Response of treatment-naive brain metastases to stereotactic radiosurgery.

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.

Vaccination recommendations for adults receiving biologics and oral therapies for psoriasis and psoriatic arthritis: Delphi consensus from the medical board of the National Psoriasis Foundation.

BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.

Repeated blood-brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial.

Here, the results of a phase 1/2 single-arm trial (NCT03744026) assessing the safety and efficacy of blood-brain barrier (BBB) disruption with an implantable ultrasound system in recurrent glioblastoma patients receiving carboplatin are reported. A nine-emitter ultrasound implant was placed at the end of tumor resection replacing the bone flap. After surgery, activation to disrupt the BBB was performed every four weeks either before or after carboplatin infusion. The primary objective of the Phase 1 was to evaluate the safety of escalating numbers of ultrasound emitters using a standard 3 + 3 dose escalation. The primary objective of the Phase 2 was to evaluate the efficacy of BBB opening using magnetic resonance imaging (MRI). The secondary objectives included safety and clinical efficacy. Thirty-three patients received a total of 90 monthly sonications with carboplatin administration and up to nine emitters activated without observed DLT. Grade 3 procedure-related adverse events consisted of pre syncope (n = 3), fatigue (n = 1), wound infection (n = 2), and pain at time of device connection (n = 7). BBB opening endpoint was met with 90% of emitters showing BBB disruption on MRI after sonication. In the 12 patients who received carboplatin just prior to sonication, the progression-free survival was 3.1 months, the 1-year overall survival rate was 58% and median overall survival was 14.0 months from surgery.

Subependymomas of the fourth ventricle: To operate or not to operate?

BACKGROUND: There is a paucity of literature regarding the clinical characteristics and management of subependymomas of the fourth ventricle due to their rarity. Here, we describe the operative and non-operative management and outcomes of patients with such tumors. METHODS: This retrospective single-institution case series was gathered after Institutional Review Board (IRB) approval. Patients diagnosed with a subependymoma of the fourth ventricle between 1993 and 2021 were identified. Clinical, radiology and pathology reports along with magnetic resonance imaging (MRI) images were reviewed. RESULTS: Patients identified (n = 20), showed a male predominance (n = 14). They underwent surgery (n = 9) with resection and histopathological confirmation of subependymoma or were followed with imaging surveillance (n = 11). The median age at diagnosis was 51.5 years. Median tumor volume for the operative cohort was 8.64 cm3 and median length of follow-up was 65.8 months. Median tumor volume for the non-operative cohort was 0.96 cm3 and median length of follow-up was 78 months. No tumor recurrence post-resection was noted in the operative group, and no tumor growth from baseline was noted in the non-operative group. Most patients (89 %) in the operative group had symptoms at diagnosis, all of which improved post-resection. No patients were symptomatic in the non-operative group. CONCLUSIONS: Surgical resection is safe and is associated with alleviation of presenting symptoms in patients with large tumors. Observation and routine surveillance are warranted for smaller, asymptomatic tumors.

Study Protocol STEREOLAB: Stereotactic Liver Ablation Assisted with Intra-Arterial CT Hepatic Arteriography and Ablation Confirmation Software Assessment.

PURPOSE: This study aims to evaluate the technical efficacy and local tumor progression-free survival (LTPFS) of a standardized workflow for thermal ablation of colorectal liver metastases (CRLM) consisting of CT during hepatic arteriography (CTHA)-based imaging analysis, stereotactic thermal ablation, and computer-based software assessment of ablation margins. MATERIALS AND METHODS: This investigator initiated, single-center, single-arm prospective trial will enroll up to 50 patients (≤ 5 CRLM, Measuring ≤ 5 cm). Procedures will be performed in an angio-CT suite under general anesthesia. The primary objective is to estimate LTPFS with a follow-up of up to 2 years and secondary objectives are analysis of the impact of minimal ablative margins on LTPFS, adverse events, contrast media utilization and radiation exposure, overall oncological outcomes, and anesthesia/procedural time. Adverse events (AE) will be recorded by CTCAE (Common Toxicity Criteria for Adverse Events), and Bayesian optimal phase-2 design will be applied for major intraprocedural AE stop boundaries. The institutional CRLM ablation registry will be used as benchmark for comparative analysis with the historical cohort. DISCUSSION: The STEREOLAB trial will introduce a high-precision and standardized thermal ablation workflow for CRLM consisting of CT during hepatic arteriography imaging, stereotactic guidance, and ablation confirmation. Trial Registration ClinicalTrials.gov identifier: (NCT05361551).

