Citations

Abstract Objective . Interleaved reverse-gradient fMRI (RG-fMRI) with a point-spread-function (PSF) mapping-based distortion correction scheme has the potential to minimize signal loss in echo-planar-imaging (EPI). In this work, the RG-fMRI is further improved by imaging protocol optimization and application of reverse Fourier acquisition. Approach . Multi-band imaging was adapted for RG-fMRI to improve the temporal and spatial resolution. To better understand signal dropouts in forward and reverse EPIs, a simple theoretical relationship between echo shift and geometric distortion was derived and validated by the reliable measurements using PSF mapping method. After examining practical imaging protocols for RG-fMRI in three subjects on both a conventional whole-body and a high-performance compact 3 T, the results were compared and the feasibility to further improve the RG-fMRI scheme were explored. High-resolution breath-holding RG-fMRI was conducted with nine subjects on the compact 3 T and the fMRI reliability improvement in high susceptibility brain regions was demonstrated. Finally, reverse Fourier acquisition was applied to RG-fMRI, and its benefit was assessed by a simulation study based on the breath-holding RG-fMRI data. Main results . The temporal and spatial resolution of the multi-band RG-fMRI became feasible for whole-brain fMRI. Echo shift measurements from PSF mapping well estimated signal dropout effects in the EPI pair and were useful to further improve the RG-fMRI scheme. Breath-holding RG-fMRI demonstrated improved fMRI reliability in high susceptibility brain regions. Reverse partial Fourier acquisition omitting the late echoes could further improve the temporal or spatial resolution for RG-fMRI without noticeable signal degradation and spatial resolution loss. Significance . With the improved imaging scheme, RG-fMRI could reliably investigate the functional mechanisms of the human brain in the temporal and frontal areas suffering from susceptibility-induced functional sensitivity loss.

Abstract OBJECTIVE Using individual pharmacogenomic phenotypes to investigate the factors affecting the efficacy and tolerability of verapamil for migraine prevention. BACKGROUND Verapamil has a wide range of dosing in headache disorders without reliable tools to predict the optimal doses for an individual. METHODS This is a retrospective chart review examining adults with existing pharmacogenomic reports at Mayo Clinic who had used verapamil for migraine. Effects of six cytochrome P450 phenotypes on the minimum effective and maximum tolerable verapamil doses for migraine prevention were assessed. RESULTS The mean minimum effective and maximum tolerable doses for the 33 patients in final analysis were 178.2(20–320) mg and 227.9(20–480) mg. A variety of CYP2C9, CYP2D6, and CYP3A5 phenotypes were found, without significant association with the verapamil doses after adjusting for age, sex, body mass index, and smoking status. CONCLUSIONS We demonstrated a wide range of effective and tolerable verapamil doses used for migraine in a cohort with various pharmacogenomic phenotypes.

OBJECTIVE Stereotactic radiosurgery (SRS) is an effective treatment for intracranial metastatic disease, but its role in triple-negative breast cancer requires further study. Herein, the authors report overall survival (OS) and local tumor control in a multiinstitutional cohort with triple-negative breast cancer metastases treated with SRS. METHODS Patients treated from 2010 to 2019 at 9 institutions were included in this retrospective study if they had biopsy-proven triple-negative breast cancer with intracranial metastatic lesions treated with SRS. Patients were excluded if they had undergone prior SRS, whole-brain radiation therapy, or resection of the metastatic lesions. A retrospective chart review was conducted to determine OS, local control, and treatment efficacy. RESULTS Sixty-eight patients with 315 treated lesions were assessed. Patients had a median Karnofsky Performance Status of 80 (IQR 70–90) and age of 57 years (IQR 48–67 years). Most treated patients had 5 or fewer intracranial lesions, with 34% of patients having a single lesion. Treated lesions were small, having a median volume owf 0.11 cm3 (IQR 0.03–0.60 cm3). Patients were treated with a median margin dose of 18 Gy (IQR 18–20 Gy) to the median 71% isodose line (IQR 50%–84%). Overall, patients had a 1-year OS of 43% and 2-year OS of 20%. Most patients (88%) were followed until death, by which time local tumor progression had occurred in only 7% of cases. Furthermore, 76% of the lesions demonstrated regression. Tumor volume was correlated with local tumor progression (p = 0.012). SRS was very well tolerated, and only 3 patients (5%) developed symptomatic radiation necrosis. CONCLUSIONS SRS is a safe and efficacious treatment for well-selected patients with triple-negative breast cancer, especially for those with a favorable performance status and small- to moderate-volume metastatic lesions.

