Real-World Use of Hypofractionated Radiotherapy for Primary CNS Tumors in the Elderly, and Implications on Medicare Spending.

BACKGROUND: For elderly patients with high-grade gliomas, 3-week hypofractionated radiotherapy (HFRT) is noninferior to standard long-course radiotherapy (LCRT). We analyzed real-world utilization of HFRT with and without systemic therapy in Medicare beneficiaries treated with RT for primary central nervous system (CNS) tumors using Centers for Medicare & Medicaid Services data. METHODS: Radiation modality, year, age (65-74, 75-84, or ≥85 years), and site of care (freestanding vs hospital-affiliated) were evaluated. Utilization of HFRT (11-20 fractions) versus LCRT (21-30 or 31-40 fractions) and systemic therapy was evaluated by multivariable logistic regression. Medicare spending over the 90-day episode after RT planning initiation was analyzed using multivariable linear regression. RESULTS: From 2015 to 2019, a total of 10,702 RT courses (ie, episodes) were included (28% HFRT; 65% of patients aged 65-74 years). A considerable minority died within 90 days of RT planning initiation (n=1,251; 12%), and 765 (61%) of those received HFRT. HFRT utilization increased (24% in 2015 to 31% in 2019; odds ratio [OR], 1.2 per year; 95% CI, 1.1-1.2) and was associated with older age (≥85 vs 65-74 years; OR, 6.8; 95% CI, 5.5-8.4), death within 90 days of RT planning initiation (OR, 5.0; 95% CI, 4.4-5.8), hospital-affiliated sites (OR, 1.4; 95% CI, 1.3-1.6), conventional external-beam RT (vs intensity-modulated RT; OR, 2.7; 95% CI, 2.3-3.1), and no systemic therapy (OR, 1.2; 95% CI, 1.1-1.3; P<.001 for all). Increasing use of HFRT was concentrated in hospital-affiliated sites (P=.002 for interaction). Most patients (69%) received systemic therapy with no differences by site of care (P=.12). Systemic therapy utilization increased (67% in 2015 to 71% in 2019; OR, 1.1 per year; 95% CI, 1.0-1.1) and was less likely for older patients, patients who died within 90 days of RT planning initiation, those who received conventional external-beam RT, and those who received HFRT. HFRT significantly reduced spending compared with LCRT (adjusted ß for LCRT = +$8,649; 95% CI, $8,544-$8,755), whereas spending modestly increased with systemic therapy (adjusted ß for systemic therapy = +$270; 95% CI, $176-$365). CONCLUSIONS: Although most Medicare beneficiaries received LCRT for primary brain tumors, HFRT utilization increased in hospital-affiliated centers. Despite high-level evidence for elderly patients, discrepancy in HFRT implementation by site of care persists. Further investigation is needed to understand why patients with short survival may still receive LCRT, because this has major quality-of-life and Medicare spending implications.

Hypofractionated re-irradiation for diffuse intrinsic pontine glioma.

BACKGROUND: Re-irradiation (reRT) increases survival in locally recurrent diffuse intrinsic pontine glioma (DIPG). There is no standard dose and fractionation for reRT, but conventional fractionation (CF) is typically used. We report our institutional experience of reRT for DIPG, which includes hypofractionation (HF). METHODS: We reviewed pediatric patients treated with brainstem reRT for DIPG at our institution from 2012 to 2022. Patients were grouped by HF or CF. Outcomes included steroid use, and overall survival (OS) was measured from both diagnosis and start of reRT. RESULTS: Of 22 patients who received reRT for DIPG, two did not complete their course due to clinical decline. Of the 20 who completed reRT, the dose was 20-30 Gy in 2-Gy fractions (n = 6) and 30-36 Gy in 3-Gy fractions (n = 14). Median age was 5 years (range: 3-14), median interval since initial RT was 8 months (range: 3-20), and 12 received concurrent bevacizumab. Median OS from diagnosis was 18 months [95% confidence interval: 17-24]. Median OS from start of reRT for HF versus CF was 8.2 and 7.5 months, respectively (p = .20). Thirteen (93%) in the HF group and three (75%) in the CF group tapered pre-treatment steroid dose down or off within 2 months after reRT due to clinical improvement. There was no significant difference in steroid taper between HF and CF (p = .4). No patients developed radionecrosis. CONCLUSION: reRT with HF achieved survival duration comparable to published outcomes and effectively palliated symptoms. Future investigation of this regimen in the context of new systemic therapies and upfront HF is warranted.

