tbuckley/cabot-search huggingface dataset:
Modeling tumor size time course in platinum resistant/refractory ovarian cancer patients treated with vanucizumab.
Authors: Christophe Boetsch, Kevin Smart, Benjamin Ribba, Francois Mercier, Oliver Krieter, Vincent Buchheit, Angelika Lahr, Alex Phipps
Journal: Journal of Clinical Oncology (2016)

e17042 Background: Vanucizumab is a novel bi-specific IgG-like antibody which is directed against both VEGF-A and ANG2, two key factors in tumor angiogenesis. As such, vanucizumab represents an encouraging approach in preventing tumor growth in a variety of cancer types Methods: Eligible patients (pts) with platinum (Pt)-resistant/ refractory epithelial OC (PROC) were treated with vanucizumab at 30 mg/kg IV Q2W until disease progression or unacceptable toxicity. Patients underwent tumor assessment by CT scan at screening, and then every 8 weeks while on study. According to RECIST 1.1, target lesions (max 5 and max 2 per organ, representative of key organs) were summed to yield summary of the longest lesion diameter (SLD). Longitudinal modeling of such SLD data allows quantification of the effect of anticancer therapies in addition to the RECIST criteria. Overall, the SLD data set contained 143 observations (SLD measurements per patient: mean 3.6, range 2-6), and pts received on average 9 cycles of treatment. Longitudinal SLD data were analyzed by means of a population mixed-effect model to quantitatively estimate metrics of efficacy, such as maximum shrinkage and time to tumor regrowth after treatment onset, together with critical kinetic parameters such as the natural growth rate of the tumor Results: Objective response as per RECIST was demonstrated in 8/41 (20%) and 8/28 (29%) for all and bevacizumab naïve pts, respectively. The maximum tumor shrinkage from baseline was calculated to be 49% (95% CI: 47-52%), with a time to re-growth of 5.5 months (95% CI: 5.2-5.7 months). The unperturbed tumor growth rate was estimated to be roughly 0.7 mm/week, suggesting that a tumor of 100 mm in size would gain approximately 5.6 mm after 8 weeks if left untreated. After 8 weeks of vanucizumab treatment, its size would be decreased by approximately 32 mm Conclusions: Longitudinal modelling of SLD data is a useful technique allowing extraction of key metrics of tumor shrinkage over time and comparison of effect between different treatments. Vanucizumab 30 mg/kg Q2W was shown to be clinically active in pts with PROC, and thus may represent a novel therapy, either alone or in combination with immunotherapy or chemotherapy. Clinical trial information: NCT01688206.
Ethnic differences in hematologic toxicity from imatinib in patients with gastrointestinal stromal cell tumor (GIST).
Authors: Sneha Purvey, Kristen Kaley, Nawal Wasif, Teresa P Rodriguez, Kenneth B Miller, Wasif M. Saif
Journal: Journal of Clinical Oncology (2018)

