Butterfield, Richard

Objective:Radiation therapy (RT) is the primary treatment of intracranial metastasis (ICM) from lung cancer (LC). Radiation necrosis (RN) has been reported post-RT with an incidence of 5% to 24%. We reviewed the spectrum of imaging changes in patients treated with RT for ICM from LC in an effort to identify potential risk factors for RN.Methods:We reviewed 63 patients with LC and ICM who received RT (radiosurgery [stereotactic radiosurgery] with/without whole brain radiation therapy) at our institution between 2013 and 2018. Data evaluated included demographics, tumor type, ICM burden and location, chemotherapy, surgery, and RT details as well as treatment choices and outcomes.Results:Of the 63 patients, clinical and radiographic criteria for RN were noted in 24 (38%) as early as 2 months and as late as 5 years posttreatment. Six patients required surgical resection due to refractory symptoms revealing pathology-proven RN and occasionally tumor. Patients were significantly more likely to develop RN if they had surgical resection of an ICM (45.8% vs. 20.5%,P=0.05). No differences were found in location, size, or genetic profile of lesions. In total, 80% of patients received treatment for symptoms and/or radiographic change. This was generally a combination of steroids, bevacizumab, laser interstitial thermal treatment, or surgical resection. Most patients required >1 treatment modality.Conclusions:This review of outcomes of RT for ICM in LC demonstrates a higher rate of RN than previously reported in the literature in those having had a surgical resection plus stereotactic radiosurgery. Our observation of RN as late as 5 years post-RT for ICM necessitates clinician awareness.

Abstract INTRODUCTION Locations of gliomas may influence clinical presentations, molecular profiles, treatment options, and prognoses. Using the Mayo Clinic Arizona Cancer Center registry, we analyzed the frequency at which gliomas were identified in different regions of the brain. We evaluated molecular profiles, clinical courses and survival by anatomic location. METHODS Registry was queried to include patients with glioma over a 10-year period. Statistical analyses were used to compare demographic, genetic, and clinical characteristics among patients with gliomas in different locations. RESULTS 182 gliomas were identified. Of the tumors confined to a single lobe, there were 51 frontal (28.0%), 50 temporal (27.5%), 22 parietal (12.1%), and 7 occipital tumors (3.8%) identified. Multifocal disease was noted in 38 patients (20.9%). Tumors affecting temporal lobe were associated with reduced overall survival when compared to all other tumors (11.0 months vs. 13.0 months, log-rank p=0.0068). However, this disparity became insignificant when adjusted for tumor grade, age, and surgical approach [HR(95% CI) 1.26(0.87, 1.82), p=0.212]. Out of 82 cases tested for IDH-1, 10 were mutated (5.5%). IDH-1 mutation was present in 6 frontal, 2 temporal, 1 thalamic, and 1 multifocal tumor. Out of 21 cases tested for 1p19q deletions, 12 were co-deleted, 9 of which were frontal lobe tumors. MGMT methylation was assessed in 45 cases; 7 of 14 frontal tumors and 6 of 13 temporal tumors were methylated. ATRX loss was detected in 2/42 assessed cases. CONCLUSION Our results support the hypothesis that the anatomical locations of gliomas influence patients’ clinical courses. Tumors involving the temporal lobe were associated with poorer survival, though this association appeared to be driven by these patients’ more aggressive tumor profiles and higher risk baseline demographics. Molecular analysis was limited by low prevalence of genetic testing in the study sample, highlighting the importance of capturing this information for all gliomas.