Intraoperative radiation therapy for pediatric sarcomas and other solid tumors.

PURPOSE: To evaluate local failure (LF) and toxicity after intraoperative radiation therapy (IORT) in pediatric solid tumors (ST). METHODS: A single-institution retrospective study of 96 pediatric patients (108 applications) with ST treated from 1995 to 2022 with IORT. LF was calculated via cumulative incidence function and overall survival (OS) by Kaplan-Meier method, both from the day of surgery. RESULTS: Median age at time of IORT was 8 years (range: 0.8-20.9 years). Median follow-up for all patients and surviving patients was 16 months and 3 years, respectively. The most common histologies included rhabdomyosarcoma (n = 42), Ewing sarcoma (n = 10), and Wilms tumor (n = 9). Most (95%) received chemotherapy, 37% had prior external beam radiation therapy to the site of IORT, and 46% had a prior surgery for tumor resection. About half (54%) were treated with upfront IORT to the primary tumor due to difficult circumstances such as very young age or challenging anatomy. The median IORT dose was 12 Gy (range: 4-18 Gy), and median area treated was 24 cm2 (range: 2-198 cm2). The cumulative incidence of LF was 17% at 2 years and 23% at 5 years. Toxicity from IORT was reasonable, with postoperative complications likely related to IORT seen in 15 (16%) patients. CONCLUSION: Our study represents the largest and most recent analysis of efficacy and safety of IORT in pediatric patients with ST. Less than one quarter of all patients failed locally with acceptable toxicities. Overall, IORT is an effective and safe technique to achieve local control in patients with challenging circumstances.

CEST MR fingerprinting (CEST-MRF) for brain tumor quantification using EPI readout and deep learning reconstruction.

PURPOSE: To develop a clinical CEST MR fingerprinting (CEST-MRF) method for brain tumor quantification using EPI acquisition and deep learning reconstruction. METHODS: A CEST-MRF pulse sequence originally designed for animal imaging was modified to conform to hardware limits on clinical scanners while keeping scan time under 2 min. Quantitative MRF reconstruction was performed using a deep reconstruction network (DRONE) to yield the water relaxation and chemical exchange parameters. The feasibility of the six parameter DRONE reconstruction was tested in simulations using a digital brain phantom. A healthy subject was scanned with the CEST-MRF sequence, conventional MRF and CEST sequences for comparison. Reproducibility was assessed via test-retest experiments and the concordance correlation coefficient calculated for white matter and gray matter. The clinical utility of CEST-MRF was demonstrated on four patients with brain metastases in comparison to standard clinical imaging sequences. Tumors were segmented into edema, solid core, and necrotic core regions and the CEST-MRF values compared to the contra-lateral side. RESULTS: DRONE reconstruction of the digital phantom yielded a normalized RMS error of ≤7% for all parameters. The CEST-MRF parameters were in good agreement with those from conventional MRF and CEST sequences and previous studies. The mean concordance correlation coefficient for all six parameters was 0.98 ± 0.01 in white matter and 0.98 ± 0.02 in gray matter. The CEST-MRF values in nearly all tumor regions were significantly different (P = 0.05) from each other and the contra-lateral side. CONCLUSION: Combination of EPI readout and deep learning reconstruction enabled fast, accurate and reproducible CEST-MRF in brain tumors.

Outcomes of intraventricular 131-I-omburtamab and external beam radiotherapy in patients with recurrent medulloblastoma and ependymoma.

