bluuebunny/crossref_metadata_2025 huggingface dataset:
A population-based study of medical cannabis utilization in patients with cancer in the pre-legalization era.
Authors: Karim Safiya , Bu Jingyu , Jess Ed , Cheung Winson Y. , Kerba Marc
Published: May 2019

e18297

Background: Between April 1, 2014 and October 17, 2018, access to cannabis for medical purposes was regulated by Health Canada. Surveys have demonstrated that cancer patients use cannabis to manage symptoms and side effects. However, medical cannabis utilization patterns in cancer patients under Health Canada’s regulatory framework have not been well-described. We aimed to determine the proportion of cancer patients who used medical cannabis, timing of use in relation to cancer treatment and sociodemographic factors predicting use in a large Canadian province. Methods: The Alberta Cancer Registry was used to identify all patients age ≥ 18 diagnosed with invasive cancer in the province from April 01, 2014 to December 31, 2016. These cases were linked to records from the College of Physicians and Surgeons of Alberta database which collects data on patients who received authorization to access medical cannabis as well as on physicians that provided the authorization. Authorization was used as a surrogate for medical cannabis utilization. Univariate and multivariate logistic regression models were constructed to determine factors associated with medical cannabis utilization. Results: We identified 41,889 patients between April 1, 2014 and December 31, 2016. Median age at cancer diagnosis was 65 and 50% were female. Among these patients, 1,070 (2.5%) used medical cannabis. Of these patients, 541 (51%) used medical cannabis within 1 year of diagnosis, 248 (52%) within one year of the start of systemic therapy and 128 (41%) within one year of the start of radiation therapy. On multivariate analysis, patients aged 18-29 (OR 12.4, 95% CI 7.8-19.7) and those receiving systemic therapy (OR 2.0, 95% CI 1.7-2.4) were more likely to use medical cannabis (p < 0.001). There were 171 unique physicians who authorized medical cannabis of which only 3.5% (6/171) were oncologists. Conclusions: A small proportion of cancer patients used medical cannabis under Health Canada’s regulatory framework. Utilization was associated with a cancer diagnosis and receiving treatment. Younger patients and those undergoing systemic treatment were predictors of medical cannabis use. Further study is required to understand utilization patterns after cannabis legalization and how to incorporate these findings into patient-centered cancer care.
Giving voice to patients: Understanding treatment preferences of patients with multiple myeloma (MM).
Authors: McKay Caroline , Maiese Eric , Chiarappa Joseph , Sarokin Laura , Cambron-Mellott M. Janelle , Maculaitis Martine , Alunni Nicole , Raje Noopur S.
Published: May 2019

e18302

Background: Findings from few studies examining preferences for MM treatment are limited in application, as they are largely missing the voices of patients (PTs). The present qualitative study elucidates PT preferences, the perceived trade-offs they are willing to make, and how these may differ by line of therapy (LOT). Methods: Semi-structured phone interviews were conducted with MM PTs (front-line [FL] = 11, early relapse 1- 2 prior-lines [1/2PL] = 10) recruited via purposive sampling from targeted panels and PT groups, April-May 2018. A discussion guide was developed and a trained interviewer conducted 1-hour interviews on the diversity and valence of factors influencing how PTs evaluate potential regimens and how preferences vary by experience (i.e., LOT). Interviews were audio recorded and transcribed, responses coded, and content analysis performed to identify key themes emerging from textual data. Results: The sample was 42% male, mean age 64 years, with mean 58 months since diagnosis. Three key themes were identified. Firstly, treatment decision-making, revealed that trust in one’s health care provider (HCP) was a potent influence on treatment choice. Whereas FL PTs reported often only one option is offered and rely on HCP to make decisions, 1/2PL PTs consider other sources of information and engage in more shared decision-making. Secondly, expectations about treatment, illustrated that HCPs discuss important factors, e.g., efficacy and tolerability, in general terms with FL PTs and provide more details to 1/2PL PTs. Lastly, “ top of mind” factors that influenced treatment decisions, effectiveness, followed by side effects, emerged as the greatest influences on preference, although 1/2PL PTs reported less concern with side effects than FL PTs. Relatedly, quality of life was described as salient; the lived experience of treatment was often mentioned within the context of side effects. Conclusions: The way PTs construct, prioritize, and communicate about treatment when assessing “benefit-risk” is a dynamic process, based on where PTs are in their treatment journey. By examining treatment preferences grounded in PTs’ lived and changing experiences with MM, the findings may contribute to better PT-HCP engagement through treatment decision-making and improve clinical care.
Review of the treatment milestones for stage I non-small cell lung cancer at a regional rural cancer center.
Authors: Harb Antoine Joseph , L'Italien G. Allen , Sinclair Sarah , Curtis Adam
Published: May 2019

