Citations

Brain metastases traditionally carried a poor prognosis with an overall survival of weeks to months in the absence of treatment. Radiation therapy modalities include whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). WBRT delivers a relatively low dose of radiation, has neurocognitive sequelae, and has not been investigated for its immunostimulatory effects. Furthermore, WBRT exposes the entire intracranial tumor immune microenvironment to radiation. SRS delivers a high dose of conformal radiation with image guidance to minimize dose to surrounding normal brain tissue, and appears to promote anti-tumor immunity. In parallel with many of these discoveries, immune checkpoint inhibitors (ICIs) have demonstrated a survival advantage in multiple malignancies commonly associated with brain metastases (e.g., melanoma). Combination SRS and ICI are theorized to be synergistic in anti-tumor immunity directed to brain metastases. The purpose of this review is to explore the synergy of SRS and ICIs, including pre-clinical data, existing clinical data, and ongoing prospective trials.

Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.

AbstractBackgroundSarcopenia, characterized by low muscle mass, associates with mortality in patients with cirrhosis. Skeletal muscle area in a single computed tomography image at the level of the third lumbar vertebrate (L3) is a valid representative of whole body muscle mass. Controversy remains regarding applicability of psoas muscle to identify patients at greater risk of mortality. We aimed to determine psoas muscle index (PMI) association with skeletal muscle index (SMI) and to evaluate the capacity of PMI to predict liver transplant waitlist mortality.MethodsWe evaluated listed adult patients with cirrhosis from 2012 to 2013 at four North American liver transplant centres. From L3 computed tomography images within 3 months of listing, we determined SMI and PMI expressed by cm2/m2. Low SMI was defined as SMI <39 cm2/m2 in women and <50 cm2/m2 in men as published by us earlier. Cut‐offs for PMI to predict mortality were established using a receiver‐operating characteristic analysis. Mortality predictors were determined using competing‐risk analysis with reported results as subdistribution hazard ratios (sHRs).ResultsOf 353 waitlist candidates, 68% were men, mean age 56 ± 9 years, and Model for End‐stage Liver Disease of 16 ± 8 points. Low SMI was present more frequently in men than women (51 vs. 36%, P = 0.02). Moderately strong correlation between SMI and PMI was observed (r > 0.7, P < 0.001). Low PMI (males < 5.1 cm2/m2; females < 4.3 cm2/m2) yielded poor and moderate concordance with low SMI in men and women, respectively (Kappa coefficient 0.31 and 0.63). SMI (39 ± 9 vs. 43 ± 7 cm2/m2; P = 0.009) and PMI (4.4 ± 1.3 vs. 5.2 ± 1.1 cm2/m2; P = 0.001) were lower in women who died and/or were delisted (compared with non‐deceased patients) whereas men who died and/or were delisted had only lower SMI (47 ± 7 vs. 51 ± 9 cm2/m2; P = 0.003), but not PMI compared with non‐deceased patients. In women, both SMI (sHR 0.94, P = 0.048) and PMI (sHR 0.58, P = 0.002) were predictors of mortality, while in men, SMI was significant (sHR 0.95, P = 0.001) and PMI showed a trend to be (sHR 0.85, P = 0.09) associated with mortality. Overall, 104 patients (29%) were misclassified between SMI and PMI categories. Using PMI cut‐offs, 66% and 28% of low SMI men and women, who have a higher risk of mortality, were incorrectly classified as low risk.ConclusionsSkeletal muscle index is a more complete and robust measurement than PMI, especially in men with cirrhosis. Low PMI identifies an incomplete subset of patients at increased risk of mortality indicated by low SMI. Given the poor performance of PMI, SMI should not be substituted by PMI.

