Targeting Cancer Lysosomes with Good Old Cationic Amphiphilic Drugs.

Being originally discovered as cellular recycling bins, lysosomes are today recognized as versatile signaling organelles that control a wide range of cellular functions that are essential not only for the well-being of normal cells but also for malignant transformation and cancer progression. In addition to their core functions in waste disposal and recycling of macromolecules and energy, lysosomes serve as an indispensable support system for malignant phenotype by promoting cell growth, cytoprotective autophagy, drug resistance, pH homeostasis, invasion, metastasis, and genomic integrity. On the other hand, malignant transformation reduces the stability of lysosomal membranes rendering cancer cells sensitive to lysosome-dependent cell death. Notably, many clinically approved cationic amphiphilic drugs widely used for the treatment of other diseases accumulate in lysosomes, interfere with their cancer-promoting and cancer-supporting functions and destabilize their membranes thereby opening intriguing possibilities for cancer therapy. Here, we review the emerging evidence that supports the supplementation of current cancer therapies with lysosome-targeting cationic amphiphilic drugs.

Improvements in urinary symptoms, health-related quality of life, and psychosocial distress in the early recovery period after radical cystectomy and urinary diversion in 842 German bladder cancer patients: data from uro-oncological rehabilitation.

PURPOSE: This study aims to investigate urinary symptoms (continence and stoma care), health-related quality of life (HRQoL) and psychosocial distress (PD) in the early postoperative period after radical cystectomy (RC) and urinary diversion for ileal conduit (IC) and ileal neobladder (INB) to obtain a better basis for patient counseling. METHODS: Data for 842 bladder cancer patients, who underwent 3 weeks of inpatient rehabilitation (IR) after RC and urinary diversion (447 IC, 395 INB) between April 2018 and December 2019 were prospectively collected. HRQoL, PD, and urinary symptoms were evaluated by validated questionnaires at the beginning (T1) and the end of IR (T2). In addition, continence status and micturition volume were objectively evaluated in INB patients by 24-h pad test and uroflowmetry, respectively. RESULTS: Global HRQoL was severely impaired at T1, without significant difference between the two types of urinary diversion. All functioning and symptom scales of HRQoL improved significantly from T1 to T2. In INB patients, all continence parameters improved significantly during IR, while patients with an IC reported fewer problems concerning urostomy management. The proportion of patients suffering from high PD decreased significantly from 50.7 to 34.9%. Age ≤ 59 years was the only independent predictor of high PD. Female patients and patients ≤ 59 years were more likely to use individual psycho-oncological counseling. CONCLUSION: HRQoL, PD and urinary symptoms improved significantly in the early recovery period after RC. Patients with urinary continence reported higher HRQoL and less PD. Psychosocial support should be offered especially to younger patients.

An Empirical Survey on the Adaption of Neoadjuvant Chemotherapy in Bladder Cancer.

INTRODUCTION: The aim of the study was to determine the adaption of neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC) in Germany, Austria, and Switzerland and especially underlying reasons for potential low adherence to guidelines. METHODS: We conducted a non-validated survey among 336 urologic departments in Germany, Austria, and Switzerland. RedCap questionnaires were electronically distributed and included 23 items concerning the general NAC administration standards and guideline compliance in patient counseling regarding the actual treatment. RESULTS: The return rate of the questionnaire was 19.1% (63/336). Although 45 departments (71.4%) claim to perform NAC as the standard of care, only 49% of eligible patients actually receive NAC. An advanced disease stage (≥cT3) and a high tumor volume were mentioned to support the application of NAC, whereas 35% of responders worry about deterioration of patients' preoperative status due to NAC. Furthermore, 26.7% of respondents are concerned about the low extent of survival benefit. CONCLUSION: Application of NAC in eligible MIBC patients in Germany, Austria, and Switzerland remains low. Although the majority of urologic departments discuss NAC and acknowledge the need for intensified treatment in advanced disease stages, not all eligible patients will actually receive NAC before radical cystectomy.

Linking human impacts to community processes in terrestrial and freshwater ecosystems.

