bluuebunny/crossref_metadata_2025 huggingface dataset:
Computer-aided classification of lung nodules on CT scans via 3D CNNs.
Authors: Liu Xiaohua , Luo Ligang , Yang Haiying , Jie Xiaoxiang , Li Peiyu , Ma Ding , Kang Yue , Gao Guangming , Luo Xiangfeng , She Yuli , Li Jinchen , Liu Yuzhe , Xie Weihao , Lu Shijie , Hu Zhongjie , Zhang Tianze
Published: May 2019

e18047

Background: Computer-aided diagnosis based on deep learning methodologies has demonstrated great potential to assist disease diagnosis with accuracy and efficiency. Specifically, the quantitative and qualitative analysis on lung nodules has proven to be important for the early-detection of lung cancer as well as its treatment in clinical practice. This study developed a 3D CNN model to facilitate the classification of pulmonary nodules. Methods: We collected 3956 lung CT scans (slice thickness≤3mm) with multiple lung nodules from 15 Class-A hospitals in China, 1155 lung CTs from Luna 16 dataset and Data Science Bowl 2017. There were 30 senior radiologists responsible for annotation and each CT scan was annotated by two of them randomly. Another 4 senior associate chief physicians were divided into two groups, each group was responsible for arbitration when conflicts occurred between the annotation doctors. All the annotated CTs were randomly selected and split to construct training, validation and test sets. We pre-processed the CTs and utilized 3D CNNs to classify these nodules as solid, partial-solid, ground glass opacity, calcified, pleural solid and pleural calcified. ROC analysis was used, and the classification capability was assessed by classification accuracy and the AUC score. Results: Table shows the overall results. The proposed model yielded an AUC score of 0.97 for the ground glass opacity and 0.90 for calcified nodules in the training set, while the AUC of them were 0.93 and 0.93 respectively in the validation set. For the test set, we got an AUC score of 0.94 for the ground glass opacity. The average classification time for each nodule was less than 0.005 sec. Conclusions: Our model may assist clinical diagnosis of lung cancer and increase its objectivity and accuracy, and the fast processing speed proves its feasibility to be applied in real clinical practice. In the future, we will enrich the dataset with clinical and genetic information, thus improving our model to boost its performance. [Table: see text]
Mutational analysis of >14,000 solid tumor NGS tests from community oncology practices: The Sarah Cannon molecular landscape.
Authors: McKenzie Andrew , Schlauch Daniel , Sharma Yasha , Picard Shaita , Higgins Connor , Misch Amanda , Xiao Yonghong , Lachs Rebecca , OConnor Niall , Correll Mick , Spigel David R. , Burris Howard A. , Jones Suzanne Fields , Dilks Holli Hutcheson
Published: May 2019

e18065

Background: Utilization of NGS-based testing for patients in community oncology settings continues to grow. A comprehensive analysis of the molecular landscape of > 14,000 patients with commercial tissue-based and plasma-based NGS (tbNGS and pbNGS) testing from Sarah Cannon’s (SC) network of community oncologists between 2012 and 2018 was performed. These data aid clinical trial design/feasibility and identify rare and actionable mutations in the community oncology setting. Methods: Medical Oncologists in the SC network ordered NGS-based molecular profiling for their patients as standard of care. Data from multiple commercial vendors starting in 2012 were harmonized and analyzed. Results: On average, tbNGS (n = 8938) and pbNGS (n = 5419) tests revealed 14 and 4 mutations/sample, respectively. The top 10 mutated genes from both tbNGS and pbNGS - tests are in the table. The most predominant mutation-types detected were SNVs in both tbNGS and pbNGS tests, and gene amplifications were detected in ~40% of tbNGS and ~22% of pbNGS tests. MET amplifications (range: 2 - 40 copies (pbNGS) and 6 - 82 copies (tbNGS)) and ERBB2 amplifications (range: 2.1 - 90.2 copies (pbNGS) and 4 - 293 copies (tbNGS)) were detected in 1.6% (MET-tbNGS) and 4.6% (MET-pbNGS) and 4.2% (ERBB2-tbNGS) and 2.69% (ERBB2-pbNGS) of patients, respectively, and informed clinical trial enrollment. Of the fusions detected, 28 NTRK rearrangements were detected (NTRK1 – 16, NTRK2 – 5, NTRK3 – 7) by tissue-based testing and 3 (NTRK1) fusions were detected by plasma-based tests. Conclusions: These data describe the mutational landscape of NGS tests ordered within community oncology practices. SC’s data infrastructure links NGS-based testing data and clinical data to support real world evidence research, and highlights the need for healthcare IT systems to marry clinical and genomic data for clinical decision support and clinical research. [Table: see text]
Employing an oncology decision-support system to quantify treatment variation.
Authors: Liang Jun , Dankwa-Mullan Irene , Ren Yan-ping , Chen Alan , Willis Van , Jackson Gretchen , Levitan Nathan , Rhee Kyu , Li Tian-le
Published: May 2019

