Immune checkpoint inhibitor (ICI) therapy has recently been found to improve survival in patients with a number of cancers, including those with metastatic disease. There is an association of adverse ...radiation effect (ARE) in patients with brain metastases who have been treated with stereotactic radiosurgery (SRS) and ICIs.
Single-institution retrospective review identified 1118 brain metastases treated with SRS between 2013 and 2018 that had received ICI therapy and 886 metastases that did not receive ICI. Toxicity grading was done via the Common Terminology Criteria for Adverse Events v4.0 grading criteria. Cumulative incidence of ARE was estimated using competing risks methodology; univariate and multivariable regression models were generated to estimate the subdistribution hazard (sHR) of ARE.
Two-year cumulative incidence of ARE was 4.5% and 2.1% in patients treated with and without ICI, respectively (Gray's P = .004). Of the 52 metastases exhibiting ARE during the follow-up period, ARE severity by Common Terminology Criteria for Adverse Events v4 was grade 1 in 14 patients, grade 2 in 15, grade 3 in 9, and grade 4 in 14. There were no grade 5 events. Factors associated with an increased sHR of ARE on univariate analysis included ICI, metastasis volume, SRS dose, prescription isodose line, cavity-directed SRS, and V12. Multivariable analysis revealed prescription isodose line (sHR 0.95, P < .01) and ICI (sHR 2.58, P < .01) as significant predictors of ARE. Increasing V12 was associated with a rapidly increasing risk of adverse radiation effect in patients who received ICI.
Our findings suggest that patients receiving ICI have an increased risk of ARE after radiosurgery for brain metastases, with large metastases being at particularly high risk.
Purpose
Patients with high rates of developing new brain metastases have an increased likelihood of dying of neurologic death. It is unclear, however, whether this risk is affected by treatment ...choice following failure of primary stereotactic radiosurgery (SRS).
Methods
From July 2000 to March 2017, 440 patients with brain metastasis were treated with SRS and progressed to have a distant brain failure (DBF). Eighty-seven patients were treated within the immunotherapy era. Brain metastasis velocity (BMV) was calculated for each patient. In general, the institutional philosophy for use of salvage SRS vs whole brain radiotherapy (WBRT) was to postpone the use of WBRT for as long as possible and to treat with salvage SRS when feasible. No further treatment was reserved for patients with poor life expectancy and who were not expected to benefit from salvage treatment.
Results
Two hundred and eighty-five patients were treated with repeat SRS, 91 patients were treated with salvage WBRT, and 64 patients received no salvage radiation therapy. One-year cumulative incidence of neurologic death after salvage SRS vs WBRT was 15% vs 23% for the low- (p = 0.06), 30% vs 37% for the intermediate- (p < 0.01), and 31% vs 48% (p < 0.01) for the high-BMV group. Salvage WBRT was associated with increased incidence of neurologic death on multivariate analysis (HR 1.64, 95% CI 1.13–2.39, p = 0.01) when compared to repeat SRS. One-year cumulative incidence of neurologic death for patients treated within the immunotherapy era was 9%, 38%, and 38% for low-, intermediate-, and high-BMV groups, respectively (p = 0.01).
Conclusion
Intermediate and high risk BMV groups are predictive of neurologic death. The association between BMV and neurologic death remains strong for patients treated within the immunotherapy era.
Organic aerosol (OA) is an air pollutant ubiquitous in urban atmospheres. Urban OA is usually apportioned into primary OA (POA), mostly emitted by mobile sources, and secondary OA (SOA), which forms ...in the atmosphere due to oxidation of gas-phase precursors from anthropogenic and biogenic sources. By performing coordinated measurements in the particle phase and the gas phase, we show that the alkylperoxy radical chemistry that is responsible for low-temperature ignition also leads to the formation of oxygenated POA (OxyPOA). OxyPOA is distinct from POA emitted during high-temperature ignition and is chemically similar to SOA. We present evidence for the prevalence of OxyPOA in emissions of a spark-ignition engine and a next-generation advanced compression-ignition engine, highlighting the importance of understanding OxyPOA for predicting urban air pollution patterns in current and future atmospheres.