Human impacts such as habitat loss, climate change and biological invasions are radically altering biodiversity, with greater effects projected into the future. Evidence suggests human impacts may differ substantially between terrestrial and freshwater ecosystems, but the reasons for these differences are poorly understood. We propose an integrative approach to explain these differences by linking impacts to four fundamental processes that structure communities: dispersal, speciation, species-level selection and ecological drift. Our goal is to provide process-based insights into why human impacts, and responses to impacts, may differ across ecosystem types using a mechanistic, eco-evolutionary comparative framework. To enable these insights, we review and synthesise (i) how the four processes influence diversity and dynamics in terrestrial versus freshwater communities, specifically whether the relative importance of each process differs among ecosystems, and (ii) the pathways by which human impacts can produce divergent responses across ecosystems, due to differences in the strength of processes among ecosystems we identify. Finally, we highlight research gaps and next steps, and discuss how this approach can provide new insights for conservation. By focusing on the processes that shape diversity in communities, we aim to mechanistically link human impacts to ongoing and future changes in ecosystems.

Supporting the planning of urban blue-green infrastructure for biodiversity: A multi-scale prioritisation framework.

Primary considerations for urban blue-green infrastructure (BGI) encompass sustainable stormwater/urban heat management while biodiversity conservation is often considered an inherent benefit rather than a core planning requirement. However, ecological function of BGI as 'stepping stones' or linear corridors for otherwise fragmented habitats is undisputed. While quantitative approaches for modelling ecological connectivity in conservation planning are well established, mismatches in scope and scale with models that support the planning of BGI makes their adoption and integration difficult across disciplines. Technical complexities have led to ambiguity around circuit and network-based approaches, focal node placement, spatial extents, and resolution. Furthermore, these approaches are often computationally intensive, and considerable gaps remain in their use for identifying local-scale critical "pinch-points" that urban planners may respond to with the integration of BGI interventions that address biodiversity enhancement among other ecosystem services. Here, we present a framework that simplifies and integrates the merits of regional connectivity assessments with a focus on urban areas to prioritise BGI planning interventions while reducing computational demands. Our framework facilitates: (1) modelling potential ecological corridors at a coarse regional scale, (2) prioritising local-scale BGI interventions based on the relative contribution of individual nodes in this regional network, and (3) inferring connectivity hot- and cold-spots for local-scale BGI interventions. We illustrate this in the Swiss lowlands, demonstrating how, compared to previous work, we are able to identify and rank different priority locations across the region for BGI interventions in support of biodiversity enhancement and how their local-scale functional design may be benefited by addressing specific environmental variables.

Physician Payments from Pharmaceutical Companies Related to Cancer Drugs.

BACKGROUND: Drug manufacturers claim that the purpose of financial payments to physicians is to facilitate education about new drugs. This claim suggests 2 testable hypotheses: payments should not be associated with drug revenue and payments for each drug should decline over time as physicians become educated. MATERIALS AND METHODS: We used open payments data on industry payments. We included payments for cancer drugs without generic/biosimilar competitors and used federal data sources to measure Medicare spending (a proxy for overall drug revenue) and a number of prescribers. We used generalized estimating equations (GEE) to model the drug-level association between industry payments and Medicare spending. Separately, we used GEE to estimate the change in payments with respect to the duration of time since initial FDA approval. RESULTS: The sample included 89 drugs and 361 drug-year observations. The total value of industry payments for oncology drugs increased, 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 to 0.004). Payments for individual drugs decreased over time; estimated payments in the subsequent year for a drug with mean, per-physician payments of $1000 in the index year was: $681* for drugs 0-4 years since approval, $825 for 5-9 years, and $679* for ≥10 years (*P < .05). CONCLUSIONS: Although industry-sponsored education may also serve marketing purposes, the absence of association between industry payments and Medicare spending and the decline in payments subsequent to approval are consistent with claims that industry payments function to facilitate physician education.

The Prescription Drug User Fee Act: Much More Than User Fees.