e18067

Background: Factors affecting cancer treatment may include evidence for effectiveness, cost, and preference. These influences can lead to treatment variation across institutions and populations. Decision-support systems have been proposed as tools to reduce variation. This study quantified concordance between treatment provided by oncologists in China and therapeutic options presented by a decision-support tool. Methods: We identified and analyzed concordance studies in nine unique institutions located in seven provinces in China, published in 2017-2018 using Watson for Oncology (WFO), a clinical decision-support tool. Published rates of concordance were compared by cancer type and institution. Results: Concordance of all combined cases was 59% (2012/3388). Concordance rates varied by cancer type and institution (Table). Concordance rates were highest for ovarian (96%), rectal (94%) and breast (89%) cancers but lowest in gastric (12%), ovarian (43%) and breast (55%) cancers. Conclusions: Concordance between treatments and therapeutic options from an oncology decision-support tool varied significantly across cancer types and institutions in China, suggesting significant practice variation. Without established guidelines for treatment, clinical decisions may be influenced by preferences and local factors. Future studies are needed to identify reasons for variation and improve adherence to regional evidence-based guidelines. [Table: see text]
Building a data foundation: How MD Anderson and Palantir are partnering to accelerate research and improve patient care.
Authors: Alfaro-Munoz Kristin , Hallatt Gemma , Sookprasong Jamie , De Groot John Frederick , Lari Bryan , Yu Emily , Jin Jeff , Futreal Andrew , Ravi Vinod
Published: May 2019

e18077

Background: MD Anderson (MDA) strives to maximize learning from the > 44,000 patients seen annually. This has historically been challenging due to the diverse, often unstructured, and siloed nature of patient data. To begin addressing these challenges, MDA constructed an institutional data warehouse and developed Natural Language Processing (NLP) capabilities. This allowed technical users to extract specific cohorts but proved challenging for many non-technical users. In 2018, MDA conducted a proof of concept with Palantir Technologies to integrate disparate data sources into a single cloud-based platform enabling both technical and non-technical users to directly access and analyze data. Methods: Through a highly iterative, collaborative process between clinical/research users, IT experts and Palantir engineers, 150 deidentified datasets were integrated from the existing data warehouse, NLP, molecular reports, public data and manually curated data, representing data from > 1.5 million patients. Data integration was validated and feedback from clinical users gathered. Results: In addition to centralizing data, the platform was found to: (1) Make data accessible to non-technical users by mapping data to real-world concepts, (2) Create reports backed by live data, with clear visibility into inputs, analysis and history, (3) Create templates for common analytical workflows (e.g. KM curve), and (4) Support increased collaboration through transparent, secure access controls. This resulted in dramatic acceleration of cohort identification, data extraction, and outcomes analyses. Conclusions: Integrating siloed data exposed gaps and errors arising from the unstructured nature of medical data and use of NLP. In response, we are piloting a combination of (1) Purposeful structured data capture at the time of care, (2) Use of logic to suggest commonly uncaptured but critical patient events such as progression, and (3) Auditing functionality to allow users to manually fill in gaps and correct data in a transparent manner. Expanding the data foundation unlocks the potential for more advanced research, fueling scientific discovery, while enhancing the quality and safety of patient care.
Proof-of-concept study evaluating a new tool for standardizing radiological assessment of tumor response to treatment in routine clinical practice.
Authors: Mastier Charles , De La Fouchardiere Christelle , Heudel Pierre-Etienne , Fayette Jerome , Sarabi Matthieu , Banaste Nathan , Barma Marion , mercier-Bischoff Elodie , Brahmi Medhi , Cassier Philippe Alexandre , Garin Gwenaelle , Pérol David , Pilleul Frank , Blay Jean-Yves
Published: May 2019

e18079

Background: Internationally recognised criteria to evaluate tumour response, such as Response Evaluation Criteria In Solid Tumors (RECIST) and iRECIST (for immunotherapeutics) are not widely used in clinical practice. The main reason is that communications amongst health professionals are insufficiently standardised. To this purpose, ON’COHUB (MIRIO in France), a newly developed tool, automatically streamlines interactions between oncologists and radiologists to optimise and facilitate response evaluation according to the standard criteria. This study aims to identify the benefits in terms of user satisfaction and to provide preliminary data for the standardisation of the tool. Methods: Five oncologists, 3 radiologists, 1 clinical research associate and 1 clinical project officer used ON’COHUB to assess patients’ tumour responses according to RECIST, in an anti-cancer center, over five months. An oncologist compared patients’ regular radiology reports (n = 110) and ON’COHUB’s reports (n = 106), using the following report quality indicators: information on the patient’s context, target and non-target lesions , baseline, NADIR, and overall evaluation. Then a questionnaire on the user’s satisfaction was administered. Two-tailed chi-square tests were performed to compare patients’ regular radiology reports and ON’COHUB’s reports. Results: ON’COHUB was reported to significantly improve the following quality indicators compared to regular reports: presence of the treatment (99% vs 42%; p < 0,001), follow-up criteria (98% vs 5%; p < 0,001); target lesion and location (100% vs 75%; p < 0,001), size of target lesions (99% vs 67%; p < 0,001), value and date of the baseline (100% vs 0% and 4%, respectively; p < 0,001 for both), value of the baseline lesion by lesion (99% vs 4%; p < 0,001), value and date of the Nadir (97% vs 0%; p < 0,001), global response according to RECIST (100% vs 17%; p < 0,001), value of target lesions response (80% vs 20%; p < 0,001), referential for RECIST calculation (98% vs 2% p < 0,001).Finally, 9 out of the 10 users declared that they would use ON’COHUB on a daily basis. Conclusions: These preliminary data suggest that ON’COHUB may have a positive impact on the quality of the treatment response evaluation in clinical trials and in routine use. These results will be confirmed with the deployment of the interoperability with IT hospital System.
An evaluation of artificial intelligence-based clinical decision supports use in Brazil.
Authors: Rocha Hermano Alexandre Lima , Dankwa-Mullan Irene , Juacaba Sergio Ferreira , Preininger Anita , Felix Winnie , Thompson Julie V , Bright Tiffani , Jackson Gretchen Purcell , Meneleu Pedro
Published: May 2019

