Citations

Background: Radiation necrosis (RN) is a clinically relevant complication of stereotactic radiosurgery (SRS) for intracranial metastasis (ICM) treatments. Radiation necrosis development is variable following SRS. It remains unclear if risk factors for and clinical outcomes following RN may be different for melanoma patients. We reviewed patients with ICM from metastatic melanoma to understand the potential impact of RN in this patient population. Methods: Patients who received SRS for ICM from melanoma at Mayo Clinic Arizona between 2013 and 2018 were retrospectively reviewed. Data collected included demographics, tumor characteristics, radiation parameters, prior surgical and systemic treatments, and patient outcomes. Radiation necrosis was diagnosed by clinical evaluation including brain magnetic resonance imaging (MRI) and, in some cases, tissue evaluation. Results: Radiation necrosis was diagnosed in 7 (27%) of 26 patients at 1.6 to 38 months following initial SRS. Almost 92% of all patients received systemic therapy and 35% had surgical resection prior to SRS. Patients with RN trended toward having larger ICM and a prior history of surgical resection, although statistical significance was not reached. Among patients with resection, those who developed RN had a longer period between surgery and SRS start (mean 44 vs 33 days). Clinical improvement following treatment for RN was noted in 2 (29%) patients. Conclusions: Radiation necrosis is relatively common following SRS for treatment of ICM from metastatic melanoma and clinical outcomes are poor. Further studies aimed at mitigating RN development and identifying novel approaches for treatment are warranted.

Background: Prior studies have reported conflicting results of persistent iatrogenic atrial septal defect (iASD) and its impact following a transcatheter edge-to-edge repair (TEER) procedure. This study aims to evaluate the incidence of iASD and its clinical and hemodynamic impact after a TEER. Methods: Consecutive patients who underwent a TEER procedure from June 2014 to September 2020 at the Mayo Clinic were identified. The presence of iASD was retrospectively identified on post-procedure transthoracic echocardiography (TTE) to group patients into an iASD+ group and an iASD− group for comparison of prognosis and cardiac function. Results: A total of 316 patients were included; the mean age was 79.1 ± 9.1 years, and 67.7% were male. Persistent iASD was diagnosed in 108 (34.2%) patients. There was no difference concerning all-cause mortality, heart failure hospitalization, and stroke/TIA between groups at follow-up (median follow-up of 9 months). Post-procedure TTE demonstrated no differences regarding right ventricle (RV) and left ventricle (LV) dimensions and function, including TAPSE (15.2 ± 4.6 vs. 15.4 ± 5.5 mm, p = 0.875), and LV ejection fraction (51.1 ± 14.0% vs. 51.3 ± 13.9%, p = 0.933). However, patients with iASD had higher RV systolic pressure (48.7 ± 14.4 vs. 45.5 ± 14.5 mmHg, p = 0.042) compared with patients without iASD. Conclusion: Notwithstanding higher RV pressures, patients with persistent iASD had no hemodynamic compromise and an equal prognosis compared with those without a residual atrial defect after a TEER procedure. These findings support the mid-term safety of procedures in which an interatrial defect needs to be created and would argue against the need for interventional closure.

Abstract INTRODUCTION Glioblastomas (GBMs) are highly aggressive tumors. A common clinical challenge after standard of care treatment is differentiating tumor progression from treatment-related changes, also known as pseudoprogression (PsP). Usually, PsP resolves or stabilizes without further treatment or a course of steroids, whereas true progression (TP) requires more aggressive management. Differentiating PsP from TP will affect the patient's outcome. This study investigated using deep learning to distinguish PsP MRI features from progressive disease. METHOD We included newly diagnosed GBM patients who met the inclusion criteria, including a new or increasing enhancing lesion size within the original radiation field and who had clinical, medication, and any histopathology available. The interpretation of the MR images at the image inclusion time point had to be indeterminate. We labeled those who subsequently were stable or improved on imaging and clinically as PSP and those with clinical and imaging deterioration as TP. A subset of subjects underwent a second resection. We labeled these subjects as PSP or TP based on the histological diagnosis. We performed skull stripping, coregistered contrast-enhanced T1 MRIs with T2-weighted images for each patient and used them as input to a 3-D Densenet121 model. We used several augmentation techniques and five-fold cross-validation to achieve more robust predictions. RESULT We included 124 patients who met the criteria, and of those, 63 were PsP and 61 were TP. We trained a deep learning model that achieved 76.4% (ranged 70%-84%, SD 5.122) mean accuracy over the 5 folds, 0.7560(ranged 0.6553-0.8535, SD 0.069) mean AUROCC, 88.72% (SD 6.86) mean sensitivity, and 62.05%(SD 9.11) mean specificity. CONCLUSION We report the development of a deep learning model that distinguishes PsP from TP in GBM patients treated per the Stupp protocol. Further refinement and external validation are required prior to widespread adoption in clinical practice.