PURPOSE: Intraventricular compartmental radioimmunotherapy (cRIT) with 131-I-omburtamab is a potential therapy for recurrent primary brain tumors that can seed the thecal space. These patients often previously received external beam radiotherapy (EBRT) to a portion or full craniospinal axis (CSI) as part of upfront therapy. Little is known regarding outcomes after re-irradiation as part of multimodality therapy including cRIT. This study evaluates predictors of response, patterns of failure, and radiologic events after cRIT. METHODS: Patients with recurrent medulloblastoma or ependymoma who received 131-I-omburtamab on a prospective clinical trial were included. Extent of disease at cRIT initiation (no evidence of disease [NED] vs measurable disease [MD]) was assessed as associated with progression-free (PFS) and overall survival (OS) by Kaplan-Meier analysis. RESULTS: All 27 patients (20 medulloblastoma, 7 ependymoma) had EBRT preceding cRIT: most (22, 81%) included CSI (median dose 2340 cGy, boost to 5400 cGy). Twelve (44%) also received EBRT at relapse as bridging to cRIT. There were no cases of radionecrosis. At cRIT initiation, 11 (55%) medulloblastoma and 3 (43%) ependymoma patients were NED, associated with improved PFS (p = 0.002) and OS (p = 0.048) in medulloblastoma. Most relapses were multifocal. With medium follow-up of 3.0 years (95% confidence interval, 1.8-7.4), 6 patients remain alive with NED. CONCLUSION: For patients with medulloblastoma, remission at time of cRIT was associated with significantly improved survival outcomes. Relapses are often multifocal, particularly in the setting of measurable disease at cRIT initiation. EBRT is a promising tool to achieve NED status at cRIT initiation, with no cases of radiation necrosis.

Clinical outcomes of pediatric patients receiving multimodality treatment of second central nervous system relapse of neuroblastoma.

BACKGROUND: In high-risk neuroblastoma, multimodality therapy including craniospinal irradiation (CSI) is effective for central nervous system (CNS) relapse. Management of post-CSI CNS relapse is not clearly defined. PROCEDURE: Pediatric patients with neuroblastoma treated with CSI between 2000 and 2019 were identified. Treatment of initial CNS disease (e.g., CSI, intraventricular compartmental radioimmunotherapy [cRIT] with 131 I-monoclonal antibodies targeting GD2 or B7H3) and management of post-CSI CNS relapse ("second CNS relapse") were characterized. Cox proportional hazards models to evaluate factors associated with third CNS relapse and overall survival (OS) were used. RESULTS: Of 128 patients (65% male, median age 4 years), 19 (15%) received CSI with protons and 115 (90%) had a boost. Most (103, 81%) received cRIT, associated with improved OS (hazard ratio [HR] 0.3, 95% confidence interval [CI]: 0.1-0.5, p < .001). Forty (31%) developed a second CNS relapse, associated with worse OS (1-year OS 32.5%, 95% CI: 19-47; HR 3.8; 95% CI: 2.4-6.0, p < .001), and more likely if the leptomeninges were initially involved (HR 2.5, 95% CI: 1.3-4.9, p = .006). Median time to second CNS relapse was 6.8 months and 51% occurred outside the CSI boost field. Twenty-five (63%) patients underwent reirradiation, most peri-operatively (18, 45%) with focal hypofractionation. Eight (20%) patients with second CNS relapse received cRIT, associated with improved OS (HR 0.1; 95% CI: 0.1-0.4, p < .001). CONCLUSIONS: CNS relapse after CSI for neuroblastoma portends a poor prognosis. Surgery with hypofractionated radiotherapy was the most common treatment. Acknowledging the potential for selection bias, receipt of cRIT both at first and second CNS relapse was associated with improved survival. This finding necessitates further investigation.

Treatment of Pediatric Low-Grade Gliomas.