e18081

Background: The Instituto do Câncer do Ceará (ICC), a 160-bed oncology hospital located in Brazil, serves approximately 23,000 patients monthly. In December of 2017, ICC implemented Watson for Oncology (WFO), an artificial intelligence (AI)-based clinical decision-support (CDS) tool to help enhance personalized cancer care. As of December 2018, 903 cases involving mainly breast, prostate and gastric cancers were entered in WFO. The purpose of this study was to investigate how implementation of WFO and use by oncologists affects clinical decision-making and workflow. Methods: 7 oncologists who employed WfO during and after the patients’ first visit were recruited to complete a survey regarding usability, decision-making and workflow. The group consisted of 1 urologist, 3 gastric surgeons, 1 gynecologist, 1 breast surgeon, 1 head-neck surgeon. Survey questions integrated the CDS Five Rights framework. Results: Most oncologists agreed that WFO is easy to understand and provides complete, relevant and actionable information at an appropriate time (Table). Opinions on the impact on treatment decisions varied. 71.4% expressed positive statements (agree or strongly agree) pertaining to the use of WFO. Conclusions: In this study, oncologists felt WFO met 5 Rights expectations for CDS; 57% felt that WFO exceed expectations. Further research is needed to understand how variation in experience affects decision impact. [Table: see text]
Artificial intelligence (AI) to improve patient outcomes in community oncology practices.
Authors: Frownfelter John , Blau Sibel , Page Ray D. , Showalter John , Miller Kelly , Kish Jonathan , Valley Amy W. , Nabhan Chadi
Published: May 2019

e18098

Background: Artificial Intelligence(AI) for predictive analytics has been studied extensively in diagnostic imaging and genetic testing. Cognitive analytics adds by suggesting interventions that optimize health outcomes using real-time data and machine learning. Herein, we report the results of a pilot study of the Jvion, Inc. Cognitive Clinical Success Machine (CCSM), an eigen vector-based deep learning AI technology. Methods: The CCSM uses electronic medical record (EMR) and publicly available socioeconomic/behavioral databases to create a n-dimensional space within which patients are mapped along vectors resulting in thousands of relevant clusters of clinically/behaviorally similar patients. These clusters have a mathematical propensity to respond to a clinical intervention which are updated dynamically with new data from the site. The CCSM generates recommendations for the provider to consider as they develop a care plan based on the patients’ cluster. We tested and trained the CCSM technology at 3 US oncology practices for the risk (low, intermediate, high) of 4 specific outcomes: 30 day severe pain, 30 day mortality, 6 month clinical deterioration (ECOG-PS), and 6 month diagnosis of major depressive disorder (MDD). We report the accuracy of the CCSM based on the testing and training data sets. Area under the curve (AUC) was calculated to show goodness of fit of classification models for each outcome. Results: In the training/testing data set there were 371,787 patients from the 3 sites: female = 61.3%; age ≤ 50 = 21.3%, 51-65 = 26.9%, > 65 = 51.9%; white/Caucasian = 43.4%, black/African American = 5.9%, unknown race = 43.4%. Cancer types were unknown/missing for 66.3% of patients and stage for 90.4% of patients. AUC range per vector: 30 day severe/recurrent pain = 0.85-0.90; 30-day mortality = 0.86-0.97; 6-month ECOG-PS decline of 1 point = 0.88-0.92; and 6-month diagnosis of MDD = 0.77-0.90. Conclusions: The high AUC indicates good separation between true positives/negatives (proper model specification for classifying the risk of each outcome) regardless of the degree of missing data for variables including cancer type and stage. Following testing, a 6 month pilot program was implemented (06/2018-11/2018). Final results of the pilot program are pending.
Patient’s insurance status impact on biomarker testing in the United States market.
Authors: Winkelman Daniel F. , Forouzan Amir , Lavin Mike , Tangudu Tanuja , Custer Kristopher , Kachadourian Anise
Published: May 2019

e18114

Background: Precision medicine in cancer treatment is driven by biomarker testing. If a patient is not biomarker tested, he or she may not receive access to targeted therapies that often offer greater efficacy. The purpose of this research study is to examine the insurance type of patients that are untested for biomarkers in the United States. Methods: BrandImpact is a longitudinal panel of 450 Oncologists who continuously report cancer treatment decisions from the point-of-care. The BrandImpact data set includes 60,465 patient visits reported in 2018. This study followed market research best practices. This research included visits by patients diagnosed with metastatic: NSCLC, melanoma and ovarian cancer who were either tested or untested for the following biomarkers: EGFR, ALK, ROS1, PD-L1, BRAF and BRCA. Results: The baseline measure for this analysis is that 18% of the patient visits reported that were not biomarker tested. The table at the end of document outlines the untested patient visits by insurance type for comparison purposes. Conclusions: The rate of biomarker testing for metastatic cancer patients treated by Oncologists differs by insurance type. Patients with Medicare Only insurance (25%) are untested at a statistically significantly higher rate than the baseline All category. It should be noted that patients without insurance or who were cash-paying had the highest rates of being non-biomarker tested. It is recommended that further research be conducted into the reasons behind the significantly higher rate of non-testing for Medicare Only patients. It seems counter intuitive that this patient population is treated less than optimally due to limited access to targeted therapies. [Table: see text]
Biomarker testing, treatment (Tx) and survival outcomes in Medicaid compared to commercially insured (CI) patients with advanced NSCLC (aNSCLC).
Authors: Yim Yeun Mi , Wu Ning , Wong William Bruce
Published: May 2019

