Citations

Abstract Stereotactic radiation therapy yields high rates of local control for brain metastases, but patients in rural or suburban areas face geographic and socioeconomic barriers to its access. We conducted a phase II clinical trial of frameless, fractionated stereotactic radiation therapy for brain metastases in an integrated academic satellite network for patients 18 years of age or older with 4 or fewer brain metastases. Dose was based on gross tumor volume: less than 3.0 cm, 27 Gy in 3 fractions and 3.0 to 3.9 cm, 30 Gy in 5 fractions. Median follow-up was 10 months for 73 evaluable patients, with a median age of 68 years. Median intracranial progression-free survival was 7.1 months (95% confidence interval = 5.3 to not reached), and median survival was 7.2 months (95% confidence interval = 5.4 to not reached); there were no serious adverse events. Outcomes of this trial compare favorably with contemporary trials, and this treatment strategy provides opportunities to expand stereotactic radiation therapy access to underserved populations.

Abstract Background Early diagnosis and appropriate management of concussion/mild traumatic brain injury (mTBI) is critical for preventing poor outcomes and minimizing health care burden. Current clinical guidelines for concussion management focus mostly on diagnosis and return to cognitive and physical activity but provide limited guidance on the use of specific therapeutic interventions. Objective To systematically review the available evidence on therapeutic interventions for concussion/mTBI and develop an evidence‐based consensus statement on the use of these interventions in clinical practice. Literature Survey A systematic literature search was performed first in 2018 and 2019, and again in 2022, to identify relevant original research on these interventions. A total of 6303 articles were retrieved through the systematic literature search and screened for inclusion. Eighty articles met inclusion criteria and were included in this review and consensus process. Methodology A multispecialty panel was convened to explore management of concussion/mTBI. Interventions evaluated included rest, exercise, rehabilitation, and return to activity (RTA) protocols. Studies were assessed for relevance and methodologic quality and were voted upon to develop an evidence‐based consensus statement on the therapeutic appropriateness of these interventions for concussion/mTBI. A meta‐analysis was not performed. Synthesis There was sufficient evidence to recommend exercise as an appropriate therapy for adolescents with acute concussion/mTBI. In other age groups and for other therapeutic modalities, although some studies demonstrated benefits for some of the interventions, mixed results and study limitations prevented the panel from drawing firm conclusions on the efficacy of those interventions. The panel found evidence of detrimental effects from strict rest and high‐intensity physical activity. Conclusions The panel recommended exercise as an appropriate therapy for acute concussion in adolescents. The evidence on other therapeutic interventions for concussion/mTBI remains limited to small randomized controlled trials and observational studies of moderate to low quality. The panel found no strong evidence to support or recommend against the other evaluated interventions but found most interventions to be safe when used judiciously and in consideration of individual patient needs. High‐quality randomized studies with sufficient power are needed to evaluate the effects of rest, rehabilitation, and RTA protocols for the management of concussion/mTBI.

Abstract AIMS High-grade glioma continues to have dismal survival with current standard-of-care treatment, owing in part to its intra- and inter-patient heterogeneity. Typical diagnostic biopsies are taken from the dense tumor core to determine the presence of abnormal cells and the status of a few key genes (e.g. IDH1, MGMT). However, the tumor core is typically resected, leaving behind possibly genetically, transcriptomically and/or phenotypically distinct invasive margins that repopulate the disease. As these remaining populations are the ones ultimately being treated, it is important to know their compositional differences from the tumor core. We aim to identify the phenotypic niches defined by the relative composition of key cellular populations and understand their variation amongst patients. METHOD We have established an image-localized research biopsy study, that samples from both the invasive margin and tumor core. From this protocol, we currently have 202 samples from 58 patients with available bulk RNA-Seq, collected between Mayo Clinic and Barrow Neurological Institute. Using a single-cell reference dataset from our collaborators at Columbia University, we used CIBERSORTx, a deconvolution method, to predict relative abundances of 7 normal, 6 glioma, and 5 immune cell states for each sample. RESULTS We find that these cell state abundances connect to patient survival and show regional differences. For example, proneural glioma states were higher in invasive regions, whereas proliferative and mesenchymal states were higher in the tumor core. CONCLUSIONS Our analysis demonstrates a need to characterize the residual tissue following glioma resection to better understand the recurrent disease.