Nivolumab and ipilimumab with concurrent stereotactic radiosurgery for intracranial metastases from non-small cell lung cancer: analysis of the safety cohort for non-randomized, open-label, phase I/II trial.

BACKGROUND: Up to 20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), for which the current standard of care is radiation therapy with or without surgery. There are no prospective data on the safety of stereotactic radiosurgery (SRS) concurrent with immune checkpoint inhibitor therapy for BM. This is the safety cohort of the phase I/II investigator-initiated trial of SRS with nivolumab and ipilimumab for patients with BM from NSCLC. PATIENTS AND METHODS: This single-institution study included patients with NSCLC with active BM amenable to SRS. Brain SRS and systemic therapy with nivolumab and ipilimumab were delivered concurrently (within 7 days). The endpoints were safety and 4-month intracranial progression-free survival (PFS). RESULTS: Thirteen patients were enrolled in the safety cohort, 10 of whom were evaluable for dose-limiting toxicities (DLTs). Median follow-up was 23 months (range 9.7-24.3 months). The median interval between systemic therapy and radiation therapy was 3 days. Only one patient had a DLT; hence, predefined stopping criteria were not met. In addition to the patient with DLT, three patients had treatment-related grade ≥3 adverse events, including elevated liver function tests, fatigue, nausea, adrenal insufficiency, and myocarditis. One patient had a confirmed influenza infection 7 months after initiation of protocol treatment (outside the DLT assessment window), leading to pneumonia and subsequent death from hemophagocytic lymphohistiocytosis. The estimated 4-month intracranial PFS rate was 70.7%. CONCLUSION: Concurrent brain SRS with nivolumab/ipilimumab was safe for patients with active NSCLC BM. Preliminary analyses of treatment efficacy were encouraging for intracranial treatment response.

National Psoriasis Foundation Telemedicine Task Force guidance for management of psoriatic disease via telemedicine.

Telemedicine emerged as an alternative care delivery system used to offer effective long-term management to patients with chronic, inflammatory conditions such as psoriatic disease. Teledermatology can provide reliable clinical information through thorough history-taking and virtual evaluations that include patient-provided images and disease activity assessment tools that may help accurately diagnose and manage patients with psoriasis. The integration of validated screening tools for psoriatic arthritis and effective teledermatology practices may improve access to specialists, thus avoiding preventable delays in the diagnosis and treatment of patients with psoriatic arthritis. Although the provision of telehealthcare should not completely replace high quality, in-person dermatologic or rheumatologic visits, the convenience and collaborative nature of teledermatology may lead to expanded access and expedited care in the appropriate setting, whether it be in a virtual or in-person visit.

Retrospective Analysis of Imaging Characteristics of Tectal Gliomas.