e18305

Background: Treatment milestones were reviewed for all stage I non-small cell lung cancer (NSCLC) patients treated at Northern Light Cancer Institute (NLCI), from 2010 to 2017. Cases in which the initial time to treatment (TTT) exceeded 6 months and those not seeking treatment were considered non-typical and were excluded from analysis, resulting in 502 cases for this time period. Methods: Analysis demonstrated that patients primarily took one of three different pathways in the diagnostic process. This process typically involved a CT scan, PET scan, and a biopsy. The three primary diagnostic pathways were: CT-PET-Biopsy (29.7%), CT-Biopsy-PET (14.3%), or CT-PET (no biopsy) (39.8%), accounting for 83.9% of eligible patients. The primary mode of treatment for most patients was surgery (63.7%). Patients not eligible for surgery received stereotactic body radiation therapy (SBRT) (26.7%). Results: Patients undergoing surgery experienced a shorter average TTT compared to patients receiving SBRT for all years except 2016. (p < 0.05). Time to treatment for surgical patients was stable at approximately 70 days from 2011-2014, at which time there was an average 27.9 day increase by 2016. TTT for SBRT patients increased from a mean of 67.4 days in 2010 to a high of 110.8 days in 2015 before decreasing to 90.0 in 2016. The different diagnostic pathways did not significantly differ from each other in terms of 3 year average TTT (2015-2017) for surgical patients (p = 0.59). SBRT patients who had a two-step diagnostic pathway (CT-PET) had TTT that was 22.7 days shorter than the three step pathway of CT-PET-Biopsy (p = 0.02). Patients receiving SBRT had a 1.56 points average higher Charlson Comorbidity Index, and were an average of 4.5 years older than those receiving surgery. Conclusions: Differences in TTT between treatment modalities are likely related to patient comorbidities and additional time needed for radiation planning and simulation. The changes seen since 2015 were thought to be secondary to the emergence of prior-authorization for procedures. This was a quality study aiming to identify the current treatment milestones and related wait times for each treatment modality in an effort to further optimize patient care.
Design and implementation of outpatient-based rapid MRI protocols to rule out metastatic spinal cord compression and brain metastases.
Authors: Fried Jessica G. , Lariviere Michael Joseph , Parikh Ravi Bharat , Sullivan Patricia Zadnik , Kanter Genevieve P. , Lee John Y.K. , Malhotra Neil R. , Brem Steven , Ozturk Ali K. , Schuster James M. , Grady M. Sean , Evans Tracey L. , Alonso-Basanta Michelle , Jones Joshua Adam , Kurtz Robert , Wolf Ronald , Zafar Hanna M. , Shulman Lawrence N. , Berman Abigail T. , Kahn Charles E.
Published: May 2019

e18307

Background: Metastatic spinal cord compression (MSCC) and symptomatic brain metastases (mets) are potential emergencies that demand coordinated multidisciplinary management. Patients (pts) with concerning symptoms are often referred to the Emergency Department (ED) for expedited imaging, but most do not require subsequent ED or inpatient management. Unnecessary ED visits incur substantial cost to the health system and patients, and cause psychosocial stress for patients often near the end-of-life. To improve access to expedited outpatient imaging for high-risk pts and reduce unnecessary ED visits, we developed outpatient rapid MRI protocols and pathways to rule out MSCC and brain mets. Methods: Tailored abbreviated MRI protocols were developed to allow rapid acquisition of brain ( < 13 minutes) and full spine ( < 25 minutes) exams. Dedicated appointments were reserved on the daily MRI schedule. Exams were immediately interpreted and reported by Radiology to the ordering clinician. This pathway was piloted within the Thoracic Oncology group beginning in 10/2018. Results: Referring specialties included Radiation Oncology (50%), Medical Oncology (36%), Pulmonology (7%), and Surgery (7%). For 6 pts who had outpatient rapid brain imaging, median time from order to exam start was 4.3 h (1.8-31) and order to final report 6.8 h (3.2-34.1). Brain mets were found in 4/6 patients. Only 1/4 positive studies required subsequent ED management. For 8 pts referred for rapid spine imaging, median time from order to exam start was 14.4 h (2.2-72.5) and order to final report 16.7 h (4.0-74.4). Only 1 patient was found to have cord compression and required ED/inpatient management. Overall, 86% of patients did not require ED or inpatient admission. 3 pts (all with negative imaging) died a median 13.4 d (1.4-28.3) after order placement. Conclusions: Outpatient rapid MRI protocols facilitate same-day imaging, interpretation, and management, improving care for thoracic oncology pts with new concerning neurologic symptoms and reducing unnecessary ED visits. Future work will expand access beyond Thoracic Oncology and further quantify improvements in cost savings and patient quality of life.
Combined oral administration of analgesia and anxiolysis for pain associated with bone marrow aspiration and biopsy.
Authors: Cerchione Claudio , Martinelli Giovanni , Catalano Lucio , Pugliese Novella , Della Pepa Roberta , Gravetti Angela , Nappi Davide , Pane Fabrizio , Martinelli Vincenzo
Published: May 2019