Abstract PURPOSE Though patients with glioblastoma generally have poor overall survival (OS), OS estimates range significantly. We sought to develop a radiomics-based model predictive of OS in glioblastoma using preoperative MRI scans to identify these differences and guide clinical care. METHODS The primary endpoint was OS, determined from the date of surgery to death or last follow-up. T1, FLAIR, T2, and post-contrast T1 (T1c) MRI sequences were obtained for all patients. Using HD-GLIO-AUTO, lesion segmentation yielded three masks corresponding to the regions of contrast enhancement, non-enhancement, and total volume. Radiomics features were extracted from each region from the T2 and T1c sequences independently (i.e. either from T2 or T1c) and in combination. Age at surgery and gender were also considered. The data was split into training (75%) and test (25%) sets, stratifying for age at surgery. Kaplan-Meier analysis and the Coxnet model were used. For Coxnet, Elastic Net was used as the penalty, with optimization of the L1 coefficient using 5-fold cross-validation and evaluation via the concordance index (C-index). RESULTS From 3 institutions, 383 patients were included. Median OS was 395 days: 346 patients died, and 37 were right-censored. Age > 65 years was predictive of decreased OS (p < 0.005), but gender was not (p=0.16). For the Coxnet model, the C-index was 0.67 (standard deviation: 0.01) considering T2 and T1c sequences for the total lesion volume, with a C-index of 0.65 for the test set. For the enhancing volume, the model had a C-index of 0.71 for the test set using T1c sequences. Overall, C-indices ranged from 0.62-0.71. CONCLUSIONS We present a novel radiomics-based model predictive of OS in glioblastoma across a multi-institutional dataset. Ongoing efforts will incorporate immediate postoperative imaging and IDH and MGMT status into the proposed model to further improve prognostic ability and help guide clinical decision-making.

AbstractBackgroundBoth dose and linear energy transfer (LET) could play a substantial role in adverse event (AE) initialization of cancer patients treated with pencil‐beam‐scanning (PBS) proton therapy. However, not all the voxels within the AE regions are directly induced from the dose and LET effect. It is important to study the synergistic effect of dose and LET in AE initialization by only including a subset of voxels that are dosimetrically important.PurposeTo perform exploratory investigation of the dose and LET effects upon AE initialization in PBS using seed spots analysis.MethodsA total of 113 head‐and‐neck (H&N) cancer patients receiving curative PBS were included. Among them, 20 patients experienced unanticipated CTCAEv4.0 grade ≥3 AEs (AE group) and 93 patients did not (control group). Within the AE group, 13 AE patients were included in the seed spot analysis to derive the descriptive features of AE initialization and the remaining 7 mandible osteoradionecrosis patients and 93 control patients were used to derive the feature‐based volume constraint of mandible osteoradionecrosis. The AE regions were contoured and the corresponding dose–LET volume histograms of AE regions were generated for all patients in the AE group. We selected high LET voxels (the highest 5% of each dose bin) with a range of moderate‐to‐high dose (≥∼40‐Gy relative biological effectiveness) as critical voxels. Critical voxels that were contiguous with each other were grouped into clusters. Each cluster was considered a potential independent seed spot for AE initialization. Seed spots were displayed in a 2D dose–LET plane based on their mean dose and LET to derive the descriptive features of AE initialization. A volume constraint of mandible osteoradionecrosis was then established based on the extracted features using a receiver operating characteristic curve.ResultsThe product of dose and LET (xBD) was found to be a descriptive feature of seed spots leading to AE initialization in this preliminary study. The derived xBD volume constraint for mandible osteoradionecrosis showed good performance with an area under curve of 0.87 (sensitivity of 0.714 and specificity of 0.807 in the leave‐one‐out cross‐validation) for the very limited patient data included in this study.ConclusionOur exploratory study showed that both dose and LET were observed to be important in AE initializations. The derived xBD volume constraint could predict mandible osteoradionecrosis reasonably well in the very limited H&N cancer patient data treated with PBS included in this study.