BACKGROUND AND PURPOSE: Tectal gliomas (TGs) are rare tumors that involve critical locations in the brainstem, including the superior and inferior colliculi and the Sylvian aqueduct. The rarity of these tumors and the lack of large clinical studies have hindered adequate understanding of this disease. We sought to determine the association between imaging characteristics of TG and progression-free survival (PFS). MATERIALS AND METHODS: In this retrospective cohort study, impact of imaging characteristics (contrast enhancement, calcifications, cystic changes, presence of hydrocephalus) on survival was analyzed for 39 patients with TG. We used the Kaplan-Meier survival analysis method for determining the association between imaging characteristics and PFS. Progression-free survival was measured from time of diagnosis to radiographic or pathological disease progression during observation period. Progression was defined as more than 25% increase of the lesion in size, per response assessment in neuro-oncology, together with clinical deterioration and/or a need for intervention. Progression-free survival differences by various imaging characteristics were assessed using the log-rank test and univariable Cox proportional hazard regression. Because most of the studies in the current literature tend to overrepresent pediatric patients, we aimed to determine the association between TG tumors' imaging characteristics and PFS in both adult and pediatric patients. All statistical analyses were performed using STATA version 16.1 (Stata Corp, College Station, Tex). RESULTS: Of the 39 patients, radiographic tumor progression was observed in 15 cases (38.5%). Median PFS for 39 patients during observation was 21.8 years. Tectal gliomas that showed contrast enhancement initially or developed contrast enhancement during surveillance on magnetic resonance imaging had significantly lower PFS than those without (hazard ratio, 3.55; 95% confidence interval, 1.09-11.58; log-rank P value, 0.02). CONCLUSIONS: Analysis of this patient population showed that contrast-enhancing TGs should not be categorically defined as benign lesions. This subgroup of patients should be followed closely for signs of progression.

Changes in outcomes and factors associated with survival in melanoma patients with brain metastases.

BACKGROUND: Treatment options for patients with melanoma brain metastasis (MBM) have changed significantly in the last decade. Few studies have evaluated changes in outcomes and factors associated with survival in MBM patients over time. The aim of this study is to evaluate changes in clinical features and overall survival (OS) for MBM patients. METHODS: Patients diagnosed with MBMs from 1/1/2009 to 12/31/2013 (Prior Era; PE) and 1/1/2014 to 12/31/2018 (Current Era; CE) at The University of Texas MD Anderson Cancer Center were included in this retrospective analysis. The primary outcome measure was OS. Log-rank test assessed differences between groups; multivariable analyses were performed with Cox proportional hazards models and recursive partitioning analysis (RPA). RESULTS: A total of 791 MBM patients (PE, n = 332; CE, n = 459) were included in analysis. Median OS from MBM diagnosis was 10.3 months (95% CI, 8.9-12.4) and improved in the CE vs PE (14.4 vs 10.3 months, P < .001). Elevated serum lactate dehydrogenase (LDH) was the only factor associated with worse OS in both PE and CE patients. Factors associated with survival in CE MBM patients included patient age, primary tumor Breslow thickness, prior immunotherapy, leptomeningeal disease, symptomatic MBMs, and whole brain radiation therapy. Several factors associated with OS in the PE were not significant in the CE. RPA demonstrated that elevated serum LDH and prior immunotherapy treatment are the most important determinants of survival in CE MBM patients. CONCLUSIONS: OS and factors associated with OS have changed for MBM patients. This information can inform contemporary patient management and clinical investigations.

Therapeutic application of machine learning in psoriasis: A Prisma systematic review.

Dermatology, being a predominantly visual-based diagnostic field, has found itself to be at the epitome of artificial intelligence (AI)-based advances. Machine learning (ML), a subset of AI, goes a step further by recognizing patterns from data and teaches machines to automatically learn tasks. Although artificial intelligence in dermatology is mostly developed in melanoma and skin cancer diagnosis, advances in AI and ML have gone far ahead and found its application in ulcer assessment, psoriasis, atopic dermatitis, onychomycosis, etc. This article is focused on the application of ML in the therapeutic aspect of psoriasis.

Treatment of Scalp Psoriasis.