e18313

Background: Bone marrow aspiration and biopsy (BMAB) is a painful procedure, and the commonly adopted local infiltration anesthesia (LIA) with lidocaine is unable to relieve the pain during the most uncomfortable phases, or the anticipatory anxiety related to pain recalling thereafter. As there are no formal guidelines for adding a sedoanalgesic premedication before beginning the BMAB, many combinations have been adopted by several authors. Our randomized and patient blinded trial aimed to evaluate, as primary end point, the efficacy and safety of opioid and benzodiazepine agent combination plus LIA in patients who underwent BMAB for hematological malignancies. Two secondary end points were: 1) to define if patients who already underwent to BMAB without LIA prefer sedoanalgesia; 2) to demonstrate if sedoanalgesia can influence the quality of the biological specimen harvested. Methods: Patients were randomly assigned into two arms for receiving either placebo plus LIA (standard group, 48,6%) or oral fentanyl citrate 200 mcg + oral midazolam 5 mg in addition to LIA (combo-group, 51,4%) during BMAB. Pre-procedural anxiety and procedural pain were assessed according to the Numered Rating Scale (NRS: 0-10), dividing the time of the procedure into five intervals (T0, T1, T2a, T2b, and T3) and evaluating discomfort grade during each moment of procedure in both groups. Cognitive function was measured before and 30 minutes after the procedure. Possible side effects were recorded, as well as the adequacy of tissue samples harvested. A total number 116 patients were enrolled in the study. 9 patients did not meet inclusion criteria and were excluded. 52 patients were randomized and assigned to standard group and 55 to combo group. Results: At T2b and T3 (corresponding to the biopsy time and time after the biopsy, respectively) there was a significantly lower ( p< 0.05) perception of pain in the patients who received sedoanalgesia (combo-group) compared to those who did not (standard group). Moreover, 100 % of the patients in combo group who had previously undergone this procedure without premedication reported that they would prefer sedoanalgesia for the subsequent procedures. Conclusions: Administration of oral analgesia and anxiolysis is a safe and feasible option to be used in outpatient setting; sedoanalgesia is very effective in reducing pain during the biopsy and it diminishes the anticipatory anxiety related to a painful procedure. Patients should have the possibility to choose between local anesthesia alone or sedoanalgesia plus local anesthesia.
Should pregnancy testing during chemotherapy be standardized?
Authors: Berger Natalie S , FitzPatrick Katherine , Klein Paula
Published: May 2019

e18314

Background: The incidence of cancer diagnosed during pregnancy is 0.1-0.2%. The incidence of women who become pregnant while on chemotherapy is less clear. As the initiative to improve awareness about the risks of infertility in premenopausal women receiving chemotherapy improves, it is also important to reinforce the risk of pregnancy during chemotherapy. Treating patients with chemotherapy, especially during the first trimester, is an absolute contraindication and a serious adverse event. Pregnancy testing prior to the initiation of chemotherapy is recommended by the NCCN and ASCO. However, recommendations on how to monitor for pregnancy after an initial screen are inconsistent and lack standardization. Methods: We surveyed five breast medical oncologists and six infusion nurses at a busy urban breast center to determine their baseline practices for pregnancy counseling and testing. We then initiated a quality improvement project over a six month period to routinely screen premenopausal patients ( < 55 years) diagnosed with breast cancer for pregnancy prior to each cycle of chemotherapy. Results: Of physicians and nurses surveyed, 40% and 33% respectively have diagnosed a pregnancy during chemotherapy. All physicians surveyed check a pregnancy test prior to the initiation of chemotherapy, 60% check urine and 40% check serum. Counseling patients on the risk of pregnancy varies with 80% of physicians counseling patients prior to initiation of chemotherapy. Half of the infusion nurses ask patients if they are concerned they may be pregnant intermittently during chemotherapy and 50% do not ask again after the initial screen. During routine screening over a 6 month period no pregnancies were detected. One patient missed a baseline screening prior to initiating chemotherapy. Two patients had a borderline result ( < 1%) on urine pregnancy testing but reflex serum testing was negative. Compliance for testing by nurses was 93%. Conclusions: Results of the survey demonstrate that pregnancy counseling and screening practices vary even within the same institution. We must improve and standardize educating patients and healthcare providers on the risks of pregnancy during chemotherapy in order to prevent unwanted pregnancies, and identify pregnancies in a timely manner. Given the very small risk of pregnancy, we would not recommend routine screening prior to each cycle of chemotherapy, but we do recommend asking all premenopausal patients if there is a chance they may be pregnant prior to each treatment and test based on the individual risk.
Implementation of ICH E6 (R2) through identification of data risks using analytics in oncology clinical trials.
Authors: Hayward Colin , Youssef Emile , Nezos Melissa , Jendrasek Debra
Published: May 2019

e18319

Background: ICH E6 (R2) has increased the level of scrutiny that we have for the data we collect in clinical trials. The emphasis is on quality-by-design with a quality management system to be incorporated and a focus on using a risk-based approach. This can be time-consuming and expensive - though the goal of this addendum is to improve quality AND efficiency, whilst ensuring patient safety and integrity of trial results. We therefore, piloted a proactive, concise and consistent method for utilizing a risk-based approach with central monitoring. Methods: Our method included 1) identifying risks within our data with 8 standard Key Risk Indicators (KRIs) across different study phases and different therapeutic areas together with 2) an off-the-shelf web-based tool for uniform and efficient review by a team of central monitors to assess which data may need more examination. These 8 KRIs are indicated in the list below, in order of the categories within the TransCelerate Risk Assessment and Categorization Tool: (S)AE rates, Enrollment Rates, Screen Failure Rates, Discontinuation Rate, Protocol Deviation Rates, Overdue Query Rate, Data Latency, and Identification of Potential Fraudulent data. Results: 15 studies were configured with the same KRIs and Visual Analytics; histograms, line- and pie-charts and data tables allowing for interactive data visualization and drill down. This represents research across different Phases 1-3 and observational studies. Based upon qualitative survey analysis from the central monitoring team 5/8 KRIs were found to be extremely valuable to focus on study quality, identifying earlier issues in study conduct for the project teams and Sponsors, while the remaining 3 were less valuable. Conclusions: We Our Risk Management team aims to increase the quality of data and ease of implementation of ICHE6 (R2) by focusing on the areas that matter the most, however identifying those areas and managing those data can sometimes be challenging. Through this innovation we have proven some core KRIs of trials that should be most closely monitored to aid decision making and will continue to evaluate to develop core oncology specific KRIs that will allow a more consistent review of data.
Implementation of malignant bowel obstruction multidisciplinary case conferences (MCCs) to improve clinical decision making in malignant bowel obstruction (MBO) in gynecologic oncology.
Authors: Bhat Gita , Madariaga Ainhoa , Bonilla Luisa , Lee Yeh Chen , Dhani Neesha C. , Jivraj Nazlin , Chawla Tanya , Buchanan Sarah , Ferguson Sarah , O'Brien Catherine , Dhar Preeti , Shlomovitz Eran , Lau Jenny , Mulumba Susan , Karakasis Katherine , Chllamma Muralidharan , Oza Amit M. , Lheureux Stephanie
Published: May 2019