Metastatic neuroendocrine tumour (NET) to brain has been reported in 1.5–5% of patients with NETs. Differentiation between intracranial NET metastasis and meningiomas can cause a diagnostic dilemma. We present a symptomatic case of a 66-year-old male with a history of left-sided skull base mass. The diagnosis of a meningioma was made based on the MRI findings and clinical presentation. The patient received radiation and the mass remained stable on serial MRI images at follow-up visits. Five years after his initial presentation, the patient’s mass showed further growth. He also complained of worsening of his recent diagnosis of irritable bowel syndrome and fluctuations in his blood pressure. Surgical resection was performed, and histopathological features were consistent with moderately differentiated neuroendocrine tumour. Further evaluation with 68 Gallium-DOTATATE positron emission-computed tomography (Ga-68 PET/CT) showed metastatic disease involving the bones, lymph nodes, and liver without convincing evidence of the location of primary malignancy within the bowel loops or the pancreas. The patient was started on combination of capecitabine and temozolomide with partial response and significant improvement of his symptoms. This case highlights the clinical and radiological behaviour of intracranial NET that can mimic the diagnosis of meningioma.

OBJECTIVE Multiple meningiomas (MMs) occur in as many as 18% of patients with meningioma, and data on progression-free survival (PFS) are scarce. The objective of this study was to explore the influence of the number of lesions and clinical characteristics on PFS in patients with WHO grade I meningiomas. METHODS The authors retrospectively reviewed the records of all adults diagnosed with a meningioma at their three main sites from January 2009 to May 2020. Progression was considered the time from diagnosis until radiographic growth of the originally resected meningioma. A secondary analysis was performed to evaluate the time of diagnosis until the time to second intervention (TTSI). Univariable and multivariable analyses were conducted to assess whether the number of lesions or any associated variables (age, sex, race, radiation treatment, tumor location, and extent of resection) had a significant impact on PFS and TTSI. RESULTS Eight hundred thirty-eight patients were included. Use of a log-rank test to evaluate PFS and TTSI between a single and multiple lesions showed a significantly shorter progression for MM (p < 0.001 and p < 0.001, respectively). Multivariable Cox regression analysis showed significantly inferior PFS on MM compared to a single lesion (hazard ratio [HR] 2.262, 95% confidence interval [CI] 1.392–3.677, p = 0.001) and a significantly inferior TTSI for patients with MM when compared to patients with a single meningioma (HR 2.377, 95% CI 1.617–3.494, p = 0.001). By testing the number of meningiomas as a continuous variable, PFS was significantly inferior for each additional meningioma (HR 1.350, 95% CI 1.074–1.698, p = 0.010) and TTSI was significantly inferior as well (HR 1.428, 95% CI 1.189–1.716, p < 0.001). African American patients had an inferior PFS when compared to non-Hispanic White patients (HR 3.472, 95% CI 1.083–11.129, p = 0.036). CONCLUSIONS The PFS of meningiomas appears to be influenced by the number of lesions present. Patients with MM also appear to be more prone to undergoing a second intervention for progressive disease. Hence, a closer follow-up may be warranted in patients who present with multiple lesions. These results show a decreased PFS for each additional lesion present, as well as a shorter PFS for MM compared to a single lesion. When assessing associated risk factors, African American patients showed an inferior PFS, whereas older age and adjuvant therapy with radiation showed an improved PFS.

Abstract IntroductionRadiotherapy is considered standard of care for adjuvant peri-operative treatment of many spinal tumors, including those with instrumented fusion. Unfortunately, radiation treatment has been linked to increased risk of pseudoarthrosis. Newerfocused radiotherapy strategies with enhanced conformalitycould offer improved fusion rates for these patients, but this has not been confirmed.MethodsWe performed a retrospective analysis of patients at three tertiary care academic institutions withprimary and secondary spinal malignancies that underwent resection, instrumented fusion, and peri-operative radiotherapy. Two board certified neuro-radiologists used theLenke fusion score to grade fusion status at6 and 12-months after surgery. Secondary outcomes includedclinical pseudoarthrosis, wound complications, and the effect of radiation timing, radiobiological dose delivered, the use of photons versus protons, tumor type, tumor location,and use of autograft on fusion outcomes.ResultsAfter reviewof 1252 spinal tumor patients, there were 60 patients with at least 6 months follow-up that were included in our analyses. Twenty-five of these patients received focused radiotherapy,20 patients received conventional radiotherapy, and 15 patients were treated with protons. There was no significant difference between the groups for covariates such assmoking status,obesity, diabetes, intraoperative use of autograft, and use of peri-operative chemotherapy. There was a significantly higher rate of fusion for patients treated with focused radiotherapy compared to those treated with conventional radiotherapy at 6-months (64.0% versus 30.0%, Odds ratio: 4.15, p=0.036) and 12-months (80.0% versus 42.1%, OR: 5.50, p=0.022). There was a significantly higher rate of clinical pseudoarthrosis in the conventional radiotherapy cohortcompared to patients in the focused radiotherapy cohort (19.1% versus 0%,p=0.037). There was no difference in fusion outcomes for any of the secondary outcomes except for use of autograft. The use ofintra-operative autograft was associated with an improved fusion at 12-months (66.7% versus 37.5%, OR: 3.33, p=0.043). ConclusionFocused radiotherapy may be associated withan improved rate of fusion and clinical pseudoarthrosis when compared to conventional radiation delivery strategiesin patients with spinal tumors.Use of autograft at the time of surgery may be associated with improved 12-month fusion rates.Further large-scale prospective and randomized controlled studies are needed to better stratify the effects of radiation delivery modality in these patients.

