bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characters of somatic DNA damage repair (DDR) gene mutations in Chinese NSCLC patients.
Authors: Ma Ke , Rong Hao , Zhu Changbin , Zhang Huachuan , He Jintao , Xiao Bo , Zhu Jiang , Peng Jun 
Published: May 2020

e13665 Background: Chinese NSCLC patients displayed unique genetic profile. NSCLC patients with DNA damage repair gene mutations showed distinct clinical appearance as well as superior response to immunotherapy. This study aims to disclose distribution of DNA damage mutations as well as their clinical characters in Chinese NSCLC patients. Methods: One hundred and ten patients with pathologically confirmed NSCLC were consecutively recruited from 2016-2018 in our center. Genomic DNA was captured and sequenced for 508 cancer related genes by BGI-seq 500. Raw data was processed followed by variant calling via in-house developed pipeline. Results: 89 (of 110) patients with median age of 55 years old (33-74 years) were included into final analysis due to complete follow-up as well as sufficient FFPE tissue for successful genomic profiling. Among them, 12 patients were squamous NSCLC, 72 patients were non-squamous NSCLC. Among 89 patients, 22 patients (24.7%) carried 36 mutations in 21 DDR genes (BRCA2 n = 6, BAP1 n = 3, ARID1A n = 2, ATM n = 2, ATR n = 2, BLM n = 2, FANCF n = 2, PARP1 n = 2,BARD1 n = 1,BRCA1 n = 1,CHEK2 n = 1, FANCD2 n = 1,FANCE n = 1,FANCG n = 1,FANCM N = 1,NBN n = 1,PARP3 n = 1,POLQ n = 1,RAD50 n = 1,RAD51C n = 1), most of them belongs to homologous recombination repair pathway (n = 19, 21.34%).8 patients carried compound mutations in DDR genes. No difference was found in age of initial diagnosis between DDR mutated and DDR wild type patients. While, ever smokers (RR (95%CI): 2.12 (1.37-3.20),P = 0.003), squamous NSCLC (RR(95%CI):4.47 (1.62-12.03), P = 0.006), male (RR (95%CI): 1.77(1.23-2.44),P = 0.006) displayed significantly higher prevalence of DDR gene mutations. Only one stage I patient carried DDR mutation(P = 0.008). Conclusions: In this study, mutation spectrum of DDR genes was proposed in Chinese NSCLC patients. DDR gene mutations more possibly occurred in male, higher disease stage as well as in squamous NSCLC and smokers. These findings show potential relevance to disease prognosis which needs further investigation.
A retrospective three-year analysis using real-world data on uptake of broad-based NextGen sequencing panels in community oncology practices.
Authors: Gierman Hinco J. , Pai Nikhil , Catasus Casey , Tam Alvin , Labrador Monica , Donaldson Joseph , Singaraju Mallika , Singleton Nick , Verniero John , Smith Robert E. , Scott Jeffrey A. 
Published: May 2020

e13668 Background: There are over 100 FDA approved targeted therapies across 15 cancer types, offering improved outcomes over existing therapies. However, many of these require genetic testing, for example, advanced non-small cell lung cancer (aNSCLC) patients have over 15 targeted therapies requiring a DNA-based test. Doing multiple tests can exhaust sample, while increasing cost and turn-around time. NGS panels, often with hundreds of genes, can address some of these issues. Here we asked across aNSCLC patients if the use of NGS panels has increased over the last 3 years in community oncology practices. Methods: The Integra Connect database, which includes electronic medical record (EMR) and claims data on over 1,000,000 US cancer patients, was queried across five community oncology practices to identify aNSCLC patients (stage IIIB or IV) treated between January 2017 and January 2020. Manual chart review abstracted tumor type, stage, treatment, and testing. Patients tested for all 7 NCCN recommended genes (EGFR, ALK, ROS1, BRAF, MET, RET, ERBB2) were grouped as “NGS Panel”, patients with less genes as “Single Gene/Small Panel”, and patients with no evidence of testing as “No Test”. A Chi-Square test was used to compare actionable results between patients with NGS panels versus small panels. Results: 1,007 aNSCLC patients were analyzed and showed a doubling of the use of broad-based NGS testing from 13% in 2017 to 26% in 2019 across over 100 oncologists (table). 23% of patients had actionable results when tested on broad-based panels versus 17% using single gene or small panels (p = .048). Targeted therapies were used in 17% of broad-based tested patients, versus 15% in patients tested for single genes or small panels. Conclusions: We see an uptake of broad-based NGS testing in community oncology, which can lead to more actionable results and better utilization of targeted therapies for those patients. However, this seems to be caused by providers shifting from small panels to large panels, rather than an overall increase in testing, as we do not see the percentage of untested patients decrease. [Table: see text]
The prognostic role of somatic BRCA mutations in ovarian cancer: Preliminary results from an observational multicenter cohort study.
Authors: Piombino Claudia , Toss Angela , Bologna Alessandra , Gasparini Elisa , Tarantino Vittoria , Filieri Maria Elisabetta , Cottafavi Luca , Giovanardi Filippo , Marcheselli Luigi , Marchi Isabella , Domati Federica , Venturelli Marta , Barbieri Elena , Grandi Giovanni , Tenedini Elena , Tagliafico Enrico , Cortesi Laura 
Published: May 2020

