bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of MammaPrint test on Chinese patient with breast cancer.
Authors: Tian Chen , Fu Lili , Wei Jiyu , Yin Pengfei , Zhang Henghui
Published: May 2020

e13671

Background: A 70-gene prognosis-signature, known as MammaPrint (MP), is validated as a good predictor of recurrence in patients with ER+/HER2- early stage breast cancer in Europe and America. Previous studies on Japanese and Korean breast cancer patients showed that the proportion of MP Low-Risk tumours is significantly lower than the percentage which reported in previous studies. Here we use MammaPrint to determine the gene profiles of breast cancer tumours from Chinese patients and investigate the test’s potential clinical applications. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumour samples or fresh tumour samples from 594 eligible breast cancer patients were collected from 97 hospitals in China. Tumor RNAs were isolated from samples and analyzed using RNA sequencing technology. Clinical risk was categorized based on the Adjuvant! algorithm as used in the MINDACT trial. Concordance between risk predicted by the MammaPrint and clinical characteristics were evaluated. We also analyzed the clinical-pathology features of patients and compared them to previous studies. Results: Overall, 315 patients were categorized as clinical high risk (182 were MP Low-Risk and 133 MP High-Risk), while 279 patients were categorized as clinical low risk (203 were MP Low-Risk and 76 MP High-Risk). The concordance rate between risk predicted by the MammaPrint and clinical characteristics was 56.57%. Among the clinical-pathology features, age, ER/PR/HER2 status, tumour grade and tumour size were significantly related to the genomic risk (p = 0.009, 0.003, < 0.001, 0.001, < 0.001, and 0.007 respectively). Conclusions: The proportion of MP Low-Risk tumours was 64.81%, which is similar to previous validated studies in Europe and America. Of the patients that were clinical high risk, 58% was categorized as MP Low-Risk, and this group of patients may have limited benefit from chemotherapy. Our results indicate that MammaPrint is applicable to Chinese patients and has potential value in clinical practice to avoid over-treatment.
Characteristics of probands with mutations predisposing to gynecologic cancers enrolled in a facilitated cascade testing protocol.
Authors: Hwang Kristina , Baumann Katherine , Brodsky Allison , Lutz Kathleen , Gerber Deanna , Martineau Jessica , Ginsburg Ophira M. , Smith Julia Anne , Levine Douglas A. , Pothuri Bhavana
Published: May 2020

e13682

Background: We sought to evaluate the feasibility of obtaining genetic testing (GT) for first- or second-degree (1°, 2°) family members of a proband known to have actionable germline mutation associated with endometrial and/or ovarian cancer through a coordinated referral system. Here we characterize the initial probands and discuss the time frame of their enrollment in facilitated cascade testing (CT). Methods: Patients with pathogenic mutations associated with gynecologic cancers were determined from cancer genetics and gynecologic oncology clinics. Consenting patients completed a RedCap survey on personal cancer history and history of GT. They were then asked to contact 1° and/or 2° relatives regarding their GT results. Relatives were advised to contact our team. Relatives who consented to the study were referred for GT and contacted for follow up to ascertain whether they received GT and/or took action to reduce cancer risk. Results: From 3/2019- 1/2020, this study has accrued 39 probands. The median age was 39 years (range: 25-68). The most commonly expressed gene mutations were BRCA1 or BRCA2 (87.18%, n=34). Other mutations included BRIP1, MLH1, MSH2, MSH6, and PMS2. The majority (62%) of probands had no personal history of cancer. Among those who had a history of cancer (n=15), 80% had breast and/or ovarian cancer, and 80% reported their genetic mutation was discovered at or after the time of their cancer diagnosis. Median age at time of enrollment in CT was 49 years (range: 29-66) for patients with a history of cancer and 32 years (range: 25- 68) for those without, (p=0.009). Among all probands, the median time between mutation identification and enrollment in CT was 2 years (range=0 to 11). There was no significant difference in time between mutation identification and enrollment in CT when comparing those with and without cancer histories (p=0.5). Conclusions: These results suggest that patients with pathogenic mutations predisposing to gynecologic cancer are willing to undergo CT even if they have no personal history of cancer. Patients with a history of cancer tend to be older at time of enrollment in CT, likely because most discover their genetic mutation at or after the time of cancer diagnosis. With an average of 2 years elapsed between time of mutation identification and enrollment in CT, there is need for expansion of CT accessibility. Increased education and awareness among patients and providers in identifying those who may benefit from CT, screening, and risk reducing surgery to prevent cancer is needed.
Role of technology in a prospective surveillance and early intervention model for preventing lymphedema: The RE-AIM framework.
Authors: Stolldorf Deonni , Koelmeyer Louise , Boyages John , Nelms Jerrod , Gaitatzis Katrina , Ridner Sheila H.
Published: May 2020

