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Background: The STRONG-HF trial demonstrated substantial reductions in the composite of mortality and morbidity over 6 months among hospitalized heart failure patients who were randomized to intensive guideline-directed medical therapy (GDMT) optimization compared to usual care. Whether an intensive GDMT optimization program would be cost-effective for patients with heart failure with reduced ejection fraction (HFrEF) is unknown. Methods: Using a 2-state Markov model we evaluated the effect of an intensive GDMT optimization program on hospitalized patients with HFrEF. Two population models were created to simulate this intervention, a "Clinical Trial" model, based off the participants in the STRONG-HF trial and a "Real-World" model, based off the Get With The Guidelines-HF Registry of patients admitted with worsening HF. We then modeled the effect of a 6-month intensive triple therapy GDMT optimization program comprised of cardiologists, clinical pharmacists, and registered nurses. Hazard ratios from the intervention arm of the STRONG-HF trial were applied to both populations models to simulate clinical and financial outcomes of an intensive GDMT optimization program from a United States healthcare sector perspective with a lifetime time horizon. Optimal quadruple GDMT use was also modeled. Results: An intensive GDMT optimization program was extremely cost-effective with incremental cost-effectiveness ratios

Peripheral nerve injuries requiring surgical repair affect over 100,000 individuals in the US annually. Three accepted methods of peripheral repair include end-to-end, end-to-side, and side-to-side neurorrhaphy, each with its own set of indications. While it remains important to understand the specific circumstances in which each method is employed, a deeper understanding of the molecular mechanisms underlying the repair can add to the surgeon's decision-making algorithm when considering each technique, as well as help decide nuances in technique such as the need for making epineurial versus perineurial windows, length and dept of the nerve window, and distance from target muscle. In addition, a thorough knowledge of individual factors that are active in a particular repair can help guide research into adjunct therapies. This paper serves to summarize the similarities and divergences of the three commonly used nerve repair strategies and the scope of molecular mechanisms and signal transduction pathways in nerve regeneration as well as to identify the gaps in knowledge that should be addressed if we are to improve clinical outcomes in our patients.

BackgroundPatients with prostate cancer treated with stereotactic body radiation therapy (SBRT) may experience gastrointestinal (GI) toxicity. The hydrogel may mitigate this toxicity by reducing the rectal radiation dose. The purpose of this study is to compare rectal radiation dose and GI toxicity in patients receiving prostate SBRT with and without hydrogel.MethodsConsecutive patients treated with SBRT between February 2017 and January 2020 with and without hydrogel were retrospectively identified. Baseline characteristics including prostate volume, rectal diameter, body mass index (BMI), age, pretreatment prostate-specific antigen (PSA), Gleason score, T-stage, and androgen deprivation therapy (ADT) usage were compared. Dosimetric outcomes (V40Gy, V36Gy, V32Gy, V38Gy, and V20Gy), rates of acute (≤90 days) and late (>90 days) GI toxicity, and PSA outcomes were evaluated for patients with and without hydrogel.ResultsA total of 92 patients were identified (51 hydrogel and 41 non-hydrogel). There were no significant differences in baseline characteristics. Rectal V38(cc) was significantly less in the hydrogel group (mean 0.44 vs. mean 1.41 cc, p = 0.0002), and the proportion of patients with V38(cc) < 2 cc was greater in the hydrogel group (92% vs. 72%, p = 0.01). Rectal dose was significantly lower for all institutional dose constraints in the hydrogel group (p < 0.001). The hydrogel group experienced significantly less acute overall GI toxicity (16% hydrogel vs. 28% non-hydrogel, p = 0.006), while the difference in late GI toxicity trended lower with hydrogel but was not statistically significant (4% hydrogel vs. 10% non-hydrogel, p = 0.219). At a median follow-up of 14.8 months, there were no biochemical recurrences in either group.ConclusionHydrogel reduces rectal radiation dose in patients receiving prostate SBRT and is associated with a decreased rate of acute GI toxicity.

BackgroundEmerging data suggest that metastasis is a spectrum of disease burden rather than a binary state, and local therapies, such as radiation, might improve outcomes in oligometastasis. However, current definitions of oligometastasis are solely numerical.ObjectiveTo characterize the somatic mutational landscape across the disease spectrum of metastatic castration-sensitive prostate cancer (mCSPC) to elucidate a biological definition of oligometastatic CSPC.Design, setting, and participantsThis was a retrospective study of men with mCSPC who underwent clinical-grade sequencing of their tumors (269 primary tumor, 25 metastatic sites). Patients were classified as having biochemically recurrent (ie, micrometastatic), metachronous oligometastatic (≤5 lesions), metachronous polymetastatic (>5 lesions), or de novo metastatic (metastasis at diagnosis) disease.Outcome measurements and statistical analysisWe measured the frequency of driver mutations across metastatic classifications and the genomic associations with radiographic progression-free survival (rPFS) and time to castrate-resistant prostate cancer (CRPC).Results and limitationsThe frequency of driver mutations in TP53 (p =  0.01), WNT (p =  0.08), and cell cycle (p =  0.04) genes increased across the mCSPC spectrum. TP53 mutation was associated with shorter rPFS (26.7 vs 48.6 mo; p =  0.002), and time to CRPC (95.6 vs 155.8 mo; p =  0.02) in men with oligometastasis, and identified men with polymetastasis with better rPFS (TP53 wild-type, 42.7 mo; TP53 mutated, 18.5 mo; p =  0.01). Mutations in TP53 (incidence rate ratio [IRR] 1.45; p =  0.004) and DNA double-strand break repair (IRR 1.61; p