e13674 Background: BRCA germline (gBRCA) mutations occur in 11-15% of women with unselected ovarian cancers (OC), whereas somatic BRCA (sBRCA) mutations occur in approximately 5-7% of cases. The impact of sBRCA mutations on OC outcome is still debated. Methods: With the aim to explore the prognostic role of sBRCA mutations, the BRCA mutational status of 149 non-mucinous and non-borderline OC and their clinical-pathological features were evaluated. BRCA1 and BRCA2 mutational profiles, either for sequence variants or copy number alterations, were evaluated by amplicon next-generation sequencing (NGS) technology. Results: 29 (19.5%) patients carried a gBRCA mutation (12.7% BRCA1 and 6.7% BRCA2). 26 (17.5%) patients presented a sBRCA mutation (6.7% BRCA1, 10% BRCA2, 0.6% BRCA1+BRCA2). Patients carrying a gBRCA mutation were slightly younger (57 years) than the others (60 years). The FIGO stage at the diagnosis was III-IV in 77.2% of cases, with no significant difference among subgroups. The most frequent histotype was serous for all the subgroups (93.1% in gBRCA, 84.6% in sBRCA, 77.7% in BRCA-negative, p = 0.08). 80.7% of sBRCA mutation carriers, 62.1% of gBRCA mutation carriers and 62.7% of BRCA-negative patients underwent upfront surgery (p = 0.46). 29.1% of sBRCA mutation carriers, 17.8% of gBRCA mutation carriers and 25.6% of BRCA-negative patients presented macroscopic residual disease after surgery (p = 0.68). Although non-statistically significant, gBRCA-associated OC were more likely to be platinum-sensitive (96.6%) than the other patients (92% in sBRCA and 87.1% in BRCA-negative patients). Overall, the median platinum-free interval (PFI) resulted shorter in sBRCA mutation patients compared to gBRCA and BRCA-negative patients (p = 0.051). No patient took PARP inhibitors as maintenance after the first line therapy. Also progression free survival 2 (PFS2) resulted shorter for sBRCA mutation patients (p = 0.008). Three sBRCA and 5 gBRCA mutation carriers took a PARP inhibitor as maintenance after the second line therapy. Finally, sBRCA mutated patients showed worse overall survival (OS) compared to the other subgroups (p = 0.014). Conclusions: Overall, 19.5% of OC patients presented a gBRCA mutation, while 17.5% of patients showed sBRCA mutations. sBRCA-related OC did not show significantly differences in clinical-pathological features (stage at diagnosis, histotype, time to surgery and residual after surgery). To our knowledge this is the first study showing shorter PFI, PFS2 and OS in patients carrying sBRCA mutations.
The positive correlation between tumor mutation burden and the purity of tumor samples in non–small cell lung cancer and colorectal cancer.
Authors: Tong Jian , Zhang Xiaoni , Qu Hongyue , Yang Qing , Duan Jingxian , Xu Mingyan 
Published: May 2020