PURPOSE OF REVIEW: Pediatric low-grade gliomas and glioneuronal tumors (pLGG) account for approximately 30% of pediatric CNS neoplasms, encompassing a heterogeneous group of tumors of primarily glial or mixed neuronal-glial histology. This article reviews the treatment of pLGG with emphasis on an individualized approach incorporating multidisciplinary input from surgery, radiation oncology, neuroradiology, neuropathology, and pediatric oncology to carefully weigh the risks and benefits of specific interventions against tumor-related morbidity. Complete surgical resection can be curative for cerebellar and hemispheric lesions, while use of radiotherapy is restricted to older patients or those refractory to medical therapy. Chemotherapy remains the preferred first-line therapy for adjuvant treatment of the majority of recurrent or progressive pLGG. RECENT FINDINGS: Technologic advances offer the potential to limit volume of normal brain exposed to low doses of radiation when treating pLGG with either conformal photon or proton RT. Recent neurosurgical techniques such as laser interstitial thermal therapy offer a "dual" diagnostic and therapeutic treatment modality for pLGG in specific surgically inaccessible anatomical locations. The emergence of novel molecular diagnostic tools has enabled scientific discoveries elucidating driver alterations in mitogen-activated protein kinase (MAPK) pathway components and enhanced our understanding of the natural history (oncogenic senescence). Molecular characterization strongly supplements the clinical risk stratification (age, extent of resection, histological grade) to improve diagnostic precision and accuracy, prognostication, and can lead to the identification of patients who stand to benefit from precision medicine treatment approaches. The success of molecular targeted therapy (BRAF inhibitors and/or MEK inhibitors) in the recurrent setting has led to a gradual and yet significant paradigm shift in the treatment of pLGG. Ongoing randomized trials comparing targeted therapy to standard of care chemotherapy are anticipated to further inform the approach to upfront management of pLGG patients.

Second cancer risk in childhood cancer survivors treated with intensity-modulated radiation therapy: An updated analysis of more than 10 years of follow-up.

BACKGROUND: It is unclear how intensity-modulated radiation therapy (IMRT) impacts long-term risk of second malignant neoplasms (SMNs) in childhood cancer patients. PROCEDURE: Patients aged ≤21 years treated with IMRT between 1998 and 2009 and who survived ≥5 years after IMRT were included. SMN site in relation to isodose level (IDL) of IMRT was evaluated. Standardized incidence ratios (SIR) and excess absolute risks (EAR) were calculated. Cumulative incidences were estimated with death as a competing risk. RESULTS: Three-hundred twenty-five patients were included with median follow-up of 11.2 years from IMRT (interquartile range: 9.4-14.0) among patients alive at the end of follow-up. Two hundred (62%) patients had ≥10 years of follow-up and 284 (87%) patients were alive at the time of analysis. Fifteen patients developed SMNs (11 solid, four hematologic). Median time from IMRT to solid SMN was 11.0 years (range: 6.8-19.2) with 10- and 15-year cumulative incidences 1.8% (95% CI: 0.7-3.9) and 3.5% (95% CI: 1.4-7.5), respectively; SIR was 13.7 (95% CI: 6.9-24.6) and EAR was 2.8 per 1000 person-years (95% CI: 1.0-4.6). Eight solid SMNs developed within the IMRT field (100% IDL [n = 5], 80% IDL [n = 1], 50% IDL [n = 1], 40% IDL [n = 1]), one within the 70%-80% IDL of a conventional field, one was out-of-field, and one could not be determined. CONCLUSIONS: With median follow-up of >10 years, many solid SMNs after IMRT in childhood cancer survivors develop in the high-dose region. These data serve as a foundation for comparison with other modalities of radiation treatment (e.g., proton therapy).

Breast conservation among older patients with early-stage breast cancer: Locoregional recurrence following adjuvant radiation or hormonal therapy.

BACKGROUND: For patients with breast cancer undergoing breast-conserving surgery (BCS), adjuvant radiation (RT) and hormonal therapy (HT) reduce the risk of locoregional recurrence (LRR). Although several studies have evaluated adjuvant HT ± RT, the outcomes of HT versus RT monotherapy remain less clear. In this study, the risk of LRR is characterized among older patients with early-stage breast cancer following adjuvant RT alone, HT alone, neither, or both. METHODS: This study included female patients from the Memorial Sloan Kettering Cancer Center (New York, New York) who were aged ≥65 years with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) T1N0 breast cancer treated with BCS. The primary endpoint was time to LRR evaluated by Cox regression analysis. RESULTS: There were 888 women evaluated with a median age of 71 years (range, 65-100 years) and median follow-up of 4.9 years (range, 0.0-9.5 years). There were 27 LRR events (3.0%). Five-year LRR was 11% for those receiving no adjuvant treatment, 3% for HT alone, 4% for RT alone, and 1% for HT and RT. LRR rates were significantly different between the groups (P < .001). Compared with neither HT nor RT, HT or RT monotherapy each yielded similar LRR reductions: HT alone (HR, 0.27; 95% CI, 0.10-0.68; P = .006) and RT alone (HR, 0.32; 95% CI, 0.11-0.92; P = .034). Distant recurrence and breast cancer-specific survival rates did not significantly differ between groups. CONCLUSIONS: LRR risk following BCS is low among women aged ≥65 years with T1N0, ER+/HER2- breast cancer. Adjuvant RT and HT monotherapy each similarly reduce this risk; the combination yields a marginal improvement. Further study is needed to elucidate whether appropriate patients may feasibly receive adjuvant RT monotherapy versus the current standards of HT monotherapy or combined RT/HT.