e18119

Background: Prior studies suggest cancer patients with Medicaid may have worse outcomes, however there is limited understanding on the drivers behind these observations. This study aimed to describe the association between insurance type with Tx patterns, biomarker testing, and survival outcomes in a real-world aNSCLC population. Methods: The Flatiron Health EHR-derived database was used to identify patients < 65 years of age diagnosed with aNSCLC between 1/1/2011 to 10/31/2018. Logistic regression was used to assess the association between insurance type and (1) the likelihood of receiving first-line Tx of cancer immunotherapy (CIT)/other targeted therapy, or no Tx, and (2) the likelihood of receiving EGFR/ALK testing. Median OS, estimated by Kaplan Meier, was compared between patients with CI and Medicaid coverage, and hazard ratios were derived from Cox proportional hazard models adjusting for baseline characteristics. Results: 6639 aNSCLC patients were identified with CI (n = 6022) and Medicaid (n = 617). After adjusting for baseline characteristics, Medicaid patients were less likely to receive ALK or EGFR testing [OR 0.59, 95% CI (0.49, 0.72)]. Medicaid patients were also less likely to receive CIT or targeted therapy [OR 0.49, 95% CI (0.36,0.67)] and more likely to not receive any systemic Tx [OR 1.45, 95% CI (1.22, 1.73)]. Medicaid patients had a higher risk of death than commercially insured patients, however this difference varied by Tx group (table). Conclusions: Medicaid insured patients were associated with a higher risk of mortality compared to CI patients. Factors influencing this difference may be access to biomarker testing, subsequent receipt of CIT/targeted therapy and differences in care among untreated patients. [Table: see text]
Lower survival outcomes in patients receiving an initial cancer diagnosis after presenting to the emergency department.
Authors: Conley Hannah L. , Delgado Raven V. , McCallen Justin D. , Harris Eleanor Elizabeth , Ju Andrew Wenhua , Rathbun Kimberly
Published: May 2019

e18122

Background: Survival outcomes in cancer are better in patients who are diagnosed at an early stage, which can potentially be detected through screening and routine visits to a primary care physician. Patients who receive their initial cancer diagnoses following a visit to the Emergency Department (ED) may present at a later Stage when survival outcomes are worse. The characteristics of patients who receive their diagnosis following an ED visit versus those who do not are not well reported in the literature. Methods: A retrospective review was conducted in which a cohort was identified of all patients who presented to the ED in a hospital system in eastern North Carolina from 10/1/2014 to 9/30/2015 with a visit associated with an oncologic ICD-9 code. The chart was reviewed to determine if the initial results that directly led to the cancer diagnosis were obtained through the ED visit. Patient characteristics, cancer characteristics, and survival outcomes were collected. Factors significant on univariate analysis were included in a multivariate analysis. Chi-square tests, Kaplan-Meier log rank tests, and Cox regression analysis were used. Results: Initial diagnosis through the ED was recorded in 38.5% of patients (n = 400/1039). Median overall survival following diagnosis was lower in individuals diagnosed through the ED (13 vs. 41 months, p < 0.001), in men (21 vs. 35 months, p < 0.001), and in patients with a Charlson Comorbidity Index (CCI) of ≥9 (18 vs. 37 months, p < 0.001) on univariate analysis. Patients diagnosed through the ED were more likely to be Stage IV (p < 0.001). There was no association on multivariate analysis between the rate of diagnosis through the ED or overall survival with insurance status or race; however, it was difficult to determine the insurance status of a patient at the time of the initial ED visit, possibly due to retroactive coverage and other issues. Conclusions: Patients who received a cancer diagnosis through the ED have significantly shorter overall survival times from diagnosis. This remained significant when controlling for CCI, gender, age, and Stage. Further investigation into the public health factors that may contribute to patients receiving their cancer diagnosis in the ED is needed. A prospective study may be needed to record the insurance status at the initial ED visit.
Prescription patterns and associated cost during periods of cancer drug stockouts in a resource-limited setting.
Authors: Davey Sonya , Grover Surbhi , Setlhako Dipho Irene I , Ralefala Tlotlo Bathethi , Manshimba Patrick , Gross Robert , DeMichele Angela , Shulman Lawrence N. , Martei Yehoda M. , Bilker Warren B.
Published: May 2019