e14005

Background: Translation of research derived technology into busy clinical practice can be difficult. The effectiveness of technology translation can be assessed by applying the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) evaluation framework. Methods: The RE-AIM evaluation framework was applied to the use of bioimpedance spectroscopy (BIS) in the prospective surveillance and early intervention model of care for breast cancer survivors at risk of arm lymphedema. Data was obtained during an interim analysis from four hospital sites (public and private settings) in Australia who were participating in the PREVENT international study. Women with breast cancer were monitored for lymphedema from a pre-treatment baseline and at regular intervals for a minimum of 12-months. Results: Each of the RE-AIM framework components were evaluated at patient, practitioner and institutional levels. Patients in both public (n = 50) and private settings (n = 61) were Reached with BIS technology which demonstrated Effectiveness of early surveillance with 16 participants being identified for an early prevention intervention. Each of the four sites Adopted the use of BIS technology using various Implemented strategies like education of all stakeholders and development of referral and care pathways. Adherence rates for mandatory study visits was 88. 48% for the prospective surveillance and the early intervention model of care group and were Maintained for a minimum 12 months following completion of the recruitment phase of the study. Conclusions: The effectiveness of using a technology such as BIS in a prospective surveillance and early intervention model of care in breast cancer in both public and private settings has been demonstrated using the RE-AIM framework. The translation of research into clinical practice has been successfully achieved with the PREVENT study. Clinical trial information: NCT02167659.
Improving provider practice patterns in ordering FDG PET/CT for breast cancer patients at a safety-net hospital.
Authors: Abolghasemi Daria , Ho Tran , Short Jennifer , Subhedar Preeti , Okoli Joel , Gogineni Keerthi , Lin Jolinta Y , Yu David S. , Carter Teralyn , Yang Steven , Gabram Sheryl G. A.
Published: May 2020

e14027

Background: Accurate staging is critical in determining treatment strategies in the management of breast cancer (BC) patients. FDG PET/CT is used to identify the presence of metastatic disease. The criteria for FDG PET/CT utilization is variable, including in any patient with nodal positivity, any patients with systemic symptoms, to those with Stage III disease or higher.. This practice variation has results in different patterns of ordering FDG PET/CT. The preliminary results of a Quality Oncology Practice Initiative (QOPI) audit performed in our Cancer Center in 2017 prompted concern for the over utilization of FDG PET/CT in our BC patients. We performed an initial audit of these practices in 2017 and confirmed these findings. The goal of this study was to re-measure our adherence to NCCN guidelines in 2019 after an educational session complimented by use of a checklist. Methods: A retrospective review was conducted for all BC patients who had FDG PET/CT ordered as initial treatment planning from 1/2017-12/2017. This revealed a 33% rate of failure to meet NCCN guidelines. We then educated our team about the NCCN guidelines for initial PET/CT ordering during our weekly multi-disciplinary conferences, created a test ordering checklist and compared the effect of this education on the use of PET/CT in patients treated at our institution from 1/2019-12/2019. Results: 65 female BC patients had an FDG PET/CT ordered to assist in initial treatment recommendation in 2017. Overall, 66.2% (n = 43) of patients met NCCN indications while 33.8% (n = 22) did not. In comparison to 2017 data, 71 female breast cancer patients had an FDG PET/CT ordered in 2019. Overall, 67 patients (94.4%) met NCCN criteria indications for undergoing FDG PET/CT while only 5 patients (5.6%) did not. Conclusions: Review of FDG PET/CT scans ordered for initial treatment in 2017 revealed that about one third of scans were ordered outside of NCCN guideline recommendations. After an educational session and implementation of a test ordering checklist, we found a marked reduction in the use of FDG PET/CT outside of NCCN guideline recommendations. Although our study is limited by small sample sizes, we identified a practice area that deviated from national recommendations and were able to improve our internal compliance in national guidelines through education and system modification.
Development and validation of a new clinical prediction model of catheter-related thrombosis in cancer patients.
Authors: Liu Binliang , Xie Junying , Sun Xiaoying , Wang Yanfeng , Yuan Zhong , Liu Xiyu , Huang Zhou , Wang Jiani , Mo Hongnan , Yi Zongbi , Guan Xiuwen , Li Lixi , Wang Wenna , Li Hong , Ma Fei , Zeng Yi-Xin
Published: May 2020

e14031

Background: The central venous catheter brings convenience for drug delivery and improves comfort for cancer patients, it also causes serious complications. The most common one is catheter-related thrombosis (CRT). This study aimed to evaluate the incidence and risk factors of CRT in cancer patients, and to develop an effective prediction model for CRT in cancer patients. Methods: The development of our prediction model was based on the data of a retrospective cohort (n = 3131) from National Cancer Center. The validation of our prediction model was done in a prospective cohort from National Cancer Center (n = 685) and a retrospective cohort from Hunan Cancer Hospital (n = 61). The predictive accuracy and the discriminative ability were determined by the receiver operating characteristic curves and calibration plots. Results: Multivariate analysis demonstrated that sex, cancer type, catheter type, position of the catheter tip, chemotherapy status, and antiplatelet/anticoagulation status at baseline were independent risk factors for CRT. The area under receiver operating characteristic (ROC) curve of our prediction model was 0.741 (CI: 0.715-0.766) in the primary cohort; 0.754 (CI: 0.704-0.803) and 0.658 (CI: 0.470-0.845) in validation cohorts respectively. Good calibration and clinical impact were also shown in primary and validation cohorts. The high-risk group had a higher incidence of CRTs than the low-risk group in the primary cohort and two validation cohort (p < 0.001). Conclusions: Our model is a novel prediction tool for CRT risk which helps to assigning cancer patients into high-risk or low-risk group accurately. Our model will be valuable for clinicians in decision making of thromboprophylaxis.
Predictors of electronic patient-reported outcomes use in the survivorship setting.
Authors: Thom Bridgette , Corcoran Stacie , Lavery Jessica A. , Sarpong Leon , Woodside Alexandria , Korenstein Deborah
Published: May 2020