BACKGROUND: The Prescription Drug User Fee Act (PDUFA) is due for reauthorization in 2022. Beyond creating the user fee program which now generates a majority of the Food and Drug Administration (FDA) Human Drugs Program budget, PDUFA has made numerous additional changes to FDA policy during its 29-year history. FDA's budgetary dependence on user fees may advantage the industry in negotiating favorable policy changes through PDUFA. METHODS: The full texts of all prior PDUFA reauthorization bills and all submitted public comments and meeting minutes for the 2022 reauthorization were reviewed. Provisions affecting FDA regulatory authority and processes were identified. FINDINGS: PDUFA legislation has instituted a broad range of changes to FDA policy, including evidentiary standards for drug approval, accelerated pathways for approval, industry involvement in FDA decision-making, rules regarding industry information dissemination to providers, and market entry of generic drugs. Negotiations over the 2022 reauthorization suggest that industry priorities include increased application of real-world evidence, regulatory certainty, and increased communication between FDA and industry during the drug application process. CONCLUSIONS: The need for PDUFA reauthorization every 5 years has created a recurring legislative vehicle through which far-ranging changes to FDA have been enacted, reshaping the agency's interactions and relationship with the regulated industry. The majority of policy changes enacted through PDUFA legislation have favored industry through decreasing regulatory standards, shortening approval times, and increasing industry involvement in FDA decision-making. FDA's budgetary dependence on the industry, the urgency of each PDUFA reauthorization's passage to maintain uninterrupted funding, and the industry's required participation in PDUFA negotiations may advantage the industry.

Compulsory Licensing of Pharmaceuticals in High-Income Countries: A Comparative Analysis.

Policy Points Pharmaceutical trade organizations and media outlets in the United States regularly point to compulsory licensing-or even its threat-as the mechanism that peer countries use to control the price of prescription drugs. Our comparative analysis shows that compulsory licensing is not frequently employed in high-income countries outside the United States as a direct response to drug prices. When its use is threatened, a license is rarely issued and even less often does it lead to a price discount. Accordingly, compulsory licensing is unlikely to contribute to price discrepancies between the United States and other developed nations. In fact, of the 21 compulsory licensing petitions we identified outside the United States, over one-third were made by pharmaceutical companies themselves and only three were threatened by a government authority. CONTEXT: Compulsory licensing is a practice whereby national authorities can license a third party to produce a patented product, such as a pharmaceutical drug, effectively enabling the production of a generic before the original patent expires. The policy was designed-and has historically been used-to improve access to essential medicines in low-income countries and during public health crises. Although it was not intended to impact drug prices directly, the threat of compulsory licensing may indeed contribute to lower drug prices in high-income countries outside the United States. Our study sought to determine the plausibility of this claim. METHODS: We compiled a comprehensive database of compulsory licensing episodes in the United States and 17 comparator nations over the 20 years following the 2001 Doha Declaration, and we recorded the motivation and outcome of each instance. Our search began with publicly available reports compiled by organizations specializing in pharmaceutical intellectual property, expanded to a query of legal proceedings in Westlaw, and concluded with a comprehensive literature review on PubMed. FINDINGS: This strategy yielded 45 unique episodes of compulsory licensing, 24 in the United States and 21 outside. A minority (24%) of petitions outside the United States were motivated by high prices, and in all countries, only three cases were clearly associated with a price discount. CONCLUSIONS: We found no evidence to suggest that compulsory licensing is either frequently threatened or successfully implemented by countries outside the United States to secure price discounts for the most expensive pharmaceuticals, those that are newly patented and just entering the market.

An empirical study on hospital-based prevention of recurrent urinary stone disease in Germany.

PURPOSE: Urinary stone disease is a common disease with a prevalence of 4.7% in Germany. The incidence increased over the last decades, and recurrence rates are up to 50% in the first 5 years after diagnosis. Adequate preventive measures can avoid up to 46% of stone recurrences. These numbers outline the importance of prevention. Especially among high-risk stone formers, specific diagnostics and measures are required. Published data indicate the divergence between the importance of prevention and its implementation in everyday clinical practice. This is the first survey among German urological departments highlighting medical care concerning the prevention of recurrent urinary stone disease, identifying challenges and providing recommendations for improvements. METHODS: Two hundred and seventy urological hospital departments in Germany were anonymously surveyed about measurements to prevent recurrent stone disease. The questionnaire comprised 23 items dealing with diagnostics, counselling, knowledge among doctors concerning preventive measures and difficulties in preventing recurrent urinary stone disease. RESULTS: Sixty-three urological departments (23.8%) answered the survey. The majority perform stone analysis at first and repeat events. Most patients with urinary stone disease receive general advice on preventive measures during their hospitalization. General recommendations focus on fluid intake and lifestyle changes. However, specific diets are infrequently recommended by inpatient urologists. Diagnostics to identify high-risk stone formers are mostly insufficient, and guideline-compliant urine tests are uncommon. CONCLUSION: The quality of secondary prevention needs to improve considerably. The focus should be put on identifying high-risk stone formers and offering those patients specific counselling. Furthermore, general advice on dietary recommendations should be extended.

