bluuebunny/crossref_metadata_2025_split huggingface dataset:
07. RETROSPECTIVE ANALYSIS OF SALVAGE SURGERY FOR LOCAL PROGRESSION OF BRAIN METASTASIS PREVIOUSLY TREATED WITH STEREOTACTIC IRRADIATION: DIAGNOSTIC CONTRIBUTION, FUNCTIONAL OUTCOME, AND PROGNOSTIC FACTORS
Authors: Mitsuya Koichi , Deguchi Shoichi , Hayashi Nakamasa , Harada Hideyuki , Nakasu Yoko 
Published: August 2020

Abstract

BACKGROUND
Stereotactic irradiation (STI) is a primary treatment for patients with newly diagnosed brain metastases. Some of these patients experience local progression, which is difficult to differentiate from radiation necrosis, and difficult to treat. Just a few studies have clarified the prognosis and effectiveness of salvage surgery after STI. We evaluated the diagnostic value and improvement of functional outcomes after salvage surgery.

METHODS
We evaluated patients with brain metastases treated with salvage surgery for local progression from October 2002 to July 2019. These patients had undergone salvage surgery based on magnetic resonance imaging findings and/or clinical evidence of post-STI local progression and stable systemic disease. We employed two prospective strategies according to the eloquency of the lesions. Lesions in non-eloquent areas had been resected completely with a safety margin, utilizing a fence-post method; while lesions in eloquent areas had been treated with minimal resection and postoperative STI. Prognostic factors for survival were analyzed.

RESULTS
Fifty-four salvage surgeries had been performed on 48 patients. The median age of patients was 64 years. The median diameter of the enhanced lesions was 35 mm (range 19–58 mm). The median overall survival was 20.2 months from salvage surgery and 37.5 months from initial STI. Primary cancers were lung 31, breast 9, and others 8. Local recurrence developed in 13 of 54 lesions (24%). Leptomeningeal dissemination occurred after surgery in 3 patients (5.6%). Primary breast cancer (breast vs. lung: HR: 0.17), (breast vs. others: HR: 0.08) and RPA class 1–2 (RPA 1 vs. 3, HR: 0.13), (RPA 2 vs 3, HR: 0.4) were identified as good prognostic factors for overall survival (OS) in multivariate analyses.

CONCLUSION
We insist that salvage surgery leads to rapid improvement of neurological function and clarity of histological diagnosis. Salvage surgery is recommended for large lesions especially with surrounding edema either in eloquent or non-eloquent areas.
13. MANAGEMENT OF BRAIN METASTASES FROM SMALL CELL LUNG CANCER USING SRS
Authors: Koffler Daniel , Viswanatha Sirisha , Fekrmandi Fatemeh , Rana Zaker , Schulder Michael , Goenka Anuj 
Published: August 2020

Abstract

PURPOSE/OBJECTIVE(S)
The management of brain metastases in patients with SCLC has become controversial in the MRI era. We examine our institutional experience treating patients with SCLC with stereotactic radiosurgery. We hypothesize that an SRS strategy in well-selected patients with close MRI surveillance will result in acceptable tumor control, and without disproportionate future neurological symptoms associated with intracranial disease.

MATERIALS/METHODS
Patients with a diagnosis of high grade neuroendocrine lung cancer who had undergone SRS between 2013 and 2019 were identified and divided into two groups: SRS-primary and SRS-salvage. SRS-primary was defined as patients who, at time of SRS, had not received previous PCI or WBRT. SRS-salvage was defined as patients who had received previous PCI or WBRT. Primary outcome was intracranial progression free survival. Secondary outcomes included overall survival and neurologic symptom free survival (N-SFS), defined as time to development of neurologic symptoms attributed disease.

RESULTS
Twenty patients were identified with median follow-up of 14.1 months. 11 patients were identified as SRS-primary, 9 as SRS-salvage. Among SRS-primary, median PFS and OS were 6.1 months (range 0.9 – 14.5 months) and 15.6 months (4.1–43.5) respectively. N-SFS was 11.2 months (range 3.6–40.0). 3 of 11 patients developed neurological symptoms attributable to disease. 3 underwent salvage SRS and 2 salvage WBRT. None died from intracranial disease. Among SRS-salvage, median PFS following PCI/WBRT was 9.8 months (range 1.8 – 23.6 months) and OS following salvage SRS 5.5 months (range 1.1 – 27.8 months). 3 of 9 patients developed further brain metastases post-SRS. 1 patient died from intracranial disease.