Abstract BACKGROUND Radiation is an integral component of the multidisciplinary treatment of patients with intracranial metastasis (ICM) from melanoma. The risk of radiation necrosis (RN) post-treatment can range from 5–25%. We retrospectively evaluated pre- and post-radiation clinical and radiographical characteristics in patients with ICM from melanoma to identify potential risk factors for RN. METHODS After IRB approval, patients with ICM from melanoma who received radiation at our institution between 2013 and 2018 were retrospectively reviewed. We recorded demographics, intracranial metastasis (burden and location), systemic therapy, resection, stereotactic radiosurgery versus whole brain radiation, and outcomes. Brain MRI was evaluated using the Response Assessment in Neuro-Oncology criteria (RANO). RESULTS A total of 27 patients were included in the study. RN was diagnosed in 14 patients (52%) at one month to three years following radiation. Cerebellar location (n=7) was significantly associated with RN (p=0.0058). Metastasis-associated hemorrhage was present in 7 patients, 6 of which developed RN (43% vs 8%, p=0.08). Surgical resection prior to radiation was performed in 9 patients, 7 of which developed RN (50% vs 15%, p=0.1). RN appeared to be less often diagnosed when ICM were treated with higher doses of radiation (24 Gy vs 20 Gy, p=0.07). Systemic treatment was administered prior to radiation in 25 patients and we found no relationship with systemic therapy type and RN. Presumed RN was treated in 12 of 14 patients (86%). Steroids or surgical resection were the primary treatment modalities, with laser ablation used in 1 case. Following treatment, improvement was noted in 3 patients radiographically and in 1 of these clinically. CONCLUSIONS This series of patients with radiotherapy-treated brain metastases from melanoma reveals cerebellar involvement, hemorrhage, and prior surgical resection as potential risk factors for radiation necrosis. Neoadjuvant systemic treatment did not appear to be a risk factor in our review.

Abstract Objective Breast implant augmentation is the most common cosmetic surgical procedure performed in the United States. The purpose of this study was to determine if patients with breast augmentation surgery are aware of the effect of breast implants on the mammographic detection of cancer. Methods An institutional review board exempt patient awareness survey was distributed at a single breast imaging facility to women undergoing screening mammography. Comparative statistical analyses were performed between patients with and without breast implants. Results The respondents were divided into three groups: no prior breast surgery (74%; 524/711), breast surgery with implants (21%; 152/711), and breast surgery without implants (5%; 35/711). Patients with breast implants were more aware that implants decrease the amount of breast tissue seen on a mammogram (75%; 105/141) and that implants result in the need for more mammogram views (70%; 103/147), as compared with patients with no surgery (46%; 221/484 and 31%; 147/478, respectively) (P < 0.001). More women with breast implants reported learning from breast imaging staff rather than from their surgeon that implants decrease the amount of breast tissue seen on a mammogram (46%; 49/106 vs. 38%; 40/106). Of 137 respondents, 35% (n = 48) reported that the effect of implants on their mammogram was discussed preoperatively. Of those who did not recall a preoperative discussion, 42% (16/38) indicated this knowledge would have factored into their decision to get breast implants. Conclusion This study highlights an opportunity for providers to engage in more education and shared decision-making with patients considering breast augmentation surgery to ensure preoperative counseling includes discussion of the effect of implants on mammography.