e18322

Background: Though patients (pts) with gynecological cancer are at higher risk of MBO, clinical management is not well defined. We implemented a coordinated team approach to evaluate MBO at Princess Margaret Cancer Centre. The Princess Margaret Cancer Centre inter-professional MBO management program includes nurse led ambulatory symptom management, inpatient treatment algorithm, patient directed bowel management education & MCCs. This study evaluates the utility of MBO MCC on clinical decision making in gynecologic oncology. Methods: Monthly MBO MCCs are conducted to discuss complex clinical management issues. A clinical summary is presented prior to the discussion with each case incorporating radiology review followed by interdisciplinary discussion. In this study, the initial management plan was compared to post-MCC consensus. A change in plan was defined as a consensus plan different from the pre-MCC plan or no definite plan prior to MCC. Barriers to implementation of the consensus were analyzed. Results: From December 2016 to November 2018, 90 pts were discussed in 22 MCCs. Of these, 60 had high grade serous ovarian carcinoma (67%) & 64 had small bowel obstruction (71%). Discussion in MCCs lead to a change in management plan in 49 cases(54%). These changes included recommendations for palliative surgery (25%) or radiation (10%), interventional radiology (23%), pharmacologic management alone (14%), imaging studies (4%) & total parenteral nutrition (TPN) (4%). Chemotherapy continuation, break or regimen changes were recommended in 20%. MCC consensus plan could not be implemented in 11 cases (23%). The barriers were refusal of surgery (8%), interventional radiology procedures (2%), TPN (4%) by patients, functional decline (6%) & inability to create a colostomy due to dense adhesions (2%). During MCC referrals to the dietitian & palliative care team were planned for 16 (18%) & 22 (24%) pts respectively. Conclusions: Interdisciplinary MBO MCCs have a significant impact on decision making in complex MBO cases. Radiology review & group discussion facilitates greater clarity in formulation of a management plan.
Assessment of end-of-life care quality indicators in veterans with cancer.
Authors: Suero-Abreu Giselle Alexandra , Johnson Camille Michelle , McKenna Marshall , Wang Jun Chih , Barajas-Ochoa Aldo , De Silva Piyumika , Perez Arturo , Zhong Fengming , Srinivas Shanthi , Chang Victor Tsu-Shih
Published: May 2019

e18327

Background: Many cancer patients (pts) receive aggressive medical care at the end-of-life (EOL) . The objective of this study was to assess quality of EOL (qEOL) care in cancer pts at our VA and to determine the implementation of do-not-resuscitate (DNR) orders. Methods: Records of Veterans followed at the VA NJ Health Care System who died from 2015-2017 were reviewed. The qEOL care was assessed using seven indicators by Earle et al. ( J Clin Oncol. 2003;21(6):1133-1138). EOL planning (use of DNRs and use of palliative and hospice services) was also assessed. Results: We identified 92 male pts with cancer (mean age 73 years ±10). There were Caucasian (n = 48, 52%) and African American (n = 38, 41%) pts. The most common malignancies were lung (22%), gastrointestinal (21%), prostate (16%) and hematological (14%). 87 pts (95%) had a DNR order at the time of death; the DNR was obtained a median of 60 days prior (IQR 7-135). Ten pts (11%) had DNR orders placed within 1 week of death. Seven pts (8%) received chemotherapy in the last 14 days of life while 6 pts (7%) received a new treatment in their last 30 days. In the last month of life, 35 pts (38%) had multiple hospitalizations and ER visits, 20 pts (22%) were admitted to the intensive care unit, 9 pts (10%) were intubated, and 3 pts [3%] received cardiopulmonary resuscitation. More pts (n = 47, 51%) died in an acute care setting, and 45 (49%) pts were admitted to hospice (median of 22 days before death, IQR 6-52). Four pts (4%) were admitted to hospice within 3 days of death. A next-of-kin was available for 64 pts (70%). Palliative care (PC) was provided to 83 pts (90%) and pain medications prescribed for 80 pts (87%). Conclusions: There was timely implementation of DNRs and referral to PC. The qEOL indicators used suggest that aggressive treatments were appropriately being held at the EOL. However, there was an increased use of acute care services. Limitations include lack of data on Veterans who died outside the VA. This data supports future quality improvement EOL interventions. [Table: see text]
How will the cost of biosimilars affect patients’ willingness to receive them?
Authors: Harvey R Donald , McGrath Megan , Cook John W. , Dixon Margie D , Pentz Rebecca D.
Published: May 2019

