Cost-Effectiveness of PET Directed Versus Combined Modality Therapy for Early-Stage Favorable Hodgkin's Lymphoma.

INTRODUCTION: The standard of care for early-stage Hodgkin Lymphoma (HL) is combined modality therapy (CMT) consisting of chemotherapy and involved site radiation therapy (ISRT). Recent treatment de-escalation trials have assessed the impact of omitting radiation with the use of positron emission tomography (PET) and have suggested a detriment in progression free survival (PFS) for patients who do not receive radiation therapy (RT) but similar overall survival. The purpose of this study was to compare the cost-effectiveness of PET-directed therapy versus standard of care CMT. METHODS: This study used a cost-effectiveness Markov model simulating 5 year outcomes for 1 million patients with early-stage HL treated with either PET-directed therapy consisting of 2 cycles of ABVD chemotherapy ± ISRT or CMT consisting of 2 cycles of ABVD + ISRT. Patients progressed to no evidence of disease, progression of disease (PD), or death. Patients with PD underwent salvage therapy with high dose chemotherapy and stem cell transplant (HDC-SCT). The primary outcome measured was the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were performed. RESULTS: We found that PET-directed therapy and CMT strategies were associated with costs of $47,362 and $41,167, respectively. The CMT strategy was equally as effective as the PET-directed therapy strategy with QALYs of 3.4. On 1-way sensitivity analyses, the model was most sensitive to CMT and HDC-SCT costs. Two-way sensitivity analyses showed the model was sensitive to the relative costs of these treatments. CONCLUSION: For patients with early-stage HL, CMT is the cost-effective strategy as compared with PET-directed therapy.

Opioid prescription patterns among radiation oncologists in the United States.

BACKGROUND: Radiation oncologists (ROs) play an important role in managing cancer pain; however, their opioid prescribing patterns remain poorly described. METHODS: The 2016 Medicare Physician Compare National Downloadable and the 2016 Medicare Part D Prescriber Data files were cross-linked to identify RO-written opioid prescriptions. RESULTS: Of 4,627 identified ROs, 1,360 (29.3%) wrote >10 opioid prescriptions. The average number of opioid prescriptions written was significantly (P ≤ .05) associated with the following RO characteristics: sex [13.1 ± 36.5 male vs 7.5 ± 16.9 female]; years since medical school graduation [4.5 ± 11.5 1-10 years vs 12.6 ± 26.0 11-24 years vs 13.3 ± 40.9 ≥25 years]; practice size [15.5 ± 44.6 size ≤10 vs 13.3 ± 25.9 size 11-49 vs 8.5 ± 12.7 size 50-99 vs 8.8 ± 26.9 size ≥100]; Medicare Physician Quality Reporting System (PQRS) participation [12.6 ± 31.8 yes vs 7.0 ± 35.4 no]; and practice location [17.4 ± 47.0 South vs 10.6 ± 29.4 Midwest vs 8.1 ± 13.9 West vs 6.9 ± 15.2 Northeast]. On multivariable regression modeling, male sex (RR 1.29, 95% CI 1.22-1.35, P < .001), ≥25 years since graduation (RR 0.78, 95% CI 0.64-0.70, 1-10 years vs ≥25 years; RR 1.00, 95% CI 0.96 - 1.04, 11-24 years vs ≥25 years; P < .001), practice size <10 members (RR 1.51, CI 1.44-1.59, ≤10 vs ≥100 members, RR 1.27, CI 1.20-1.34, 10-49 vs ≥100 members, RR 0.86, CI 0.80-0.92, 50-99 vs ≥100 members, P < .001), PQRS participation (RR 1.12, CI 1.04-1.19, P < .002), and Southern location (RR 0.67, CI 0.64-0.70, Midwest vs South; RR 0.39, CI 0.37-0.41, Northeast vs South; RR 0.43, CI 0.41-0.46, West vs South; P < .001) were predictive of higher opioid prescription rates. CONCLUSIONS: Factors associated with increased number of RO-written opioid prescriptions were male sex, ≥25 years since graduation, group practice <10, PQRS participation, and Southern location. Additional research is required to establish optimal opioid prescribing practices for ROs.

CRISPR screening using an expanded toolkit of autophagy reporters identifies TMEM41B as a novel autophagy factor.

The power of forward genetics in yeast is the foundation on which the field of autophagy research firmly stands. Complementary work on autophagy in higher eukaryotes has revealed both the deep conservation of this process, as well as novel mechanisms by which autophagy is regulated in the context of development, immunity, and neuronal homeostasis. The recent emergence of new clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-based technologies has begun facilitating efforts to define novel autophagy factors and pathways by forward genetic screening in mammalian cells. Here, we set out to develop an expanded toolkit of autophagy reporters amenable to CRISPR/Cas9 screening. Genome-wide screening of our reporters in mammalian cells recovered virtually all known autophagy-related (ATG) factors as well as previously uncharacterized factors, including vacuolar protein sorting 37 homolog A (VPS37A), transmembrane protein 251 (TMEM251), amyotrophic lateral sclerosis 2 (ALS2), and TMEM41B. To validate this data set, we used quantitative microscopy and biochemical analyses to show that 1 novel hit, TMEM41B, is required for phagophore maturation. TMEM41B is an integral endoplasmic reticulum (ER) membrane protein distantly related to the established autophagy factor vacuole membrane protein 1 (VMP1), and our data show that these two factors play related, albeit not fully overlapping, roles in autophagosome biogenesis. In sum, our work uncovers new ATG factors, reveals a malleable network of autophagy receptor genetic interactions, and provides a valuable resource (http://crispr.deniclab.com) for further mining of novel autophagy mechanisms.