e14038

Background: Patient-reported outcomes (PRO) offer insight into patient perception of health and symptom burden. Despite a shift toward electronic PRO (ePRO), optimal administration methods are unclear. Our institution recently began ePRO collection in survivorship clinics: patients are invited via email to complete a health survey on our online patient portal prior to annual visits, enabling clinician review of symptoms in advance of the visit. Patients who do not complete an ePRO survey at home are offered an iPad or paper survey at visit check-in. In the first year of ePRO, 87 patients inadvertently submitted multiple responses to the questionnaire, across two modalities. This study aimed to 1) assess determinants of ePRO completion across modalities (portal, iPad, paper); and, 2) among patients who submitted multiple surveys, compare consistency of responses in surveys completed within 30 days of each other. Methods: We reviewed records for 10194 patients seen in breast, thoracic, colorectal, and gynecologic survivorship clinics over one year. Demographics, disease/treatment details, and PRO responses (symptoms, health behaviors, etc.) were extracted. For aim 1, we used multivariate regression to determine predictors of completion method. For aim 2, we calculated Cohen’s kappa coefficients to compare responses based on completion modality. Results: Most patients (65.6%) completed the survey on an iPad in clinic; 16.7% on the portal, 17.7% on paper in clinic. Younger age (p < .001), white race (p < .001), less fatigue (p = .01), and English as primary language (p < .001) were associated with portal use in multivariate analyses. In general, Cohen’s Kappa analyses revealed high agreement between surveys. Conclusions: Our findings highlight demographic gaps in ePRO acceptance. Although most patients completed an ePRO (portal or iPad), few completed it at home in advance of their visit, which has implications for clinic flow and clinician preparation for visits. However, our finding of consistent symptom reporting across mode and location of completion is reassuring. Future work should seek to improve comfort with ePRO completion at home among groups less likely to accept it and explore the implications of symptom burden on ePRO acceptance.
Multistate Markov modelling of long-term outcomes in immunotherapy for metastatic renal cell carcinoma (mRCC) using machine-learned dynamic Bayesian networks.
Authors: Gupta Alind , Brenner Darren , Arora Paul
Published: May 2020

e14049

Background: Patient-level heterogeneity in response to treatment remains a major challenge in cancer immunotherapy. Long-term individual-level modelling of survival, tumour response and safety outcomes jointly can help improve efficacy and durable clinical benefits. Machine-learned Bayesian networks provide a solution to the “black box” problem of other machine-learning approaches. Objectives: To develop a dynamic Bayesian network model for multivariate risk prediction, survival modelling and long-term simulations of immunotherapy patients using a simulated trial dataset. Methods: A simulated randomized clinical trial dataset for second line immunotherapy of patients with renal cell carcinoma was used for analysis. We machine-learned a dynamic Bayesian network from censored data with incorporation of prior clinical knowledge. Classification performance, probability calibration, goodness-of-fit metrics and prognostic variables were calculated following TRIPOD guidelines. Results: The machine-learned graphical model encoded expected relationships between variables with minimal prior information. Visual and numerical goodness-of-fit checks for survival extrapolations showed that the model fitted data well and was appropriate. Probability calibration was < 10% from ideal. Classification performance for overall survival was high ( c-statistic ~0.85) soon after treatment initiation and gradually plateaued over time. Prognostic variables were calculated by treatment arm for overall survival and severe adverse events. Conclusions: Dynamic Bayesian network model was useful for transparently representing joint relationships between all variables in the trial dataset, for multivariate risk prediction and long-term extrapolations that can be used in economic evaluations for health technology assessments in oncology.
Electronic patient-reported outcomes (ePROs) and machine learning (ML) in predicting the presence and onset of immune-related adverse events (irAEs) of immune checkpoint inhibitor (ICI) therapies.
Authors: Iivanainen Sanna , Ekström Jussi , Kataja Vesa V , Virtanen Henri , Koivunen Jussi
Published: May 2020

e14058

Background: ICIs have introduced novel irAEs, arising from various organ systems without strong timely dependency on initiation and discontinuation of the therapy. Early detection of the irAEs could result in improved safety profile of the treatment and better quality of life for patients. Symptom data collected by ePROs could be used as an input for ML based prediction models for early detection of irAEs. Methods: The utilized dataset consisted of two data sources. The first dataset consisted of 16 540 reported symptoms from 33 ICI-treated cancer patients, including 18 monitored symptoms collected using Kaiku Health digital platform. The second dataset included prospectively collected irAE data, including initiation and end dates, CTCAE class, and severity of 26 irAEs (the longest irAE lasted 799 days, and the shortest two days while median duration was 61 days). Two ML models were built using extreme gradient boosting, a well-known classification algorithm. Using the ePRO data, the first model was trained to detect the presence and the second model to detect the onset (0-21 days prior to diagnosis) of irAEs. The dataset was split into training (70 % of the data) and test sets (30 % of the data) by random allocation. The test set was left out from the model training and tuning, and was used only to evaluate the model performance. Results: The model trained to predict the presence of irAEs had an excellent performance with the test dataset. The prediction of the irAE onset was more difficult, but the model performance was still at a very good level. The performance metrics for the ML models are presented in Table. Conclusions: Current study suggests that ML based prediction models, using ePRO data as input for the models, can predict the presence and onset of irAEs with high accuracy. Thus, it indicates that digital symptom monitoring combined with ML could enable the detection of irAEs in ICI-treated cancer patients. The results should be validated with a larger dataset from prospective clinical trials. Clinical trial information: NCT03928938. [Table: see text]
Machine learning for prospective identification of immunotherapy related adverse events (irAEs).
Authors: Margalski Daniel , Lycan Thomas , Rajendran Suraj , Topaloglu Umit
Published: May 2020