e18338

Background: The cost of oncology care is increasing. The NIH projects that the oncology drug market will reach $111.9 billion by 2020. Studies show that oncology patients experience considerable financial burden, regardless of insurance status and in general believe that oncology medications are too expensive. However, there is some evidence outside of oncology that suggests patients may not trust generics or cheaper medications. Therefore, there is a need to assess oncology patients’ views of a biosimilars and their potential to reduce costs. Methods: We surveyed a convenience sample of 79 oncology patients in clinics and the infusion center. The survey consisted of five questions on cost and patient participation in decision making. Results: Of 79 patients approached, 75 (95%) completed the survey. Fifty (66%) believed that expensive medications do not work better than less costly ones for the same disease; yet only 30 of those 50 (60%) and 44% overall (33/75) would prefer that their doctor prescribe them the cheaper version of their anti-cancer medication. Of the 20 respondents who believed that expensive drugs do not work better but still wanted the more expensive drugs for themselves, 8 believed cancer was too serious of an illness to take any chances with a cheaper medication, 5 wanted the most expensive that insurance would cover and 2 wanted the best possible medication. 90.67% respondents (68/75) wanted to know if their physician was prescribing a cheaper version of their drug. Conclusions: Our results show that, overall, oncology patients agree that cheaper medications work as well as more expensive ones, but there are definite concerns among some patients that drug price may be a proxy for quality, particularly in cancer. Overcoming these negative perceptions among patients will be important if optimal cost savings are going to be realized with expanded biosimilar use.
Cost-effectiveness of primary prophylaxis with pegfilgrastim in early-stage breast cancer patients receiving chemotherapy in China.
Authors: Xia Wen , Wang Shusen , Hu Hao , Xu Fei , Jiang Kuikui , Yuan Zhongyu , Shi Yanxia , Zhao Kun , Huang Jia Jia , Xue Cong , Bi XiWen , Lu Qianyi
Published: May 2019

e18349

Background: Guidelines recommend primary prophylaxis(PP) use for patients receiving chemotherapy regimens with a high risk of febrile neutropenia (FN), which is 20% or higher. This study aim to evaluate the cost effectiveness of PP with pegfilgrastim (Brand name:Jinyouli), PP with filgrastim or no prophylaxis in women with early-stage breast cancer(BC) in China. Methods: A two-phase Markov model was developed for a hypothetical cohort of patients age 45 with stage II BC. First phase modeled costs/outcomes of 4 cycles docetaxel combined cyclophosphamide(TC×4) chemotherapy, with assumptions based on literature reviews including FN rates(Base-case (DSA range),0.29(0.24–0.35)) and related events (FN case-fatality, 3.4 (2.7–4.1)). Second phase models the long term survival which was suggested to link with the relative dose intensity (RDI)( Mortality HR for RDI < 85% vs. ≥85%,1.45 (1.00–2.32)). Clinical effectiveness, costs, and utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results: Compared to PP filgrastim and no prophylaxis, PP pegfilgrastim was associated with higher costs 5208.19RMB and 5222.73RMB respectively, and increased quality-adjusted life-year (QALY) gained 0.066 and 0.297 respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79146.3RMB and 17558.77 RMB per QALY, which are both below the three times GDP per capita as the willingness to pay (WTP) threshold suggested by the WHO. Conclusions: Although the cost of PP pegfilgrastim is higher, considering the additional benefits, the administrating of PP pegfilgrastim is likely to be a cost-effective alternative to PP filgrastim and no prophylaxis in patients with early stage breast cancer in China.
Modeling an oncology outcomes-based contract using a blockchain database approach: Cost and technology considerations.
Authors: Hinkel Jennifer M. , Ray Arka , Brar Sirtaj , Lalmalani Rahul
Published: May 2019

e18360

Background: Cost of care is an ongoing concern for all oncology stakeholders. Outcomes Based or Risk Sharing contracts are increasingly discussed, but difficult and costly to implement. The literature notes barriers of outcomes definition, reliable data sources, and technology enablement. The authors sought to design and test software that could enable faster, lower-cost, and auditable administration of such contracts. Methods: The authors developed software using blockchain databases and transactional proof of work to simulate such a contract and to compare the financial result to usual fee-for-service reimbursement (FFSR). The software processed a synthesized Medicare claims dataset and Average Sales Price (ASP) data from 2008-2010, looking for use of the Bevacizumab(BV)/Carboplatin/Paclitaxel(CP) regimen in non-small cell lung cancer (NSCLC). The contract hypothesized a scenario that offered payers a discount for “underperforming” BV doses (defined as doses given to a patient with < 9 mo. BV duration) and required a bonus payment for “overperforming” BV doses (defined as doses given to a patient with > 14 mo. BV duration). These parameters were selected based on survival data supporting the 2007 FDA approval of BV/CP in 1L tx of advanced nonsquamous NSCLC. Results: The software successfully processed the claims dataset and projected financial results (additional/saved cost) to the payer in this hypothetical contract compared to FFSR. The software also enabled comparison of different hypothetical contracts, inclusion/exclusion rules for claims, and discount structures. The software accurately categorized doses according to the defined logic. Conclusions: Outcomes based contracts have potential for better aligning oncology reimbursement with meaningful results, particularly for costly therapeutics and where patient response or outcome is difficult to predict. While such agreements are recognized as difficult to implement, a software platform that facilitates efficient and scalable design, simulation, and implementation of such agreements, under constraints of real world data availability and sharing, may advance their adoption.
Frequency and causes of oncologists’ burnout in community practices.
Authors: Nabhan Chadi , Bapat Bela , Smith Yolaine , Klink Andrew , Feinberg Bruce A.
Published: May 2019

