tbuckley/cabot-search huggingface dataset:
A phase II trial of bevacizumab in patients with recurrent solid tumor brain metastases who have failed whole brain radiation therapy (WBRT).
Authors: Priya Kumthekar, Karan Dixit, Sean Aaron Grimm, Rimas Vincas Lukas, Margaret A. Schwartz, Alfred Rademaker, Laura Sharp, Valerie Nelson, Jeffrey J. Raizer
Journal: Journal of Clinical Oncology (2019)

2070 Background: Brain metastases (BM) are the most common intracranial malignancy with overall a poor prognosis estimated at approximately 4 months from time of initial diagnosis for treated patients, and even lower after failing WBRT after which treatment options have been limited and outcomes poor. Methods: This is an open label phase 2 study where patients who have previously failed WBRT received bevacizumab at a dose of 10 mg/kg intravenously every two weeks until CNS disease progression with one cycle being defined as 4 weeks. The primary endpoint was objective radiographic tumor response as defined by modified Response Assessment in Neuro-oncology (RANO) criteria. Secondary endpoints included progression free survival (PFS) at 6 months, time to progression, time to response, duration of response, overall survival (OS), quality of life (QOL) as measured by the FACT-G and FACT-Br and safety. Results: A total of 27 patients were consented and registered to study of which 24 were evaluable for ORR (3 came off study prior to first follow up MRI brain). Medianage was 53 (range 27-73), median number of cycles was 5.5 (range 1-20) with a median follow up of 8.7 months (range 2.4-47.9mo). Of the 24evaluable patients, there were 6 Partial response, 16 stable disease and 2progressive disease. The 6 month PFS: 46% (95% CI: 25% - 67%) and median PFS was 5.3 months. Median OS was 9.5 months (95% confidence interval 6.3m – 15.0m). For the patients who completed sequential QOL assessments, there was no significant decline in QOL but there was a nonsignificant improvement in the FACT-Br scores. Overall, treatment was well tolerated with 3grade 3 adverse events seen: hypertension (n = 3), headache (n = 1) and thrombotic event (n = 1). Conclusions: For this WBRT failure BM population, we were able to show a 25% disease response to bevacizumab therapy along with good drug tolerability and no noted central nervous system bleeding. Improved survival as compared to historical controls was seen 9.5 m. Of the 24 evaluable patients, 81% (22/24) experienced clinical benefit defined as stable disease or better. Bevacizumab therapy could be a viable option for solid tumor BM patients who experience progression following WBRT, however a larger trial is required to confirm this data. Clinical trial information: NCT01898130.
Challenges in sentinel node (SN) pathology in the era of adjuvant treatment: The risk of over and undertreatment stress the need for expert pathology review.
Authors: Viola Franke, Max Fullah Madu, Carolien Bierman, Willem M.C. Klop, Winan J. van Houdt, Michel W.J.M. Wouters, Bart A. Van De Wiel, Alexander Christopher Jonathan Van Akkooi
Journal: Journal of Clinical Oncology (2019)

9593 Background: With the approval of adjuvant therapy for stage III melanoma, accurate staging in melanoma patients is important more than ever to prevent over- or undertreatment. Sentinel node biopsy (SNB) is an accurate staging tool, yet the presence of capsular nevi (CN) can lead to a false positive diagnosis. We compared positive SNB and CN patient outcomes and aimed to evaluate the cause of false positive SNB and discern diagnostic pitfalls in their evaluation. Methods: Retrospective analysis of AJCC 7th Edition stage IIIA melanoma patients (N1-2a, non-ulcerated primary tumor) who were treated at our institute between 2000 and 2015. SNB slides were reviewed for this study by an expert melanoma pathologist. Baseline characteristics were assessed for SN+ and CN+ patients. Concordance rates for SNB evaluation before and after revision were documented and diagnostic pitfalls were discerned. Results: 169 patients were diagnosed, 10 could not be reviewed due to lack of evaluable slides. Of these 159 cases, 14 patients originally diagnosed with metastatic melanoma were shown to have capsular nevi (8.8%). Another 2 patients were shown to have melanophages that were incorrectly interpreted as metastases (1.3%). Thus, 10.1% was considered false positive after revision. In 14 patients the SN tumor burden was originally reported &gt; 1 mm, but turned out to have &lt; 1 mm SN tumor burden. 4 patients originally reported as SN tumor burden &lt; 1 mm before revision turned out to have &gt; 1 mm SN tumor burden. These 32 patients (20%) might have potentially been over- or undertreated in the current era of adjuvant therapy for stage III melanoma. Conclusions: False positive sentinel node results in melanoma are real, they can occur for a number of reasons, but distinguishing metastatic melanoma from benign capsular nevi and melanophages can be a diagnostic challenge. We plead for an expert pathologists’ review in any case, but certainly when using the SNB+ results to determine treatment consequences for SN+ melanoma patients.
A randomized phase II study of tremelimumab and durvalumab with or without radiation for patients with relapsed small cell lung cancer (SCLC).
Authors: Taofeek Kunle Owonikoko, Kristin Ann Higgins, Zhengjia Chen, Chao Zhang, Rathi Narayana Pillai, Conor Ernst Steuer, Nabil F. Saba, Suchita Pakkala, Dong Moon Shin, Guojing Zhang, Shuhua Wang, Mohammed S Hossain, Tyler Beardslee, Anne Engelhart, Janine Revenig, Fadlo Khuri, Walter John Curran, Sagar Lonial, Edmund K. Waller, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2019)