e14064

Background: The ubiquitous implementation of immunotherapy has significantly improved outcomes in the treatment of cancer patients; however, once rare adverse events from these therapies have increased in lock step. We now face an increased burden of identification on providers with limited experience in the diagnosis of irAEs. We use machine learning to develop prediction models that will aid providers in identifying patients at high risk for developing irAEs as well as for multiple downstream applications. Methods: We have manually extracted progress notes from 462 patients with non-small cell lung cancer treated with immunotherapy who had known irAEÕs, with focus on pneumonitis, colitis, and rash; the most common symptomatic irAEÕs. Labels were applied by clinician review to train the machine learning algorithm to identify the predictive signals at the earliest stage of recognition possible. As a standard Natural Language Processing method, we cleaned the notes to standardize punctuation, numbers and special characters. Next, we created a word embedding matrix utilizing word2vec as well as Google News Vector. Finally, we implemented a Convolutional Neural Network (CNN) on the Microsoft Azure Databricks platform. Due to class imbalance, we deployed a Synthetic Minority Over-sampling Technique algorithm as a correction. We prioritized F1 score in the analysis given the heterogeneity of the data, but will present accuracy, precision and recall as well. Results: We trained our CNN with 10 epochs resulting in an F1 of 0.428, accuracy of 0.895, precision of 0.75 and recall of 0.3. There was no significant difference in results between the word embedding matrices. Conclusions: Using machine learning, we created an algorithm for irAE prediction that was accurate but lacked recall. This will serve as the foundation of implementations including the creation of a clinical decision support tool to guide focused and appropriate treatment of the unique toxicity of irAEs. Although informative as a starting point, this model had a final F1 score that was lower than expected presumably due to class imbalance of input data and the temporal nature of progress notes, which limits the utility of a CNN. Future iterations of the algorithm will include supplementary documentation and implement recurrent neural networks with long short-term memory architecture to address these limitations.
Evaluation of a regularly updated knowledge base for curation of somatic mutations detected in whole exomes of melanoma and lung, colorectal, and breast cancers.
Authors: Yaung Stephanie J. , Li Jian , Pek Adeline , Niu Lili , Palma John F. , Schmid Maximilian
Published: May 2020

e14072

Background: Evolving medical guidelines and complex multi-variant data from next-generation sequencing (NGS) testing of cancer samples make routine clinical interpretation of somatic variants challenging. We assessed the ability of NAVIFY(R) Mutation Profiler*, a CE-IVD somatic variant interpretation tool, to yield accurate time- and geography-specific clinical content on 2511 samples from The Cancer Genome Atlas (TCGA) across six solid tumor types. Methods: Whole exomes from lung adenocarcinoma (n = 469), lung squamous cell carcinoma (n = 325), colon adenocarcinoma (n = 368), rectum adenocarcinoma (n = 149), breast invasive carcinoma (n = 806), and skin cutaneous melanoma (n = 394) cases were analyzed. We utilized TCGA data from the Multi-Center Mutation Calling in Multiple Cancers (MC3) project to obtain consensus calling results of single nucleotide variants and indels. The open-access Mutation Annotation Format (MAF) file (v0.2.8) that stores variant calls was lifted to human reference genome GRCh38 and converted to individual Variant Call Format (VCF) files per case. VCF files were uploaded to NAVIFY Mutation Profiler to interpret actionable mutations according to a highly curated and up-to-date knowledge base (Roche Content v2.13.0 released December 6, 2019). We further assessed the accuracy of interpreting co-occurrences of actionable mutations. Results: Over 1.24 million somatic mutations across 20,590 genes were assessed with NAVIFY Mutation Profiler, which reported tier classifications of variants based on consensus recommendations from AMP, ASCO, CAP, and ACMG. 86% of cases had variants of strong (Tier I-A or I-B) or potential (Tier II-C or II-D) clinical significance; 56% of these cases had Tier I classifications, supported by robust clinical evidence. Potentially actionable variant-variant interactions were found in 14% of cases. The tool also identified appropriate tier classifications by geographic region in accordance with local medical guidelines. Conclusions: To benchmark against other tools, we utilized available exome data from TCGA MC3 to assess NAVIFY Mutation Profiler. While this study likely underestimates the fraction of cases with actionable mutations, given that copy number alterations or rearrangements are also present in TCGA samples, we found a higher yield of potentially actionable annotation than other published methods. * This product has not been evaluated by the Food and Drug Administration and is not commercially available in the United States.
Leveraging clinical pathways to identify patient-reported clinical trial enrollment barriers.
Authors: McKinney Mishellene , Stefaniak Nessa , Samborski Cynthia , Murphy Monica L. , Edge Stephen B. , Attwood Kristopher , Liu Lu , Eakle Katherine , Lash Stephen , Yu Wei
Published: May 2020