Abstract BACKGROUND Treatment of recurrent high-grade glioma remains a clinical challenge. There are very few agents active in this disease and short of enrollment in a clinical trial, the choice of therapy for a patient at the time of recurrence remains challenging. Several groups, including our own have developed ex vivo drug sensitivity assays to evaluate susceptibility of the tumor tissue to specific chemotherapeutics. To our knowledge, there is only one commercially available platform from the US based company Kiyatec. This tool, in addition to the molecular analysis of the tumor might provide another layer of confidence in choosing treatments for patients with recurrent high-grade gliomas. MATERIAL AND METHODS We present the data from our initial experience with the 3D PredictTM platform (Kiyatec, Greenville, SC, USA). We used the platform for 6 patients with recurrent high-grade gliomas undergoing tumor resection at the time of recurrence. We followed the company protocol for obtaining, preserving and shipping the tissue. RESULTS Out of the 6 specimens shipped for analysis, 4 assays were completed with full results available for analysis and clinical use. In two cases, the ex vivo tissue expansion was unsuccessful and drug testing was not completed. For the remaining 4 cases, spheroids created from the expansion of the harvested tissue were exposed to 12 drugs (temozolomide, lomustine, procarbazine, abemaciclib, carboplatin, dabrafenib, etoposide, everolimus, irinotecan, osimertinib, rucaparib and trametinib). We have observed different levels of sensitivity to several agents graded as: NO RESPONSE, MODERATE RESPONSE and RESPONSE. In 3 cases the results were used for clinical decision making and 2 patients were started on temozlomidede and carboplatin respectively and remain on treatment. In one case where sensitivity to etoposide was detected, we were not able to proceed with therapy due to insurance denial for the chosen drug. CONCLUSION In our experience, this platform is easy to use in a standard clinical setting, the success rate for creating viable spheroids for testing is high and the information derived from the drug sensitivity testing can be useful in clinical practice. Large, prospective clinical trial is need to validate this approach for routine clinical use.

AbstractBackgroundThe HIV Organ Policy Equity (HOPE) act afforded transplantation of organs from donors who have HIV. Herein we compared the long‐term outcomes of recipients with HIV by donor HIV testing status.MethodsUsing the Scientific Registry of Transplant Recipients, we identified all primary adult kidney transplant recipients who were HIV‐positive between 1/1/16‐12/31/21. Recipients were grouped into three cohorts according to the donor HIV status based on antibody (Ab) and nucleic acid testing (NAT): Donor Ab−/NAT− (n = 810), Donor Ab+ /NAT− (n = 98), and Donor Ab+/NAT+ (n = 90). We compared recipient and death‐censored graft survival (DCGS) by donor HIV testing status using Kaplan–Meier curves and Cox proportional hazards regression, censored at 3 years posttransplant. Secondary outcomes were delayed graft function (DGF) and the following 1‐year outcomes: acute rejection, re‐hospitalization, and serum creatinine.ResultsIn Kaplan–Meier analyses, patient survival and DCGS were similar by donor HIV status (log rank p = .667; log rank p = .388). DGF occurred more frequently in donors with HIV Ab−/NAT− testing compared with Ab+/NAT− or Ab+/NAT+ testing (38.0% vs. 28.6% vs. 26.7%, p = .028). Average dialysis time before transplant was twice as long for recipients who received organs from donors with Ab−/NAT− testing (p < .001). Acute rejection, re‐hospitalization and serum creatinine at 12 months did not differ between the groups.ConclusionsPatient and allograft survival for recipients living with HIV remains comparable irrespective of donor HIV testing status. Utilizing kidneys from deceased donors with HIV Ab+/NAT− or Ab+/NAT+ testing shortens dialysis time prior to transplant. image