Prophylaxis of Recurrent Stone Disease in Outpatient Clinics in Germany: A Quality-of-Care Concern.

INTRODUCTION: The aim of the study was to survey current practices for preventing recurrent stone disease in an outpatient clinic setting in Germany. METHODS: Two invitations to complete an anonymous REDCap® survey were emailed to members of the occupational union of German urologists who work as outpatient urologists ("Berufsverband Deutscher Urologen e.V."). The survey included questions on diagnostic modalities and counselling to prevent stone disease. RESULTS: A total of 130 outpatient urologists completed the survey. 84.6% of urologists give general advice to first-time stone formers. Recommendations comprise increased fluid uptake in 100%, two-thirds advice on calcium and oxalate intake, and one-third on salt and protein intake. 64.6% perform a metabolic evaluation for high-risk stone formers. However, patients with risk factors other than repeat stone disease are often overlooked. Urologists agreed that a lack of time (73.1%) and reimbursement (64.6%), as well as insufficient patient compliance (60.8%), pose significant challenges. The majority of urologists agreed that training is required. CONCLUSION: General recommendations for stone formers are usually provided, but nutritional advice tends to be incomplete. Our results raise quality-of-care concerns: Metabolic evaluation of stone formers at high risk of recurrence is uncommon. Structural changes are required due to time constraints, and poor remuneration must be addressed to improve patient care.

Industry Payments to Physicians Are Kickbacks. How Should Stakeholders Respond?

Payments from the pharmaceutical industry to US physicians are common. In determining which payments rise to the level of an illegal kickback under the Anti-Kickback Statute (AKS), the Department of Health and Human Services' Office of Inspector General (OIG) has stated in nonbinding guidance that influencing or "swaying" physician prescribing is key. OIG has highlighted as a compliance standard the Pharmaceutical Research and Manufacturers of America Code on Interactions with Health Professions, which stipulates that permissible payments are those that do not interfere with prescribing. However, recent evidence has shown that most payments influence physician prescribing, driving higher prescription drug costs by increasing use of brand-name and low-value drugs. This evidence implies that many payments that are currently commonplace could be subject to prosecution under AKS. Given that these payments increase costs to patients and the health care system, there is a public interest in curtailing them. This article proposes a range of actions available to stakeholders-including industry, providers, regulators, and payers-to mitigate the cost-increasing effect of industry payments to physicians.

Reconciling cities with nature: Identifying local Blue-Green Infrastructure interventions for regional biodiversity enhancement.

Increasing urbanization degrades quantity, quality, and the functionality of spatial cohesion of natural areas essential to biodiversity and ecosystem functioning worldwide. The uncontrolled pace of building activity and the erosion of blue (i.e., aquatic) and green (i.e., terrestrial) landscape elements threaten existing habitat ranges and movability of wildlife. Local scale measures, such as nature-inspired engineered Blue-Green Infrastructure (BGI) are emerging mitigation solutions. Originally planned to promote sustainable stormwater management, adaptation to climate change and improved human livability in cities, such instruments offer interesting synergies for biodiversity in support of existing ecological infrastructure. BGI are especially appealing for globally declining amphibians, a rich and diverse vertebrate assemblage sensitive to urbanization. We integrated biological and highly resolved urban-rural land-cover data, ensemble models of habitat suitability, and connectivity models based on circuit theory to improve multi-scale and multi-species protection of core habitats and ecological corridors in the Swiss lowlands. Considering a broad spectrum of amphibian biodiversity, we identified distributions of amphibian biodiversity hotspots and four landscape elements essential to amphibian movability at the regional scale, namely i) forest edges, ii) wet-forest habitats, iii) soils with variable moisture and iv) riparian zones. Our work shows that cities can make a substantial contribution (e.g., up to 15% of urban space in the study area) to wider landscape habitat connectivity. We highlight the importance of planning BGI locally in strategic locations across urban and peri-urban areas to promote the permeability and availability of 'stepping stone' habitats in densely populated landscapes, essential to the maintenance of regional habitat connectivity and thereby enhancing biodiversity and ecosystem functioning.