e14086

Background: Only about 3% of adult cancer treatment is within a clinical trial (CT). Patient personal factors may impact willingness to participate. We leveraged CTs embedded in Clinical Oncology Pathways (COP) to examine patient barriers to CT participation. Methods: A COP program used in an academic cancer center embeds CTs that are open for accrual at the center. Providers must either select the CT to alert the research team for patient screening for the CT or provide a reason for bypassing the CT before the COP presents standard care options. This study includes patients with solid tumors receiving systemic therapy for whom a CT is presented in the COP and the provider documented that the patient was “not interested in this trial”. Prior to being offered the survey, these patients were asked if they had been interested in participating in a CT and were considered ineligible for the survey if they said “yes”. The survey was comprised of 29 Likert, demographic, multiple choice and open-ended questions. We categorized patients’ reasons for declining to enroll in a CT, and attitudes about CTs. Results: Among 1108 patients with CTs presented to the provider in COPs from May 2018 to June 2019 there were 164 identified by the provider as not interested in a CT. 23 were deceased, and 54 were not able to be contacted. 57 were otherwise ineligible. Of these, 33% did not recall being offered a CT. Of the 30 patients approached, 9 declined and 21 completed the survey (70% participation). Cancer types included gastrointestinal (33%), breast (19%), non-small cell (14%), pancreas (14%) and others (20%). 66% were female and 80% had metastatic cancer. Age ranged from 41 to 69 years (median 66). Race/ethnicity was Caucasian (81%), African American (10%), American Indian/Alaskan Native (5%) and non-specified (5%). When asked, “How do you view being asked to participate in cancer research, 76% saw it as “a positive thing”. Patient primary concerns were desire for more information on study outcomes (42%), concerns about additional appointments or tests (28%) and concerns about receiving a placebo (23%). Conclusions: There is a gap between patients’ positive views of clinical trials and their willingness to participate. This suggests that barriers identified are modifiable. Many who initially decline CTs may be open to joining a clinical trial with further education.Interventions such as the Meropol et al Preparatory Education About Clinical Trials (J Clin Oncol 2015:34:469) should be considered for broad implementation.
Professional medical writing assistance in oncology clinical trials.
Authors: Abi Jaoude Joseph , Kouzy Ramez , Mainwaring Walker , Lin Timothy , Miller Austin B. , Jethanandani Amit , Espinoza Andres F. , Taniguchi Cullen M. , Ludmir Ethan B.
Published: May 2020

e14088

Background: Academic publishing remains the cornerstone of biomedical research and scientific communication. Researchers often assign professional medical writers (PMWs) to craft publications, as these individuals may improve the overall writing quality and/or reduce time to publication. We sought to characterize the landscape of PMW utilization in phase III cancer clinical trials. Methods: We searched ClinicalTrials.gov for phase III randomized clinical trials between the years 2003 and 2018. Randomized multi-arm trials assessing a therapeutic intervention in cancer patients were included. After identifying the corresponding publications, we identified whether a PMW was involved in writing the manuscript based on author disclosures, along with any related funding information. Results: Six-hundred oncology RCTs with corresponding manuscripts were identified. In total, 260 (43.3%) trials used a PMW. Financial support to medical writers was largely provided by the industry (247/260, 95.0%). In multivariate analyses, PMW utilization was higher among industry-funded trials compared to non-industry-funded trials (OR: 14.2, p= 0.001). PMWs were used more frequently to report successful trials that met their primary endpoint (OR: 1.8, p= 0.03) but did not differ between English-speaking and non-English-speaking countries ( p= 0.19). Cooperative group trials used PMWs with less frequency compared to non-cooperative groups (OR 0.68, p < 0.001). PMWs were used more often in trials that led to subsequent drug FDA approval (69.6% vs 40.6% in trials that did not lead to subsequent FDA approval), but this association did not reach statistical significance in multivariate analysis ( p = 0.744). The use of PMWs has increased significantly over time (OR: 1.11/year, p =0.001). Conclusions: In this analysis, we show a strikingly high prevalence of PMW utilization in phase III oncology trials, with a vast majority of industry-supported studies using PMWs. We believe that professional writing assistance plays an important role in clear and efficient scientific communication. However, the disproportionate role of PMWs in reporting positive, industry-funded trials may represent a conflict of interest. We urge continued and increased reporting of utilization and funding of professional writing assistance in cancer clinical trials.
Associations between concordance with oncology clinical decision support and clinical outcomes in lung cancer patients.
Authors: Suwanvecho Suthida , Suwanrusme Harit , Jirakulaporn Tanawat , Lungchukiet Palita , Thanakarn Nittaya , Taechakraichana Nimit , Decha Wimolrat , Boonpakdee Wisanu , Wongrattananon Pattanawadee , Preininger Anita M , Solomon Metasebya , Wang Suwei , Hekmat Rezzan , Esquivel Jaime , Dankwa-Mullan Irene , Patel Vimla L , Shortliffe Edward , Arriaga Yull Edwin , Jackson Gretchen Purcell , Kiatikajornthada Narongsak
Published: May 2020