e18375

Background: Physician burnout, which is often characterized as exhaustion of physical or emotional strength because of prolonged stress or frustration, has become a worsening phenomenon in medicine. Some have suggested that the rate of burnout among oncologists may be higher than other specialties. Methods: US oncologists/hematologists were queried via a web-based survey from Sep-Nov 2018. Physicians were asked about frequency of burnout symptoms, drivers of burnout, and management of increasing workload. Results: Among the 163 physicians surveyed, 46.0% felt substantial amount of stress at work. Most physicians felt emotionally (85.3%) and physically (86.5%) exhausted. Majority of physicians felt lethargic (66.9%), ineffective (63.8%), and/or detached (62.6%). Additionally, 57.1% of physicians described their practice atmosphere as busy or very busy. In a typical workweek, 92.6% stated they needed additional time, beyond time allocated to clinical care, to complete work responsibilities (23.3% needed 1-3 hours; 15.3% needed ≥10 hours). Most (81.6%) physicians felt lack of work life balance as one of their main stressors. Electronic health record (EHR) responsibilities caused moderate to excessive stress among 66.9% of physicians, 79.1% physicians worked on EHR at home. Other sources of excessive stress were changing reimbursement models (33.1%), interactions with payers (31.3%), increasing patient and caregiver demands (30.7%). Due to increasing demands, 19.6% physicians have considered retiring early, while 14.7% physicians have considered changing their career path. However, 62.6% of physicians stated they had optimal or good control over their workload. To combat burnout, physicians’ practices have used following strategies: employed APPs (46.0%), invested in information technology (33.1%), and/or hired additional administrative staff (31.3%). Conclusions: Most oncologists in the US experience burnout and require additional time beyond that allocated to clinical care to complete their workload. The discordance between oncologists feeling burdened by stress and exhaustion while claiming good control over those same burdens is noteworthy. Additional follow-up will assess whether remedial strategies are effective.
Do the ASCO Value Framework and the ESMO Magnitude of Clinical Benefit Scale measure Absolute or Relative clinical benefit?
Authors: Saluja Ronak , Everest Louis , Cheng Sierra , Cheung Matthew C. , Chan Kelvin K.
Published: May 2019

e18378

Background: It is unclear whether the clinical benefit scores from the ASCO or ESMO valuation frameworks were intended to measure absolute or relative survival benefit. To empirically examine the measurement characteristics of these frameworks, we compared their survival efficacy components (ASCO-CBS and ESMO-PMCBGs) with established measures of absolute (median survival difference and restricted mean survival time (RMST) difference) and relative (HRs) survival benefit. Methods: FDA’s Hematology/Oncology Approvals and Safety Notifications pages were reviewed to identify phase III RCTs cited in oncology drug approvals between January 2006 and December 2017. In our primary analysis, ASCO-CBS and ESMO-PMCBGs were calculated for the included trials using the framework defined endpoint (Fr). Sensitivity analyses were conducted by calculating the scores using 1) Fr + tail-of-curve bonus points (ASCO) or long-term plateau adjustments (ESMO) (defined as Fr + TOC), 2) overall survival (OS) data only, and 3) progression-free survival (PFS) data only. For both primary and sensitivity analyses, Spearman correlation coefficients were calculated to examine the relationships between 1) ASCO-CBS/ESMO-PMCBGs and RMST difference, 2) ASCO-CBS/ESMO-PMCBGs and median survival difference, and 3) ASCO-CBS/ESMO-PMCBGs and HRs. Results: 107 RCTs were included. Compared to measures of absolute survival, ESMO-PMCBG showed low-moderate correlations with RMST difference and moderate-high correlations with median survival difference (Rho = 0.44 and 0.64, respectively). ASCO-CBS showed low-moderate correlations with both measures of absolute benefit (Rho = 0.43 and 0.44 for RMST difference and median survival, respectively). Compared to a relative measure of survival (HRs), ESMO-PMCBG revealed a moderate correlation (Rho = 0.47) while ASCO-CBS showed a higher correlation (Rho = 0.76). Conclusions: Both frameworks do not perform solely as absolute measures of survival benefit. We recommend that the frameworks consider incorporating a direct measure of absolute clinical benefit, such as RMST difference, into the survival efficacy components of their algorithms.
Patterns of healthcare utilization in patients with newly diagnosed advanced lung cancer.
Authors: Ray Emily Miller , Hinton Sharon Peacock , Reeder-Hayes Katherine Elizabeth
Published: May 2019