CONCLUSION
Among well-selected patients followed with MRI surveillance, our data suggest SRS as primary management of brain metastases from SCLC may be reasonable. Symptomatic intracranial disease was uncommon after SRS, and no patients undergoing upfront SRS died from intracranial disease. Prospective data are required to validate these results.
14. DELAYED MRI RESPONSE TO LITT IN PATIENTS UNDERGOING IMMUNOTHERAPY
Authors: Hong Christopher , Chiang Veronica 
Published: August 2020

Abstract
Laser interstitial thermal therapy (LITT) is an effective treatment for regrowing lesions after previous radiosurgery to brain metastases, typically resulting in decreased perilesional edema within weeks followed by delayed reduction in lesion size. We have anecdotally observed that patients on immunotherapy (IT) at time of LITT may exhibit a delayed edema resolution response to laser ablation. Post-operative imaging for cases of LITT, performed by the senior author from June 2012-July 2019, for regrowing lesions after prior radiosurgery for brain metastases were retrospectively reviewed. The IT group was defined as any patient receiving IT treatment within 3 months of LITT. Post-operative MRIs obtained at serial time points after surgery (2 weeks, 6 weeks, 3 months, 6 months, and 12 months) were reviewed for treatment response to LITT, defined as change in surrounding edema on T2 FLAIR and change of lesion size on T1-weighted post-contrast images. Out of 60 ablated lesions, 22 were in the IT and 38 were in the non-IT groups. There were no differences in distribution of original cancer pathology (IT: 9 melanoma, 8 lung, 5 other, non-IT: 6 melanoma, 20 lung, 12 other; p&gt;0.05). Time to lesion size response on T1-weighted post-contrast MRI neared but did not reach statistical significance between the IT and non-IT groups: median 3.0 versus 2.25 months (HR 1.5, 0.8–2.5, 95% CI, p=0.08), respectively. However, time to reduction of perilesional edema on T2-weighted MRI was significantly longer in the IT group, compared to the non-IT group: median 2.25 versus 1.5 months (HR 1.5, 0.9–2.5, 95% CI, p=0.04), respectively. These data suggest that IT around the time of LITT may lead to delayed edema reduction on MRI after LITT. We hypothesize IT may enhance normal immune-mediated mechanisms thus increasing perilesional inflammation after LITT. Further studies are needed to corroborate our observations and explore the underlying pathophysiology.
16. GAMMA KNIFE CLINICAL DOSE PROFILE FOR EXTENSIVE BRAIN METASTASES
Authors: Bowden Greg , Kim Jong , Faramand Andrew , Fallon Kevin , Flickinger John , Lunsford L Dade 
Published: August 2020

Abstract

BACKGROUND
The use of Gamma Knife stereotactic radiosurgery (GKSRS) for the treatment of extensive intracranial metastases has been expanding due to its superior dosimetry and efficacy. However, there remains a dearth of data regarding the dose parameters in actual clinical scenarios. We endeavored to calculate the radiation dose to the brain when treating &gt;15 brain metastases with GKSRS.

METHODS
This retrospective analysis reviewed dosage characteristics for patients requiring single session GKSRS for the treatment of 315 brain metastases. Forty-two patients met the inclusion criteria between 2008 and 2017. The median number of tumors at the initial GKSRS procedure was 20 (15–39) which accounted for 865 tumors in this study. The median aggregate tumor volume was 3.1cm3(0.13–13.26) and the median marginal dose was 16Gy (14-19Gy).

RESULTS
The median of the mean brain dose was 2.58Gy (range 0.95–3.67Gy) and 79% of patients had a dose &lt;3Gy. The 12Gy dose volume was a median of 12.45cm3, which was equivalent to 0.9% of the brain volume. The median percentage of brain receiving 5Gy and 3Gy was 6.7% and 20.4%, respectively. There was no correlation between the number of metastases and the mean dose to the brain (p=0.8). A higher tumor volume was significantly associated with an increased mean brain dose (p&lt;0.001). The median of the mean dose to the bilateral hippocampi was 2.3Gy. Sixteen patients had supplementary GKSRS, resulting in an additional mean dose of 1.4Gy (0.2–3.8Gy) to the brain.

CONCLUSION
GKSRS is a viable means of managing extensive brain metastases. This procedure provides a relatively low dose of radiation to the brain, especially when compared to traditional whole brain radiation protocols.
22. COMPARATIVE EFFICACY OF ALK-INHIBITORS IN ALK INHIBITOR-NAIVE ALK+ LUNG CANCER BRAIN METASTASES: A NETWORK META-ANALYSIS
Authors: Haddad Philip , Hammoud Dalia , Gallagher Kevin 
Published: August 2020

Abstract

BACKGROUND
Lung cancer has been the leading cause of cancer death for both men and women worldwide. Non-small-cell lung cancer (NSCLC) displays an array of molecular abnormalities most commonly involving ALK and EGFR pathways. NSCLC with ALK rearrangements comprises around 5% of cases. Over the years, several ALK inhibitors (ALKI) have been approved with notable activity in brain metastases. However, there have been limited comparative studies exploring their relative efficacies. This analysis was conducted to compare the relative efficacy of ALKIs against ALKI-naïve ALK+ lung cancer brain metastases.