e14114

Background: Watson for Oncology (WfO) is an artificial intelligence-based clinical decision-support system which provides therapeutic options and associated scientific evidence to cancer-treating physicians. Oncologists at Bumrungrad International Hospital (BIH) have used WfO since 2015. We examined the association between concordance of WfO therapeutic options and BIH treatment decisions with short-term clinical outcomes for lung cancer patients. Methods: This study included lung cancer patients seen at BIH for treatment and follow-up care and for whom WfO was used from 2015 to 2018. Charts were reviewed for concordance with WfO, documentation of disease progression, response to treatment, and survival. We evaluated concordance between oncologists’ treatments and therapeutic options listed as “recommended” by WfO. We evaluated association between WfO concordance and partial or complete response rates over a 24-month period by comparison of proportions with odds ratio. Progression-free survival (PFS, time from diagnosis until progression or death) was evaluated by Kaplan-Meier log-rank test. Results: Seventy-nine lung cancer patients were included. We identified a trend towards higher response rates in concordant cases (59.2%, N = 32), as compared to discordant (48.0%, N = 12), with an odds ratio of 1.56 (see table). There was not a significant difference in PFS between concordant and discordant cohorts. Conclusions: In this small-cohort, retrospective study, lung cancer patients receiving treatments that are concordant with WfO recommended therapeutic options trended towards higher response rates than patients with discordant treatments. Use of a clinical decision-support system may help support cancer-treating physicians in delivering best practice and evidence-based care that may improve short-term outcomes. Prospective studies with larger samples and other cancer types are underway. [Table: see text]
Using multiple perspectives analysis to propose state cancer control policy in Abia State, Nigeria.
Authors: Eguzo Kelechi Ngozi , Ekanem Uwemedimbuk Smart , Chukwuemeka Oluoha , Nnah Kingsley Kelechi , Olatunbosun Olufemi , Muller Andries , Walker Vivian , Mpofu Chris , Ramsden Vivian R
Published: May 2020

e14132

Background: Beyond the National Cancer Control Plan, most States in Nigeria do not have State cancer control policies. Using the multiple perspectives analysis framework, this research sought to explore the perspectives of patients diagnosed with cancer, healthcare providers and health policymakers regarding cancer policy in Abia State. Methods: A concurrent mixed methods action research design was used. Sample included individuals aged ≥18 years who were diagnosed with cancer (patients), provided cancer treatment (providers) or made health policy (policymakers) in the State. Data were collected using surveys and key informant interviews. Data analysis involved descriptive statistics, chi-square test and a deductive thematic analysis. Results: Participants were 29 patients, 50 providers and 33 policymakers (n = 122), with an average age of 45 (±11) years. Challenges identified by ≥60% of participants were: low public awareness (75.9%); limited availability of treatment options (62.6%); lack of treatment pathways (92.8%); lack of local cancer data (95.2%); and, absence of support groups for patients (88.0%). Each group of participants (n = 3) rated cancer 9 out of 10 as a public health priority. Some qualitative themes were: low cancer awareness, delays in cancer treatment and financial burden on patients. “One thing I’d like to include in the policy is to make cancer a reportable disease in the State.” -Policymaker. Most participants (80%, 90/112) recommended that health insurance should fund ≥16% of cancer control activities, although policymakers were more likely to make quarterly insurance contributions than patients (7 out of 10 vs. 5 out of 10). Conclusions: Cancer control was an important issue for people in the State. Inadequate prevention services with a background of > 3-month diagnostic delays, characterized cancer control in Abia State. Future cancer control policy should emphasize cancer prevention, the creation of local clinical pathways and a blended financing model. [Table: see text]
How the NIH Genetic Testing Registry and Medical Genetics Summaries can help oncologists adopt pharmacogenetics guidelines.
Authors: Malheiro Adriana Jose , Dean Laura Charlotte , Hoeppner Marilu A , Lyoshin Vitaliy , Gu Baoshan , Chen Chao , Liu Chunlei , Maddipatla Zenith , Shi Wenyao , Jang Wonhee , Hoffman Douglas , Zhou George , Chitipiralla Shanmuga , Mitchell Joe , Maglott Donna R. , Kattman Brandi L.
Published: May 2020