Association between Site-of-Care and the Cost and Modality of Radiotherapy for Prostate Cancer: Analysis of Medicare Beneficiaries from 2015 to 2017.

Among 84,447 radiotherapy (RT) courses for Medicare beneficiaries age ≥ 65 with prostate cancer treated with external beam RT (EBRT), brachytherapy, or both, 42,608 (51%) were delivered in hospital-affiliated and 41,695 (49%) in freestanding facilities. Freestanding centers were less likely to use EBRT + brachytherapy than EBRT (OR 0.84 [95%CI 0.84-0.84]; p < .001). Treatment was more costly in freestanding centers (mean difference $2,597 [95%CI $2,475-2,719]; p < .001). Adjusting for modality and fractionation, RT in hospital-affiliated centers was more costly (mean difference $773 [95%CI $693-853]; p < .001). Freestanding centers utilized more expensive RT delivery, but factors unrelated to RT modality or fractionation rendered RT more costly at hospital-affiliated centers.

Multi-domain neurocognitive classification of primary brain tumor patients prior to radiotherapy on a prospective clinical trial.

INTRODUCTION: We investigated multi-domain baseline neurocognition of primary brain tumor patients prior to radiotherapy (RT), including clinical predictors of function and association between pre-RT and post-RT impairment on a prospective trial. METHODS: A multi-domain neuropsychological battery (memory, executive functioning, language, attention, processing) was performed on 37 patients, pre-RT and 3-(n = 21), 6-(n = 22) and 12-(n = 14) months post-RT. Impairment rate was the proportion of patients with standardized T-scores ≤ 1.5 standard deviations below normative means. Per-patient impairment across all domains was calculated using a global deficit score (GDS; higher value indicates more impairment). Associations between baseline GDS and clinical variables were tested. Global GDS impairment rate at each time point was the fraction of patients with GDS scores > 0.5. RESULTS: Statistically significant baseline neurocognitive impairments were identified on 4 memory (all p ≤ 0.03) and 2 out of 3 (p = 0.01, p = 0.027) executive functioning tests. Per-patient baseline GDS was significantly associated with tumor volume (p = 0.048), tumor type (p = 0.043), seizure history (p = 0.007), and use of anti-epileptics (p = 0.009). The percentage of patients with the same impairment status at 3-, 6-, and 12-months as at baseline were 88%, 85%, and 85% respectively. CONCLUSIONS: Memory and executive functioning impairment were the most common cognitive deficits prior to RT. Patients with larger tumors, more aggressive histology, and use of anti-epileptics had higher baseline GDS values. GDS is a promising tool to encompass multi-domain neurocognitive function, and baseline GDS can identify those at risk of cognitive impairment.

Volitional control of single-electrode high gamma local field potentials by people with paralysis.

