Integrating a Grassroots Well-Being Curriculum into a Radiation Oncology Residency Program.

PURPOSE: The burnout rate among US radiation oncology residents was 33% in 2016. To our knowledge there are no published interventions addressing burnout among radiation oncology residents. We describe the implementation of a well-being curriculum, cocreated by a psychologist, a medical humanities professional, and radiation oncology attending and resident physicians. METHODS AND MATERIALS: Radiation oncology residents at our institution were surveyed to determine themes that induced burnout. A curriculum was developed, with monthly small group sessions focused on 1 identified topic. Sessions alternated between psychological tool-focused approaches and humanities exercises. These were led by a psychologist or medical humanities professional. Residents were given protected time to attend sessions during business hours. Participation was optional. Participants were assigned a random identifier, and the Stanford Professional Fulfillment Index (PFI) was assessed at baseline and 3-month intervals. PFI trends were analyzed after 1 year. At the end of the year, a focus group was held to evaluate work satisfaction and self-reported interactions with patients and coworkers. This information was used to improve the curriculum. RESULTS: All 12 residents in the radiation oncology program participated in the curriculum. There was an equal number of residents of postgraduate years 2 through 5. Six of the participants were female. Of the participants, 11 completed the PFI. At baseline, 80% of residents met criteria for burnout. This decreased to 67%, 50%, and 33% at 3, 6, and 9 months, respectively. The proportion of residents meeting criteria for very good professional fulfillment was 30%, 56%, 38%, and 22% at baseline and 3, 6, and 9 months, respectively. On average, 9 of 12 residents attended each session. CONCLUSIONS: Our experience demonstrates the feasibility of collaborating with residents in the development of a well-being curriculum to cater programming to their needs, which we believe led to excellent engagement and attendance at each session.

Biologic Dose and Imaging Changes in Pediatric Brain Tumor Patients Receiving Spot Scanning Proton Therapy.

PURPOSE: To evaluate the incidence of imaging changes in our pediatric brain tumor population treated with spot-scanning proton therapy and analyze the spatial correlation of imaging changes with a novel biologic dose model. METHODS AND MATERIALS: All pediatric patients treated during the first year of our institution's experience who received a minimum treatment planning dose (TPD) of 5040 cGyE with available follow-up magnetic resonance imaging scans were selected for analysis. Posttreatment magnetic resonance imaging scans were fused with the treatment planning computed tomography. All T1 post-gadolinium enhancement, T2 fluid attenuated inversion recovery changes, TPD, and biologic dose (BD) volumes outside of the original gross tumor volume were contoured for analysis. RESULTS: Thirty patients were included in the analysis, 7 of whom developed posttreatment radiologic changes. The volumetric overlap of the T2 fluid attenuated inversion recovery changes and BD volumes was significantly greater than the overlap with the TPD volumes. Median volumetric overlaps of 85%, 18%, and 0% were observed with the BD105%, BD110%, and TPD105%, respectively. A nonsignificant increase in the volumetric overlap of the T1C+ changes and BD volumes was also observed. No correlation was observed between the total volume of BD110%, BD105%, or physical dose 105% and the development of imaging changes. CONCLUSIONS: Within our pediatric brain tumor population treated with spot-scanning proton therapy, our BD model demonstrated superior volumetric overlap with posttreatment T2 changes compared with the TPD model. Using a BD model in treatment planning for spot-scanning proton therapy may help avoid delivery of excessive BD to critical structures and may help minimize the risk of radiation-related late effects.

Increased utilization of external beam radiotherapy relative to cystectomy for localized, muscle-invasive bladder cancer: a SEER analysis.

OBJECTIVE: To assess recent utilization patterns of radiotherapy (RT) relative to cystectomy for muscle-invasive bladder cancer (MIBC) and evaluate survival trends over time in patients receiving RT. MATERIALS AND METHODS: The surveillance, epidemiology, and end results program (SEER) was used to identify patients diagnosed between 1992 and 2013 with localized MIBC. Patients with a prior history of non-bladder malignancy, who received no treatment, or did not have available treatment information, were excluded. Treatment utilization patterns were assessed using Cochran-Armitage tests for trend, and patient characteristics were compared using chi-square tests. Overall survival (OS) and cause-specific survival (CSS) were estimated using the Kaplan-Meier method. All-cause (ACM) and cause-specific mortality (CSM) were evaluated with multivariable Cox proportional hazards regression. RESULTS: Of 16175 patients analyzed, 11917 (74%) underwent cystectomy, and 4258 (26%) were treated with RT. Patients who received RT were older (median age 79 vs. 68, P < 0.01). Over time, the proportion of patients receiving RT relative to cystectomy increased (24% 1992-2002 vs. 28% 2003-2013, P < 0.01), despite median patient age throughout the study period remaining unchanged (71 for each 1992-2002 and 2003-2013, P = 0.41). For RT, compared with patients diagnosed earlier, those diagnosed from 2010-2013 showed improved OS (64% vs. 60% at 1 year, P < 0.01; 38% vs. 29% at 3 years, P < 0.01) and CSS (71% vs. 67% at 1 year, P = 0.01; 51% vs. 40% at 3 years, P < 0.01). On multivariable analysis, diagnosis from 2010-2013 was associated with a lower estimated risk of ACM (hazard ratio 0.77; 95% confidence interval 0.66-0.89, P < 0.001) and CSM (hazard ratio 0.81; 95% confidence interval 0.67-0.97, P = 0.02). CONCLUSION: Utilization of RT for localized MIBC increased relative to cystectomy from 1992 to 2013, despite the median age of treated patients remaining unchanged. More recent survival outcomes for patients receiving RT were improved, supporting continued use of bladder preservation strategies utilizing RT.

