Patterns of Failure After Radiation Therapy in Primary Spinal High-Grade Gliomas: A Single Institutional Analysis

Background Primary spinal high-grade gliomas (S-HGG) are rare aggressive tumors; radiation therapy (RT) often plays a dominant role in management. We conducted a single-institution retrospective review to study the clinicopathological features and management of S-HGGs. Methods Patients with biopsy-proven S-HGG who received RT from 2001 to 2020 were analyzed for patient, tumor, and treatment characteristics. Kaplan–Meier estimates were used for survival analyses. Results Twenty-nine patients were identified with a median age of 25.9 years (range 1–74 y). Four patients had GTR while 25 underwent subtotal resection or biopsy. All patients were IDH wildtype and MGMT-promoter unmethylated, where available. H3K27M mutation was present in 5 out of 10 patients tested, while one patient harbored p53 mutation. Median RT dose was 50.4 Gy (range 39.6–54 Gy) and 65% received concurrent chemotherapy, most commonly temozolomide. Twenty-three (79%) of patients had documented recurrence. Overall, 16 patients relapsed locally, 10 relapsed in the brain and 8 developed leptomeningeal disease; only 8 had isolated local relapse. Median OS from diagnosis was 21.3 months and median PFS was 9.7 months. On univariate analysis, age, gender, GTR, grade, RT modality, RT dose and concurrent chemotherapy did not predict for survival. Patients with H3K27M mutation had a poorer PFS compared to those without mutation (10.1 m vs 45.1 m) but the difference did not reach statistical significance (P = .26). Conclusions The prognosis of patients with spinal HGGs remains poor with two-thirds of the patients developing distant recurrence despite chemoradiation. Survival outcomes were similar in patients ≤ 29 years compared to adults \u3e 29 years. A better understanding of the molecular drivers of spinal HGGs is needed to develop more effective treatment options

Polarization transfer in the 16^{16}O(p,p′)(p,p') reaction at forward angles and structure of the spin-dipole resonances

Cross sections and polarization transfer observables in the $^{16}$O$(p,p')$ reactions at 392 MeV were measured at several angles between $\theta_{lab}=$ 0$^\circ$ and 14$^\circ$. The non-spin-flip (${\Delta}S=0$) and spin-flip (${\Delta}S=1$) strengths in transitions to several discrete states and broad resonances in $^{16}$O were extracted using a model-independent method. The giant resonances in the energy region of $E_x=19-$27 MeV were found to be predominantly excited by ${\Delta}L=1$ transitions. The strength distribution of spin-dipole transitions with ${\Delta}S=1$ and ${\Delta}L=1$ were deduced. The obtained distribution was compared with a recent shell model calculation. Experimental results are reasonably explained by distorted-wave impulse approximation calculations with the shell model wave functions.Comment: 28 pages RevTex, including 9 figures, to be published in Phys. Rev. C.; a typo in Eq. (3b) was correcte

Second surgery for progressive glioblastoma: a multi‐centre questionnaire and cohort‐based review of clinical decision‐making and patient outcomes in current practice

PURPOSE: Glioblastoma prognosis is poor. Treatment options are limited at progression. Surgery may benefit, but no quality guidelines exist to inform patient selection. We sought to describe variations in surgical management at progression, highlight where further evidence is needed, and build towards a consensus strategy. METHODS: Current practice in selection of patients with progressive GBM for second surgery was surveyed online amongst specialists in the UK and Europe. We complemented this with an assessment of practice in a retrospective cohort study from six United Kingdom neurosurgical units. We used descriptive statistics to analyse the data. RESULTS: 234 questionnaire responses were received. Maintaining or improving patient quality of life was key to decision making, with variation as to whether patient age, performance status or intended extent of resection was relevant. MGMT methylation status was not important. Half considered no minimum time after first surgery. 288 patients were reported in the cohort analysis. Median time to second surgery from first surgery 390 days. Median overall survival 815 days, with no association between time to second surgery and time to death (p = 0.874). CONCLUSIONS: This is the most wide-ranging examination of contemporaneous practice in management of GBM progression. Without evidence-based guidelines, the variation is unsurprising. We propose consensus guidelines for consideration, to reduce heterogeneity in decision making, support data collection and analysis of factors influencing outcomes, and to inform clinical trials to establish whether second surgery improves patient outcomes, or simply selects to patients already performing well

Discovery and Mass Measurements of a Cold, 10-Earth Mass Planet and Its Host Star

We present the discovery and mass measurement of the cold, low-mass planet MOA-2009-BLG-266Lb, made with the gravitational microlensing method. This planet has a mass of m_p = 10.4 +- 1.7 Earth masses and orbits a star of mass M_* = 0.56 +- 0.09 Solar masses at a semi-major axis of a = 3.2 (+1.9 -0.5) AU and an orbital period of P = 7.6 (+7.7 -1.5} yrs. The planet and host star mass measurements are enabled by the measurement of the microlensing parallax effect, which is seen primarily in the light curve distortion due to the orbital motion of the Earth. But, the analysis also demonstrates the capability to measure microlensing parallax with the Deep Impact (or EPOXI) spacecraft in a Heliocentric orbit. The planet mass and orbital distance are similar to predictions for the critical core mass needed to accrete a substantial gaseous envelope, and thus may indicate that this planet is a "failed" gas giant. This and future microlensing detections will test planet formation theory predictions regarding the prevalence and masses of such planets.Comment: 38 pages with 7 figure

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma

BACKGROUND: Ipilimumab is a novel FDA-approved recombinant human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 and has been used to treat patients with metastatic melanoma. Immune-related neurological adverse effects include inflammatory myopathy, aseptic meningitis, posterior reversible encephalopathy syndrome, Guillain-Barré syndrome, myasthenia gravis–type syndrome, sensorimotor neuropathy, and inflammatory enteric neuropathy. To date, there is no report for ipilimumab-induced chronic inflammatory demyelinating polyneuropathy (CIDP), transverse myelitis (TM), or concurrent myositis and myasthenia gravis–type syndrome. Our objective is to raise early recognition of atypical neurological adverse events and to share our therapeutic approach. METHODS: We report 3 cases of metastatic melanoma treated with ipilimumab in which the patients developed CIDP, TM, and concurrent myositis and myasthenia gravis–type syndrome, respectively, at the MD Anderson Cancer Center between July 2012 and June 2013. Patients consented to release of medical information for publication/educational purposes. RESULTS: Our 3 cases of metastatic melanoma treated with ipilimumab developed CIDP, TM, and concurrent myositis and myasthenia gravis–type syndrome, respectively. The median time to onset of immune-related adverse events following ipilimumab treatment ranged from 1 to 2 weeks. Ipilimumab was discontinued due to the severe neurological symptoms. Plasmapheresis was initiated in the patients with CIDP and concurrent myositis and myasthenia gravis–type syndrome; high-dose intravenous steroids were given to the patient with TM, and significant clinical response was demonstrated. CONCLUSIONS: Ipilimumab could induce a wide spectrum of neurological adverse effects. Our findings support the standard treatment of withholding or discontinuing ipilimumab. Plasmapheresis or high-dose intravenous steroids may be considered as the initial choice of treatment for severe ipilimumab-related neurological adverse events. Improvement of neurological symptoms may be seen within 2 weeks