Intracortical brain-computer interfaces (BCIs) can enable individuals to control effectors, such as a computer cursor, by directly decoding the user's movement intentions from action potentials and local field potentials (LFPs) recorded within the motor cortex. However, the accuracy and complexity of effector control achieved with such "biomimetic" BCIs will depend on the degree to which the intended movements used to elicit control modulate the neural activity. In particular, channels that do not record distinguishable action potentials and only record LFP modulations may be of limited use for BCI control. In contrast, a biofeedback approach may surpass these limitations by letting the participants generate new control signals and learn strategies that improve the volitional control of signals used for effector control. Here, we show that, by using a biofeedback paradigm, three individuals with tetraplegia achieved volitional control of gamma LFPs (40-400 Hz) recorded by a single microelectrode implanted in the precentral gyrus. Control was improved over a pair of consecutive sessions up to 3 days apart. In all but one session, the channel used to achieve control lacked distinguishable action potentials. Our results indicate that biofeedback LFP-based BCIs may potentially contribute to the neural modulation necessary to obtain reliable and useful control of effectors. NEW & NOTEWORTHY Our study demonstrates that people with tetraplegia can volitionally control individual high-gamma local-field potential (LFP) channels recorded from the motor cortex, and that this control can be improved using biofeedback. Motor cortical LFP signals are thought to be both informative and stable intracortical signals and, thus, of importance for future brain-computer interfaces.

The role of cancer in marijuana and prescription opioid use in the United States: A population-based analysis from 2005 to 2014.

BACKGROUND: For patients with cancer, marijuana may be an alternative to prescription opioid analgesics. This study analyzed self-reported marijuana and prescription opioid use among people with cancer over a 10-year time period. METHODS: Population-based data sets from the US National Health and Nutrition Examination Survey between 2005 and 2014 were compiled for respondents aged 20 to 60 years. Respondents with cancer and respondents without cancer were propensity score-matched (1:2) by demographics to compare substance use. Outcomes included current marijuana and prescription opioid use (ie, within the past 30 days). Pearson chi-square tests and logistic regressions were performed; a 2-tailed P value < .05 was significant. RESULTS: There were 19,604 respondents, and 826 people with cancer were matched to 1652 controls. Among the respondents with cancer, 40.3% used marijuana within the past year, and 8.7% used it currently. Respondents with cancer were significantly more likely to use prescription opioids (odds ratio [OR], 2.43; 95% CI, 1.68-3.57; P < .001). Cancer was not associated with current marijuana use in a multivariable conditional logistic regression but was associated with current opioid use (OR, 1.82; 95% CI, 1.17-2.82; P = .008). Among all survey respondents, the odds of marijuana use significantly increased over time (OR, 1.05; 95% CI, 1.01-1.10; P = .012), whereas the odds of opioid use did not significantly change. There were no significant differences in the longitudinal odds of marijuana or opioid use over time between respondents with a cancer diagnosis and those without one. CONCLUSIONS: This population-based analysis revealed a considerable proportion of respondents with cancer self-reporting marijuana use (40.3%) and a significantly higher prevalence of opioid use among respondents with cancer. In the midst of an opioid epidemic, an evolving political landscape, and new developments in oncology, quantifying the prevalence of opioid and marijuana use in the US population, especially among patients with cancer, is particularly relevant. Although opioid use did not significantly change from 2005 to 2014 among all respondents, marijuana use did increase, likely reflecting increased availability and legislative changes. A cancer diagnosis did not significantly affect longitudinal opioid or marijuana use.

Stable long-term BCI-enabled communication in ALS and locked-in syndrome using LFP signals.

Restoring communication for people with locked-in syndrome remains a challenging clinical problem without a reliable solution. Recent studies have shown that people with paralysis can use brain-computer interfaces (BCIs) based on intracortical spiking activity to efficiently type messages. However, due to neuronal signal instability, most intracortical BCIs have required frequent calibration and continuous assistance of skilled engineers to maintain performance. Here, an individual with locked-in syndrome due to brain stem stroke and an individual with tetraplegia secondary to amyotrophic lateral sclerosis (ALS) used a simple communication BCI based on intracortical local field potentials (LFPs) for 76 and 138 days, respectively, without recalibration and without significant loss of performance. BCI spelling rates of 3.07 and 6.88 correct characters/minute allowed the participants to type messages and write emails. Our results indicate that people with locked-in syndrome could soon use a slow but reliable LFP-based BCI for everyday communication without ongoing intervention from a technician or caregiver. NEW & NOTEWORTHY This study demonstrates, for the first time, stable repeated use of an intracortical brain-computer interface by people with tetraplegia over up to four and a half months. The approach uses local field potentials (LFPs), signals that may be more stable than neuronal action potentials, to decode participants' commands. Throughout the several months of evaluation, the decoder remained unchanged; thus no technical interventions were required to maintain consistent brain-computer interface operation.