OBJECTIVE The authors aimed to demonstrate the feasibility and advantages of carbon fiber–reinforced PEEK (CFRP) composite implants in patients with both primary and secondary osseous spinal tumors. METHODS Twenty-eight spinal tumor patients who underwent fixation with CFRP hardware were retrospectively identified in a Spine Tumor Quality Database at a single institution. Demographic, procedural, and follow-up data were retrospectively collected. RESULTS The study population included 14 females and 14 males with a mean age of 60 years (range 30–86 years). Five patients had primary bone tumors, and the remaining patients had metastatic tumors. Breast cancer was the most common metastatic tumor. The most common presenting symptom was axial spine pain (25 patients, 89%), and the most common Spine Instability Neoplastic Score was 7 (range 6–14). Two patients in this series had anterior cervical procedures. The remaining patients underwent posterior thoracolumbar fixation. The average fusion length included 4.6 vertebral segments (range 3–8). The mean clinical follow-up time with surgical or oncology teams was 6.5 months (range 1–23 months), and the mean interval for last follow-up imaging (CT or MRI) was 6.5 months (range 1–22 months). Eighteen patients received postoperative radiation at the authors’ institution (16 with photon therapy, 2 with proton therapy). Eleven of the patients (39%) in this series died. At the last clinical follow-up, 26 patients (93%) had stable or improved neurological function compared with their preoperative status. At the last imaging follow-up, local disease control was observed in 25 patients (89%). Two patients required reoperation in the immediate postoperative period, one for surgical site infection and the other for compressive epidural hematoma. One patient was noted to have lucencies around the most cephalad screws 3 months after surgery. No hardware fracture or malfunction occurred intraoperatively. No patients required delayed surgery for hardware loosening, fracture, or other failure. Early tumor recurrence was detected in 3 patients. Early detection was attributed to the imaging characteristics of the CFRP hardware. CONCLUSIONS CFRP spinal implants appear to be safe and comparable to conventional titanium implants in terms of functionality. The imaging characteristics of CFRP hardware facilitate radiation planning and assessment of surveillance imaging. CFRP hardware may enhance safety and efficacy, particularly with particle therapy dosimetry. Larger patient populations with longer-term follow-up are needed to confirm the various valuable aspects of CFRP spinal implants.

Objective: To evaluate the incidence of and characterize the presentation of neuropsychiatric symptoms and/or Parkinsonism as a presentation of central nervous system lymphoma (CNSL) in either its primary CNSL form or when it spreads to the brain in systemic diffuse large B-cell lymphoma (secondary CNSL). Patients and Methods: With Institutional Review Board approval we identified patients who had been treated at Mayo Clinic from 1998 to 2018 and were recorded to have a combination of ICD 9/10 codes for CNSL and various psychiatric diagnoses. Results: A total of 20 of the 232 patients (9%) were noted to have neuropsychiatric symptoms preceding diagnosis. The average age at diagnosis was 62, with even split for sex. The majority (85%) of patients had primary CNSL. The average duration of symptoms before the diagnosis was 4.8 months. Confusion (80%), depression (40%), apathy (30%), anxiety (30%), and agitation (30%) were the most common symptoms identified. The majority (65%) of patients had subcortical lesions followed by the frontal lobe (50%). Parkinsonism was identified in 5 of the 20 patients with 4 demonstrating resolution of symptoms with treatment of the lymphoma. Conclusions: Neuropsychiatric symptoms are a rare but notable symptom before the presentation of CNSL. There is an increasing awareness of neurological illness presenting as pure psychiatric disturbance, prompting the need to exclude organic and treatable diseases, particularly in elderly patients. Acknowledgment and diagnosis are important for an appropriate management as there is a significant impact on patient and caregiver quality of life.