Abstract Treatment options for glioblastoma remain limited, particularly for those who are not eligible for traditional resection, whether due to lesion location or inability to tolerate open craniotomy. Maximal-safe resection followed by radiation with concurrent and adjuvant temozolomide offers the best outcomes for patients. Unfortunately, not all tumors are amenable to conventional surgical resection at the time of diagnosis with only about 1/3 of patients able to receive a gross-total resection and 15-25% of patients receiving biopsy only, thus reducing their projected overall survival to 9 months. Laser interstitial thermal therapy (LITT) is a minimally invasive, cytoreductive tool, that has demonstrated safety as a surgical approach to treat primary brain tumors. METHODS Data from LAANTERN prospective multicenter registry (NCT02392078) was analyzed to determine clinical outcomes for patients with new and recurrent IDH wild-type glioblastoma (N=89). Demographics, intraprocedural data, adverse events, KPS, health-economics, and survival data were prospectively collected then analyzed separately for newly diagnosed GBM (N=29) and recurrent GBM (N=60). RESULTS Median overall-survival was 9.73 months (95% CI: 5.16, 15.91) for newly diagnosed patients and median post-procedure survival was 8.97 (6.94, 12.36) months for recurrent patients. Median overall-survival for newly diagnosed patients receiving post-LITT chemoradiotherapy was 16.14 months (6.11, not reached). The median length of hospital stay was 50 hours and 80% of patients were discharged to home. CONCLUSIONS LITT offers an effective cytoreductive approach for patients with newly diagnosed and recurrent IDH wild-type glioblastoma. Importantly, its use in newly diagnosed patients who receive post-LITT chemoradiotherapy leads to a median OS similar to that of patients treated with conventional surgical resection. LITT remains an important alternative for patients with inoperable tumors or those not amenable to resection. Enrollment in LAANTERN is ongoing and these cohorts will be revisited as data continues to mature. Benefits beyond cytoreduction are also being actively explored.

AbstractAcute treatments for migraine and cluster headache are necessary to abort attacks, relieve pain and associated symptoms, and restore an individual's ability to function. Acute headache treatments consist of a variety of medication and nonmedication options. In this article, we discuss the approach to acute treatment of migraine and cluster headache. We summarize the level of evidence to support each acute medication class according to recent systematic reviews and meta-analyses, as well as guideline recommendations from the American Headache Society, American Academy of Neurology, and European Federation of Neurological Society.

Abstract Objective To provide an overview of the current available literature on peripheral nerve blocks for the management of migraine and other headache disorders in adults. Background Peripheral nerve blocks have been commonly performed in the headache practice for migraine, cluster headache, occipital neuralgia, and other headache disorders, despite a paucity of evidence supporting their use historically. In the past decade, there has been an effort to explore the efficacy and safety of peripheral nerve blocks for the management of headache, with the greatest interest centered around greater occipital blocks. Design We performed a search in PubMed using key words including “occipital nerve blocks,” “peripheral nerve blocks,” “occipital nerve,” “migraine,” “cluster headache,” and “neuralgia.” We reviewed the randomized controlled trials (RCTs), observational studies, and case series, and summarized the anatomy, techniques, and the evidence for the use of peripheral nerve blocks in different headache disorders, with particular focus on available RCTs. Case reports were included for a detail review of adverse events. Results Of 12 RCTs examining the use of greater occipital nerve blocks for migraine, all but one demonstrate efficacy with reduction in headache frequency, intensity, and/or duration compared to placebo. Studies have not demonstrated a difference in clinical outcomes with the use of corticosteroids for nerve blocks compared to blocks with local anesthetic in the treatment of migraine. There are two RCTs supporting the use of greater occipital blockade for cluster headache, both showing benefit of suboccipitally injected corticosteroid. One RCT suggests benefit of greater occipital nerve blocks for cervicogenic headache. Observational studies and case series/reports show that greater occipital nerve block may be effective in prolonged migraine aura, status migrainosus, post‐dural puncture headache, and occipital neuralgia. Overall, peripheral nerve blocks are well tolerated. Serious side effects are rare but have been reported, including acute cerebellar syndrome and infection. Conclusions Peripheral nerve blocks, especially occipital nerve blocks, are a viable treatment option for migraine and may be helpful in cluster headache as a transitional therapy or rescue therapy. Additional prospective studies are needed to investigate the efficacy and safety of occipital nerve blocks for long‐term migraine prevention, as well as for other headache disorders, such as occipital neuralgia.