AbstractBackgroundWe previously identified air quality as a risk factor of interest for pediatric multiple sclerosis. The purpose of this study is to more closely examine the association between the six criteria air pollutants and pediatric MS as well as identify specific areas of toxic release using data from the Toxic Release Inventory.MethodsPediatric MS cases (N = 290) and healthy controls (N = 442) were included as part of an ongoing case–control study. We used the National Emissions Inventory system to estimate particulate exposure by county of residence for each participant. Proximity to Toxic Release Inventory (TRI) sites was also assessed using ArcGIS mapping tools. Risk‐Screening Environmental Indicators (RSEI) classified counties at risk to exposure of environmental toxic releases.ResultsFine particulate matter (PM2.5), carbon monoxide (CO), sulfur dioxide (SO2), and lead air emissions were associated with increased odds for pediatric MS (P < 0.01) for those residing within 20 miles of an MS center. Most study participants (75%) resided within 5 miles of at least one TRI site; however, the mean total pounds of stack air releases was higher for sites near MS cases (81,000 tons) compared to those near healthy controls (35,000 tons, P = 0.002). Average RSEI scores did not differ significantly between cases and controls.ConclusionOut of several air pollutants examined, we show that fine particulate matter and three other criteria pollutants (SO2, CO, and lead) were statistically associated with higher odds for pediatric MS.

69 Background: Healthcare organizations can cultivate the strength of a diverse workforce in creating a culture of excellence. Enabling the team to understand how personal and cultural beliefs affect our decision making and how we interact with patients and colleagues is integral. Gaps in care exist in cancer diagnoses and treatment in many minority groups. A need for education in the nature of assumptions, unconscious biases, and awareness around the existence of healthcare disparities, was identified through culture transformation work within multiple healthcare institutions. Methods: An experiential course was designed for multi-disciplinary groups of providers. Designed to meet the evolving demographics in the country and help participants recognize how their own cultural beliefs and values affect their decision making. Topics include cultural awareness, assumptions and unconscious bias, effective use of interpreters, and skills to recognize when cultural differences may be playing a role and how to successfully navigate these situations. Raising awareness of healthcare disparities is highlighted, including disparities in cancer care diagnosis, treatment and outcomes for different ethnicities and socioeconomic groups. Examples include disparities in diagnosis, treatment and outcomes of lung cancer, colon cancer and breast cancer in minorities. Results: Participants engage in skills-based work. Participants develop a plan how they can take this information and education back to help create an awareness of disparities and skills to successfully navigate these situations. After this program, participants will be cognizant of the nature of assumptions and unconscious bias and understand the strength of diversity as an asset rather than a hindrance. Conclusions: Healthcare disparities can have a significant impact on patient experience, quality and outcomes. Specific inequities in cancer diagnosis and treatment in minorities is highlighted. Participants are provided with information and skills that can be introduced to their home institutions to have all caregivers recognize and successfully navigate culturally sensitive situations.

158 Background: There is limited research on methods for alerting clinicians to concerning patient-reported outcome (PRO) responses and how often PROs trigger alerts to nurses during cancer care. Methods: In two randomized trials, adults with advanced cancer receiving chemotherapy were enrolled. Participants were randomized to usual care vs. weekly PROs completed between visits (with automated feedback to nurses). PRO responses in the intervention arm triggered automated email alerts to nurses for frequent, severe, or worsening symptoms in the last 7 days. Alert thresholds for PROs were chosen a priori but were unique to each study. The “Symptom Tracking and Reporting” (STAR) trial was conducted at one academic medical center. The “PROs to Enhance Cancer Treatment” (PRO-TECT [AFT-39]) cluster-randomized trial is being conducted in > 30 community practices. Results: In STAR, 766 patients participated (58% female, 38% ages ≥65, 17% minority, 28% ≤high school). 441 participants were randomized to the intervention arm, where 1,431/84,212 items (2%) triggered a concerning symptom alert, during 1,070/8,498 weeks (13%). Frequent alerts were for fatigue (62%), pain (32%), and appetite (16%). In PRO-TECT (AFT-39), 300 patients have been enrolled (58% female, 49% ages ≥65, 8% minority, 47% ≤high school) out of 1,000. 146 participants have been randomized to the intervention arm, where 1,422/24,739 items (6%) triggered an alert, during 824/2249 weeks (37%). Common alerts were for pain (48%), physical function (35%), and diarrhea (15%). PRO-TECT provided clinical decision support with alerts. Conclusions: In two randomized trials in advanced cancer, PROs collected during care delivery enabled tailored treatment based on issues identified on PROs. Pain, physical function, appetite, and diarrhea commonly triggered alerts for concerning symptoms. Early PRO-TECT results are showing a trend for higher weekly alert rates for concerning symptoms (37% vs. 13% in STAR), which may indicate that the PRO intervention will be even more effective in community practices. Results assist in addressing logistical considerations for implementing PROs into routine care. Clinical trial information: NCT03249090.