Abstract Background: Myelofibrosis (MF) is a bone marrow disorder characterized by anemia, splenomegaly and constitutional symptoms. There has been substantial work documenting quality of life (QoL) in patients with MF, however, very little data about patients following allogeneic stem cell transplant (alloSCT) for MF. Many patients decline alloSCT due to concerns secondary to QoL. Methods: Medical facts and patient reported outcomes (PRO) measures were collected within a month prior to transplant, at day 30, 100 and 1 year post alloSCT. PRO measures include Brief Fatigue Inventory, Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), global assessment of change and the Myeloproliferative Neoplasms Symptom Assessment Form (MPN-SAF). The group was measured as a whole, and the patients in the upper quartile of MPN-TSS (the aggregate score of the 10 core items of the MPN-SAF) were also considered. Results: Fifty patients were enrolled on this study, 47 who proceeded with transplant. The median age of the patients was 63, ranging from 35-74. The majority of the patients were male (29, 66%), and Caucasian (43 (96%)). Most patients had primary MF (26, 59%), 9 patients had post-PV MF, and 9 patients had post-ET MF. Twenty patients had DIPSS Intermediate 2 risk disease, and 16 had DIPSS high risk disease. Twenty-six (51%) had a matched unrelated donor, 12 (30%) had a matched related donor and 5 (12%) had a mismatched unrelated donor. The majority of the patients had RIC regimens (35, 88%). At baseline the mean MPN-TSS was 27.7 (out of possible 100), and at day 30, day 100 and 1 year it was 24.6, 32.0, and 25.0, which reflected no significant change between the time points. Interestingly, all the MPN specific symptoms (including fevers, night sweats, pruritis, abdominal pain) had a significant improvement at least one time point following alloSCT. Patients in the highest quartile based on baseline TSS score (12 patients with scores at baseline greater than or equal to 37), had significant improvement in TSS score at day 100, headache at day 30, insomnia at day 100, night sweats at day 100, itching at day 100 and overall QOL at day 100. With regards to the FACT BMT, as would be expected, there was a significant decline in the FACT BMT total score, as well as trial outcome index (TOI) at day 30, but a return to close to baseline by one year. In the global assessment of change, on day 30, 11 (27.5%) of patients reported feeling a little/moderately/very much better overall quality of life since their transplant and 27 (67.5%) felt a little/moderately/very much worse quality of life. At day 100, 11 (31.4%) reported better quality of life and 20 (57%) reported worsening since transplant. By one year, 17 (60.7%) reported feeling better and 7 (25%) reported worsening. These findings did not appear to have a correlation with presence or absence of graft versus host disease. We were unable to assess the impact of conditioning as the majority of the patients had RIC conditioning. Discussion/ Conclusions: Our study evaluated the quality of life in patients with myelofibrosis who have undergone bone marrow transplantation. We have shown that there is very little change in symptom burden over the first year following transplant in general; however, significant improvement was observed in MF specific symptoms, and in patients who had a high symptom burden at baseline. By one year 61% felt that their QoL was better than it was prior to transplant. Our findings suggest that many of the patients do not experience a significant decline in QoL at 1 year after alloSCT, and actually report that their QoL improves. Further investigation is required to validate these findings. Figure. Figure. Disclosures Palmer: Novartis: Research Funding. Dueck:Phytogine: Employment; Pfizer: Honoraria; Bayer: Employment. Mesa:Novartis: Consultancy; NS Pharma: Research Funding; Incyte Corporation: Research Funding; UT Health San Antonio - Mays Cancer Center: Employment; Pfizer: Research Funding; CTI Biopharma: Research Funding; Celgene: Research Funding; Promedior: Research Funding; Gilead: Research Funding; Genentech: Research Funding.

Objectives (1) To perform a systematic literature review to evaluate associations between post‐dural puncture headache (PDPH) and opening pressure (OP), closing pressure (CP), and volume of cerebrospinal fluid (V) removed. (2) To perform a case‐control study to evaluate pressure‐volume index (PVI) as a novel risk factor for PDPH. Background According to the International Classification of Headache Diagnoses, 3rd Edition (ICHD‐3), the diagnosis of PDPH requires documentation of intracranial hypotension. However, this remains an unproven concept. Methods A systematic literature review was conducted, searching Cochrane Database of Systematic Reviews, Ovid EMBASE, OVID MEDLINE, Scopus, and Web of Science. Study inclusion required a comparison of headache incidence following a LP as a function of OP, CP, and/or V. A retrospective, case‐control study with 1:1 matching was conducted utilizing ICHD‐3 criteria. Patients with factors that could influence CSF pressure were excluded. Results In our case‐control study, we did not identify a paired difference in either median (95% CI) elastance (0.05 [−0.09, 0.11], P = .503) or PVI (4.53 [−7.98, 19.97], P = .678). We identified 22 references, evaluating V (n = 14), OP (n = 11), and/or CP (n = 4). There was no convincing evidence for an association of PDPH with either OP or CP. A minority of studies documenting an association with V included patients with high‐volume CSF removal, and/or stratified patients by the timing of the headache onset. Conclusions The overall risk of PDPH does not appear to be influenced by OP, CP, V or PVI. PDPH may be related to V in instances of high‐volume removal, and depend on the timing of outcome assessment. Future revision of criteria should consider the existence of immediate and delayed PDPH subtypes, and not presume intracranial hypotension as a mandatory feature.