e13683 Background: Tumor mutation burden (TMB) is reported to be a biomarker for predicting immunotherapy responses in patients with non–small cell lung cancer (NSCLC). To provide a more accurate calculation of TMB, the correlation between tumor purity and TMB was investigated. Methods: 959 patients were enrolled in this study from July 2019 to January 2020, including 663 patients with primary NSCLC and 296 patients with primary colorectal cancer (CRC). Formalin-Fixed Paraffin-Embedded (FFPE) and paired white blood cells were collected from each patient. These FFPE samples were stained with HE for the evaluation of tumor purity. DNA was extracted from samples and sequenced using a 605-gene panel on the Illumina platform (approximately 3,000× coverage). TMB was calculated for each sample based on the sequencing data. Results: The median TMB of 663 NSCLC patients was 2.29mut/Mb, and the TMB is positively correlated with the purity of tumor samples. Among samples in which tumor cells accounted for ≥40% of the sample cells (n = 456), the median TMB reached 2.29 mut/Mb, and 90.35% (412/456) patients had a TMB higher than 0 mut/Mb. In samples that tumor cells accounted for 20% to 40% of sample cells (n = 120), the median TMB was 1.53mut/Mb and 72.5% (87/120) of patients had a TMB larger than 0 mut/Mb. The median TMB was 0.76 mut/Mb for samples contained less than 20% of tumor cells, and only 50.57% (44/87) patients had a TMB larger than 0 mut/Mb. Similar results were obtained in 296 CRC samples, which exhibited a median TMB of 3.55mut/Mb. Tumor cells accounted for 40% of the sample cells in 191 cases. The median TMB of those samples was 4 mut/Mb, and 96.34% (184/191) samples had a TMB larger than 0 mut/Mb. When tumor cells accounted for 20% to 40% of total sample cells, the median TMB was 2.94mut/Mb, and 94.44% (51/54) of patients had a TMB larger than 0 mut/Mb. In 50 samples that contained less than 20% of tumor cells, the median TMB was 2.29mut/Mb, and 80 % (40/50) samples had a TMB larger than 0 mut/Mb. Conclusions: TMB is positively correlated with the purity of tumor samples. Moreover, data suggest that the TMB is more reliable when tumor cells account for more than 40% of the sample population.
A tailored predication model to improve outcomes and mortality in geriatric indigenous women with breast cancer of western Australia.
Authors: Khan Azim , Martin Hilary Laura , Spalding Lisa , Redfern Andrew D. 
Published: May 2020

e14000 Background: Indigenous women with breast cancer (BrCa) have higher mortality than Non-Indigenous women. Remoteness, aggressive tumour biology, treatment acceptance and compliance are all contributory factors. A retrospective study of geriatric indigenous women (aged 55 years more) with BrCa has shown high co-morbidity and treatment-related toxicity scores translating to high mortality comparing to the non-indigenous geriatric population (aged 65 years or more). An algorithm allowing prediction of risk of morbidity and mortality to enable optimisation of care for this patient group, catering to needs, values, beliefs and resources of geriatric Indigenous patients is warranted. Methods: To create a predictive algorithm and model of care based on the demographics, social environment, biology, co-morbidity burden and predicted chemotherapy toxicity scores of Indigenous women with BrCa to then be applied to a validatory prospective study.A cohort of 132 indigenous geriatric patients was identified from the Western Australian Cancer Registry from 2001 to 2010 along with remoteness matched geriatric non-Indigenous women in a 1:1 ratio. Data was collated on cancer biology, chemotherapy toxicity, mortality, co-morbidity burden (by the Charlson Co-Morbidity Index -CCI) and predicted chemotherapy toxicity (by CARG toxicity score). An algorithm was created based on these factors to identify patients at greatest risk of morbidity and mortality. Results: Elements identified as predicting morbidity and mortality were; remoteness based on distance from Perth (scored 0-3), lymph node status (scored 0-1), social isolation (scored 0-1), the Carg score (scored 0-3), and the CCI (scored 0-4). The KR Geri-Indigenous Rx Model was created using these components and scored out of 12. Conclusions: The score has been used to create three risk categories, low (1-3) intermediate (4-8) and high risk (9-12). A model of care was designed with staged increases in service elements and intensity for increasing risk category. These include the addition of Indigenous health worker review initially in clinic as well as at home during chemotherapy, initial geriatric assessment and potential geriatrician review, optimization of co-morbidities and medications, consideration of dose adjustments, social worker visits to increase services, increased surveillance, with telehealth contact and GP update with treatment planning as well as on treatment completion. A prospective study based on this model is planned.
Applying the Collaborative Care Model to treat depression and anxiety in breast cancer (BC) patients.
Authors: Johns Kevin Nathaniel , Kalister Steven , Mwandha Noah , Adams Elizabeth J. , Basinger Heidi , Fugett Susan , Crawford Danielle , Draime Michelle , Shinde Namrata Vilas , Kassem Mahmoud , Radcliff Lindsey , Unthank Brittany , Cherian Mathew Amprayil , Sardesai Sagar D. , Stover Daniel G. , Vandeusen Jeffrey , Wesolowski Robert , Williams Nicole Olivia , Ramaswamy Bhuvaneswari , Lustberg Maryam B. 
Published: May 2020