8515 Background: The combination of PD-1 and CTLA-4 inhibition has demonstrated activity in the second line therapy setting for SCLC. Radiotherapy enhanced the effectiveness of immunotherapy in NSCLC. We conducted this signal finding study to assess the efficacy of combined ICI with or without radiation in relapsed SCLC. Methods: Patients with relapsed SCLC who have received not more than 2 lines of therapy were enrolled and randomized to either Arm A: [Tremelimumab (T) 1500mg/durvalumab (D) 75mg i.v. every 4 weeks without SBRT] or Arm B: T/D with immune sensitizing SBRT to one selected tumor site (9 Gy x 3 fractions). Treatment continued until progression or maximum of 2 years. Paired tumor biopsies and serial samples of peripheral blood were employed for correlative endpoints (changes in intratumoral and circulating lymphocyte repertoire and immune cytokines). The study was designed to show a promising efficacy signal in either Arm with a hypothesized median PFS of 7 months (10 patients give 87% power at 1-sided alpha of 0.1). Results: Study randomized 17 patients to Arm A (8 patients) or B (9 patients); median age of 70 yrs; females 41.2%; White, 70%, Black 17.6%. Best response in 14 overall evaluable patients was PD in 9 (64.3%), PR in 2 (14%) and SD in 3 (21.4%); median PFS of 2.76 months and OS of 4.47 months. There was no significant difference in efficacy between Arms A and B but a trend of improved PFS and OS with T/D plus SBRT (see table): Median PFS of 2.1 vs. 3.3 months [HR: 2.44 (0.75-7.93); p = 0.122] and median OS of 2.6 vs. 5.7 months [HR: 1.50 (0.45-4.99); p = 0.5068]. Observed grade ≥ 3 adverse events were: Cytopenia (4), Dyspnea (1), and endocrine disorders (3) in Arm A; diarrhea (3) and cytopenias (1) in Arm B. There was an increase in circulating CD8(+) lymphocytes on treatment versus baseline in patients with objective tumor response. Conclusions: The study did not show sufficient signal of efficacy for ICI with or without SBRT in relapsed SCLC. Detailed result of the biomarker analysis will be available at the meeting. Clinical trial information: NCT02701400. [Table: see text]
Laboratory and clinical data integration: Toward an evidence development framework.
Authors: Lori Anderson, Patricia Goede, Jacob Koskimaki, Sirisha Kakamada, Wendy S. Rubinstein
Journal: Journal of Clinical Oncology (2019)