Abstract Background Guidelines to provide recommendations about driving restrictions for patients with brain metastases are lacking. We aim to determine whether clinical neurologic examination is sufficient to predict suitability to drive in these patients by comparison with an occupational therapy driving assessment (OTDA). Methods We prospectively evaluated the concordance between neurology assessment of suitability to drive (pass/fail) and OTDA in 41 individuals with brain metastases. Neuro-oncology evaluation included an interview and neurological examination. Participants subsequently underwent OTDA during which a battery of objective measures of visual, cognitive, and motor skills related to driving was administered. Results The mean age of patients who failed OTDA was age 68.9 years vs 59.3 years in the group members who passed (P = .0046). The sensitivity of the neurology assessment to predict driving fitness compared with OTDA was 16.1% and the specificity 90%. The 31 patients who failed OTDA were more likely to fail Vision Coach, Montreal Cognitive Assessment, and Trail Making B tests. Conclusions There was poor association between the assessment of suitability to drive by neurologists and the outcome of the OTDA in patients with brain metastases. Subtle deficits that may impair the ability to drive safely may not be evident on neurologic examination. The positive predictive value was high to predict OTDA failure. Age could be a factor affecting OTDA performance. The results raise questions about the choice of assessments in making recommendations about driving fitness in people with brain metastases. OTDA should be strongly considered in patients with brain metastases who wish to continue driving.

5063 Background: The systemic therapies available to patients with metastatic prostate cancer (mPC) have improved dramatically over the past decade. Prior to 2010, the only agents with a proven survival benefit for patients with metastatic disease were androgen deprivation therapy and docetaxel. Since then, five new agents have been FDA approved and have proven survival benefit in phase III trials. Anecdotal experience suggests that the increased available lines of therapy have changed the profile of mPC to include a higher prevalence of visceral metastases. Methods: A retrospective review of 474 patients with prostate cancer who died in 2009 and in 2016 was performed. Patients with metastatic disease who had imaging within 6 months of death were included. A total of 164 patients were eligible for analysis. Results: Mean age at death overall was 77.4 years (SD 9.5) and did not differ signifiantly by cohort. Overall rates of visceral and distant metastases to include lung, liver, adrenal, brain, renal, spleen, and thyroid, were higher in patients who died in 2016 as compared to those who died in 2009 (40.0% and 26.1%, respectively, p = 0.07). Lung metastases were more prevalent in patients who died in 2016 versus in 2009 at 26.3% and 13.0%, respectively (p = 0.05). Patients who died in 2009 received a median of 3 (range 1-10) systemic treatments versus 4 (range 0-13) in those who died in 2016 (p = 0.005). Forty-four percent of patients who died in 2016 used five or more lines of systemic treatments compared to 26.1% of patients in 2009. Conclusions: The emergence of new systemic therapies for mPC is changing the natural history of the disease. Forty percent of patients now develop visceral metastases compared to 26% in the past. These changes will drive the need for new treatment approaches targeting visceral metastases. [Table: see text]

Abstract Background Women may benefit from radial artery access (RAA) for percutaneous coronary interventions (PCI) due to a higher risk of bleeding compared to men; however, RAA may be underutilized in women. We sought to determine the frequency and predictors of RAA use in patients undergoing PCI. Methods We studied 21,123 (29.0% female) participants in the Mayo Clinic PCI Registry from January 1, 2006–December 31, 2016. Data were analyzed as a cohort and by time tertiles. Frequency of RAA versus femoral access and bleeding events were recorded. Logistic regression was used to identify predictors of RAA. Results In the overall cohort, women compared to men were older (69.6 ± 12.6 vs. 65.6 ± 11.9; p < .001), more likely to present with acute coronary syndrome (82.0% in women vs. 80.0% in men; p = .0008) and had more comorbidities. RAA increased from tertile one (3.5% for women vs. 4.0% for men; p = .3) through tertile three (46.8% for women vs. 50.3% for men; p = .01), but remained lower in women. In multivariable analysis, female sex is associated with 22% less RAA use (OR 0.78, 95% CI 0.72–0.84; p < .0001). Women compared to men experienced more bleeding (6.3 vs. 3.0%; p < .0001) but bleeding was less likely in RAA (OR 0.45, 95% CI 0.36–0.56; p < .0001). Conclusion Women undergoing PCI are less likely to receive RAA compared to men despite having a higher risk of bleeding. This trend persists despite increase in RAA use. Given the potential benefit of RAA in women, sex should be considered in patient selection for RAA.