bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of price transparency for prostate-directed radiation therapy relative to radical prostatectomy.
Authors: Prasad Rahul Neal , Royce Trevor Joseph , Wang Shang-Jui 
Published: June 2022

1579 Background: For patients with low to favorable-intermediate risk prostate cancer (PC), management with active surveillance, radical prostatectomy (RP), external beam radiation therapy (EBRT), and brachytherapy (BT) are all National Cancer Center Network-supported definitive monotherapy options. Because therapy is non-urgent and choosing therapy can be complex, patients routinely seek second opinions and cost can be an important consideration. Recent federal price transparency (PT) guidance requires hospitals to provide payer-negotiated prices for ≥300 common services in a “shoppable,” user-friendly, online format. 70 services, including RP, are specified, while the remainder are left to institutional discretion. Despite equipoise between radiation therapy (RT, inclusive of EBRT and BT) and RP in definitive treatment for PC, inclusion of prices for RT is optional. National Cancer Institute (NCI)-designated cancer centers (NCI-CC) are high volume referral centers who have the option to volunteer prices for RT; the rate at which NCI-CC choose to report payer-negotiated price estimates for prostate-directed RT is unknown. We hypothesize that reporting rates for BT and EBRT are significantly lower than for RP. Methods: Through online query, we identified “shoppable” price tools for NCI-CC in December 2021. Using billing codes and keyword searches, we queried these price tools for cost estimates for RP, EBRT (delivered using intensity modulated radiation therapy), and BT. Descriptive statistics, include frequency counts and proportions, were performed. The rate of reporting of “shoppable,” negotiated prices for each therapy was assessed. These rates were compared using the chi-squared test (significance level of α = 0.05). Results: Of the 63 NCI-CC offering clinical care, 58 (92%) published “shoppable” tools. 6 (10%), 7 (11%), and 51 (81%) published “shoppable” prices for EBRT, BT, and RP, respectively, demonstrating a significantly higher rate of publication of prices for RP than for EBRT or BT ( P < 0.001). All of the published prices for BT were for high dose rate BT. The 11 Medicare Prospective Payment System–exempt NCI-CC had the highest rates of reporting “shoppable” prices at 91%, with 64%, 27%, and 36% including prices for RP, EBRT, and BT, respectively. Conclusions: Under existing regulations, patients with PC can obtain payer-negotiated price estimates for EBRT and BT from just roughly 10% of NCI-CC, while price estimates for RP are offered by > 80% of these institutions. This represents a potential obstacle to informed decision making, undermines the stated goals of US PT health policy, and the impact on utilization rates (or patient choice of therapy) is unknown. Moving forward, mandating the inclusion of common RT services (EBRT and BT) in “shoppable” price tools is a straightforward intervention that may be highly beneficial in this common cancer population.
Pharmaceutical industry payments to physicians for the promotion of cancer drugs.
Authors: Mitchell Aaron Philip , Meza Akriti Mishra , Trivedi Niti U. , Bach Peter Brian , Gonen Mithat 
Published: June 2022

1580 Background: Personal financial payments from the pharmaceutical industry to oncologists are common and increasing. A prevalent view is that the purpose of industry payments to physicians is to facilitate education on new drugs. However, little is known regarding the distribution and trends in industry payments related to cancer drugs. The goal of this study was to characterize current patterns in industry payments related to cancer drugs, and test whether these patterns are consistent with an educational purpose. Methods: We included on-patent cancer drugs without generic/biosimilar competitors, and used publicly-available federal data sources to measure Medicare spending (proxy for overall drug revenue), number of prescribers, and industry payments (Open Payments, which includes data regarding which the drug[s] was the subject of each payment) for each calendar year from 2014-2018. We analyzed General Payments to individual physicians, which encompasses payment types such as meals, travel, consulting, and speaking fees. We tested two hypotheses implied by the claim that industry payments serve educational purposes. First, payment amounts should not be associated with drug revenue. To test this hypothesis, we used generalized estimating equations (GEE) to model the association between mean per-physician industry payments and Medicare spending. Second, payments related to a given drug should decline over time as physicians become educated. To test this hypothesis, we determined the relative year-to-year change in industry payments for all cases wherein consecutive years were observed, and used GEE to estimate the year-to-year change with respect to duration of time since initial FDA approval. Results: The sample included 89 drugs and 361 drug-year observations. The total amount of industry payments for oncology drugs increased during the study period, from $53,333,854 in 2014 to $90,343,731 in 2018. There was no association between log-transformed mean, per-physician industry payments and per-physician Medicare spending (estimate -0.001, 95%CI: -0.005, 0.004). In aggregate, Industry payments for cancer drugs were greatest immediately after FDA approval and trended downward over time; the estimated industry payments in the subsequent year for a drug with mean payments of $1,000 per-physician in the index year was: $681* for drugs 0-4 years since approval, $825 for drugs 5-9 years, and $679* for drugs≥10 years (*p<0.05). Conclusions: The absence of association between industry payments and Medicare spending and the decline in industry payments for drug subsequent to approval are consistent with claims that these payments function to facilitate physician education.