Comparative Evaluation of Juices from Red-Fleshed Apples after Production with Different Dejuicing Systems and Subsequent Storage.

In this work, two vintages (2019 and 2020) of red-fleshed 'Weirouge' apples were processed with the innovative spiral filter press technology to investigate juice production in an oxygen-reduced atmosphere. After pressing, a more brilliant red color and appreciably higher amounts of oxidation-sensitive constituents (ascorbic acid, anthocyanins, and colorless (poly)phenols) were seen in spiral filter pressed juices compared to those produced with conventional systems (horizontal filter press and decanter). In a subsequent stability study (24 weeks storage at 4, 20, and 37 °C), the color and phenolic compounds were monitored and differences in the juices produced with the different pressing-systems were widely maintained during the storage period. The analyses of the anthocyanins and colorless (poly)phenols were conducted by UHPLC-DAD-ESI-QTOF-HR-MS/MS and UHPLC-DAD. The spiral filter press emerged as a promising technology for the production of juices with a more attractive color and a better retention of oxidation-sensitive constituents during processing and storage compared to conventional juices.

Personal Payments from Pharmaceutical Companies to Authors of Oncology Clinical Practice Guidelines.

BACKGROUND: Oncologists who author clinical practice guidelines frequently have financial relationships with the pharmaceutical industry. It is unknown whether participation on clinical practice guideline committees is associated with differences in the amounts of industry money received. MATERIALS AND METHODS: We conducted a nested case-control study from August 2013 to December 2018. We manually abstracted membership records of National Comprehensive Cancer Network (NCCN) Guidelines committees for the 20 most common cancers and linked to Open Payments. The study sample included medical oncologists selected to join an NCCN Guidelines committee ("joiners") during the study period. Joiners were matched 1:2 to medical oncologists who had no participation on NCCN committees (controls) by gender, NCCN institution, and medical school graduation year. We performed difference-in-differences (DiD) estimation to assess whether selection to an NCCN committee was associated with the dollar value of payments received from industry, using generalized estimating equations to address correlation between matched pairs and between repeated observations of the same pair. RESULTS: During the study period, 54 physicians joined an NCCN Guidelines committee. These physicians received more payments than matched controls in the year prior to joining ($11,259 vs. $3,427; p = .02); this difference did not increase in the year after joining (DiD = $731; p = .45). CONCLUSION: Medical oncologists selected to NCCN Guidelines committees had greater financial ties to industry than their peers. The potential influence of industry in oncology clinical practice guidelines may be reduced through the selection of committee members with fewer ties to industry. IMPLICATIONS FOR PRACTICE: Oncologists who author clinical practice guidelines frequently have financial conflicts of interest with the pharmaceutical industry. This creates concern about the potential for industry influence on guidelines. However, it is unknown whether oncologists who author guidelines have greater industry relationships than their peers. This study compared medical oncologists who were newly selected to join a National Comprehensive Cancer Network (NCCN) Guidelines panel with medical oncologists at the same institutions and at similar career stages. At the time they joined, oncologists joining NCCN Guidelines panels had received more than three times the dollar value of industry payments than their peers. The potential for industry influence may be reduced by the selection of less-conflicted panel members.

Increasing Financial Payments From Industry to Medical Oncologists in the United States, 2014-2017.