Rapid continuous 3D printing of customizable peripheral nerve guidance conduits.

Engineered nerve guidance conduits (NGCs) have been demonstrated for repairing peripheral nerve injuries. However, there remains a need for an advanced biofabrication system to build NGCs with complex architectures, tunable material properties, and customizable geometrical control. Here, a rapid continuous 3D-printing platform was developed to print customizable NGCs with unprecedented resolution, speed, flexibility, and scalability. A variety of NGC designs varying in complexity and size were created including a life-size biomimetic branched human facial NGC. In vivo implantation of NGCs with microchannels into complete sciatic nerve transections of mouse models demonstrated the effective directional guidance of regenerating sciatic nerves via branching into the microchannels and extending toward the distal end of the injury site. Histological staining and immunostaining further confirmed the progressive directional nerve regeneration and branching behavior across the entire NGC length. Observational and functional tests, including the von Frey threshold test and thermal test, showed promising recovery of motor function and sensation in the ipsilateral limbs grafted with the 3D-printed NGCs.

Types and Distribution of Payments From Industry to Physicians in 2015.

IMPORTANCE: Given scrutiny over financial conflicts of interest in health care, it is important to understand the types and distribution of industry-related payments to physicians. OBJECTIVE: To determine the types and distribution of industry-related payments to physicians in 2015 and the association of physician specialty and sex with receipt of payments from industry. DESIGN, SETTING, AND PARTICIPANTS: Observational, retrospective, population-based study of licensed US physicians (per National Plan & Provider Enumeration System) linked to 2015 Open Payments reports of industry payments. A total of 933 295 allopathic and osteopathic physicians. Outcomes were compared across specialties (surgery, primary care, specialists, interventionalists) and between 620 166 male (66.4%) and 313 129 female (33.6%) physicians using regression models adjusting for geographic Medicare-spending region and sole proprietorship. EXPOSURES: Physician specialty and sex. MAIN OUTCOMES AND MEASURES: Reported physician payment from industry (including nature, number, and value), categorized as general payments (including consulting fees and food and beverage), ownership interests (including stock options, partnership shares), royalty or license payments, and research payments. Associations between physician characteristics and reported receipt of payment. RESULTS: In 2015, 449 864 of 933 295 physicians (133 842 [29.8%] women), representing approximately 48% of all US physicians were reported to have received $2.4 billion in industry payments, including approximately $1.8 billion for general payments, $544 million for ownership interests, and $75 million for research payments. Compared with 47.7% of primary care physicians (205 830 of 431 819), 61.0% of surgeons (110 604 of 181 372) were reported as receiving general payments (absolute difference, 13.3%; 95% CI, 13.1-13.6; odds ratio [OR], 1.72; P < .001). Surgeons had a mean per-physician reported payment value of $6879 (95% CI, $5895-$7862) vs $2227 (95% CI, $2141-$2314) among primary care physicians (absolute difference, $4651; 95% CI, $4014-$5288). After adjusting for geographic spending region and sole proprietorship, men within each specialty had a higher odds of receiving general payments than did women: surgery, 62.5% vs 56.5% (OR, 1.28; 95% CI, 1.26-1.31); primary care, 50.9% vs 43.0% (OR, 1.38; 95% CI, 1.36-1.39); specialists, 36.3% vs 33.4% (OR, 1.15; 95% CI, 1.13-1.17); and interventionalists, 58.1% vs 40.7% (OR, 2.03; 95% CI, 1.97-2.10; P < .001 for all tests). Similarly, men reportedly received more royalty or license payments than did women: surgery, 1.2% vs 0.03% (OR, 43.20; 95% CI, 25.02-74.57); primary care, 0.02% vs 0.002% (OR, 9.34; 95% CI, 4.11-21.23); specialists, 0.08% vs 0.01% (OR, 3.67; 95% CI, 1.71-7.89); and for interventionalists, 0.13% vs 0.04% (OR, 7.98; 95% CI, 2.87-22.19; P < .001 for all tests). CONCLUSIONS AND RELEVANCE: According to data from 2015 Open Payments reports, 48% of physicians were reported to have received a total of $2.4 billion in industry-related payments, primarily general payments, with a higher likelihood and higher value of payments to physicians in surgical vs primary care specialties and to male vs female physicians.