Background and purposeStereotactic body radiation therapy (SBRT) has become a standard-of-care option for localized prostate cancer. While prostate SBRT has traditionally been delivered using computed-tomography-guided radiation therapy (CTgRT), MR-imaging-guided radiation therapy (MRgRT) is now available. MRgRT offers real-time soft-tissue visualization and ease of adaptive planning, obviating the need for fiducial markers, and potentially allowing for smaller planning target volume (PTV) margins. Although prior studies have focused on evaluating the cost-effectiveness of MRgRT vs CTgRT from a payor perspective, the difference in provider costs to deliver such treatments remains unknown. This study thus used time-driven activity-based costing (TDABC) to determine the difference in provider resources consumed by delivering prostate SBRT via MRgRT vs CTgRT.MethodsData was collected from a single academic institution where prostate SBRT is routinely performed using both CTgRT and MRgRT. Five-fraction SBRT (40 Gy total dose) was assumed to be delivered through volumetric-modulated arc therapy for CTgRT patients, and through step-and-shoot, fixed-gantry intensity-modulated radiation therapy for MRgRT patients. Process maps were constructed for each portion of the radiation delivery process via interviews/surveys with departmental personnel and by measuring CTgRT and MRgRT treatment times. Prior to simulation, only CTgRT patients underwent placement of three gold fiducial markers. Personnel capacity cost rates were calculated by dividing total personnel costs by the annual minutes worked by a given personnel. Equipment costs included both an annualized purchase price and annual maintenance costs. Ultimately, the total costs of care encompassing personnel, space/equipment, and materials were aggregated across the entire chain of care for both CTgRT and MRgRT patients in a base case.ResultsDirect costs associated with delivering a 5-fraction course of prostate SBRT were $1,497 higher with MRgRT than with CTgRT - comprised of personnel costs ($210 higher with MRgRT), space/equipment ($1,542 higher with MRgRT), and materials ($255 higher with CTgRT). Only CTgRT patients underwent fiducial placement, which accounted for $591. MRgRT patients were assumed to undergo both CT simulation (for electron density calculation) and MRI simulation, with the former accounting for $168. Mean time spent by patients in the treatment vault per fraction was 20 minutes (range 15-26 minutes) for CTgRT, and 31 minutes (range 30-34 minutes) for MRgRT. Patient time spent during fiducial placement (CTgRT only) was 60 minutes. Modifying the number of fractions treated would result in the cost difference of $1,497 (5 fractions) changing to $441 (1 fraction) or to $2,025 (7 fractions).ConclusionThis study provides an approximate comparison of the direct resources required for a radiation oncology provider to deliver prostate SBRT with CTgRT vs MRgRT. We await findings from the currently accruing phase III MIRAGE trial, which is comparing these modalities, and will subsequently measure acute and late genitourinary/gastrointestinal (GU/GI) toxicities, temporal change in quality-of-life outcomes, and 5-year biochemical, recurrence-free survival. Results from studies comparing the efficacy and safety of MRgRT vs CTgRT will ultimately allow us to put this cost difference into context.

PurposeOur purpose was to study the effect of 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) positron emission tomography (PET)-computed tomography (CT) on staging/treatment recommendations of previously untreated prostate cancer. We report here results of a prospective single center single arm imaging trial within Veterans Affairs (Greater Los Angeles): the frequency of patients upstaged to M1 disease (primary endpoint) and the frequency of patients with change in treatment recommendations (secondary endpoint). This is the first report of prostate-specific membrane antigen PET-CT exclusive to U.S. veterans.Methods and materialsVeterans with Gleason ≥4 + 3, clinical stage ≥T2c, or prostate-specific antigen >10 ng/mL were eligible. Patients underwent conventional imaging (99mTc-methyl diphosphonate bone scan or 18F-NaF PET-CT; and pelvic CT or pelvic magnetic resonance imaging) in addition to 18F-DCFPyL PET-CT. The effect of 18F-DCFPyL PET-CT on treatment change was determined by applying prespecified treatment recommendations based on National Comprehensive Cancer Network guidelines and modern clinical practice.ResultsOne hundred patients underwent 18F-DCFPyL PET-CT. Nineteen out of 84 (23%) patients initially thought to be nonmetastatic were upstaged to M1; 8/16 (50%) patients initially thought to have M1 disease were downstaged to M0. In total, 39/100 (39%) had a change in prespecified treatment recommendations, including change of radiation therapy volume/dose in 39/100 (39%) and starting abiraterone in 22/100 (22%).ConclusionsIncorporation of 18F-DCFPyL PET-CT into the initial conventional imaging workup for prostate cancer can substantially affect staging/treatment recommendations.

