MDCT/VRTLD, 100%, 100%, 100% (91.96%-100.00%); MDCT alone, 88.24%, 100%, 95.45% (84.53%-99.44%); VRTLD alone, 82.35%, 96.3%, 90.91% (78.33%-97.47%); plain radiographs, 52.94%, 100%, 81.82% (67.29%-91.81%). Conclusions Multidetector computed tomography with VRTLD series seems best for evaluation of spinal instrumentation after tumor resection and reconstruction.

Purpose We seek to establish the feasibility of using spine stereotactic radiosurgery (SSRS), allowing for spinal cord dose constraint relaxation, as the primary management of metastatic epidural spinal cord compression (MESCC) in inoperable patients. Methods and Materials Inoperable patients with thoracic MESCC and no history of radiation were enrolled on this prospective phase 1 single-institution protocol. SSRS was delivered to a histology-dependent prescription dose of 18 or 24 Gy. Incremental spinal cord constraint relaxation was performed from a Dmax cohort of 10 Gy up to 16 Gy only if tumor progression occurred and the risk of radiation-induced myelopathy (RM) remained lower than the risk of tumor progression. Results Thirty-two patients enrolled on the trial; 4, 12, 9, and 7 patients were in the 10 Gy, 12 Gy, 14 Gy, and 16 Gy cord Dmax cohorts, respectively. At baseline, there were 2 sites with MESCC grade 1A, 10 sites with grade 1B, 10 sites with grade 1C, 9 sites with grade 2, and 1 site with grade 3 disease. Among the 28 evaluable patients, the median overall survival was 28.6 months (95% confidence interval [CI], 9.2-48.0 months), and the 1-year local control was 89% (95% CI, 74%- 97%). With a median follow-up of 17 months, there were no cases of RM (upper 95% CI, 12%). In the cohort receiving a cord Dmax of 16 Gy, there were no cases of RM (upper 95% CI, 39%) with a median follow-up of 17 months (range, 12.7-21.0 months). Conclusions SSRS is a safe and effective tool in patients with MESCC. In high-risk inoperable patients with MESCC receiving SSRS, dose constraint relaxation of the cord constraint dmax to 16 Gy may be considered to optimize local control, with the acknowledgment that this is based on 6 evaluable patients who received this dose in this trial.

Objectives Metastatic melanoma patients with leptomeningeal disease (LMD) have an extremely poor prognosis, with a median survival measured in weeks, and few treatment options. Outcomes of a retrospective cohort of patients with LMD that were treated with intrathecal interleukin-2 (IT IL-2) were reviewed to assess the long-term efficacy of this therapy. Methods The records of metastatic melanoma patients with LMD who were treated with IT IL-2 from 2006 to 2014 in a Compassionate Investigational New Drug study were reviewed. IL-2 (1.2 mIU) was administered intrathecally via Ommaya reservoir up to five times per week in the inpatient setting for 4 weeks; patients with good tolerance and clinical benefit received maintenance IT IL-2 every 1–3 months thereafter. Results The cohort included 43 patients. The median age of the patients was 47 years (range 18–71), and 32 (74%) were male. 23 patients (53%) had positive cerebrospinal fluid (CSF) cytology and radiographic evidence of LMD, 8 (19%) had positive CSF cytology only, 9 (21%) had radiographic evidence only and 3 (7%) were diagnosed based on pathology review after craniotomy. The median overall survival (OS) from initiation of IT IL-2 was 7.8 months (range, 0.4–90.8 months), with 1-year, 2-year and 5-year OS rates of 36%, 26% and 13%. The presence of neurological symptoms (HR 2.1, P=0.03), positive baseline CSF cytology (HR 4.1, P=0.001) and concomitant use of targeted therapy (HR 3.0, P=0.02) was associated with shorter OS on univariate analysis. All patients developed symptoms due to increased intracranial pressure which was managed with supportive medications and/or CSF removal, and there were no treatment-related deaths. Conclusion These results demonstrate that despite their historically dismal prognosis a subset of metastatic melanoma patients with LMD treated with IT IL-2 can achieve long-term survival, but these data need to be verified in a prospective trial setting.