Variation in telemedicine usage in gynecologic cancer: Are we widening or narrowing disparities?
Authors: Andriani Leslie , Smith Anna Jo Bodurtha , Alvarez Rafael , Heintz Jonathan , Ko Emily Meichun 
Published: June 2022

1593 Background: Telemedicine rapidly increased with the COVID-19 pandemic and may be a way to reduce care disparities. Our aim was to evaluate sociodemographic (race, insurance), patient, health system, and cancer factors associated with use of telemedicine in gynecologic cancers. Methods: We conducted a retrospective cohort study of patients with documented endometrial or ovarian cancer using the nationwide de-identified electronic health record-derived Flatiron Health data. We used multi-level regression models to analyze the association of telemedicine usage during COVID-19 pandemic (2020-2021) with sociodemographic, patient, health system, and cancer factors overall. Results: Of 13,450 patients with endometrial or ovarian cancer, 14.4 % (95%CI 14.0-16.1) used telemedicine during COVID-19 for their cancer care within the Flatiron Health network. Insurance was not associated with likelihood of telemedicine in any model. Region was significantly associated with telemedicine usage across models with patients living in the Northeast more likely to use telemedicine. Conclusions: In this large cohort study, we found regional disparities across cancer types and oncology settings. Expanding access to telemedicine may improve racial and geographic disparities in gynecologic cancer. [Table: see text]
A targeted gene expression biomarker and association with meningioma outcomes and radiotherapy.
Authors: Chen William Cheng , Choudhury Abrar , Vasudevan Harish , Lucas Calixto-Hope C. , Nguyen Minh P. , Young Jacob S , Yu Theresa , Chan Jason , Oberheim Bush Nancy Ann , Schulte Jessica , Villanueva-Meyer Javier , Braunstein Steve E. , Butowski Nicholas A. , Sneed Penny , Berger Mitchell , Perry Arie , Solomon David , McDermott Michael W , Magill Stephen T. , Raleigh David R. 
Published: June 2022

2007 Background: Improvements in risk stratification of meningioma are needed to guide post-operative management and application of adjuvant therapy. Although profiling of DNA methylation, copy number variants (CNVs), RNA sequencing, and exome sequencing have better elucidated meningioma biology, these approaches have not revealed clinically tractable biomarkers for radiotherapy responses. In this study, we develop and validate a targeted gene expression biomarker to predict meningioma outcomes and benefit from radiotherapy. Methods: Targeted gene expression profiling was performed on a development set of 173 meningiomas (median follow-up 8.1 years) and a validation set of 331 consecutive meningiomas (median follow-up 6.1 years) treated at independent institutions (70% WHO grade 1, 24% WHO grade 2, 6% WHO grade 3). All patients underwent surgery (n = 504) with or without postoperative radiotherapy (n = 73 with radiation). Regularized Cox regression within the development set resulted in a continuous gene expression risk score for local freedom from recurrence (LFFR). The model (34 genes and 7 housekeeping genes) and thresholds for low, intermediate, and high-risk scores were locked and applied to the validation set. Results: The gene expression risk score outperformed WHO grade (validation 5-year LFFR delta-AUC 0.15, 95% CI 0.076-0.229, p = 0.001) and DNA methylation grouping (delta-AUC 0.075, 95% CI 0.006-0.130, p = 0.01) for LFFR, disease-specific survival, and OS, achieving a negative predictive value for recurrence at 5-years of 93.2%. The biomarker reclassified 35.8% of WHO grade 1 tumors as intermediate or high risk (5-year LFFR/OS 62%/79%), and 18.3% of WHO grade 2-3 tumors as low risk (5-year LFFR/OS 78%/100%). The biomarker was independently prognostic after accounting for WHO grade, extent of resection, primary versus recurrent presentation, CNV status, DNA methylation group, and Ki67 labeling index, and was predictive for LFFR after postoperative radiotherapy, with a hazard ratio of 0.41 for intermediate to high risk propensity-matched meningiomas (95% CI 0.2-0.9, p = 0.0002) versus 0.79 for low risk meningiomas (95% CI 0.1-8.8, p = 0.5182). Conclusions: Targeted gene expression profiling of 504 meningiomas resulted in a biomarker which improved discrimination of meningioma local recurrence, disease-specific survival, and overall survival, and also predicted benefit from radiotherapy.