e18386

Background: Advanced lung cancer (ALC) is a symptomatic disease that is often diagnosed in the context of hospitalization. The index hospitalization may be a window of opportunity to improve cancer care delivery. We aimed to define the frequency of ALC diagnosis associated with hospitalization and the relationship to subsequent cancer care and readmissions. Methods: We identified patients in the SEER-Medicare database with: ALC (stage IIIB-IV non-small cell or small cell), diagnosed 2007 to 2013; with continuous enrollment in Medicare from 6 months prior to lung cancer diagnosis through death or 12/2014; and an index hospitalization within 7 days of their ALC diagnosis. Our primary outcomes of interest were 30-day re-hospitalization and emergency department (ED) use. We examined: utilization of services during index hospitalization, including intensive care and oncology or palliative care consultation; discharge destination; receipt of systemic therapy; and hospice enrollment. Results: Fifty-four percent (n = 28,976) of ALC patients had an index hospitalization, with 90% of those having their cancer diagnosed while hospitalized. During their index hospitalization, 16% had oncology consultation, and 6% had palliative care (PC) consultation. Thirty-three percent were in the intensive care unit. At discharge, 59% returned home, 8% died, and 11% went to hospice. Of those who survived to discharge, 69% later returned to the ED or were re-hospitalized, with 49% of re-hospitalizations and 35% of ED visits occurring within 30 days of the index hospitalization. Thirty-five percent of these patients eventually received systemic treatment for their cancer. By 180 days post-discharge, 77% had enrolled in hospice with a median of 10 days on hospice care. Conclusions: Newly diagnosed ALC patients are high risk for acute care utilization, and many patients experience a return to the hospital early in their cancer trajectory. These patients may benefit from additional health system support prior to hospital discharge to help prevent high-cost, low-value healthcare utilization.
A novel drug to treat advanced melanoma.
Authors: Meng Lingbin , Xu Xiaochun , Xin Ying
Published: May 2019

e21000

Background: Advanced melanoma is a type of malignant skin cancer without effective treatment. Ginsenoside-Rg3 (Rg3), a saponin component extracted from ginseng roots, has been revealed to have an anti-cancer effect. However, there is limited data about its involvement in advanced melanoma. In this study, we investigated the role of Rg3 in melanoma by evaluating its in-vivo efficacy to inhibit melanoma growth, lung metastasis and melanoma-induced angiogenesis. We also revealed the potential underlying mechanisms by examining ERK and Akt pathways. Methods: 6-week-old C57BL/6 mice were purchased and maintained in our animal center. A highly metastatic subline of murine B16 melanoma cells was kindly provided by Dr. Xiaochun Xu, M.D. Anderson Cancer Center. Five groups were designed for this experiment: control (PBS), 3 groups with different doses of Rg3(0.3mg/kg, 1.0mg/kg, and 3.0mg/kg), and 5-FU (20mg/kg). 7 mice per group were given subcutaneous injection of 2 x 106 melanoma cells on the right flank for xenograft assay. 5 x 105 melanoma cells wrer subcutaneously injected on the right hind footpad for metastasis assay.The formed tumor tissues and lungs were collected for tumor growth and metastasis analysis, immunohistochemical staining, and western blotting. Results: For tumor growth, all the 3 Rg3 groups had smaller size of tumor and reduced expression of PCNA, a marker for cancer cell proliferation. For lung metastasis, the 3 Rg3 groups showed a lower number of tumor colonies with a dose-dependent manner. For angiogenesis, the 3 Rg3 groups displayed suppression of tumor-induced neovascularization through inhibition of VEGF. Western results demonstrated both ERK and Akt pathways were down-regulated in the Rg3 groups. Interestingly, immunohistochemical staining showed a higher number of CD8+ T cell in Rg3 groups lungs, suggesting immune response may be activated to fight against melanoma. Conclusions: Rg3 can decrease melanoma growth and metastasis by down-regulating ERK and Akt pathways. It may also inhibit melanoma metastasis by mediating VEGF-activated angiogenesis. More importantly, Rg3 may activate immune system to fight against advanced melanoma. Our study is the first to indicate Rg3 may be a promising novel drug for advanced melanoma. Based on these results, we are performing a clinical trial to test its efficacy to treat advanced melanoma.
Inhibition of glucose metabolism through treatment of BRAF mutated metastatic melanoma with vemurafenib.
Authors: Warrier Govind , Lanceta Lilibeth , Imbert-Fernandez Yoannis , Chesney Jason Alan
Published: May 2019

e21005

Background: Increased glucose metabolism is a hallmark of neoplastic cells that allows self-promotion of growth and survival. The enzyme 6-phosphofructo-2-kinase (PFKFB3) is an integral controller of glycolysis by promoting the synthesis of fructose 2,6-bisphosphonate (F2,6BP) which activates 6-phoshofructo-1-kinase (PFK-1), a rate-limiting enzyme and essential control point in the glycolytic pathway. Additionally, mitogen-activated protein kinase (MAPK) is a key signaling pathway in a number of cancers with mutations of the BRAF component, described most commonly in melanoma, resulting in constitutive activation of the MAPK pathway. We aim to demonstrate that vemurafenib, a BRAF inhibitor, has antiglycolytic activity in sensitive melanoma cell lines which may help guide development of future therapies with specific attention to PFKFB3 as a potential enzymatic target to decrease glycolytic flux thereby inhibiting tumor growth and survival. Methods: Vemurafenib sensitive and resistant variants of two separate human metastatic melanoma cell lines (451Lu and WM983) were treated with 3 mM Vemurafenib for 24 and 48 hours. Additionally, cells from aforementioned lines were probed for PFKFB3 after 24 hours of treatment with vemurafenib. Glycolysis was measured by incubating cells in complete media containing 1 mCi [5-3H]glucose for 60 minutes. [3H]H2O produced by glycolysis through enolase was measured. Results: A decrease in PFKFB3 protein expression was found in vemurafenib sensitive cells compared to controls but not in resistant cells after 24h treatment with 3 mM vemurafenib in both 451Lu and WM983 metastatic melanoma cell lines (n = 2). Treatment with vemurafenib led to decrease in glycolysis compared to untreated controls in both vemurafenib sensitive metastatic melanoma cell lines but not in resistant cell lines (n = 5). Additionally, there was a significant reduction in glycolysis in vemurafenib resistant WM983 at 48 hours compared to resistant untreated control. Conclusions: BRAF mutated metastatic melanoma cells showed decrease in PFKFB3 protein expression and decreased glycolysis after treatment with BRAF inhibitor vemurafenib. Future studies will focus on assessing metastatic melanoma cell viability and glycolytic activity after treatment with combination BRAF inhibition and PFKFB3 specific inhibition.
Nivolumab and Pembrolizumab in advanced cutaneous melanoma : Results from real-life data in patients from France— Evaluation of use, current practices and medico economic approach.
Authors: Grude Francoise , Travers Muriel , Moiteaux Brice , Beneton Nathalie , Jacobzone Caroline , Le Corre Yannick , Legoupil Delphine , Plantin Patrice , Porneuf Marc , Sassolas Bruno , Marhuenda Fanny , Deniel Lagadec Delphine , Pracht Marc
Published: May 2019