Object Laser-interstitial thermal therapy (LITT) has been proposed as an alternative treatment to surgery for radiation necrosis (RN) in patients treated with stereotactic radiosurgery (SRS) for ...brain metastases. The present study sought to retrospectively analyze LITT outcomes in patients with RN from SRS. Methods This was a single-institution retrospective study of 30 patients treated from 2011-2018 with pathologically-proven RN after SRS for brain metastases (n=28) or proximally treated extracranial lesions treated with external beam radiotherapy (n=2). Same-day biopsy was performed in all cases. Patients were prospectively followed with Functional Assessment of Cancer Therapy - Brain (FACT-Br), EuroQol-5 Dimension (EQ-5D), Hopkins Verbal Learning Test (HVLT) and clinical history and examination. Adjusted means, standard errors and tests comparing visits to pre-LITT were generated. Kaplan-Meier method was used to estimate time overall survival. Competing risk analysis was used to estimate cumulative incidence of LITT failure. Results In our patient population, median time from radiotherapy to LITT was 13.1 months. Median SRS dose and median LITT treatment target volume were 20 Gy (IQR 18-22) and 3.5 cc (IQR 2.2-4.6), respectively. Seventy-seven percent of our patients tapered off steroids within one month. There were only two instances of RN recurrence after LITT, with recurrence defined as recurrence of symptoms after initial improvement. These recurrences occurred at 1.9 and 3.4 months. The three-, six- and nine-month freedom from recurrence rates were 95.7%, 90.9%, and 90.9%. Median survival in our patient population with pathologically confirmed RN treated with LITT was 2.1 years. Regarding the quality of life questionnaires with which some patients were followed as part of different prospective studies, completion rates were 22/30 for FACT-Br, 16/30 for the EQ-5D and 8/30 for HVLT. Quality of life questionnaire results were overall stable from baseline. Mean FACT-Br scores were stable from baseline (17.9, 16.6, 21.4 and 22.8) to three months (18.8, 15.4, 18.4 and 23.4) (p=0.38, 0.53, 0.09 and 0.59). The mean EQ-5D Aggregate score was stable from baseline (7.1) to one month (7.6) (p=0.25). Mean HVLT-R Total Recall was stable from baseline (20.6) to three months (18.4) (p=0.09). There was a statistically significant decrease in mean Karnofsky Performance Scale (KPS) score from baseline (84) to three-month follow-up (75) (p=0.03). Conclusions LITT represents a safe and durably effective treatment option for RN in the brain. Results demonstrate a median survival of 2.1 years from LITT with only two recurrences, both within four months of treatment and salvageable. Patient-reported outcomes showed no severe declines after LITT. Quality of life questionnaires demonstrated stable well-being and functionality from baseline. LITT should be considered for definitive treatment of RN, especially in cases where patients have significant side effects from standards medical therapies such as steroids or if steroids are minimally effective.
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Background: Palliative radiation therapy (PRT) offers effective symptomatic relief to cancer patients. Increased focus on quality of care and healthcare efficiency necessitate a ...better understanding of the temporal relationships between consultation for/initiation of PRT and length of hospital stay (LOS). This study aims to assess whether durations from admission to PRT consult/PRT initiation affect LOS. Methods: In an institutional review of patients who received PRT as inpatients between January 2017 and December 2018, 67 met inclusion criteria. Duration of time from admission to consultation or start of PRT were categorized using various thresholds. LOS was compared across groups using the Wilcoxon rank sum test and factors were evaluated as predictors of LOS using bivariate linear regression. Results: PRT was given for pain (37%), neurologic deficits/brain metastases (31%), and respiratory symptoms (19%). Multiple sites were treated in 31%; treatment sites included spine (45%), non-spine bone (27%), chest (22%), abdomen/pelvis (12%), brain (10%) and soft tissue (6%). At admission, patients had known metastases (66%), no prior cancer diagnosis (19%), or known primary cancer (15%). Median LOS was 12 days (IQR 7-18) for all patients. There was a significant difference in LOS for patients referred for PRT within 3 days of admission versus greater than 3 days (11 v. 21 days, p < 0.01). This difference was slightly greater using a threshold of 4 days (11 v. 25 days, p < 0.01) and 5 days (11 v. 26 days, p < 0.01), both of which remained significant when analyzing only patients with prior cancer diagnosis (n = 54). There was no difference in LOS using a threshold of 1 or 2 days. As a continuous variable, duration from admission to PRT was associated with LOS (OR 2.40, p < 0.01). Similar patterns were noted when analyzing by time from admission to PRT start. Conclusions: Earlier radiation oncology consultation for PRT is associated with shorter LOS in patients treated with PRT for symptomatic malignancy. Further research is needed to better define this relationship and improve systematic processes to facilitate early consultation and treatment. A palliative radiation oncology clinic was recently developed to address these issues at our institution.