BACKGROUND: Personal payments from the pharmaceutical industry to US physicians are common and are associated with changes in physicians' clinical practice and interpretation of clinical trial results. We assessed temporal trends in industry payments to oncologists, with particular emphasis on payments to authors of oncology clinical practice guideline and on payments related to immunotherapy drugs. METHODS: We included US physicians with active National Plan and Provider Enumeration System records and demographic data available in the Centers for Medicare & Medicaid Services Physician Compare system who had a specialty type of medical oncology or general internal medicine. Medical oncologists serving on NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Panels were identified manually. Industry payments, and the subset associated with PD-1/PD-L1 drugs, were identified in Open Payments, the federal repository of all transactions of financial value from industry to physicians and teaching hospitals, from 2014 to 2017. RESULTS: There were 13,087 medical oncologists and 85,640 internists who received payments. The mean, annual, per-physician value of payments to oncologists increased from $3,811 in 2014 to $5,854 in 2017, and from $444 to $450 for internists; the median payment increased from $152 to $199 for oncologists and remained at $0 for internists. Oncologists who served on NCCN Guidelines Panels received a greater value in payments and experienced a greater relative increase: mean payments increased from $10,820 in 2014 to $18,977 in 2017, and median payments increased from $500 to $1,366. Among companies marketing PD-1/PD-L1 drugs, mean annual per-oncologist payments associated with PD-1/PD-L1 drugs increased from $28 to $773. Total per-oncologist payments from companies marketing PD-1/PD-L1 drugs experienced a 165% increase from 2014 to 2017, compared with a 31% increase among similar companies not marketing PD-1/PD-L1 drugs. CONCLUSIONS: Pharmaceutical industry payments increased for US oncologists from 2014 to 2017 more than for general internists. The increase was greater among oncologists contributing to clinical practice guidelines and among pharmaceutical companies marketing PD-1/PD-L1 drugs. The increasing flow of money from industry to US oncologists supports ongoing concern regarding commercial interests in guideline development and clinical decision-making.

An Empirical Study on the Operative Treatment of Symptomatic Urolithiasis in Germany.

PURPOSE: The guidelines of the German, European, and American Urological Associations on urolithiasis advise against general ureteral stenting before and after an uncomplicated ureterorenoscopy (URS). However, German and European guidelines state that stenting prior to URS facilitates stone extraction and reduces intraoperative complications. According to the published literature, German practice seems to deviate from recommendations. This nationwide survey aimed to evaluate the treatment modalities of urolithiasis. METHODS: In November 2018 and March 2019, a total of 199 urological hospital departments in Germany were anonymously surveyed about operative care of symptomatic urolithiasis. The response rate was 72.9%. The survey consisted of 25 questions about diagnostics, surgical technique, and aftercare of the URS. This questionnaire is available in the appendix. RESULTS: A primary URS is performed in ≤10% in 49.6% of the hospitals. In every second urological department (49.7%), the German Diagnosis Related Group (G-DRG) system influences the period of pre-stenting before a secondary URS. After a secondary URS, which is performed in 53.8% of the departments in over 80% of the patients, 14% of the departments omit stenting. The standard for stenting seems to be a 28-cm-long 7 Charrière double-J stent in Germany. CONCLUSION: In Germany, the percentage of primary URS is low, and a ureter stenting is performed in most of the urological departments after URS. Delaying therapy due to economic aspects is the standard in almost half of all urological departments.

A Low-Cost Water Depth and Electrical Conductivity Sensor for Detecting Inputs into Urban Stormwater Networks.

High-resolution data collection of the urban stormwater network is crucial for future asset management and illicit discharge detection, but often too expensive as sensors and ongoing frequent maintenance works are not affordable. We developed an integrated water depth, electrical conductivity (EC), and temperature sensor that is inexpensive (USD 25), low power, and easily implemented in urban drainage networks. Our low-cost sensor reliably measures the rate-of-change of water level without any re-calibration by comparing with industry-standard instruments such as HACH and HORIBA's probes. To overcome the observed drift of level sensors, we developed an automated re-calibration approach, which significantly improved its accuracy. For applications like monitoring stormwater drains, such an approach will make higher-resolution sensing feasible from the budget control considerations, since the regular sensor re-calibration will no longer be required. For other applications like monitoring wetlands or wastewater networks, a manual re-calibration every two weeks is required to limit the sensor's inaccuracies to ±10 mm. Apart from only being used as a calibrator for the level sensor, the conductivity sensor in this study adequately monitored EC between 0 and 10 mS/cm with a 17% relative uncertainty, which is sufficient for stormwater monitoring, especially for real-time detection of poor stormwater quality inputs. Overall, our proposed sensor can be rapidly and densely deployed in the urban drainage network for revolutionised high-density monitoring that cannot be achieved before with high-end loggers and sensors.

Impact of provider volume on front-line chemotherapy guideline compliance and overall survival in elderly patients with advanced ovarian cancer.