A controlled comparison of cerebral volume loss after brain irradiation with proton versus photon radiotherapy.
Authors: Gardner Melissa , Stahl Franziska , Dietrich Jorg , Gerstner Elizabeth R. , Sherman Janet , Shih Helen Alice , Parsons Michael 
Published: June 2022

2017 Background: Previous work has demonstrated cerebral volume loss after glioma treatment with concurrent photon radiotherapy (PHT) and chemotherapy. Proton radiotherapy (PRT) minimizes exposure of normal brain tissue compared with PHT. The objective of this study was to compare neurotoxic effects of PRT vs PHT in a retrospective case-matched control series of WHO grade 2 and 3 gliomas. Methods: PRT subjects were selected from ongoing longitudinal single-arm outcome studies being conducted at our institution (NCT01358058, NCT03286335). PHT subjects were identified via medical record search and were individually matched to PRT subjects using an eleven-tiered criterion (i.e., age, sex, tumor type, tumor location, laterality, IDH mutation status, 1p19q deletion status, concurrent chemotherapy, adjuvant chemotherapy, total Gy dose, and number of fractions). When individual matching was not possible on all 11 variables, efforts were made to identify the closest possible match. Only those subjects with at least two years of progression free survival and available T1 and T2/FLAIR MRI at baseline, one year, and two years following RT were included. The resulting sample included 17 PRT and 17 PHT patients with grade 2 and 3 gliomas (19 male; mean age = 40.10y; SD = 11.27). Non-parametric analyses were used to compare groups on demographic and tumor/treatment-related variables. Diffuse cerebral volume loss was estimated by manually measuring lateral ventricular volume in the tumor-free hemisphere. Results: Mann-Whitney tests of independence showed no significant differences between groups on any of the demographic variables or clinical characteristics. One-way ANOVA demonstrated that ventricular volume increase after two years was significantly greater in patients treated with PHT than with PRT, (F(1, 32.00) = 5.90, p <.021, η2 =.156). Change in ventricular volume in the PHT group was 24.85% (SD = 14.45%) and in the PRT group was 12.03% (SD = 16.3%). Conclusions: The findings of this study suggest that 2 years post treatment for glioma, PRT is associated with less brain volume loss and ventricular expansion than PHT. The findings support the hypothesis that PRT can reduce neurotoxicity within the tumor-free hemisphere. This study is limited by the retrospective design and lack of randomization to treatment arms, though cohorts were well-matched following a rigorous set of criteria. The effects of PRT beyond 2 years after treatment remain unknown. Preservation of brain structure may be critically important for maintenance of brain function in this population of patients who have prolonged survival. Longitudinal cognitive assessment in brain tumor patients undergoing PHT vs PRT is needed and is currently being collected in NRG BN-005 (NCT03180502), which may provide important data regarding functional impact of the brain changes we have demonstrated.
Brain metastases in the setting of stable extracranial disease: A systematic review and meta-analysis.