e14141

Background: Oncology is one of the few medical specialties where pharmacogenetic dosing is becoming a routine part of patient management. In the US, oncology drugs account for one-third of all drugs with pharmacogenetic data in their labeling. The NIH Genetic Testing Registry (GTR, www.ncbi.nlm.nih.gov/gtr ) is a freely available database of orderable genetic tests voluntarily provided by laboratories, and supports easy identification of both diagnostic and therapy-based tests. Medical Genetics Summaries (MGS, www.ncbi.nlm.nih.gov/books/NBK61999 ) presents actionable pharmacogenetic information by collating guidelines from authoritative professional (e.g. FDA, CPIC) and medical (e.g. ASCO) societies. MGS is regularly updated and can be found by searching PubMed. To increase oncologist adoption of pharmacogenetic recommendations, we analyzed the relationship between genetic tests in GTR and practice guidelines in MGS. Methods: The GTR database was queried to extract content, and we consulted the FDA Table of Pharmacogenomic Biomarkers in Drug Labeling. Results: Of the 90 oncology drugs that have pharmacogenetic information in their labeling, 29 drugs have at least one test for drug response in GTR. The oncology drugs most tested are mercaptopurine and irinotecan with 13 tests each, followed by thioguanine (12) and tamoxifen (9). For the remaining 61 drugs, only one drug (Pertuzumab) has a guideline, which is summarized in MGS. In total, MGS offers 10 summaries focused on oncology drugs. The 90 drug labels mention 49 distinct biomarkers (e.g. genes and variants). All 49 biomarkers can be interrogated using tests via the GTR. In total, GTR has approximately 3,500 tests for cancer diagnostics, 500 tests for cancer management, and 37 pharmacogenetic tests for cancer drugs. Conclusions: Searching for a genetic test in GTR by biomarker (100% coverage) is more efficient than by drug name (32% coverage) because of how laboratories describe their tests. Clinicians need to quickly find the best pharmacogenetic test and how tests are represented in the community affect the ability to search and find them. This presentation will show busy clinicians how to optimally use GTR and MGS. This work was supported by the Intramural Research Program of the National Library of Medicine, National Institutes of Health.
Complementary and alternative medicine use among cancer patients at a private hospital in Brazil.
Authors: Ricardo Eliza Dalsasso , Oishi Denise , Dos Santos Marcelo Oliveira , D'Alpino Renata D'Alpino
Published: May 2020

e14144

Background: Complementary and alternative medicine (CAM) use is relatively common among cancer patients. Data regarding CAM use in Brazil is scarce. We sought to define CAM use by cancer patients and investigate factors that might influence it. Methods: We conducted a cross-sectional survey of adults diagnosed with any cancer type who came to appointments at our outpatient clinic in January 2020. Chi-square tests were used to investigate the association between CAM use and age and gender Results: We interviewed 156 patients who consented to the face-to-face interview and all of them completed the questionnaires. Most patients were between 51 and 70 years-old; 56% were female and 55% had their cancer diagnosed in the last 12 months. Most cancer types were breast (17.4%), colorectal (16.7%), and lung (16.1%). More than 90% of the participants were on any active treatment. The prevalence of current CAM use was 29.6%. 58.7% of the patients did not believe CAM has anti-cancer properties, including 32.6% of patients who reported CAM use. Two-thirds of the participants have never discussed about CAM with their oncologists. Only 5.1% of the respondents would abandon conventional cancer treatment in order to use just CAM. Among CAM users, 55% referred multiple therapies use. Of those therapies, spiritual surgery was the most prevalent one. There was a significant higher proportion of females reporting CAM use (p = 0,029) as well as a higher proportion of CAM use among younger patients (p = 0,008). Conclusions: CAM use was common among our study population, especially spiritual surgery. Women and younger patients were more prone to use CAM. Although most patients would not abandon conventional treatment, many of them have never discussed about CAM with their oncologists.
Using a tele-oncology service provides a direct benefit to patients and caregivers in rural communities in the Intermountain West.
Authors: Haslem Derrick S. , Reese Zachary , Emfield Kimberlee , Gill David Michael , Wilcox Ryan Eldredge , Rhodes Terence Duane , Tudor Brian P.
Published: May 2020

e14153

Background: Cancer treatment is becoming more complex, necessitating subspecialty expertise and multidisciplinary approaches to treatment planning. Simultaneously, there is increasing demand to provide care as close to home as possible. Oncology services are in high demand with a geographical mismatch between where oncologists work and where patients live. Traditionally, patients have been required to travel long distances to seek care outside of their communities resulting in increased financial expense and emotional distress caused by leaving the comforts of their support system. Leveraging existing technologies, most of modern cancer care, including infusions can be delivered through a coordinated effort from consulting/ordering oncologists, onsite administrators, physicians, nurses and ancillary staff. Methods: Using a secure video-conferencing platform, Intermountain Healthcare has implemented 5 tele-oncology clinics (Site A- Sevier, UT; B- Cassia, ID; C- Teton, ID; D- Uintah Basin, UT, E- Star Valley, WY) in rural communities of Utah, Idaho and Wyoming. Patients are referred to the clinic by local providers. With the assistance of a nurse navigator, oncologists meet with patients via video conference for initial consults, follow-up, supportive care, survivorship care and systemic treatment including chemotherapy, immunotherapy, and targeted therapy. Standard NCCN/ASCO guidelines are followed in the treatment strategies for these patients. Care is taken to ensure any treatment that can safely be delivered in the local facility/community is coordinated to take place there. Based on distances from the rural facility to nearest tertiary cancer center, we calculated the mileage avoided and hours traveled avoided by using tele-oncology. Results: Since 2017, the tele-oncology service has managed 269 unique patients (A- 200; B- 21, C- 22, D- 18, E- 8) with 1,237 total tele-oncology visits (A- 1,068; B- 69; C- 39; D- 32; E- 29). In total, there were 397,326 driving miles avoided (A- 326,808; B- 26,358; C- 22,932; D- 9,280; E- 11,948). Travel hours avoided in total were 6,062 hours (A- 4,989; B- 380; C- 341; D- 155; E- 197). Conclusions: Intermountain Healthcare’s tele-oncology program benefits patients and communities by easing travel burden and improving quality of life by making cancer care more convenient and providing the care closer to home. Work is ongoing to prospectively evaluate the effects on the communities in addition to cancer related outcomes.
CNS outcomes in EGFR/ALK wild-type NSCLC patients with brain metastases treated with immune checkpoint inhibitors (ICI).
Authors: Shultz David Benjamin , Lau Sally CM , Poletes Christopher , Le Lisa W , MacKay Kate , Shepherd Frances A. , Bradbury Penelope Ann , Leighl Natasha B. , Liu Geoffrey , Sacher Adrian G.
Published: May 2020