e18129

Background: Cancer drug stockouts occur at high frequencies globally, however their clinical effects are understudied in sub-Saharan Africa (SSA). We aim to describe prescription patterns and cost of systemic chemotherapy in cancer patients in Botswana during periods of stockout. Methods: Using a retrospective cohort study of the ten most common solid tumor malignancies treated with systemic chemotherapy at Princess Marina Hospital (PMH), Gaborone in 2016, we conducted a subset analysis of suboptimal events, defined as a cycle with ≥ 7 days delay or therapy switch from initiated guideline regimen, that occurred during drug stockout vs non-stockout periods. We estimated financial cost of therapy per cycle using Management Sciences for Health International Price Indicator Guide. Chi-squared and Wilcoxon rank sum were used for comparisons. Results: 167/378 patients contributed to 320 suboptimal events. 63% (201/320) of events occurred during a drug stockout, of which 43%, 43% and 14% were delays, switches, or both, respectively. There were significantly more delays (56% vs 44%, p < .0001) and switches (75% vs 26%, p < .0001) during stockout periods vs no stockout. The majority of switches during drug stockouts occurred in breast cancer patients receiving curative therapy: 48% (20/42) were “paclitaxel + trastuzumab” ($4673) to “paclitaxel alone” ($35) in HER2 positive patients resulting in a 99% cost decrease; and 29% (12/42) were paclitaxel ($35) to docetaxel ($108) resulting in a 209% cost increase per cycle switched. Colon cancer patients receiving palliative-intent therapy were the second most frequent patients with therapy switches during stockout periods: 42% (8/19) were “capecitabine + oxaliplatin” ($259) to “capecitabine alone” ($105) resulting in a 59% cost decrease. Conclusions: Breast cancer patients form the majority of patients treated with systemic chemotherapy at PMH and experienced the most delays and switches in therapy during drug stockout periods. Changes in drug prescription patterns during stockout periods may be associated with switches leading to inferior but less costly regimens, and in some cases costly regimens with higher toxicity. Interventions that minimize cancer drug stockouts are imperative and further studies to understand impact of stockout on survival are needed in SSA.
Participation of African Americans in clinical trials supporting FDA approval of cancer drugs.
Authors: Al Hadidi Samer , Mims Martha P. , Miller-Chism Courtney Nicole , Kamble Rammurti T.
Published: May 2019

e18135

Background: African Americans comprise 12% of the total United States population. Lifetime probability of developing cancer in African Americans is 37.55%. The 5-year relative survival rate is 68% in Caucasians and 61% in African Americans for all cancers combined. Concerns exist that African Americans are underrepresented in trials of cancer medications. We sought to examine African Americans participation for pivotal cancer medications trials submitted to the U.S. Food and Drug Administration (FDA) supporting marketing applications. Methods: On the basis of publicly available FDA reviews, the authors assessed enrollment of African Americans in trials supporting 75 drug approvals from 2014 to 2018. Prevalence-corrected estimates for the participation of African Americans were calculated as the percentage of African Americans among trial participants divided by the percentage of African Americans in the disease population (participation to prevalence ratio [PPR]), with a range between 0.8 and 1.2 reflecting similar representation of African Americans in the trial and disease population. Results: A total of 61763 patients enrolled in clinical trials, which resulted in subsequent FDA approval. The proportion of African Americans enrolled in the clinical trials that led to cancer medication approval in the 5-year period was 7.44%. The calculated PPR for participation of African Americans in clinical trials that led to drug approval for all cancers combined was 0.31. The results were consistent across major cancer subtypes including breast cancer (PPR of 0.29), prostate cancer (PPR of 0.18), and lung cancer (PPR of 0.15). Skin cancer, colorectal cancers and hematological malignancies results were also consistent with low PPR. Conclusions: African Americans were under represented in trials of drugs for all cancer types combined. Efforts should be made to increase the proportion of participation of African Americans in clinical trials.
Expanded access for cancer patients: The 5-year FDA CBER experience.
Authors: Colbert Laronna S. , Bross Peter F. , Liu Ke
Published: May 2019

e18158

Background: Expanded access (EA) refers to the use of an investigational drug when the primary purpose is to diagnose, monitor, or treat a patient’s disease rather than to generate scientific data that is generally derived from clinical trials. FDA has long facilitated expanded access to investigational drugs for patients with serious or immediately life-threatening diseases and who lack therapeutic alternatives. EA requests include single-patient use protocols under existing INDs, single-patient investigational new drug applications (INDs or SPIs), and intermediate-size or treatment protocols/INDs. Methods: We searched the Center for Biologics Evaluation and Research (CBER) internal databases and reviewed all EA requests for cancer patients to receive investigational products regulated by CBER's Office of Tissues and Advanced Therapies (OTAT) from 2014-2018. These products included cellular and gene therapies, cancer vaccines and microbe-based therapies. Results: From 2014-2018, OTAT received 395 EA requests for solid tumor (ST) or hematologic malignancies (HM). One-hundred ninety-seven (197) requests were for individuals who could not be enrolled in an ongoing oncology clinical trial to receive an investigational agent (single-patient use protocols). Of 197 requests, 7 (3%) were either withdrawn or canceled by the treating physicians (sponsors). The remaining 190 (100%) were approved. One hundred seventy-three (173) EA requests, 102 for ST and 71 for HM, came from sponsors to make available to patients an investigational agent for which there were no ongoing clinical trials (SPIs). Of 173 requests, 45 (26%) were withdrawn or cancelled by the sponsors. Of the remaining 128, 127 (99%) were approved. One request was denied. Twenty-five of 395 EA requests were for intermediate-size or treatment protocols/INDs. Conclusions: From 2014-2018 there has been an increase in oncology EA requests for products regulated by CBER/OTAT, which pose unique challenges for evaluating their risks and benefits. Despite the complexities of these novel biological products, nearly all EA requests were approved.
Reassessing existing expanded access programs and planning forward in the time of Right to Try.
Authors: Cropp Anne , Hassan Alita , Alummootil Sarah
Published: May 2019