Authors: Li Alyssa Y. , Gaebe Karolina , Zulfiqar Amna , Lee Grace , Jerzak Katarzyna Joanna , Sahgal Arjun , Erickson Anders W. , Das Sunit 
Published: June 2022

2022 Background: Intracranial metastatic disease (IMD) is a life-altering complication for many patients with cancer. Improvements in systemic therapies have transformed the epidemiology of IMD, with some patients presenting with IMD in the context of stable extracranial disease (IMD-SECD). Among patients with metastases in other sites with similarly stable systemic disease, surgical resection and targeted therapy can result in long-term disease control and extended overall survival (OS), yet little is known about the clinical outcomes for patients with IMD-SECD. Methods: We searched MEDLINE, EMBASE, CENTRAL, and grey literature sources up to June 21, 2021 for studies reporting brain metastasis (BrM) with controlled extracranial disease (ECD) as well as IMD-SECD secondary to any primary cancer (criteria: presence of BrM and ≤2 extracranial metastatic sites, with no prior second-line chemotherapy and second-line brain-directed therapy). In studies comparing IMD-SECD and IMD patients, hazard ratios (HR) for OS and intracranial progression-free survival (iPFS) were pooled using random-effects meta-analysis, while medians for OS were estimated from single-arm IMD-SECD studies based on distribution-free summary survival curves. Results: Of 1067 records identified, 68 studies involving 5325 patients with IMD-SECD were included. Patients with IMD-SECD had prolonged OS (HR 1.93; 95% CI, 1.44-2.59; n = 10 studies; n = 877 patients) and iPFS (HR 1.59; 95% CI 1.31-1.92; n = 4 studies; n = 673 patients) compared with IMD patients. Subgroup analysis of patients with BrM and controlled versus uncontrolled ECD found prolonged OS with controlled ECD (HR 2.46; 95% CI, 1.36-4.44; n = 4 studies; n = 135 patients). Pooled median OS for all IMD-SECD patients was 20.85 months (mo) (95% CI, 16.35-25.98; n = 27 studies; n = 2159 patients). Stratification by primary cancer type showed median OS 20.18 mo (95% CI, 10.43-38.20; n = 2 studies; n = 109 patients) and 27.46 mo (95% CI, 18.27-49.66; n = 13 studies; n = 497 patients) for patients with IMD-SECD secondary to breast cancer and non-small cell lung cancer, respectively. Conclusions: Patients with IMD-SECD demonstrate prolonged OS and iPFS compared with patients with IMD, who may have more extensive systemic disease. Our results suggest that patients with IMD-SECD may represent a distinct subpopulation of patients with IMD with a uniquely favourable prognosis. It is possible that aggressive and timely treatment may significantly prolong survival for these patients. Future prospective trials should aim to investigate the efficacy of current treatment regimens in patients with IMD-SECD to further clarify optimal treatment pathways in this unique population of patients.
Paxalisib in patients with newly diagnosed glioblastoma with unmethylated MGMT promoter status: Final phase 2 study results.
Authors: Wen Patrick Y. , de Groot John Frederick , Battiste James , Goldlust Samuel A. , Garner James Stuart , Friend John , Simpson Jeremy Andrew , Damek Denise , Olivero Alan , Cloughesy Timothy Francis 
Published: June 2022

2047 Background: Paxalisib, a potent oral selective brain-penetrant small molecule PI3K/mTOR inhibitor, has shown activity in nonclinical brain cancer models and promising phase 1 data in progressive / recurrent high-grade gliomas (NCT01547546). This multicenter phase 2 progressive design trial (NCT03522298) aimed to establish the maximum tolerated dose (MTD) for once-daily (QD) dosing, and to evaluate safety, tolerability, pharmacokinetics (PK), and clinical activity of paxalisib in patients with newly diagnosed glioblastoma and unmethylated MGMT promotor status. Methods: Eligible patients were males or females, aged ≥18 years, who had undergone surgical resection and chemoradiotherapy (Stupp Regimen), and were considered to be progression free before starting adjuvant paxalisib. Stage 1 used a standard 3+3 dose-escalation design to determine the MTD in this population. Stage 2 was a two-arm, open-label, expansion cohort with patients randomized 1:1 to receive paxalisib at the MTD under fed or fasted conditions. In both stages, treatment comprised daily paxalisib administered in 28-day cycles, continuously until disease progression or unacceptable toxicity. Efficacy analyses are based on investigator review and from date of diagnosis. Results: Patients (n = 30; 70.0% males, 83.3% white, mean age 58.5 years) had a mean time since diagnosis of 3.75 months. The majority (n = 29) received between 1 and 6 treatment cycles and one received 29 cycles. In Stage 1 (n = 9), an MTD of 60mg was established on the dose-limiting toxicities of hyperglycemia (n = 1) and stomatitis (n = 1) at 75mg. Paxalisib at 60mg was well-tolerated and adverse events were consistent with other PI3K inhibitor medicines. At the MTD (60mg), the PK profile was linear and dose-proportional with no differences in Tmax and elimination half-life under fed and fasted conditions. For the overall ITT population, the median progression free survival was 8.4 months (RANO) and 8.6 months (mRANO) and the median overall survival was 15.7 months. In a mITT (n = 22 patients treated with 60mg daily and ≥1 post-baseline assessment), the median PFS was 9.6 months (mRANO). Conclusions: The primary study endpoints were met; PK and safety were consistent with prior clinical experience. The MTD showed encouraging clinical activity, prolonging PFS and improving OS. Further efficacy confirmation of paxalisib 60 mg QD in newly diagnosed glioblastoma in a pivotal trial is ongoing (GBM AGILE, NCT03970447). Clinical trial information: NCT03522298.