Phase-sensitive deep reconstruction method for rapid multiparametric MR fingerprinting and quantitative susceptibility mapping in the brain.

INTRODUCTION: This study explores the potential of Magnetic Resonance Fingerprinting (MRF) with a novel Phase-Sensitivity Deep Reconstruction Network (PS-DRONE) for simultaneous quantification of T1, T2, Proton Density, B1+, phase and quantitative susceptibility mapping (QSM). METHODS: Data were acquired at 3 T in vitro and in vivo using an optimized EPI-based MRF sequence. Phantom experiments were conducted using a standardized phantom for T1 and T2 maps and a custom-made agar-based gadolinium phantom for B1 and QSM maps. In vivo experiments included five healthy volunteers and one patient diagnosed with brain metastasis. PSDRONE maps were compared to reference maps obtained through standard imaging sequences. RESULTS: Total scan time was 2 min for 32 slices and a resolution of [1 mm, 1 mm, 4.5 mm]. The reconstruction of T1, T2, Proton Density, B1+ and phase maps were reconstructed within 1 s. In the phantoms, PS-DRONE analysis presented accurate and strongly correlated T1 and T2 maps (r = 0.99) compared to the reference maps. B1 maps from PS-DRONE showed slightly higher values, though still correlated (r = 0.6) with the reference. QSM values showed a small bias but were strongly correlated (r = 0.99) with reference data. In the in vivo analysis, PS-DRONE-derived T1 and T2 values for gray and white matter matched reference values in healthy volunteers. PS-DRONE B1 and QSM maps showed strong correlations with reference values. CONCLUSION: The PS-DRONE network enables concurrent acquisition of T1, T2, PD, B1+, phase and QSM maps, within 2 min of acquisition time and 1 s of reconstruction time.

Trends in Utilization and Medicare Spending on Short-Course Radiation Therapy for Breast and Prostate Cancer: An Episode-Based Analysis From 2015 to 2019.

PURPOSE: Evidence supports the value of shorter, similarly efficacious, and potentially more cost-effective hypofractionated radiation therapy (RT) regimens in many clinical scenarios for breast cancer (BC) and prostate cancer (PC). However, practice patterns vary considerably. We used the most recent Centers for Medicare and Medicaid Services data to assess trends in RT cost and practice patterns among episodes of BC and PC. METHODS AND MATERIALS: We performed a retrospective cohort analysis of all external beam RT episodes for BC and PC from 2015 to 2019 to assess predictors of short-course RT (SCRT) use and calculated spending differences. Multivariable logistic regression defined adjusted odds ratios of receipt of SCRT over longer-course RT (LCRT) by treatment modality, age, year of diagnosis, type of practice, and the interaction between year and treatment setting. Medicare spending was evaluated using multivariable linear regression controlling for duration of RT regimen (SCRT vs LCRT) in addition to the above covariables. RESULTS: Of 143,729 BC episodes and 114,214 PC episodes, 63,623 (44.27%) and 25,955 (22.72%) were SCRT regimens, respectively. Median total spending for SCRT regimens among BC episodes was $9418 (interquartile range [IQR], $7966-$10,983) versus $13,602 (IQR, $11,814-$15,499) for LCRT. Among PC episodes, median total spending was $6924 (IQR, $4,509-$12,905) for stereotactic body RT, $18,768 (IQR, $15,421-$20,740) for moderate hypofractionation, and $27,319 (IQR, $25,446-$29,421) for LCRT. On logistic regression, receipt of SCRT was associated with older age among both BC and PC episodes as well as treatment at hospital-affiliated over freestanding sites (P < .001 for all). CONCLUSIONS: In this evaluation of BC and PC RT episodes from 2015 to 2019, we found that shorter-course RT resulted in lower costs than longer-course RT. SCRT was also more common in hospital-affiliated sites. Future research focusing on potential payment incentives encouraging SCRT when clinically appropriate in the 2 most common cancers treated with RT will be valuable as the field continues to prospectively evaluate cost-effective hypofractionation in other disease sites.