e23513 Background: There is a wide variability in pharmacokinetics, pharmacodynamics & tolerance of anticancer drugs based on ethnicity. Myelosuppression is common in pts with cancer who receive chemotherapy and contributes to therapy-induced morbidity & mortality. GIST is a rare cancer (~1% of GI cancers). Imatinib is used in the neoadjuvant, adjuvant & metastatic setting. The purpose of this study was to investigate difference in tolerance to imatinib among different ethnicities when treated for GIST in any setting. Methods: Pts treated with imatinib for GIST from July 2005 - Jan 2018 were identified. Data including age, gender, ethnicity, pathology, adverse effects, dose modifications & administration of pegfilgrastim was collected. Grading was done according to CTCAE v4.0. Results: A total of 57 pts received imatinib [median age 61 yrs (range 32-87); 58% ≥ 65; M:F = 37:20] with pathologically confirmed GIST with KIT expression during this period. All pts initially received imatinib 400 mg daily: 40 metastatic, 17 adjuvant. Ethnicities included White 37; M:F = 30:7 (65%), African-American (AA) 11; M:F = 4:7 (19%), Asian 7; M:F = 2:5 (12%) and Hispanic 2; M:F = 1:1 (3%). Grade 3 & 4 neutropenia was seen in 6 pts (10%): 5 AA; M:F = 1:4 (83%) and 1 Asian male (17%). 45% (5/11) of all AA pts developed severe neutropenia. Median absolute neutrophil count (ANC) nadir was 700/µL (488-840). Median duration on drug prior to neutropenia was 4.5 wks (3-12). Median duration of neutropenia was 4 wks (2-10) and 1 pt developed febrile neutropenia. Dose interruptions were needed in 3 pts & dose reduction in all pts, 1 pt discontinued & 1 pt was escalated back to 400 daily, 3 pts required pegfilgrastim. Concomitant anemia was seen in 4 pts & pancytopenia in 1. Bone marrow biopsy done in 2 pts showed no abnormality. Conclusions: This is the first study to report ethnic variations in myelosuppression associated with imatinib in GIST (more in AA). It is possible that this difference has not been reported in CML as the aim is to bring blood counts down. Though being a small sample size, our data underlines the importance of studying ethnic variation in relation to imatinib dosing and necessitates close monitoring & dose adjustments.
Phase I factorial study of temozolomide plus memantine, mefloquine, and metformin as post-radiation adjuvant therapy for newly diagnosed glioblastoma.
Authors: Stefania Maraka, Morris D. Groves, Aaron Gerald Mammoser, Isaac Melguizo-Gavilanes, Charles A. Conrad, Ivo Tremont-Lukats, Monica Elena Loghin, Barbara Jane O'Brien, Vinay K. Puduvalli, Erik P. Sulman, Kenneth R. Hess, Kenneth D. Aldape, Mark R. Gilbert, John Frederick De Groot, W. K. Alfred Yung, Marta Penas-Prado
Journal: Journal of Clinical Oncology (2018)

2044 Background: Repurposing non-cancer drugs may represent a new source of novel therapies for glioblastoma (GBM). Memantine, mefloquine, and metformin have putative anticancer activity potentially relevant to gliomas. The aim of this phase I factorial study was to determine the maximum tolerated doses (MTD) of combinations of these agents with temozolomide (TMZ) for newly diagnosed GBM. Methods: Adults (≥18 years of age) with newly diagnosed GBM who received chemoradiation with TMZ, with no progressive disease on post-treatment imaging, were eligible. The patients were sequentially enrolled to one of seven treatment arms (doublet, triplet, or quadruplet therapy with TMZ combined with mefloquine, memantine, and/or metformin). Dose-limiting toxicities (DLTs) were determined over the first 28 days of treatment, using a 3+3 study design. Results: Of 85 enrolled patients, 81 patients completed the MTD period. The final MTDs for doublet therapy arms (TMZ plus 1 drug) were memantine 20 mg twice a day (BID), mefloquine 250 mg 3 times/week, and metformin 850 mg BID. For triplet therapy arms, the MTDs were memantine 10 mg BID, mefloquine 250 mg 3 times/week, and metformin 850 mg BID. For quadruplet therapy, the MTDs were memantine 10 mg BID, mefloquine 250 mg 3 times/week, and metformin 500 mg BID. DLTs included dizziness related to memantine and gastrointestinal effects related to metformin. Lymphopenia was the most common adverse event (66%); fatigue was the second most common (65%). From study entry, median survival was 21 months; the 2-year survival rate was 43%. Conclusions: Memantine, mefloquine, and metformin can be safely combined with TMZ as treatment for newly diagnosed GBM. The MTDs determined by this study can be used for subsequent clinical trials.
Analytical validation of multiplex assays on Simple-Plex Ella platform for the measurement of cytokines.
Authors: Vinita Gupta
Journal: Journal of Clinical Oncology (2016)

e14501 Background: Immune check point inhibitors such as anti-PD-L1 have exhibited durable anti-tumor responses in a variety of cancer indications which break down the tolerogenic state of immune cells and activate T-lymphocytes. These activated lymphocytes release cytokines that directly stimulate immune effector cells at the tumor site and enhance cell recognition by cytotoxic effector cells for elimination of tumors. Measurement of cytokines is actively being pursued to study pharmacodynamic changes which can help understand the mechanism of action of immune checkpoint inhibitors. Methods: In this study, we describe bioanalytical validation of cytokines assays in plasma on a novel multiplex platform, Simple-Plex Ella. Ella allows multiplexing of four analytes and consumes small sample volume of 25µl. Compared to conventional multiplex immunoassays such as Luminex, Ella offers the specificity of a single-plex ELISA since each sample is run in four channels, each specific to a unique analyte. Results: The assays exhibited excellent sensitivity and specificity. The accuracy and precision were 80-120% and 10% respectively. Conclusions: The assays were considered fit for purpose to support clinical biomarker studies.
Soluble human histocompatibility antigens (HLA) as potential biomarkers for early detection of non-small lung carcinoma (NSCLC).
Authors: Smriti Kanangat, Melissa R Pergande, Cristina L. Fhied, Gabriela C Lobato, Imad Tarhoni, Gary Chmielewski, Michael J. Liptay, Christopher W. Seder, Jeffrey Allen Borgia
Journal: Journal of Clinical Oncology (2016)