e14004 Background: Depression and anxiety are frequent causes of excess morbidity for cancer patients, but access to mental health care, including outpatient psychiatry, is limited across academic and community settings. The Collaborative Care Model (CoCM) is a team-based model of care that is proven to leverage limited mental health resources across a wider population in primary care (Raney L, Am J Psychiatry, 2015). Evidence suggests that CoCM can be effectively applied to cancer populations too (Walker J, Gen Hosp Psychiatry, 2009). Methods: The investigators adapted CoCM to treat depression and anxiety in an academic BC clinic. A quality protocol was approved by the institutional board. All English-speaking BC patients were screened for depression using the PHQ-2 and PHQ-9. Patients with PHQ-9 ≥15 or clinical suspicion of severe anxiety or depression were referred to CoCM. The CoCM intervention included social work care management and regular case reviews by a psychiatrist. Medical oncologists prescribed all psychiatric medications. Patients were referred to mental health services in the community as needed. Results: From November 2018 through January 2020, a total of 74 patients were enrolled in CoCM. Median age was 50 years (range: 28-74 years) with BC stages I-III (n = 49, 66.2%) and stage IV (n = 25, 33.8%). Treatments within the cohort include: endocrine therapy (n = 39, 52.7%), chemotherapy (n = 18, 24.3%), observation (n = 9, 12.1%), single agent HER2 inhibitor targeted therapy (n = 4, 5.4%), immunotherapy (n = 2, 2.7%), single agent CDK4/6 inhibitor (n = 1, 1.4%), and radiation (n = 1, 1.4%). Of the 74 patients, 28 had PHQ-9 scores ≥15 at enrollment. On average, ending PHQ-9 scores decreased 39% from the initial score (average beginning score of 19.3 and ending score of 11.3 [n = 19]). 50 patients had GAD-7 ≥10 at enrollment. On average, ending GAD-7 scores decreased 36% from the initial score (average beginning score of 15.4 and ending score of 9.9 [n = 32]). On a 5-point scale, the average patient satisfaction score was 4.3 [range: 4.1-4.5] and the average medical oncology satisfaction score was 4.6 [range: 4.5-4.7]. Financial viability is promising based on projections that 93.4% of psychiatry costs (10% salary + benefits) are covered by reimbursements for care and 2 existing social workers serving as care managers. Conclusions: The collaborative care model is an effective and financially sustainable approach to promptly address depression and anxiety symptoms in BC. Further studies are needed to assess its applicability to patients with other forms of cancers.
Advancing precision medicine in clinical oncology: Whole exome paired tumor-normal DNA and RNA sequencing at a single-institution cancer center.
Authors: McDonnell Kevin , Kulkarni Amit , Woodhouse Melissa , Smith Sidney A , Hong Christine , Melas Marilena , Heller Kathleen , Lazaris Charalampos , Sturgeon Duveen , Ricker Charité , Solomon Ilana , Culver Julie , Lowstuter Katrina , Morales Pichardo Jennifer , Jones Veronica , Idos Gregory , Bonner Joseph D , Gruber Stephen B. 
Published: May 2020

e14006 Background: Next generation sequencing (NGS) allows for reliable, comprehensive and cost-effective identification of clinically actionable genetic and genomic alterations. The increasing adoption of NGS in clinical oncology has increased our ability to identify germline alterations predisposing to cancer development as well as somatic changes enabling prescription of individualized cancer treatment and enhanced clinical trial participation. Here we summarize implementation of an NGS-based precision medicine initiative involving oncology patients from a single institution cancer center. Methods: IRB-approved NGS matched whole exome (WES) germline and solid tumor somatic tumor sequencing together with somatic tumor RNA sequencing (RNA-seq) were performed using germline DNA extracted from peripheral blood lymphocytes and nucleic acids for tumor DNA and RNA sequencing obtained from formalin-fixed, paraffin-embedded tumor specimens. Results of sequencing and analyses were presented to a multi-disciplinary tumor board to establish recommendations for management of germline pathogenic variation, therapeutic drug matching, clinical trials eligibility and molecularly informed patient prognosis. Results: A total of 1,005 patients completed sequencing. Germline and somatic WES exceeded 100X and 250X mean target coverage, respectively; somatic RNA-seq exceeded 200 million mean reads. Patients ranged in age from 17 to 90 years. The study cohort comprised comparable numbers of female (51%) and male (49%) patients. Ethnicities and races were broadly represented with 22% of participants identifying as Hispanic, 14% as Asian, 4% as Black, 55% as Non-Hispanic White and 5% as other. The most common solid tumor histological classification was colorectal (18%), followed by breast (16%), prostate (7%), head and neck (7%), sarcoma (7%), ovarian (5%), melanoma (4%) and lung (3%). Bioinformatic analyses and precision medicine tumor board review established that 12% of patients harbored a germline pathogenic variant and 43% carried clinically actionable genetic/genomic alterations; a majority of patients met molecular requirements for participation in a clinical trial. Conclusions: This study confirms the feasibility and utility of clinical NGS and precision medicine tumor board review in clinical oncology to identify germline genetic pathology, deliver personalized cancer therapeutics, increase clinical trial enrollment and clarify diagnosis and prognosis.
Effect of accreditation best practice systems on time to treatment delays: Three-year review of a South African internationally accredited site.
Authors: Benn Carol , Rapoport Bernardo Leon , van Loggerenberg Dominic 
Published: May 2020