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Background: Palliative radiotherapy (PRT) is a common and effective modality for the relief of symptoms due to malignancy. Members of the supportive care team may be hesitant to ...refer for PRT due to concerns regarding timeliness of treatment and patient/caregiver time burden. The current structure of most radiation oncology clinics is not conducive to the delivery of timely PRT and few metrics aimed at quality improvement have been reported. Methods: We reviewed all courses of PRT delivered at our institution between January 2017 and December 2018. Hematologic/myeloma primary and postoperative cases were excluded. The dates of referral, consultation, PRT planning simulation, PRT start and end were recorded. An inherent delay was noted if PRT was purposefully delayed (workup, imaging). Time to PRT (TTPRT) was defined as the number of days between referral and start of PRT. A remaining life ratio (RLR) representing TTPRT as a proportion of survival from the time of referral, was developed as a practical metric to represent timeliness of PRT with respect to prognosis. Results: 338 courses of PRT were included from 67% outpatient and 33% inpatient referrals. Indications included pain (55%), neurologic deficits/brain metastases (23%), respiratory symptoms (10%), bleeding (6%) and other (7%). Median TTPRT was 13 d (IQR 4-19), comprised of: referral to consult (3 d), consult to simulation (4 d), and simulation to PRT (6 d). Factors associated with TTPRT included ECOG, PRT indication, site (non-spine bone, chest, or brain), outpatient referral and delay. TTPRT was not associated with age, gender, rural residence, distance to hospital, race, median household income, insurance or marital status. Of 229 patients who died, factors associated with increased RLR were outpatient referral (13% v. 5%), abdomen/pelvis treatment site (16% v. 9%) and delay (17% v. 8%). Conclusions: TTPRT is associated with patient, treatment, and systematic factors, some of which are associated with increased RLR, elucidating several opportunities for improvement. Based on these results, our group has established a dedicated Palliative Radiation Oncology Clinic focused on timely, quality PRT, the outcomes of which will be assessed prospectively.
The chemical composition of particulate matter (PM) in biomass-burning smoke evolves upon aging in the atmosphere. The effect of this evolution on the toxicity of biomass-burning PM is understudied. ...Here, we burned oak foliage, pine needles, and hickory twigs in an environmental chamber. We used UV radiation to initiate photochemical aging of the emissions leading to the production of secondary organic aerosol (SOA), quantified using online particle size distribution measurements, and an overall increase in the PM oxygenation and decrease in the relative abundance of aromatic and condensed aromatic structures, obtained using ultra-high-resolution electrospray ionization mass spectrometry. In vitro exposure of human lung epithelial cells to PM from hickory combustion led to the strongest reduction in metabolic activity, followed by pine and oak, which was associated with the heavy metal content of the PM from the three fuels, quantified using induction-coupled plasma mass spectrometry. Furthermore, exposure to the fresh PM led to more reduction in metabolic activity than the aged PM for all fuels, whereas the aged PM induced more cell death by apoptosis. The differential cellular response to the fresh and aged PM indicates that the increase in oxygenation and decrease in aromaticity associated with photochemical aging alters the toxicity mechanisms exhibited by the PM, with a possible role of decreasing the heavy metal content (gram-metals per gram-PM) due to SOA formation. Together, these findings highlight the complex effect of photochemical aging on biomass-burning PM toxicity and motivate further studies to elucidate the underlying differences in toxicity mechanisms between fresh and aged PM.
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•Biomass-burning organic aerosol is toxic toward human lung epithelial cells.•Heavy metals potentially play an important role in the observed toxicity.•Photochemical aging renders the aerosol more potent at inducing cell death.•Photochemical aging renders the aerosol less potent at reducing metabolic activity.
A Sweeter Solution to CT Skin Marking Hiatt, Kevin D.; Glenn, Chase W.; Caudill, Herbert C. ...
Journal of radiology nursing,
12/2023, Letnik:
42, Številka:
4
Journal Article
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