Cell type-specific regulation of the Drosophila FMRF-NH2 neuropeptide gene by Apterous, a LIM homeodomain transcription factor

We describe the direct and cell-specific regulation of the Drosophila FMRFa neuropeptide gene by Apterous, a LIM homeodomain transcription factor. dFMRFa and Apterous are expressed in partially overlapping subsets of neurons, including two of the seventeen dFMRFa cell types, the Tv neuroendocrine cells and the SP2 interneurons. Apterous contributes to the initiation of dFMRFa expression in Tv neurons, but not in those dFMRFa neurons that do not express Apterous. Apterous is not required for Tv neuron survival or morphological differentiation. Apterous contributes to the maintenance of dFMRFa expression by postembryonic Tv neurons, although the strength of its regulation is diminished. Apterous regulation of dFMRFa expression includes direct mechanisms, although ectopic Apterous does not induce ectopic dFMRFa. These findings show that, for a subset of neurons that share a common neurotransmitter phenotype, the Apterous LIM homeoprotein helps define neurotransmitter expression with very limited effects on other aspects of differentiation

Yield of Surveillance Imaging in Long-Term Survivors of Brain Metastasis Treated With Stereotactic Radiosurgery

Although patients with brain metastasis treated with stereotactic radiosurgery (SRS) in the definitive or post-operative setting have high rates of local control, surveillance imaging is necessary to assess for central nervous system (CNS) recurrence. Guidelines recommend magnetic resonance imaging (MRI) of the brain every three months for surveillance in asymptomatic patients post-SRS. However, optimal frequency and duration of surveillance imaging in long-term survivors is unknown. Our objective is to define the yield and cost of surveillance MRIs in long-term (> 1 year) survivors following SRS. We identified a cohort of patients with brain metastases treated with SRS in the definitive or postoperative setting at a single institution from 8/2014 to 9/2019. Eligible patients had at least one-year of follow-up with absence of CNS disease failure up to and including the first MRI of the brain after 12 months from SRS. Each post-treatment MRI of the brain was assessed for disease progression or new lesions. CNS disease-free survival was time from SRS to last follow-up, death or CNS failure. Delay to diagnosis and cost per patient were estimated using hypothetical MRI schedules of 2, 3, 4 and 6 months from 1-year post-treatment while CNS disease-free. Delay to diagnosis was calculated as time from actual CNS progression to hypothetical imaging date. Medicare reimbursement median cost of $498 per MRI brain with and without contrast was used for this analysis. A total of 373 patients treated with SRS for brain metastasis were identified at our institution. 61 patients met eligibility criteria for inclusion in this study (median follow-up 2.50 years, median age at treatment 60 years). The median CNS disease-free survival in this population was 2.37 years from date of SRS. 15 patients (24.6$1156 was spent annually on MRIs of the brain after 12 months with average annual yield of 17.0%. The cost per diagnosis of CNS progression was $6806. A 2-month, 3-month, 4-month and 6-month MRI schedule had a respective estimated delay to diagnosis of 0.69 months, 1.13 months, 1.44 months and 3.19 months. The respective mean total cost of each MRI schedule per patient from one-year post-treatment while CNS disease-free was$4662, $3053,$2229 and $1380. Patients with metastatic disease to the brain treated definitively or postoperatively with SRS without evidence of CNS recurrence at one year have a low rate of CNS failure and relatively good prognosis. Based strictly on limiting delay of diagnosis, a 2-month MRI Brain schedule is optimal in this population, albeit with a relatively small increase in financial cost over the patient's lifespan. We propose a multi-institutional study of long-term survivors with brain metastasis to strengthen these findings. B.J. Rich: None. D. Kwon: None. Y.S. Soni: None. D.L. John: None. J.B. Bell: None. G. Azzam: None. E.A. Mellon: None. R. Yechieli: Support and guide school in strategic and management related matters; Toras Chaim Toras Emes, Miami FL.C. Benjamin: None. R. Benveniste: None. R.J. Komotar: None. M. Ivan: None. J. Morcos: None. T. Diwanji: None

Disparities in Use of Salvage Whole Brain Radiation Therapy vs. Salvage Stereotactic Radiosurgery After Initial Stereotactic Radiosurgery for Brain Metastases

Patients undergoing stereotactic radiosurgery (SRS) for brain metastases often relapse and require additional radiation. Due to the paucity of data, the decision to offer salvage re-irradiation with whole brain radiation therapy (WBRT) versus SRS is made on an individual basis. Our objective is to determine the clinical and demographic factors associated with SRS versus WBRT for salvage of first intracranial failure (ICF), i.e., local and/or locoregional failures. We identified a cohort of 374 consecutive patients with brain metastases treated with SRS in the definitive or postoperative setting, at a single institution, from August 2014 to September 2019. Eligible patients received subsequent salvage radiation at our institution with WBRT or SRS at least one month after initial SRS. Clinical and demographic characteristics were retrospectively recorded. Univariate (UVA) and multivariate analyses (MVA) were performed to determine if there was a significant correlation between these factors and the use of salvage SRS versus WBRT. Odds ratios (ORs) and corresponding P-values were estimated from logistic regression model. A survival analysis was also performed to assess the impact of these factors on survival. All tests were two sided and P-value of < 0.05 was used for significance. A total of 110 patients (median age 60, median time to salvage radiation 5.85 months, median follow-up from initial treatment 1.47 years and 0.81 years from salvage treatment) met eligibility criteria for inclusion in this study. 78 patients received SRS and 32 patients received WBRT at the time of first ICF. On UVA the following factors were associated with salvage SRS: having a single new lesion (OR 9.86, P = 0.012), ≥1 stable lesions (OR 5.06, P = 0.001). On UVA the following factors were associated with decreased use of salvage SRS: male gender (OR 0.42, P = 0.044), patient primary language of Spanish (OR = 0.42, P = 0.050), and local progressive lesions (1 lesion OR 0.13, P 70, Stable/absent systemic disease, and receipt of salvage SRS. The strongest factor associated with selection of salvage WBRT vs. SRS for ICF following initial SRS is local progression. There was also found to be a significant disparity in the form of decreased salvage SRS for male patients that remained significant when controlling for other disease and socioeconomic factors. Possible etiologies of this difference could be provider or patient driven but warrant further exploration. In this cohort, salvage SRS was associated with a statistically significant improvement in OS, however, this may also represent a selection bias. Y.S. Soni: None. B.J. Rich: None. D. Kwon: None. W. Zhao: None. D.L. John: None. C.S. Seldon: None. C. Benjamin: None. R. Benveniste: None. R.J. Komotar: None. P. Prieto: None. M. De La Fuente: None. G. Azzam: None. E.A. Mellon: None. T. Diwanji: None