PurposeThis study aimed to evaluate the feasibility and safety of prostate stereotactic body radiation therapy (SBRT) neoadjuvant to radical prostatectomy (RP) in a phase 1 trial. The primary endpoint was treatment completion rate without severe acute surgical complications. Secondary endpoints included patient-reported quality of life and physician-reported toxicities.Methods and materialsPatients with nonmetastatic high-risk or locally advanced prostate cancer received 24 Gy in 3 fractions to the prostate and seminal vesicles over 5 days, completed 2 weeks before RP. Patients with pN1 disease were treated after multidisciplinary discussion and shared decision making. Patient-reported quality of life (International Prostate Symptom Score and Expanded Prostate Cancer Index Composite 26-item version questionnaires) and physician-reported toxicity (Common Terminology Criteria for Adverse Events, version 4.03) were assessed before SBRT, immediately before surgery, and at 3-month intervals for 1 year.ResultsTwelve patients were enrolled, and 11 completed treatment (1 patient had advanced disease on prostate-specific membrane antigen positron emission tomography after enrollment but before treatment). There were no significant surgical complications. After RP, 2 patients underwent additional radiation therapy to nodes with androgen suppression for pN1 disease. Median follow-up after completion of treatment was 20.1 months, with 9 of 11 patients having a follow-up period of >12 months. Two patients had biochemical recurrence (prostate-specific antigen ≥0.05) within the first 12 months, with an additional 2 patients found to have biochemical recurrence after the 12-month period. The highest Common Terminology Criteria for Adverse Events genitourinary grades were 0, 1, 2, and 3 (n = 1, 4, 4, and 2, respectively), and the highest gastrointestinal grades were 0, 1, and 2 (n = 9, 1, and 1, respectively). At 12 months, incontinence was the only grade ≥2 toxicity. One and 2 of 9 patients had grade 2 and 3 incontinence, respectively. On the Expanded Prostate Cancer Index Composite (26-item version), the mean/median changes in scores from baseline to 12 months were -32.8/-31.1 for urinary incontinence, -1.6/-6.2 for urinary irritative/obstructive, -2.1/0 for bowel, -34.4/-37.5 for sexual function, and -10.6/-2.5 for hormonal. The mean/median change in International Prostate Symptom Score from baseline to 12 months was 0.5/0.5.ConclusionsRP after neoadjuvant SBRT appears to be feasible and safe at the dose tested. The severity of urinary incontinence may be higher than RP alone.

PurposeHealth systems have increased telemedicine use during the SARS-CoV-2 outbreak to limit in-person contact. We used time-driven activity-based costing to evaluate the change in resource use associated with transitioning to telemedicine in a radiation oncology department.Methods and materialsUsing a patient undergoing 28-fraction treatment as an example, process maps for traditional in-person and telemedicine-based workflows consisting of discrete steps were created. Physicians/physicists/dosimetrists and nurses were assumed to work remotely 3 days and 1 day per week, respectively. Mapping was informed by interviews and surveys of personnel, with cost estimates obtained from the department's financial officer.ResultsTransitioning to telemedicine reduced provider costs by $586 compared with traditional workflow: $47 at consultation, $280 during treatment planning, $237 during on-treatment visits, and $22 during the follow-up visit. Overall, cost savings were $347 for space/equipment and $239 for personnel. From an employee perspective, the total amount saved each year by not commuting was $36,718 for physicians (7243 minutes), $19,380 for physicists (7243 minutes), $17,286 for dosimetrists (7210 minutes), and $5599 for nurses (2249 minutes). Patients saved $170 per treatment course.ConclusionsA modified workflow incorporating telemedicine visits and work-from-home capability conferred savings to a department as well as significant time and costs to health care workers and patients alike.

BackgroundThe treatment paradigm for metastatic hormone-sensitive prostate cancer (mHSPC) patients is evolving. PET/CT now offers improved sensitivity and accuracy in staging. Recent randomized trial data supports escalated hormone therapy, local primary tumor therapy, and metastasis-directed therapy. The impact of combining such therapies into a multimodal approach is unknown. This Phase II single-arm clinical trial sponsored and funded by Veterans Affairs combines local, metastasis-directed, and systemic therapies to durably render patients free of detectable disease off active therapy.MethodsPatients with newly-diagnosed M1a/b prostate cancer (PSMA PET/CT staging is permitted) and 1-5 radiographically visible metastases (excluding pelvic lymph nodes) are undergoing local treatment with radical prostatectomy, limited duration systemic therapy for a total of six months (leuprolide, abiraterone acetate with prednisone, and apalutamide), metastasis-directed stereotactic body radiotherapy (SBRT), and post-operative fractionated radiotherapy if pT ≥ 3a, N1, or positive margins are present. The primary endpoint is the percent of patients achieving a serum PSA of