e18318 Background: Decision making in precision oncology relies on the timeliness of diagnostic testing. Uncertainty surrounding the clinical utility of laboratory developed molecular and next generation sequencing (NGS) tests (LDTs) has engendered a predominantly manual claims review process. Denials and delays may create hurdles for optimally treating patients, and denials may contribute to financial toxicity. ASCO’s CancerLinQ aggregates clinical data from EHRs of participating oncology practices to improve the quality of care for patients. We hypothesized that standardized clinical data could be used in the short term to appeal denials of NGS LDTs and in the long run, lead to evidence-based coverage decisions. Methods: Using National Provider Index IDs, CancerLinQ participating physicians were cross-walked to ordering physicians of tests offered from 100 U.S. laboratories using XIFIN for billing services in 2018 to evaluate the feasibility of using CancerLinQ clinical data for claims adjudication. We determined the proportion of molecular and NGS tests (based on CPT coding) initially denied and the proportion of successful appeals through a manual submission process for clinical documentation (not including CancerLinQ data). CancerLinQ clinical data were evaluated for key elements necessary for successful appeals. Results: Sixty-five percent of CancerLinQ participating physicians ordered tests from the laboratories identified. Approximately 80% of NGS and 40% of molecular services were initially denied. After appealing with clinical information through the manual process, 55% of denials were successfully overturned. Key clinical data provided manually could be automatically extracted from CancerLinQ at high rates, such as ICD-9/ICD-10 cancer diagnosis (100% of 1,082,606 patients), Stage Group (47.6 %), and treatment plan (35.9%). Metastatic disease status is available through M1-stage (23.2% of total M-Stage), AJCC Stage IV (29.0% of total AJCC Stage) and Metastatic diagnosis codes (17.2%). Conclusions: CancerLinQ contains key data elements necessary for successful appeals and can streamline the claims adjudication process, ultimately helping to build the evidence base for coverage decisions.
The predictive power of free (vs. total) testosterone in aggressive prostate cancer.
Authors: Maxwell M Towe, Linda My Huynh, Farouk El Khatib, Mohamad M Osman, Faysal A Yafi, Thomas Edward Ahlering
Journal: Journal of Clinical Oncology (2019)

e16570 Background: The role of testosterone in prostate growth and the development of prostate cancer is a controversial topic. Most current data suggest that lower testosterone leads to higher grade conversion, whereas higher testosterone may serve a protective role in preventing both development and recurrence. We seek to analyze whether free testosterone (FT) values can predict aggressiveness in prostate cancers. Methods: We retrospectively reviewed 830 patients who presented to a single surgeon for evaluation and management of prostate cancer. Total Testosterone (TT) and FT values were obtained on each patient at initial visit. All patients underwent radical prostatectomy and samples from surgery were sent for grading and staging. Patients were stratified by FT quartile (25 th [≤ 4.42 ng/dL], 50 th [4.43 – 5.60 ng/dL], 75 th [5.61 – 6.95 ng/dL], and 100 th [≥ 6.96 ng/dL]). Results: Of 830 patients, 168 (22.2%), 330 (39.8%), 188 (22.7%), 46 (5.5%), and 98 (11.8%) had GS 3+3, 3+4, 4+3, 4+4, and ≥4+5, respectively. Mean FT values for each Gleason grade group (GGG) were significantly different (p = 0.008). Mean FT was also lower in patients with higher stage disease (p = 0.01). In contrast, TT did not differ significantly among GGG (p = 0.489) or stage (p = 0.670). Patients who had a FT level in the lowest quartile (≤ 4.42 ng/dL) had a higher proportion of GGG 5 (15.6%) than patients in the highest quartile (≥ 6.96 ng/dL) (6.2%) (p = 0.002). After adjusting for age, prostate specific antigen (PSA), and body mass index (BMI) in multivariate analysis, lower FT was a significant predictor of high-risk score 9-10 (OR: 0.912, 95% CI: 0.836-0.994, p = 0.036). These trends showed strong correlation in pathologic stage (p = 0.057), but larger numbers are needed to gauge effect size. Conclusions: Based on our data, biochemically low FT may be a risk factor for high grade and high stage cancer. These results have implications for the current recommendations for testosterone therapy, which is contraindicated in men with prostate cancer. [Table: see text]
Effects on histologic subgroup, race, and BMI in 2,110 breast cancer patient: Results from single institution in Georgia.
Authors: Ricardo H. Alvarez, Rebecca Rollins, Joe Ensor, Daniel W. Nixon, Jonathan Ramey, Rachel Pannell, Karen Rados, Eugene R Ahn, Sramila Aithal, Cynthia Lynch, Haritha Pabbathi, Damien Hansra, John Edward McKnight, Elizabeth MH Kim, Anita Johnson
Journal: Journal of Clinical Oncology (2019)