In-frame fusion KIF5B (the-kinesin-family-5B-gene)-RET transcripts have been characterized in 1-2% of non-small cell lung cancers and are known oncogenic drivers. The RET tyrosine kinase inhibitor, vandetanib, suppresses fusion-induced, anchorage-independent growth activity. In vitro studies have shown that vandetanib is a high-affinity substrate of breast cancer resistance protein (Bcrp1/Abcg2) but is not transported by P-glycoprotein (P-gp), limiting its blood-brain barrier penetration. A co-administration strategy to enhance the brain accumulation of vandetanib by modulating P-gp/Abcb1- and Bcrp1/Abcg2-mediated efflux with mTOR inhibitors, specifically everolimus, was shown to increase the blood-brain barrier penetration. We report the first bench-to-bedside evidence that RET inhibitor combined with an mTOR inhibitor is active against brain-metastatic RET-rearranged lung cancer and the first evidence of blood-brain barrier penetration. A 74-year-old female with progressive adenocarcinoma of the lung (wild-type EGFR and no ALK rearrangement) presented for therapy options. A deletion of 5'RET was revealed by FISH assay, indicating RET-gene rearrangement. Because of progressive disease in the brain, she was enrolled in a clinical trial with vandetanib and everolimus (NCT01582191). Comprehensive genomic profiling revealed fusion of KIF5B (the-kinesin-family-5B-gene) and RET, in addition to AKT2 gene amplification. After two cycles of therapy a repeat MRI brain showed a decrease in the intracranial disease burden and PET/CT showed systemic response as well. Interestingly, AKT2 amplification seen is a critical component of the PI3K/mTOR pathway, alterations of which has been associated with both de novo and acquired resistance to targeted therapy. The addition of everolimus may have both overcome the AKT2 amplification to produce a response in addition to its direct effects on the RET gene. Our case report forms the first evidence of blood-brain barrier penetration by vandetanib in combination with everolimus. Further research is required in this setting.

ObjectThe authors' institution previously reported a 69% rate of crude local control for surgical management of lateral ventricle metastases at the University of Texas MD Anderson Cancer Center. For comparison, the authors here report their institutional experience with use of stereotactic radiosurgery (SRS) to treat intraventricular metastases.MethodsTo identify patients with intraventricular metastases for this retrospective review, the authors queried an institutional SRS database containing the medical records of 1962 patients with 5800 brain metastases who consecutively underwent SRS from June 2009 through October 2013. End points assessed were local control (crude and locoregional), distant failure–free survival, progression-free survival, and overall survival.ResultsOf the 1962 records examined, those for 25 (1.3%) patients with 30 (0.52%) intraventricular metastases were identified. Median patient age at SRS was 55.8 years. The most common primary malignancy was renal cell carcinoma (n = 13), followed by melanoma (n = 7) and breast adenocarcinoma (n = 5). Median tumor volume was 0.75 cm3 (range 0.01–5.6 cm3). Most lesions were located in the lateral ventricles (n = 25, 83.3%) and were treated to a median dose of 20 Gy (range 14–20 Gy). A total of 12 (48%) patients received whole-brain radiation therapy, most (n = 10) before SRS. With a median follow-up of 11.4 months (range 1.6–39.2 months), the rate of crude local control was 93.3%, and the rates of 6-month and 1-year actuarial locoregional control were 85.2% and 56.2%, respectively. The median overall survival time after SRS was 11.6 months (range 1.3–38.9 months), and the 6-month and 1-year actuarial rates were 87.1% and 46.7%, respectively. Disease dissemination developed in 7 (28%) patients as a second intraventricular metastatic lesion (n = 3, 12%), leptomeningeal disease (n = 3, 12%), or both (n = 1, 4%). Radiographic changes developed in 5 (20%) patients and included necrosis (n = 2, 8%) and hemorrhage (n = 3, 12%). A primary diagnosis of renal cell carcinoma was associated with an improved rate of distant failure–free survival (p = 0.05) and progression-free survival (p = 0.08).ConclusionsSRS provides excellent local control for intraventricular metastases, with acceptable treatment-related toxicity, thereby supporting nonsurgical treatment for these lesions. The propensity for intraventricular dissemination among intraventricular metastases seems to be histologically dependent.