METHODOLOGY
A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of ALKI-naïve ALK+ lung cancer trials with brain metastases; treatment with Crizotinib (CRZ), Alectinib (ALC), Brigatinib (BRG), and Ceritinib (CER); and comparative studies reporting brain metastases specific responses/events. A Bayesian and a frequentists network meta-analysis were conducted using netmeta package and the random-effects model.

RESULTS
Eight studies comprising a total of 665 participants with ALKI-naive ALK+ lung cancer brain metastases were included. When compared pair-wise to CRZ, ALC (RR=0.49;95%CI:0.36–0.66), BRG (RR=0.39;95%CI:0.24–0.64), and CER (RR=0.36;95%CI:0.19–0.68) demonstrated significantly superior response rates in patients with untreated or previously treated lung cancer brain metastases. When the efficacy of each ALKI was compared to each other, BRG and CER were ranked the highest followed by ALC then CRZ in decreasing order.

CONCLUSIONS
This network meta-analysis is the first to compare and rank ALKIs used in treating metastatic ALK+ lung cancer. It indicates that BRG, CER, and ALC are better therapeutic options for patients with ALK-naive ALK+ lung cancer brain metastases when compared to CRZ.
29. ROLE OF AGE AND CNS MYELOID CELLS ON BREAST CANCER BRAIN METASTASIS
Authors: Lai Wu Alex Man , Gossa Selamawit , Samala Ramakrishna , Chung Monika , Gril Brunilde , Yang Howard , Thorsheim Helen , Tran Andy , Wei Debbie , Isanogle Kristine , Yang Yuan , Dolan Emma , Robinson Christina , Difilippantonio Simone , Lee Maxwell , Smith Quentin , McGavern Dorian , Wakefield Lalage , Steeg Patricia 
Published: August 2020

Abstract
Women diagnosed with breast cancer at a younger age (typically defined as &lt; 40 years old) often have a poorer prognosis and an increased risk of brain metastasis compared to their older counterparts. Multivariate analyses accounting for differences in tumor characteristics have shown that age is an independent predictor of worse outcome. We therefore hypothesized that rather than intrinsic tumor properties, extrinsic microenvironmental factors contribute to age-related differences in aggressiveness. The effect of age was examined by injecting brain-selected breast cancer cells into young (2 – 6 months) and older (&gt;12 months) mice. In four brain metastasis models examined, young mice developed 2- to 16-fold (p &lt; 0.05) more brain metastases compared to older mice. The effect of age was not observed in mouse breast cancer models that metastasize to liver and lungs, suggesting that this is an organ-specific phenomenon. Flow cytometry-based immune-profiling of mouse brains showed that T-cells (CD4+, CD8+, and FOXP3+CD25+ regulatory T-cells), monocytes and neutrophils were elevated in brains with metastases, but the abundance of these populations did not vary dramatically with age. Furthermore, antibody-based depletion of T-cells, monocytes and neutrophils did not significantly alter brain metastasis development. Microglia, which are resident CNS myeloid cells, were 1.5-fold more abundant in young brains compared to older brains. Depletion of CNS myeloid cells using the colony stimulating factor-1-receptor inhibitor PLX3397 reduced brain metastatic tumor burden in young mice by 2.1-fold (p &lt; 0.001). Importantly, loss of CNS myeloid cells/microglia, which are normally more activated in aged mice and thus may protect the older brain against metastasis, did not augment brain metastasis formation in older mice. These results suggest that the younger brain is more permissive for breast cancer metastasis and that targeting resident CNS myeloid cells may be an effective strategy to prevent brain metastasis development in younger patients.
31. RADIATION NECROSIS IN STEREOTACTIC RADIOSURGERY AND CHECKPOINTS INHIBITORS FOR BRAIN METASTASES FROM LUNG ADENOCARCINOMA
Authors: Jurica James , Dalwadi Shraddha , Baskin David , Bernicker Eric , Butler Brian , Rostomily Robert , Teh Bin , Tremont-Lukats Ivo , Farach Andrew 
Published: August 2020

Abstract

PURPOSE
Treatment with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) is increasingly common for brain metastases (BM) from lung adenocarcinoma. Rates of radiation necrosis (RN) with SRS in the setting of ICIs is an ongoing area of research. We investigated rates of RN in patients with BM from lung adenocarcinoma treated with SRS with or without concurrent ICIs.