e21009

Background: In 2016, Nivolumab (N) and Pembrolizumab (P) have been registred for first line ECOG PS 0-1 adult patients with non-resecable or metastatic melanoma. The Brittany and Pays de la Loire Cancer Observatory has collected data on their real-life indications, current management, safety, efficacy and medico-economics Methods: All non opposing adult patients (pts) with advanced cutaneous melanoma who initiated a treatment with N (3 mg/kg q2w) or P (2 mg/kg q3w) in 2016 and 2017 were included. Minimum follow-up for survival was 12 months. Sex, age, mutation profile, lines of treatment, toxicities, response rate, survival and treatment cost have been collected. Results: 149 pts were treated by N and 201 pts by P with a median age of respectively 68 [21-88] and 69 years [28-96]. Of the 350 patients, 34% were at least 75 years and around 30% presented a BRAF mutation. The median duration of treatment was 4.9 months [0-34.6] for N and 4.2 [0-35.8] for P (Not Significant NS). 65% of pts were treated in 1st line for N and 69% for P. 24% of the pts were treated in 2nd line for both treatments. 81% of the pts had a baseline PS of 0 or 1. All lines combined (first line for wt BRAF and first or second line for m BRAF melanoma), clinical benefit was 53% for N and 47% for P. Median OS was respectively 21.7 m for N and 22.8 m for P (NS). mPFS were respectively 6.4 m and 4.6 m (NS). 18% of pts presented grade III/IV toxicities with N and 17% with P. wt BRAF pts showed more grade III/IV toxicities than m BRAF pts (p = 0.046). For N, pts with grade III/IV toxicities showed better PFS (p = 0.051) and OS (p = 0.064). For both cohorts, PS ≥2, BRAF status and treatment line identified subgroup of pts with worsened PFS and OS 55% (24/44) of pts who stopped N or P because of death had a baseline PS of 0-1 showing PS alone is not sufficient to predict survival. Aggressive diseases (high metastasis rate, cerebro-meningeal metastasis, high tumor growth rate with any previous treatment) appear to be the worse candidates for immunotherapy. N and P courses during the 2 years costed 6.6 and 9.7 millions of euros respectively with approximatively 84% or 79% of this cost for N and P clinically benefitting pts. Conclusions: Immunotherapy in real-life setting in cutaneous advanced melanomas confirms literature’s data regarding clinical benefit, survival rate and safety profile and suggests to think about a composite predictive biomarker including BRAF status, ECOG PS, toxicity and treatment line.
Expression of tryptophan metabolizing enzymes (TMEs) and its transporter, LAT1, in metastatic melanoma (MM): Prognostic and therapeutic implications.
Authors: Trembath Dimitri G. , Googe Paul B. , Frank Jill S. , Kowalski Madeline H , Spearman Marcus , Lagler Taylor Marie , Ezzell Jennifer Ashley , Thomas Nancy E. , Ollila David W. , Moschos Stergios J.
Published: May 2019

e21014

Background: The ECHO-301/KEYNOTE-252 trial failed to show clinical benefit of adding epacadostat to pembrolizumab in PD-1 inhibitor-naïve MM. We reasoned that the expression of other TMEs and/or LAT1 by melanoma cells plays a more important role. Methods: Melanoma tissues from stage III/IV pts were stained for the 4 TMEs (TPH1, TPH2, TDO2, IDO1) and LAT1 by single-color immunohistochemistry. Tissues were scored for the status of tumor-infiltrating lymphocytes (TILs) and the expression of 5 proteins separately in melanoma cells and TILs (if present). Association between protein expression, TIL status, and melanoma-specific overall survival was performed. Results: Tissues from 87 pts (stage IV, n = 25) were available. Expression of all 4 TMEs and LAT1 was significantly higher in melanoma cells compared to TILs ( p< 0.001); TPH1, TPH2, and TDO2 expression in melanoma cells was significantly higher than IDO1 (p < 0.001). Lower TPH1 expression in melanoma cells was associated with presence of TILs. Multivariate analysis using a Cox proportional hazards model that included expression of the 5 proteins in melanoma cells showed that high IDO1 was a favorable and high LAT1 expression was an adverse prognostic factor. Conclusions: Expression of TMEs and LAT1 by melanoma cells may have more important role in metastatic melanoma by depleting an essential amino acid from the tumor microenvironment. Pharmacologic targeting of TPH1/TPH2 (e.g. telotristat) may be more clinically relevant in MM as opposed to IDO1 inhibition.