Prostate cancer (PCa) accounted for more than 34,000 deaths in US males [...]

Abstract Multiple Myeloma (MM) is a hematologic malignancy marked by uncontrolled clonal expansion of plasma cells. Previous research has examined single-cell transcriptome profiles of Monoclonal gammopathy of undetermined significance (MGUS) and MM tumor microenvironment (TME) and found that natural killer (NK) cell abundance is elevated in the early stages and correlated with altered chemokine receptor expression. This study suggested the critical role of immune cells on myeloma progression from asymptomatic MGUS to symptomatic MM. Up to date, however, there are no published studies comprehensively comparing tumor and immune populations differences between MM NON-progressors (NPs) and FAST-progressors (FPs) and investigating how clonal plasma cells affect disease progression in a large cohort. Therefore, understanding how tumor and immune cells influence disease progression within symptomatic MM is of great interest.Here, we subjected CD138-negative Bone Marrow Mononuclear cells (BMMC) samples from 418 MM patients to scRNA-seq. From MMRF CoMMpass study (NCT01454297), we also have whole exome sequencing (WES) and bulk RNA-seq from CD138-positive fraction of BMMC samples. Based on time to progressive disease (TTPD), we classified patients into 2 categories. Patients with TTPD less than 18 months were classified as FAST-progressors (FPs), whereas patients with TTPD more than 5 years were classified as NON-progressors (NPs). By analyzing patient genomic alterations and its association with progression, we found that there was a significant association of slow MM progression with t(11;14) (p = 0.048), consistent with previous study. In our preliminary analysis, we profiled 83 CD138-sorted MM bone marrow samples using scRNA-seq. Interestingly, we found plasma cells from samples with the same genetic alterations tend to cluster together, highlighting the important role of genetic drivers in transcriptome profiles of plasma cells. Moreover, integrated analysis of bone marrow samples from 83 MM patients and 4 healthy donors revealed an atypical naïve-B cell subset with enrichment of cells from fast-progressors and partial expression of MS4A1. Differentially expressed genes for this naïve-B cell subset includes KLF9, BCL2L11, JOSD1, and IRS2, etc. Overall, as part of MMRF immune profiling research, this study will help to interrogate how genetic alterations and disease progression interplay MM tumor and TME and provide a sufficiently broad and valuable dataset for systematically characterizing MM at single-cell resolution. Hopefully, this study could identify novel targets for MM immunotherapies, and ultimately identify patients with high risk of fast progression for early intervention in the clinic. Citation Format: Lijun Yao, Tianjiao Wang, Kazuhiro Sato, Reyka Jayasinghe, I-Ling Chiang, Darwin D'souza, William Pilcher, Edgar Gonzalez-Kozlova, Yered Pita-Juarez, Taxiarchis Kourelis, Deon Bryant Doxie, Beena Thomas, Brian Lee, Swati Sharma Bhasin, Upadhyaya Bhaskar, Mark Fiala, Julie Fortier, Travis Dawson, John Leech, Shaji Kumar, Hearn Cho, Seunghee Kim-Schulze, Bee Raj, Stephen Oh, the MMRF Immune Profiling Research Team, John Dipersio, Ravi Vij, Adeeb Rahman, Ionnis Vlachos, Shaadi Mehr, Mark Hamilton, Daniel Auclair, Surendra Dasari, David Avigan, Madhav Dhodapkar, Sacha Gnjatic, Manoj Bhasin, Li Ding. Single-cell transcriptome profiling of multiple myeloma bone marrow samples suggests that disease progression interplays with tumor and tumor microenvironment in The MMRF CoMMpass Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1729.