e18172

Background: Desperately ill patients who have exhausted treatment options often seek access to therapy through investigational therapies. Participation in a clinical trial may be one option. When a clinical trial is not an option, physicians and patients are left with Expanded Access (EA), and Right to Try (RTT). The 21st Century Cures legislation requires pharmaceutical manufacturers to make information on their EA policy, contact information, and response time readily accessible. RTT became law in 2018, and this path is rarely an option. Methods: To determine best practice in the age of changing legislation of pre-approval access to investigational drugs, we compared pathways by which pharmaceutical companies are providing access to investigational medications. Data has been gathered on presentation of policy, intake of expanded access requests, and education to the public on the company’s internal pathway to access. We conducted a survey of the top 100 Pharma companies to assess compliance with regulations, policy availability, and RTT information. Results: The data has shown that companies show a range of compliance in expanded access. Many companies have published all required aspects outlined in the legislation to be fully adherent to the guidelines with additional education and guidelines for patients and physicians. Others have provided the minimum requirement to be compliant: a policy and contact information. We also see companies that have not established a stance of process in expanded access and therefore provide no public facing information on their policy and pathways toward treatment. Information on RTT remained elusive. Conclusions: While RTT is increasingly requested as a possible path, the mechanism to request RTT remains a barrier and source of confusion to physicians and patients. Companies should take the opportunity to clearly define their policy and process for Expanded Access as well as reevaluate the organization of their current procedure to ensure highest efficiency and full compliance with legislation.
Racial and socioeconomic disparities in follicular lymphoma survival.
Authors: Sheppard Richard Stephen , Adekunle Adewumi , Beale Stefani , Ahluwalia Meena
Published: May 2019

e18173

Background: Follicular Lymphoma (FL) is a the second most common Non Hodgkin's Lymphoma (NHL) diagnosed in the United States with 2.6 per 100,000 men and women per year from 2011 to 2015 when age adjusted as per the National Cancer Institute with the number of deaths of 0.5 per 100,000 men and women per year. It known that FL is one of the most clinically indolent NHL and due to this, survival rates are generally more favorable when compared to other B Cell Lymphomas. With this study, we aim to analyse socioeconomic and racial disparities in the survival rates for FL. Methods: The authors identified patients diagnosed with FL between 1973 and 2015 using the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival was estimated and compared between racial/ethnic groups using the log-rank test. Our outcome variables were 1-year, 5-year and mortality. Our independent variables were race and socioeconomic status. We controlled for age, demographic characteristics, time of diagnosis, pathological classification, treatment and socioeconomic status. Results: A total of 66 127 patients were identified; 90% of the patients were White, 4% Black, and 4% Asian. We noted significant differences in disease presentation, socioeconomic status, and outcomes. Asian/Pacific Islander had the lowest survival with a mean of 228 survival months, Blacks had a mean survival months of 237, and Whites had a mean survival months of 234. Conclusions: Disparities exist in the care and outcomes of FL. A low socioeconomic status is correlated with decreased survival.
Risk of neutropenia-related hospitalization (NRH) related to duration of short-acting granulocyte colony stimulating factor (sG-CSF) for primary prophylaxis.
Authors: Li Shuling , Liu Jiannong , Gong Tingting , Guo Haifeng , Gawade Prasad L. , Kelsh Michael Anthony , Bradbury Brian D. , Belani Rajesh , Lyman Gary H.
Published: May 2019

e18181

Background: In clinical trials, efficacy of 1011 days of primary prophylactic (PP) sG-CSF is similar to a single dose of pegfilgrastim for preventing febrile neutropenia (FN). However, most patients receive < 10 days of PP sG-CSF in clinical practice. This study assessed the effect of PP sG-CSF duration on the risk of NRH. Methods: Using Medicare 20% sample data, we conducted a nested case-control study within a cohort of patients aged ≥66 y with breast, colorectal, lung, ovarian, or prostate cancer or NHL who initiated first cycle of chemotherapy 1/1/20089/30/2016, had ≥1 y continuous coverage in Medicare parts A and B before cycle day 1 (baseline), and received PP sG-CSF. We identified NRH cases (ICD-9, 288.0X; ICD-10, D70.X) from cycle day 5 to end of cycle 1. We matched each case to up to 4 controls based on age (± 1 y), tumor type, regimen risk for FN (intermediate/high [ > 10%], other), and year using incidence density sampling. Duration of sG-CSF (days of use from cycle day 1 to the day before case date) was categorized as < 5 and ≥5 days. We used conditional logistic regression adjusted for race, sex, and Charlson comorbidity index (CCI) at baseline to estimate relative risk of NRH related to duration of sG-CSF. Results: Of 1431 patients receiving PP sG-CSF, 68 cases matched 231 controls. Cases were similar to controls in age (76 vs 75 y), tumor type (NHL, 62% vs 62%; lung cancer, 25% vs 25%), intermediate-/high-risk regimen (65% vs 67%), and male sex (50% vs 48%) but had slightly higher CCI (3.9 vs 3.3). The percentage of patients with ≥5 days of PP sG-CSF use was 26% in cases and 41% in controls. The adjusted OR (95% CI) for NRH was 0.48 (0.250.93) for ≥5 vs < 5 days of PP sG-CSF; results were consistent across sensitivity analyses (Table). Conclusions: Among elderly cancer patients receiving PP sG-CSF, ≥5 days of sG-CSF use was associated with substantial reduction in the risk of NRH.[Table: see text]
Upper extremity deep venous thrombosis in 10 common malignancies: Analysis of incidence, risk factors, and effect on mortality from the California Cancer Registry.
Authors: Poh Christina , Brunson Ann , Mahajan Anjlee , Keegan Theresa , Wun Ted
Published: May 2019