Targeted expression of µ-opioid receptors in a subset of striatal direct-pathway neurons restores opiate reward.

µ-opioid receptors (MORs) are necessary for the analgesic and addictive effects of opioids such as morphine, but the MOR-expressing neuronal populations that mediate the distinct opiate effects remain elusive. Here we devised a new conditional bacterial artificial chromosome rescue strategy to show, in mice, that targeted MOR expression in a subpopulation of striatal direct-pathway neurons enriched in the striosome and nucleus accumbens, in an otherwise MOR-null background, restores opiate reward and opiate-induced striatal dopamine release and partially restores motivation to self administer an opiate. However, these mice lack opiate analgesia or withdrawal. We used Cre-mediated deletion of the rescued MOR transgene to establish that expression of the MOR transgene in the striatum, rather than in extrastriatal sites, is needed for the restoration of opiate reward. Our study demonstrates that a subpopulation of striatal direct-pathway neurons is sufficient to support opiate reward-driven behaviors and provides a new intersectional genetic approach to dissecting neurocircuit-specific gene function in vivo.

Pavlovian conditioning of multiple opioid-like responses in mice.

Conditional responses in rodents such as locomotion have been reported for drugs of abuse and similar to the placebo response in humans, may be associated with the expectation of reward. We examined several conditional opioid-like responses and the influence of drug expectation on conditioned place preference and concomitant conditional locomotion. Male C57BL/6J mice were conditioned with the selective mu opioid receptor agonist fentanyl (0.2mg/kg, i.p.) in a novel context and subsequently given a vehicle injection. In separate experiments, locomotor activity, Straub tail, hot plate sensitivity, and conditioned place preference (CPP) were measured. Mice exhibited multiple conditional opioid-like responses including conditional hyperlocomotion, a conditional pattern of opioid-like locomotion, Straub tail, analgesia, and place preference. Modulating drug expectation via administration of fentanyl to "demonstrator" mice in the home cage did not affect the expression of conditioned place preference or the concomitant locomotor activity in "observer" mice. In summary, Pavlovian conditioning of an opioid in a novel context induced multiple conditional opioid-like behaviors and provides a model for studying the neurobiological mechanisms of the placebo response in mice.

Morphine analgesic tolerance in 129P3/J and 129S6/SvEv mice.

Morphine analgesic tolerance is heritable in both humans and rodents, with some individuals and strains exhibiting little and others exhibiting robust tolerance. 129S6/SvEv and 129P3/J mice reportedly do not demonstrate tolerance to morphine analgesia. Using our laboratory's standard morphine tolerance regimen and a between-subjects design, tolerance developed in the hot plate and tail withdrawal assays as indicated by a change in analgesic efficacy following a morphine challenge dose. Furthermore, the non-competitive NMDA receptor antagonist MK-801 (dizocilipine) blocked morphine tolerance in 129S6/SvEv and CD-1 mice in the hot plate assay. As previously reported, when a within-subjects design and cumulative dosing was employed, no tolerance was observed in the 129P3/J strain. However, using the same morphine regimen and a between-subjects design, comparable tolerance developed between 129P3/J and C57BL/6J strains following a single challenge dose of morphine. Spontaneous hyperalgesia was observed in the tail withdrawal assay following chronic morphine in C57BL/6J, but not 129P3/J mice. Additionally, morphine-tolerant C57BL/6J mice, but not 129P3/J mice, exhibited a large increase in the frequency of tail flicks during the first second following the baseline nociceptive response which may facilitate detection of the response during the tolerant state. We conclude that the method of tolerance assessment affects the ability to detect tolerance and thus may affect the degree and pattern of heritability of this trait and this could have implications for gene mapping studies.