e14009 Background: The Netcare Breast Care Centre has been an operational multi-disciplinary centre since 2000. It was proposed that formalised accreditation would improve patient services thus three years of patient time to treatment data were analysed comparing the pre-accreditation average to the mid accreditation and post accreditation. Methods: Patients for this comparison met the following criteria: The treating physicians were members of the unit, no arm of the care was external; they underwent a combination therapy of surgery; systemic treatment (neo-adjuvant or post-operative); The patients fell within a clearly defined treatment time frame. The time to treatment was judged from date of diagnosis to date starting first treatment whether surgery or systemic. patients who delayed treatment for longer than 100 days beyond the reasonable allowance within the centre’s Standard operating procedure were excluded. Results: Pre accreditation time to treatment was an average of 36.5 days from the date of initial diagnosis,. An even split of primary surgery (48%) to systemic (52%). During the implementation of new accredited systems, the time to treatment average saw a reduction of 20%, down to 29 days from the date of diagnosis. An even split of primary surgery (47%) to systemic (53%) remained. After full implementation of the new systems and full international accreditation being achieved the time to treatment saw a further 20% improvement (41% from initial value) of 21 days from diagnosis to treatment. Case mix was now heavily weighted towards the systemic treatment of 71% and primary surgery 29%. Conclusions: The implementation of accredited systems and optimization of the MDM environment saw a dramatic improvement to the service provided to patients. Over the course of the accreditation period, the systems allowed for a two-week reduction in time to treatment (40% improvement) from a previous 5-week standard.
Lessons learned from clinical trial queries on small biopsy collections from an academic cancer center.
Authors: Voyten Jamie , Holtzman Matthew Peter , Pantanowitz Liron , Dhir Rajiv , Beasley H. Scott , Cuda Jackie , Monaco Sara Elizabeth 
Published: May 2020

e14016 Background: Small biopsies and cytology specimens are becoming increasingly important for clinical trials and biomarker testing. Thus, institutions must ensure that there is adequate lesional material meeting specifications for a multitude of different protocols, which can involve rapid on-site evaluation (ROSE). The aim of this study is to look at the recent clinical trial biopsy characteristics and feedback on these collections at our institution. Methods: Clinical trial biopsies performed at our institution and trial feedback (so called “queries”) were analyzed from the past two years (2017-2019). The query data was reviewed in detail, in addition to protocol modifications related to biopsy requirements and study protocol changes. Results: A total of 698 biopsy collections were performed for clinical trial purposes for 95 trials, with the majority of these requiring biopsies at more than 1 time point (63.2%), for phase 1 or 2 trials (92.6%), and for specific tumor types (67.4%). Only 18 (18.9%) of the 95 trials requiring fresh tissue biopsies provided feedback. This included 90 (12.9%) cases, of which 27 (30.0%) had queries regarding insufficient (10, 37.0%) or borderline (17, 63.0%) tumor, and only 1 (3.7%) of these had ROSE by cytology. ROSE was performed due to institutional guidelines (45.3%), requirement by study (1.1%), or trial modification (5.3%).(Table). Conclusions: This investigation shows the high volume of clinical trial biopsies managed at our academic cancer center. Feedback from trials is low at 18.9%, and frequently involves suboptimal cases without ROSE at acquisition, which has led to more widespread adoption of ROSE to mitigate insufficient biopsies and repeat procedures. The high volume of clinical trial biopsies and variability in trial needs necessitates a collaborative multi-disciplinary network to facilitate these important biopsies for cancer patients. [Table: see text]