e13112 Background: Disparities in breast cancer (BC) care still clearly exist among Whites (W) and African-Americans (AA) racial groups. These disparities resulting in higher mortality among AA compared to W. The objective of this analysis was to estimate the prevalence of BC subtypes in a population-based sample of BC cases, collected in a Breast Cancer Database (BCD) and to examine correlations with demographic and clinicopathologic variables and patient survival. Methods: retrospective analysis of patients registered at BCD was performed. Pts with BC were analyzed for differences in survival based on histologic subgroup (HS), race and BMI. Median Kaplan Meyer estimate for potential follow-up was 13.1 months with 95% CI (10.6, 15.0). Univariate and multivariate analysis were used to identify factors associated with demographic and cancer biology variables. Results: A total of 2,110 patients were registered at BCD and were available for this analysis.The median age at diagnosis was 50.8 years with 95% CI of (50.2, 51.0). 50% were W and 46.6% were AA. HS were classified by immunohistochemistry CLIA central lab, ER+ 61.1%, HER2+ 21.8% and TNBC 17%.Fisher’s exact test showed statistically difference in HS distribution among the races (p &lt; 0.0001); 25% and 11.7% TNBC, for AA and W, respectively. The mean BMI was 29.0 with 95% CI of (29.6, 30.2). BMI characteristics were obese 47.2%, overweight 28.6% and normal 22.2%. Fisher’s exact test showed statistically difference in BMI distribution among the races, 57% and 39% obesity, for AA and W, respectively (p &lt; 0.0001). Log-rank test showed that 2-years OS is worse for TNBC (48%), than for ER+ (72%) and HER2+ (75%). In the multivariable model AA survival was statistically inferior than for W ( p= 0.0094). Cox proportional hazard model was constructed to assess the effect of age, BMI, race and HS (Table). Conclusions: This single institution analysis demonstrated a statistically differences between TNBC, AA, and abnormal BMI as poor prognostic factors in BC pts impacting OS. Further research should investigate how to improve care for AA women who are at higher risk for breast cancer mortality. [Table: see text]
A first-in-human phase I study of FS118, an anti-LAG-3/PD-L1 bispecific antibody in patients with solid tumors that have progressed on prior PD-1/PD-L1 therapy.
Authors: Timothy A Yap, Kyriakos P. Papadopoulos, Patricia LoRusso, Deborah J.L. Wong, Siwen Hu-Lieskovan, Josefin-Beate Holz
Journal: Journal of Clinical Oncology (2019)

TPS2652 Background:PD-1/PD-L1 checkpoint inhibitors demonstrated remarkable anti-tumor activity, but only a minority of patients achieve full clinical benefit with deep and durable responses. Translational studies suggest resistance to cancer immunotherapy can be mediated by additional immune checkpoints e.g. lymphocyte-activation gene 3 (LAG-3). The combination of LAG-3 and PD-1 mAbs synergistically improved anti-tumor response in murine models and early clinical trials. In a small cohort, TIL LAG-3 expression enriched for responsiveness in PD-1/PD-L1 relapsed/refractory patients. FS118 is a novel bispecific antibody incorporating a LAG-3 binding Fc-region into a PD-L1-specific IgG1 antibody to potentially deliver superior anti-tumor efficacy while limiting immunotherapy-related adverse effects by dual targeting. Methods: The FiH study (NCT03440437) is being conducted in adult patients with solid tumors who failed prior PD-1/PD-L1 treatment. Primary objectives of the study are to determine safety, PK and the maximum tolerated/recommended Phase 2 dose of FS118. Secondary objectives include preliminary evidence of efficacy, immunogenicity, PD profile and exposure/response correlation. 50 subjects from four study sites in the USA are planned to enrol in dose escalation initiated with accelerated titration (5 single subject cohorts) followed by 3+3 design and expansion cohorts. FS118 is administered weekly IV in 21-day treatment cycles until progression, unacceptable toxicity, withdrawal, or death. Patients are followed for safety, overall survival and initiation of subsequent therapy. DLT clearance, dose escalation and cohort expansion (to further characterise safety, PK/PD or clinical efficacy) are supervised by a safety review committee (SRC). Translational studies assess PD-L1/LAG-3 receptor occupancy, soluble PD-L1/LAG-3 levels and the correlation of FS118 exposure with selected PD markers of target engagement and response. Translational endpoints include TIL analysis, transcriptomic profiles and target expression analyses on tumor tissues. Cohorts 1 through 6 have been completed, enrollment in cohort 7 began December 2018. Clinical trial information: NCT03440437.
Discovering HPV16 and HPV18 infection status and cancer gene variations in cervical cancer patient specimens by using Next-generation sequencing.
Authors: Bo Meng, Lili Quan, Wenjuan Yang, Jidong Lang, Lanyou Chen, Ruyi Dong, Juanyu Zhao, Geng Tian
Journal: Journal of Clinical Oncology (2019)