e23061 Background: Early detection of non-small cell lung cancer (NSCLC) is critical for successful treatment; however, current screening methods cannot reliably distinguish between benign and malignant nodules. The human histocompatibility antigens (HLA), which regulate the immune response, are critical to tumor immunity escape mechanisms. Increased HLA levels in the blood of cancer patients have been reported. This study explored the possibility that circulating HLA concentrations may be used to distinguish between benign and malignant lung nodules in the setting of CT-based lung cancer screening studies. Methods: HLA class I (ABC) and class II (DRB1 and DQ) antigen levels were immunoblotted in conditioned media isolated from NSCLC cell lines H358 (epithelial; non-invasive) and H1703 (mesenchymal; invasive). Then, serum specimens from 25 patients with benign nodules and 25 patients with stage I NSCLC were evaluated in a similar fashion for HLA-class I (ABC), HLA-class II (DRB1, DQA1, DQ, DMB) antigens. The Mann-Whitney U test (two-tailed) was used to evaluate differences in biomarker expression whereas a receiver operator characteristics (ROC) curve analysis was used to evaluate biomarker performance relative to cancer status (expressed as an ‘area-under the curve’, AUC). Results: Higher concentrations of HLA class I antigens were observed in conditioned medium from the invasive cell line, H1703, relative to conditioned medium from the non-invasive cell line (p< 0.05). Patients with malignant lung tumors also demonstrated higher levels of both class I and class II HLA molecules, relative to those with benign nodules (p< 0.05). The ROC analysis revealed the greatest performance for ABC (AUC = 0.687), DQ (AUC = 0.694), and DQA1 (AUC = 0.737) for distinguishing malignant from benign nodules in this same cohort. Conclusions: These preliminary data suggest that HLA class I and class II antigens may have value as diagnostic biomarkers for early stage NSCLC. Validation of these findings using the Luminex platform is currently underway using sera from a lung cancer screening cohort (n = 125).
TCT-514 Balloon-expandable Sapien 3 29mm versus self-expandable Evolut R 34mm in TAVR patients with a large annulus: Is there a difference in performance and risk of cerebral embolization?
Authors: Christina Brinkmann, Amnon Eitan, Timo Haselbach, Julian Witt, Friedrich-Christian Rieß, Joachim Schofer
Journal: Journal of the American College of Cardiology (2018)
Are surrogate endpoints unbiased metrics compared to hazard ratio for death? An evaluation of clinical benefit scores (CBS) in the American Society of Clinical Oncology (ASCO) value framework.
Authors: Mahin Iqbal Qureshi, Matthew C. Cheung, Sierra Cheng, Di Maria Jiang, Erica McDonald, Vanessa Sarah Arciero, Doreen Anuli Ezeife, Alexandra Chambers, Kelley-Anne Sabarre, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2017)