e18190

Background: Upper extremity deep venous thrombosis (UE DVT) is a known complication in patients with cancer. However, the cumulative incidence by cancer type, risk factors associated with UE DVT and impact on survival is not well-described. Methods: Using the California Cancer Registry , we identified patients with 10 common malignancies (2005-2014) and linked this to the California hospitalization and emergency department databases to find patients with an incident UE DVT event using specific ICD-9-CM codes. We determined cumulative incidence of UE DVT adjusted for the competing risk of death. Using Cox proportional hazards regression, stratified by tumor type and adjusted for other prognostic covariates including central venous catheters (CVC), we identified risk factors for developing UE DVT and the impact of UE DVT on overall survival. Patients with venous thromboembolism prior to malignancy diagnosis were excluded. Results: Among 785,444 patients with malignancy, 6,099 (0.8%) had an incident UE DVT. The 24-month cumulative incidence of UE DVT varied by cancer type (Table). Most UE DVT (62.2%) occurred in patients with CVC. VTE after cancer diagnosis and CVC substantially increased the risk for UE DVT across all cancers. UE DVT was also associated with worse overall survival for all malignancies with hazard ratios ranging from 1.52 to 3.72. Conclusions: UE DVT is a rare but important complication among patients with malignancy, with incidence highest in leukemia and lowest in prostate cancer. Although uncommon, UE DVT may affect prognosis in patients with malignancy as it is associated with an increased hazard of death. Table: 24-month cumulative incidence of UE DVT, adjusted for the competing risk of death, in 10 common malignancies among California cancer patients, 2005-2014. [Table: see text]
Factors associated with receipt and overall survival of concurrent chemoradiotherapy versus single modality therapy in unresectable stage III NSCLC.
Authors: Gomez Jorge E. , Ryan Kellie , Bobbili Priyanka J. , Dua Akanksha , DerSarkissian Maral , Duh Mei Sheng
Published: May 2019

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Background: While concurrent chemoradiotherapy (cCRT) is standard of care for patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC), some pts receive single modality therapy. This study identified predictors of therapy and differences in overall survival (OS) in a Medicare population. Methods: This retrospective study used Surveillance, Epidemiology and End Results -Medicare data (2009-2014). Stage III NSCLC pts aged ≥65 yrs, with ≥1 claim for systemic therapy or radiotherapy (RT) within 90 days of diagnosis were included. cCRT pts had overlapping claims for chemotherapy and RT ≤90 days from start of therapy; remaining pts were grouped by first therapy received. Sequential CRT patients and those with surgical resection of tumor were excluded from this analysis. Logistic regression was used to analyze predictors of cCRT. Multivariable Cox proportional hazards models were used to compare OS between therapies. Results: Of 4,544 pts identified, 51% received cCRT, 21% systemic therapy, and 27% RT. Across groups, cCRT patients were likely younger (p < 0.001), White (p < 0.001), male (p = 0.015), and with a good predicted performance status (PS) (p < 0.001). After adjustment, several variables were predictive of receiving cCRT (Table). Median OS was 14.7 months (mo) for cCRT vs. 10.9 mo for systemic therapy (adjusted hazard ratio [HR]: 1.36, 95% CI: 1.24-1.49, p < 0.001) vs. 7.8 mo for RT (adjusted HR: 1.55, 95% CI: 1.42-1.69, p < 0.001). Conclusions: Only 51% of pts received cCRT. Age, race, stage, PS and comorbidity index were predictive of cCRT. Given the survival benefit, physicians should be encouraged to pursue cCRT in all eligible pts. Further efforts to develop less morbid therapies are critical in this population. [Table: see text]
Gastrointestinal symptoms and diagnosis preceding ovarian cancer diagnosis: Delays in diagnosis and resulting effects on treatment allocation.
Authors: Chase Dana Meredith , Harrow Brooke , Perhanidis Jessica , Monk Bradley J.
Published: May 2019

e18195

Background: Ovarian cancer (OC) has a very poor clinical prognosis, with an average 5-year survival rate of < 50%. Symptoms indicating OC are often nonspecific and overlap with gastrointestinal (GI) diagnosis (eg, gastroesophageal reflux disease [GERD], diverticulosis, irritable bowel syndrome [IBS]). Thus, OC diagnosis can be difficult, with most cases diagnosed at an advanced stage. This study examined whether women with a prior GI diagnosis are more likely to undergo neoadjuvant chemotherapy (CT) as their initial OC treatment modality compared to those without a prior GI diagnosis who may be likely candidates for primary debulking surgery (PDS). Methods: This retrospective study identified patients with newly diagnosed OC in the United States from January 2014–July 2018 using MarketScan Commercial and Medicare Supplemental Databases. Analysis was limited to women with commercial or Medicare coverage for ≥12 months before and ≥1 month after the index date (defined as the earliest date of an OC diagnosis or surgery) who underwent CT or PDS. Patients with GI symptoms were identified by diagnosis codes from claims in the year before the OC index date. Logistic regression analysis was used to test the hypothesis that women with a prior GI diagnosis are diagnosed with more advanced OC as signaled by their initial OC treatment (CT vs PDS) compared to women without a prior GI diagnosis. Results: Of the 5865 patients with OC identified, 23% had a diagnosis of ≥1 of the following GI disorders before their OC diagnosis: IBS, inflammatory bowel disease, diverticulosis, and GERD. Of these patients, 40% and 60% had GI disorders that occurred 6–12 months before and < 6 months before their OC diagnosis, respectively. Women with a GI diagnosis were more likely to undergo CT versus PDS as their first OC treatment (odds ratio [OR], 1.37; P < 0.0001), even when controlled for age, region, insurance plan type, and index year (OR, 1.23; P = 0.0021). Conclusions: In this administrative claims database, nearly one-quarter of women with OC had a prior GI diagnosis within the past year and were at greater odds of being diagnosed with more advanced disease requiring CT prior to surgical intervention.
Patient characteristics, treatment received, and outcomes of non-metastatic breast cancer patients in Haiti: Report from retrospective cohort.
Authors: Fadelu Temidayo , Damuse Ruth , Pecan Liz , Dubuisson Cyrille , Greenberg Lauren , Danjoue Satyre , Lormil Joarly Kerwick , Rebbeck Timothy , Shulman Lawrence N.
Published: May 2019