Scalp involvement is seen in a majority of individuals with psoriasis, a chronic autoimmune skin disease with variable phenotypes. Occasionally, isolated scalp involvement is observed; and this causes significant psychosocial morbidity. Management of scalp psoriasis is difficult, in part due to the difficulty of applying topical agents and its refractory nature. Various treatment options are available with variable efficacy. Topical agents include topical steroids, keratolytics, tar and anthralin compounds, vitamin D analogues, and vitamin A derivatives. The combination treatment of topical betamethasone and calcipotriene is the most effective topical therapy. Systemic agents include conventional agents such as methotrexate, cyclosporine, and oral retinoids. Biologics offer a greater efficacy, with near complete or complete clearance of the scalp. In this article we review the published literature on adult and scalp psoriasis to highlight its treatment. Articles published in peer-reviewed journals were included for qualitative analysis of the literature, including reviews, clinical trials, case series, case reports published in the electronic database (MEDLINE/PubMed) through June 2021, cross references of respective articles, and trials from clinicaltrials.gov. J Drugs Dermatol. 2022;21(8):833-837. doi:10.36849/JDD.6498.

An interdisciplinary consensus on the management of brain metastases in patients with renal cell carcinoma.

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454-489.

Assessing mobility in primary brain tumor patients: A descriptive feasibility study using two established mobility tests.

Background: Patients with primary brain tumors (PBT) face significant mobility issues related to their disease and/or treatment. Here, the authors describe the preliminary utility and feasibility of two established mobility measures, the Timed-Up-and-Go (TUG) and Five-Times Sit-to-Stand (TSS) tests, in quickly and objectively assessing the mobility status of PBT patients at a single institution's neuro-oncology clinic. Methods: Adult patients undergoing routine PBT care completed the TUG/TSS tests and MD Anderson Symptom Inventory-Brain Tumor module (MDASI-BT), which assessed symptom burden and interference with daily life, during clinic visits over a 6-month period. Research staff assessed feasibility metrics, including test completion times/rates, and collected demographic, clinical, and treatment data. Mann-Whitney tests, Kruskal-Wallis tests, and Spearman's rho correlations were used to interrogate relationships between TUG/TSS test completion times and patient characteristics. Results: The study cohort included 66 PBT patients, 59% male, with a median age of 47 years (range: 20-77). TUG/TSS tests were completed by 62 (94%) patients. Older patients (P < .001) and those who were newly diagnosed (P = .024), on corticosteroids (P = .025), or had poor (≤80) KPS (P < .01) took longer to complete the TUG/TSS tests. Worse activity-related (work, activity, and walking) interference was associated with longer TUG/TSS test completion times (P < .001). Conclusions: The TUG/TSS tests are feasible for use among PBT patients and may aid in clinical care. Older age, being newly diagnosed, using corticosteroids, poor (≤80) KPS, and high activity-related interference were associated with significant mobility impairment, highlighting the tests' potential clinical utility. Future investigations are warranted to longitudinally explore feasibility and utility in other practice and disease settings.

Treatment of Nail Psoriasis.

Nail psoriasis has a considerable negative impact on the quality of life by limiting the patient’s household chores, professional activities and social interactions. Treatment for nail psoriasis is often overlooked with treatment for skin and joint involvement being more emphasized. It is also challenging since the clinical improvement takes a long time to be observed and is often met with poor compliance with treatment. This review focuses on the various treatment options for nail psoriasis after review of literature. The literature research considered published journal articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) and reference lists of respective articles. Only articles available in English were considered for this review. J Drugs Dermatol. 2022;21(2):146-150. doi:10.36849/JDD.4969.

Intralesional Mode of Drug Administration in Psoriasis.

The use of various conventional systemic and topical therapies in psoriasis has resulted in various major and minor side effects. Hence, we need to switch to intralesional administration of antipsoriatic drugs, to achieve better safety and efficacy profile. Intralesional drug therapy is most suitable for scalp, nail, and localized and recalcitrant plaque psoriasis. However, there are specific drugs, which can be used for this purpose, under strict monitoring. We have attempted to review all the possible drugs and indications where intralesional administration is feasible, along with their efficacy, adverse effects, dosage, and recommended duration of treatment. J Drugs Dermatol. 2022;21(2):186-190. doi:10.36849/JDD.6196.