METHODS
We identified 39 patients at a single institution who underwent SRS treatment for BM from lung adenocarcinoma. Of these, 19 (49%) received SRS without ICIs and 20 (51%) patients received ICIs within a month of SRS. The rate of RN, defined by MRI features and histology when available, was compared between each group using multivariate analysis. Kaplan Meier survival estimates were calculated based on overall survival and compared to median survival predicted by the graded prognostic assessment.

RESULTS
Overall survival for all patients from diagnosis of brain metastases was 16.6 months (range 3.6–45.9) and median survival predicted by the graded prognostic assessment was 13.7 months (range 6.9–26.5). In total 11 (28%) patients developed MRI and/or histologic evidence for RN during the follow-up period; 5 of 20 (25%) from the SRS with ICI group and 6 of 19 (31%) from the SRS without ICI group. In multivariate analysis, ICI treatment had no significant impact on rates of RN between groups (OR 0.72 [95% CI: 0.17–2.93]; p=0.65) while bevacizumab treatment was associated with a decreased RN risk (OR 0.88 [95% CI: 0.43–0.99]; p=0.02).

CONCLUSION
Retrospective analysis of patients with BM from lung adenocarcinoma treated with SRS suggested that administration of ICIs does not increase risk for development of RN. Further, concomitant treatment with bevacizumab may decrease risk of RN. These findings suggest that patients with BM from lung adenocarcinoma can be treated with combination therapy without increased risk of neurologic toxicity.
33. SYSTEMATIC REVIEW AND META-ANALYSIS OF BREAST CANCER BRAIN METASTASIS AND PRIMARY TUMOR RECEPTOR EXPRESSION DISCORDANCE
Authors: Kotecha Rupesh , Tonse Raees , Rubens Muni , McDermott Michael , Odia Yazmin , Appel Haley , Mehta Minesh 
Published: August 2020

Abstract

BACKGROUND
Discordance in hormone receptor (estrogen [ER] and progesterone [PR]) and human epidermal growth factor receptor2 (HER2) status between the primary tumor and brain metastases and its effect on tumor classification subtype switching has been described but remains understudied.

METHODS
Using the PRISMA guidelines, a systematic review was performed of series published prior to April 2020 of biopsied or resected breast cancer brain metastasis (BCBM) from the Medline database using the keywords “breast cancer” and “brain metastasis” combined with “estrogen receptor/ER,” “progesterone receptor/PR,” “HER2/neu,” and “receptor conversion/dis- or concordance.” Weighted random effects models were used to calculate pooled estimates.

RESULTS
Fifteen full-text articles met inclusion criteria and cumulatively reported on 1373 patients who underwent biopsy or resection of at least one BCBM to compare to their primary tumor. At initial diagnosis, receptor expression profiles were 45.0% ER+, 41.0% ER-, 31.0% PR+, 51.0% PR-, 35% HER2+, and 47.0% HER2-. Corresponding receptor expression profiles from the BCBM were 19.0% ER+, 31.0% ER-, 13.0% PR+, 40.0% PR-, 21.0% HER2+, and 26.0% HER2-. Intra-patient receptor discordance comparisons revealed that 540 patients (42.6%) exhibited discordance in any receptor with 17.0% (95% CI: 13.0%-23.0%) discordance for ER status, 23.0% (95% CI: 18.0%-30.0%) for PR status, and 12.0% (95% CI: 8.0%-16.0%) for HER2 status. The most common receptor discordance events found in BCBM compared to primary tumors were ER loss 11.0% (95% CI: 8.0%-16.0%), PR loss 15.0% (95% CI: 11.0%-21.0%), and HER2 gain 9.0% (95% CI: 7.0%-11.0%).

CONCLUSIONS
BCBM commonly exhibit receptor expression changes on comparison to primary tumors including a 10% HER2 gain rate, a potential actionable target. Classification patterns need to be updated to reflect changes in overall tumor subtype grouping and which factors predict for BCBM/primary tumor discordance. Overall, tumor subtype switching and its effect on clinical management remains underappreciated.
44. EFFECT OF STEREOTACTIC RADIOSURGERY ON NON-SMALL CELL LUNG CANCER BRAIN METASTASIS: CONTINUED CORRELATIVE RADIOBIOLOGIC ANALYSIS OF DNA AND RNA GENOMIC PROFILES FROM PHASE-II CLINICAL TRIAL NCT03398694
Authors: Henriquez Mario , Huff Wei , Shireman Jack , Monaco Gina , Agrawal Namita , Hong Park Choel , Saathoff Miranda , Watson Gordon , Ahmed Atique , Dey Mahua 
Published: August 2020

Abstract

BACKGROUND
Stereotactic radiosurgery (SRS) is an increasingly common modality used with or without surgery for the treatment of brain metastases (BM). However, the effects of SRS on tumors in vivo is unknown.