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Background: Few studies have reported outcomes of breast cancer (BC) patients in Haiti. Since 2013, University Hospital Mirebalais, a tertiary government hospital, has offered treatment for BC, in partnership with Dana-Farber Cancer Institute and Zanmi Lasante, a Haitian non-profit. Standard chemotherapy and hormone therapy are available, but HER2 therapies and radiation are not. Here, we comprehensively describe patient characteristics, treatments delivered and outcomes of non-metastatic BC patients in this program. Methods: We conducted a retrospective observational study including 339 patients with non-metastatic BC, who presented between January 1, 2013 and June 30, 2016. We conducted detailed chart abstraction of patient characteristics, clinical diagnostic and treatment data, and outcomes. Our endpoint was disease-free survival (DFS) defined as time from presentation to cancer recurrence, progression or death. We used Kaplan-Meier estimation to plot survival curves, censoring at the time of last follow-up. Log-rank test was used to examine subgroup differences. Results: The median age in the cohort was 49, inter-quartile range of 42 to 58; 35.7% were post-menopausal. Invasive ductal carcinoma was the most common histology (65.5%). At presentation, 52.8% had T3/T4 disease, while 54.6% had locally advanced disease, and 37.5% were poorly differentiated. There was incomplete documentation of stage (18.3%), ER status (44.2%) and histologic grade (39.5%). 156 patients received neoadjuvant therapy with hormonal therapy (26.2%), chemotherapy (67.9%), or both (5.8%), while 227 received adjuvant therapy (25.5%, 26.5% and 48.0% respectively). 275 patients (81%) completed surgical resection. Median follow up time for the cohort was 24.8 months. 23 patients died; 75 had recurrences; and 9 had progression. Median DFS was 50.8 months (95% CI, 40.6 to 57.0). There was no DFS difference by ER status. Median DFS for early-stage patients was not reached compared to locally advanced patients of 40.4 months (95% CI, 34.0 to 49.7), P-value < 0.0001. Conclusions: Non-metastatic BC patients in Haiti present with more advanced disease and have poorer prognostic factors compared to high-income countries. Although these patients have comparatively worse outcome, curative treatment is feasible in Haiti.
Patient-reported disease burden in chronic lymphocytic leukemia, diffuse large B-cell lymphoma, and follicular lymphoma: Results from a national patient advocacy survey.
Authors: Price Mark , Ravelo Arliene , Sae-Hau Maria , Torney Peggy Ann , Gonzalez Victor , Weiss Elisa S , Mansfield Carol , Mange Brennan , Comenencia Ortiz Eydith , Masaquel Anthony , Dawson Keith Lamont
Published: May 2019

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Background: Evaluations of patients’ (pt) burden and priorities are increasingly important as novel treatments are developed. We aimed to better understand pt-reported disease burden in chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL). Methods: We developed a survey to understand pt disease burden, designed in consultation with medical experts, pt advocacy organizations, and survey scientists. Concept elicitation and cognitive pretesting were conducted. The survey was administered electronically to pts who had received either initial or subsequent treatment within the past year and consisted of categorical Likert options that quantified the impact of disease on physical function, sleep, cognition, work, emotional health, and quality of life (QoL). Results: The Leukemia & Lymphoma Society and the Lymphoma Research Foundation recruited 424 pts: 309 with CLL, 59 with DLBCL, and 69 with FL; 51% were female. Mean age was 66 (range: 22–95). Results suggest that pts experience substantial disease burden across all surveyed subtypes. The most noteworthy results are highlighted in the following table that indicates the percentage of pts who agreed or strongly agreed to statements about disease burden. Additionally, large proportions of pts worried about their disease returning or getting worse (72% of pts with CLL, 83% of pts with DLBCL, and 79% of pts with FL), indicating high impact regardless of the indolent or aggressive nature of their disease. Most pts indicated that delaying disease progression was important to them (96% of pts with CLL, 96% of pts with DLBCL, and 92% of pts with FL). Employment status changed for 31% of pts who were working full or part time or on contract because of their diagnosis and treatment. Conclusions: Pts with CLL, DLBCL, and FL report experiencing substantial disease burden. Data from studies focusing on pt-reported disease burden can be used for education of the clinical community to address the key concerns of pts.[Table: see text]