PURPOSE: We sought to evaluate whether provider volume or other factors are associated with chemotherapy guideline compliance in elderly patients with epithelial ovarian cancer (EOC). METHODS: We queried the SEER-Medicare database for patients ≥66 years, diagnosed with FIGO stage II-IV EOC from 2004 to 2013 who underwent surgery and received chemotherapy within 7 months of diagnosis. We compared NCCN guideline compliance (6 cycles of platinum-based doublet) and chemotherapy-related toxicities across provider volume tertiles. Factors associated with guideline compliance and chemotherapy-related toxicities were assessed using logistic regression. Overall survival (OS) was compared across volume tertiles and Cox proportional-hazards model was created to adjust for case-mix. RESULTS: 1924 patients met inclusion criteria. The overall rate of guideline compliance was 70.3% with a significant association between provider volume and compliance (64.5% for low-volume, 72.2% for medium-volume, 71.7% for high-volume, p = .02). In the multivariate model, treatment by low-volume providers and patient age ≥ 80 years were independently associated with worse chemotherapy-guideline compliance. In the survival analysis, there was a significant difference in median OS across provider volume tertiles with median survival of 32.8 months (95%CI 29.6, 36.4) low-volume, 41.9 months (95%CI 37.5, 46.7) medium-volume, 42.1 months (95%CI 38.8, 44.2) high-volume providers, respectively (p < .01). After adjusting for case-mix, low-volume providers were independently associated with higher rates of mortality (aHR 1.25, 95%CI: 1.08, 1.43). CONCLUSIONS: In a modern cohort of elderly Medicare patients with advanced EOC, we found higher rates of non-compliant care and worse survival associated with treatment by low-volume Medicare providers. Urgent efforts are needed to address this volume-outcomes disparity.

Trends in Female Representation on NCCN Guideline Panels.

BACKGROUND: NCCN produces highly influential disease-specific oncology clinical practice guidelines. Because the number of women in academic oncology has increased, we assessed whether the composition of NCCN Guidelines Panels reflected this trend. METHODS: Using historical guidelines requested from NCCN, we investigated time trends for female representation on 21 NCCN Guidelines Panels and analyzed the trends for female-predominant cancers (breast, ovarian, uterine, and cervical) compared with all cancers. RESULTS: From 2013 to 2019, there was an increase from 123 women of 541 total panelists (22.7%) to 175 women of 542 panelists (32.3%). Within the 4 female-predominant cancers, the increase was more rapid: from 30 of 101 total panelists (29.7%) to 66 of 118 panelists (56.4%). Excluding female-predominant cancers, increases were minimal. CONCLUSIONS: There could be multiple explanations for these differing trends, including the possibility of more rapid increases in the underlying pool of female physician-scientists in female-predominant specialties or more efforts to increase the representation of women in decisions about the standard of care in cancers predominantly affecting women.

Association Between Clinical Value and Financial Cost of Cancer Treatments: A Cross-Sectional Analysis.

BACKGROUND: The cost of cancer treatment has increased significantly in recent decades, but it is unclear whether these costs have been associated with commensurate improvement in clinical value. This study aimed to assess the association between the cost of cancer treatment and 4 of the 5 NCCN Evidence Blocks (EB) measures of clinical value: efficacy of regimen/agent, safety of regimen/agent, quality of evidence, and consistency of evidence. METHODS: This is a cross-sectional, observational study. We obtained NCCN EB ratings for all recommended, first-line, and/or maintenance treatments for the 30 most prevalent cancers in the United States and calculated direct pharmacologic treatment costs (drug acquisition, administration fees, guideline-concordant supportive care medications) using Medicare reimbursement rates in January 2019. We used generalized estimating equations to estimate the association between NCCN EB measures and treatment cost with clustering at the level of the treatment indication. RESULTS: A total of 1,386 treatments were included. Among time-unlimited treatments (those administered on an ongoing basis without a predetermined stopping point), monthly cost was positively associated with efficacy ($3,036; 95% CI, $1,782 to $4,289) and quality of evidence ($1,509; 95% CI, $171 to $2,847) but negatively associated with safety (-$1,470; 95% CI, -$2,790 to -$151) and consistency of evidence (-$2,003; 95% CI, -$3,420 to -$586). Among time-limited treatments (those administered for a predetermined interval or number of cycles), no NCCN EB measure was significantly associated with treatment cost. CONCLUSIONS: An association between NCCN EB measures and treatment cost was inconsistent, and the magnitude of the association was small compared with the degree of cost variation among treatments with the same EB scores. The clinical value of cancer treatments does not seem to be a primary determinant of treatment cost.