Radiation necrosis (RN) is a potential late complication of radiotherapy for intracranial malignancy, which is often associated with significant neurological morbidity. Prolonged treatment with high-dose corticosteroids or surgical resection has been the standard care for RN, but protracted steroid use can lead to significant side effects and surgical resection is not always feasible. The antivascular endothelial growth factor monoclonal antibody bevacizumab induces clinical and radiographic improvements in RN, with overall good tolerance. However, evidence supporting its use for RN in melanoma brain metastases is minimal, likely secondary to concern for intracranial bleeding. Immunotherapy is now one of the most commonly used and effective therapies for metastatic melanoma. A higher risk of RN has been reported with immunotherapy, making alternative treatment for RN in this population a priority, especially as prolonged use of steroids may counteract the treatment efficacy of immunotherapy. We report on seven melanoma patients who developed RN after stereotactic radiosurgery with or without whole-brain radiation therapy who were treated with 2-6 doses of bevacizumab. All patients experienced improvements in symptoms and quality of life, with a concurrent improvement in imaging in six patients. Furthermore, bevacizumab was well tolerated and none of the seven patients experienced intracranial or extracranial bleeding. Our series suggests that in selected melanoma brain metastases patients, bevacizumab may be a safe and effective treatment for RN, especially for those who are undergoing immunotherapy, and should be further evaluated in a prospective setting.

To develop a model using radiomic features extracted from MR images to distinguish radiation necrosis from tumour progression in brain metastases after Gamma Knife radiosurgery.We retrospectively identified 87 patients with pathologically confirmed necrosis (24 lesions) or progression (73 lesions) and calculated 285 radiomic features from four MR sequences (T1, T1 post-contrast, T2, and fluid-attenuated inversion recovery) obtained at two follow-up time points per lesion per patient. Reproducibility of each feature between the two time points was calculated within each group to identify a subset of features with distinct reproducible values between two groups. Changes in radiomic features from one time point to the next (delta radiomics) were used to build a model to classify necrosis and progression lesions.A combination of five radiomic features from both T1 post-contrast and T2 MR images were found to be useful in distinguishing necrosis from progression lesions. Delta radiomic features with a RUSBoost ensemble classifier had an overall predictive accuracy of 73.2% and an area under the curve value of 0.73 in leave-one-out cross-validation.Delta radiomic features extracted from MR images have potential for distinguishing radiation necrosis from tumour progression after radiosurgery for brain metastases.• Some radiomic features showed better reproducibility for progressive lesions than necrotic ones • Delta radiomic features can help to distinguish radiation necrosis from tumour progression • Delta radiomic features had better predictive value than did traditional radiomic features.

PURPOSE To facilitate detection of tumor recurrence, the authors reviewed the MRI characteristics of myocutaneous and fasciocutaneous free flaps following orbital exenteration for treatment of orbital or maxillofacial tumors. METHODS The authors retrospectively reviewed the MRI characteristics, including T1 and T2 signal intensity, and enhancement pattern of 28 such flaps. RESULTS The study included 17 myocutaneous flaps and 11 fasciocutaneous flaps placed in 28 patients. For 23 flaps, additional imaging was performed after baseline imaging (range, 2-65 months after surgery). On precontrast T1 imaging, 15 of 17 myocutaneous flaps demonstrated a striated appearance similar to that of native muscle. Twenty-six of the 28 flaps in the series were T2 hyperintense. On baseline imaging, 26 flaps showed linear (n = 5), patchy (n = 10), or homogeneous (n = 11) enhancement. No flaps demonstrated mass-like enhancement. Five fasciocutaneous and 5 myocutaneous flaps showed decreased enhancement on follow-up imaging, while 4 myocutaneous flaps showed increased enhancement. Fourteen patients received postoperative radiation, 4 of which demonstrated increased enhancement, which subsequently decreased in 3 flaps. Fourteen of 23 followed flaps became smaller over time. CONCLUSIONS On MRI, both myocutaneous and fasciocutaneous flaps placed after orbital exenteration generally demonstrate persistent non-mass-like enhancement and T2 hyperintensity, and both types of flaps may become smaller over time. Head and neck radiologists, ophthalmologic and plastic surgeons, and oncologists should be aware of the range of imaging features of these flaps to avoid misinterpreting the postoperative appearance as tumor recurrence.