METHODS
Patients were treated with SRS prior to surgery as per clinical trial NCT03398694. Resected tumor was divided into two groups: ‘center’ and ‘periphery’ with respect to SRS treatment. Tissue were analyzed by DNA and RNA sequencing and compared between the two and to non-radiated tumor.

RESULTS
DNA analysis showed at the individual level, matched comparison of SRS samples from the center or periphery of the same tumor had mutational burden differences. RNA analysis revealed no differentially expressed genes between center and periphery, but there were 62 and 192 differentially expressed genes between the center or periphery and non-radiated control, respectively. At an individual level, matched center and periphery tumor had an average of 16641 differentially expressed genes. Comparing total number of up- and downregulated genes with SNP and Indel mutations of matched patient samples, in patients with higher mutational burdens in peripheral tumors as compared to center there was a higher number of upregulated genes. Reciprocally, when mutation burden was higher in center tumor, total number of genes that were either up- or downregulated were about the same. Pooled analysis revealed significant downregulation of oncogenes, such as TP63 and RECQL4, in the SRS group. DO enrichment analysis also revealed pathways related to NSCLC and lung carcinoma significantly altered in radiation cohort.

CONCLUSION
In summary, this study demonstrates that SRS alters the molecular and genomic profile of NSCLC BM. It results in downregulation of oncogenes and pathways related to lung cancer. Additionally, by sampling the tumor at the center and periphery, there are differential effects of the dose gradient on the cellular and molecular response to ionizing radiation.
55. A RANDOMIZED, MULTICENTER PHASE III TRIAL OF SURGERY PLUS STEREOTACTIC RADIOSURGERY (SRS) COMPARED WITH SURGERY PLUS PERMANENTLY IMPLANTED COLLAGEN TILE BRACHYTHERAPY (CTBT) FOR RESECTABLE METASTATIC BRAIN TUMORS-PROTOCOL IN PROGRESS
Authors: Weinberg Jeffrey , McAleer Mary Frances , Tawbi Hussein , Lang Frederick 
Published: August 2020

Abstract

BACKGROUND
Resection (R) followed by single or multi-fraction stereotactic radiosurgery (SRS) lowers resection bed recurrence compared to R alone. Nevertheless for larger brain metastasis (&gt;2.5 cm) 12-month recurrence rates after R+SRS can exceed 20–30%. Aiming to improve outcomes, a permanently implanted collagen tile brachytherapy (CTBT) device (GammaTile, GT Medical Technologies, Tempe AZ) utilizing Cs-131 was developed, hypothesizing that immediate adjuvant radiotherapy (RT) and/or RT dose intensification could improve outcomes. The device received FDA clearance for this indication, based on a single-arm pre-commercial study and in early commercial use due to the excellent safety and local control of R+CTBT. It is hypothesized that R+CTBT will increase the time to post-resection-recurrence, while prolonging survival and reducing the impact on functional and neurocognitive status compared to R+SRS.

STUDY DESIGN
Multicenter, randomized, comparison trial. Patients with resectable, previously untreated “index” brain metastases measuring &gt;2.5–5 cm and 0–3 other tumors will be preoperatively randomized 1:1 to undergo either R+ SRS or R+CTBT to the index lesion; unresected tumors in both groups will receive SRS. Planned sample size is 160 from ~5 sites; accrual to start in Q3-2020. Primary endpoint is surgical bed-recurrence free survival. Secondary endpoints include overall survival, quality of life (Functional Assessment of Cancer Therapy-Brain, Linear Analog Self-Assessment), neurocognition (Hopkins Verbal Learning Test, Trail Making Tests, Mini-Mental Status Exam, Controlled Oral Word Association), functional decline (Karnofsky Performance Scale, Barthel-ADL), and adverse events. Follow-up will be at 1,3,6,9, and 12 months, then q 6 months through 5 years.

CONCLUSIONS
This will be the first randomized trial comparing R+SRS versus R+CTBT delivered by Cs-131 sources in permanently implanted resorbable collagen tile carriers. Primary and secondary outcome measures will be captured to elucidate the potential risks and benefits of these two differing approaches for patients with metastatic brain tumors.