e13040 Background: Human papillomavirus (HPV) infection has been reported as an important cause of cervical cancer for many years. HPV16 and HPV18 are the two most prevalent types in cervical cancer5. Integration of HPV DNA is a crucial genetic event in cervical carcinogenesis. Therefore, it is important to know the HPV integration hot spots in human genome to predict the cervical cancer development status of patients. Although many studies have addressed the HPV integration sites in human genome, it is still a technique barrier to precisely determine the HPV integration sites of each patient, especially at early disease development stage with limited integration sites existing. Methods: To solve this problem, we first designed HPV probes to capture HPV integrated sequences of genome using next generation sequencing (NGS). And then we analyzed the integration sites by two methods with the NGS results, HPV Detector. We applied the study on 17 patient samples, 15 of them were found HPV16 positive and 2 of them were found HPV18 positive. Among them 16 were detected with HPV integration sites. Results: The results indicated that different samples showed different numbers of integration sites with limited overlapped positions in genome. The integrated positions of HPV16/18 located in all the genes of the virus, but mostly distributed in gene E1, L1 and L2. We identified integration sites HPV16 E6/GATC， E6/WWTR1， L2/DGKB, E1/EHHADH, ect. Some of the integrated sites in human genome are belong to intergenic region. We also used cancer gene panel, which cover 143 cancer related genes exon regions, to identify the mutation sites of each samples. We summed up a highly occurred mutated cancer gene list, which include ALK, NF1, PIK3R1, ROS1, TSC1, TSC2, ect. Most of them are either cancer driver genes or have been found highly related to cervical cancer. Further study is still carrying on. Conclusions: In conclusion, our HPV probe could successfully detect HPV16 and HPV18 in patient samples and enrich HPV integration sites in human genome of cervical samples significantly. It could provide detailed information for cervical cancer discovery and early detection.
BIG DATA in geriatric oncology: How could we assess effective working time?
Authors: Borja Lopez De San Vicente, Paula Jaureguibeitia, Ane Zumarraga, Maria López Santillan, Fernando Pikabea, Elena Galve, Maitane Nuño, Patricia Novas, Teresa Abad, Juan Fernando Arango, Maria Teresa Perez-Hoyos, Laura Sande, Angeles Sala, Jairo Legaspi, Josune Azcuna, Maria Purificacion Martínez
Journal: Journal of Clinical Oncology (2019)

e18073 Background: Electronic Medical Records (EMR) were born as a result of medicine digitalization. Healthcare information systems (HIS) hold great value to the workflow management and patient care. New technologies not only allow us work with a faster and more reliable medical history, but also understand how health professionals think and work. Time consumption is one of the biggest issues that geriatric assessment (GA) has to deal with. Hurria et al. developed a brief tool which requires minimal resources and time spent (≈30 mins) by healthcare providers. On the other hand, patients´ medical history review, writing reports or tumor board discussions are often underestimated on daily time schedule. The aim of this study is to analyse the effective working time (EWT) invested in geriatric assessment in our centre by Big Data analytics. Methods: From 1 March 2018 to 31 december 2018, &gt; 70 years-old patients were prospectively recruited from the outpatient oncology practices at Basurto University Hospital. Nurse-guided geriatric assessment was scheduled 45 mins before oncologist’s first visit, and functional status, comorbidity, cognitive function, psychological state, social support, polypharmacy, nutritional status, and nurse interventions were measured. Patterns of nurse and medical behaviors from EMRs were tracked. The model to figure out active behaviour in HIS was defined as &gt; 23 events/hour. EWT was established as time spent between first and last access to HIS. Isolated events and interventions by users other than oncologists and nurses were excluded. Results: 280 patients were enrolled, 54.3% men. Geriatric assessment detected: cognitive impairment 17 pts (6.9%), mental health alteration 78 pts (27.8%), Poor social support 10 pts (3,7%), polypharmacy 239 pts (89,28%), and severe malnutrition 34 pts (13.2%). Nurse specific intervention was made in 90 pts (32,6%). The median EWT by nurses for a GA was 39 minutes (SD 0:21), and 46 mins (SD 0:17) by oncologists´global evaluation. Nurses started in average 3 mins (SD 0:27) before scheduled visit, and oncologists 9 mins (SD 0:28) after. Conclusions: Big data analytics show an assumable effective working time for a geriatric assessment in our patients. HIS users behavior analysis could help in the management of our healthcare systems.