e14505

Background: Anti-tumor lymphocytes activated in response to ICIs may cross the blood brain barrier with effect on brain metastases (BM). Preliminary evidence suggests that ICIs alone are effective for melanoma BMs. However, the ability of ICI to effectively control NSCLC BMs without radiotherapy is controversial. By comparing serial MRIs and patterns of progression in ICI and chemotherapy treated patients, we sought to investigate the role of ICI in BM control in NSCLC patients. Methods: Serial MRIs were reviewed in ICI treated NSCLC patients with known BMs. Eligible patients must have a minimum of one baseline MRI and a follow-up within 3 months of CNS directed treatment. Patients with EGFR/ ALK mutations were excluded. A control cohort of patients who had never received ICIs was selected using the same criteria. The primary outcome was cumulative CNS progression and intracranial progression free survival (iPFS) analyzed using an accelerated failure time model and competing risk analysis. Results: We identified 137 ICI treated NSCLC patients with known BMs. After excluding for patients without serial MRIs, we analyzed 40 ICI treated patients and 39 controls. All patients received upfront radiotherapy or surgery and the modality used was similar (p = 0.13). CNS failure was less common in the ICI group (p = 0.02). ICI treated patients had a trend to longer iPFS in the PD-L1 ≥50% subgroup (p = 0.058). Cumulative incidence of progressive BM at 12 and 24 months were significantly lower in the ICI treated PD-L1 ≥50% subgroup: 19%/19% vs 50%/56% (p = 0.02). Patients in the PD-L1 ≥50% subgroup who achieved a systemic partial response (n = 10) did not experience any CNS events despite extracranial progression in some. Conclusions: Durable CNS disease control is observed with ICIs in NSCLC with PD-L1 ≥50% and demonstrates a high level of concordance with systemic response. The need for radiotherapy in PD-L1 ≥50% disease should be investigated and may be reasonably delayed in asymptomatic patients with small BMs. Importantly, the same trend was not observed in PDL1 < 50% patients and caution is needed in employing this strategy in this subset of patients.
Prospective investigation of patent foramen ovale as a mechanism for brain metastasis in patients without prior lung involvement.
Authors: Levin-Epstein Rebecca , Rusheen Joshua , Kumar Preetham , Gevorgyan Rubine , McWatters Zoe , Kim Won , Kaprealian Tania Betty , West Brian , Tobis Jonathan
Published: May 2020

e14510

Background: Brain metastases can lead to significant morbidity and mortality in patients with advanced cancer. Preventing metastatic disease to the brain could thus substantially improve outcomes. The mechanism of brain metastasis is incompletely understood. Circulating tumor cells drain to the right heart and through the pulmonary circulation, where they may manifest as lung metastases, and can circulate further to the left heart and then to the brain. However, in patients who develop brain metastases without prior lung involvement, metastatic cells may take an alternate route. We hypothesized that cancer cells may pass directly from the right to left heart via a patent foramen ovale (PFO), akin to paradoxical embolism. The prevalence of PFO is approximately 20-30% in the general population; if further elevated in this population, PFO may play a role in brain metastasis development, and ultimately, prophylactic PFO closure may provide benefit. We conducted a pilot study to investigate whether PFO is associated with brain metastases in patients without prior lung involvement. Methods: We prospectively identified patients with brain metastases from a non-lung primary cancer with no preceding lung metastases. Participants underwent a transcranial Doppler study to assess for PFO. Agitated saline was injected intravenously at rest and with Valsalva maneuver. High intensity signals were counted in the middle cerebral arteries for 1 minute after each injection. Spencer grade ≥3 indicated a positive study, consistent with the presence of PFO. Results: We accrued 9 participants who met inclusion criteria. Primary cancers were breast (6 participants), upper gastrointestinal (2 participants), and thyroid (1 participant). A positive study was identified in 2/9 (22.2%) participants. One individual was a female with breast cancer who had no preceding extracranial metastases, and the other individual was a male with duodenal adenocarcinoma whose only prior metastatic disease was distant lymphadenopathy, not active at brain metastasis diagnosis. No participants have developed lung metastases as of their most recent imaging. Conclusions: In this prospective pilot study, we found no increased prevalence of PFO in patients who develop brain metastases without preceding lung involvement compared to estimates for the general population. Though a larger study is needed, the development of brain metastases in these patients may reflect tumors’ biological factors directing metastasis organotropism, rather than a structural pathway.