Prognostic value of hPG80 (circulating progastrin) in IDH-wild type glioblastoma treated with radio-chemotherapy.
Authors: Doucet Ludovic , Cailleteau Axel , Vaugier Loig , Gourmelon Carole , Bureau Mathilde , Salaud Celine , Roualdes Vincent , Samarut Edouard , Aumont Maud , Zenatri Morgan , Loussouarn Delphine , Quillien Veronique , Bocquet Francois , Payen-Gay Lea , Mahi Younes , Prieur Alexandre , Robert Marie , Frenel Jean-Sebastien 
Published: June 2022

2049 Background: hPG80 (circulating progastrin) is a protein secreted by many cancer types, playing a role in tumorigenesis by regulating cancer stem cells, angiogenesis, proliferation/differentiation and decreasing apoptosis. hPG80 is detectable in plasma of cancer patients and previous studies have shown its prognostic role in various cancers. Given the lack of circulating biomarker in glioblastoma, we evaluated the prognostic value of plasma hPG80 in patients with IDH wild type glioblastoma Methods: This multicentric retrospective study included IDHwt glioblastoma patients treated with standard radio-chemotherapy. The ELISA DxPG80.lab kit (Biodena Care, Lausanne, Switzerland) was used to measure hPG80 levels after surgery with a detection threshold of 1 pM in all plasma EDTA samples according to the manufacturer’s instruction. The prognostic impact of hPG80 was evaluated on patient’s progression-free survival (PFS) and overall survival (OS). Results: We included 70 patients (38 males /32 women) with a median age of 64 years (Range 19 - 84). Karnofsky index was > 70% in 52 (91%) of 57 evaluable patients. Tumor biopsy (B), partial resection (PR), complete resection (CR) were performed in 22, 25 and 23 patients respectively. MGMT promotor was methylated in 22 (40%) of the 55 evaluable patients. After surgery, hPG80 was detected in 48 (69%) patients (hPG80+) with a median concentration of 9.52 pM (IQR 5.21 - 21.20). Complete surgery was associated with undetectable levels of hPG80 (52% (CR) vs 28% (PR) vs 14% (B), p = 0.006) and lower concentration if hPG80+ (CR: 5.8 pM [IQR 1.92 - 11.38] vs PR: 12.84 pM [IQR 8.09 - 37.09]; p = 0.04 vs B: 9.86 pM [IQR 4.66 - 21.63]; p = 0.16). With a median follow-up of 39 months (22.4-NR), 86% of patients had progressed and 70% had died. In univariate analysis, hPG80 positivity was associated with PFS (5.6m vs 8.5m, p = 0.053) and OS (14.5 vs 22m, p = 0.04) in hPG80+ vs hPG80- patients respectively. hPG80+ patients with complete surgery had worse median OS than hPG80- patients (14.5 vs 22.0 m; p = 0.051 respectively. Cox proportional hazards model did not fit for covariate analysis. Conclusions: Our findings show that hPG80 could serve as a new circulating prognostic biomarker in IDHwt glioblastoma patients treated with radio-chemotherapy. Further explorations are ongoing in larger cohorts including longitudinal evaluation during the course of the disease.