6600 Background: Clinical benefit scores (CBS) are a key element of the American Society of Clinical Oncology (ASCO) value framework's Net Health Benefit valuation of cancer therapies. CBS are assigned based on a hierarchy of efficacy endpoints, from hazard ratio for death (HR OS), to median overall survival (mOS), HR for disease progression (HR PFS), median progression-free survival (mPFS), and response rate (RR). When HR OS is unavailable, other endpoints in the hierarchy are used as "surrogates" to calculate CBS via their scaling factors. We aim to examine whether surrogate-derived CBS offer unbiased scoring of clinical benefit compared to HR OS-derived CBS. Methods: CBS for advanced-disease settings were computed for randomized clinical trials (RCTs) of oncology drug approvals by the Food and Drug Administration, European Medicines Agency, and Health Canada, between 2006 and August 2015. Spearman's correlation assessed association between CBS derived from surrogates and HR OS. Mean bias (surrogate-derived CBS minus HR OS-derived CBS) evaluated the tendency for surrogate-derived CBS to over- or under- estimate clinical benefit. Mean absolute error (MAE), a measure of average deviation, assessed precision of surrogate-derived CBS in relation to HR OS-derived CBS. Results: Scored RCTs (n=104) yielded 69, 93, 88, and 89 paired CBS between HR OS and mOS, HR PFS, mPFS, and RR, respectively. See table for results. Restricting to RCTs reporting all endpoints (n=59) and RCTs without OS as primary endpoint (n=68) showed similar results. Conclusions: Findings suggest HR PFS-, mPFS-, and RR-derived CBS are poor "surrogates" as they are imprecise and weakly correlated to HR OS-derived CBS. HR PFS and particularly mPFS exhibit bias to overestimate CBS. [Table: see text]
Preliminary findings from a pilot program to provide access to low-dose CT screening for high-risk patients.
Authors: Katherine Sharpe, Lesley Watson, Kara Riehman
Journal: Journal of Clinical Oncology (2018)

e18844 Background: Evidence suggests that there is a mortality reduction benefit from low-dose CT (LDCT) scans for patients at high-risk for lung cancer, yet screening rates remain low. The American Cancer Society has implemented a pilot program to improve access to lung cancer screening in vulnerable populations with high lung cancer mortality rates in Memphis, Tennessee and Charleston, West Virginia through partnerships with Community Health Centers (CHCs) that serve limited resource patients. The program focuses on developing systems within CHCs for identifying screening-eligible patients, patient education, shared decision-making referral and navigation to screening, and appropriate follow-up. The program also helped CHCs stimulate collaboration among local partners and develop long-term structures and relationships needed to improve the links of care in the community to deliver lung cancer screening. This presentation focuses on evaluation results related to the 3 core components of the program–provider education, navigation, and the development of tools and resources. Methods: Participating CHCs submitted quarterly monitoring reports tracking the number of patients they assessed for program eligibility, shared decision-making visits, screenings, screening results, and cancer diagnoses. Evaluators also conducted key informant interviews to determine processes used by CHCs when implementing the program, as well as program facilitators and barriers. Results: To date, the program has screened 193 patients. Of those, 45 received an abnormal result that required follow-up and there have been two cancer diagnoses. Qualitative results indicate that CHCs face challenges with identifying eligible patients due to EHR barriers and difficulties with pack-year calculations. Conclusions: This project adds to the growing knowledge base of effective lung cancer screening practices, specifically for patient populations with access barriers. The project also identifies challenges to implementation that can be used to help CHCs looking to initiate similar lung cancer screening programs.
P01.082 International survey regarding use of MGMT analyses for glioma
Authors: A Malmström, B Winther Kristensen, R Henriksson, P Söderkvist
Journal: Neuro-Oncology (2018)

MGMT promotor methylation status is part of glioma diagnostics, supporting clinical decision making. Internationally different methods and cut-off levels are used to determine whether a tumor is methylated or unmethylated. Treatment decisions can be inadequate, when methylation status of the tumor can change due to the analysis and cut-off used. We conducted an international survey, consisting of 27 questions, to clarify which methods are regularly used in different clinico-pathological settings and why a specific method is selected. We also asked about opinions regarding an international consensus on methods and cut-off levels. The survey was answered by 146 respondents - mainly neuropathologists - from 24 countries. The responses show that MGMT methylation status is determined for all gliomas in 37% of laboratories, while 8% do not perform the analysis. The most commonly used methods are msPCR (37%) and pyrosequencing (34%). The main reasons for choosing a specific method are simplicity (56%), cost-effectiveness (49%) and reproducibility of results (49%). For those using pyrosequencing, the most common number of CpG sites analyzed is four, but varies between 1–3 and more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites should be examined, while 33% select the sites themselves. Selection of cut-off is equally distributed between a cut-off a) published in the literature, b) defined by the lab or c) defined by the company performing the analysis. This cut-off varies between different pathology departments. In one lab tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. For others cut-off for methylated varies from 1% to 30%. Some report tumor as unmethylated or weakly versus highly methylated. An international consensus on MGMT methylation method is believed to be of advantage by 66%, while only 20% do not find this necessary. A consensus on a cut-off is warranted by 76%. Most suggest that the consensus method should be msPCR (45%) or pyrosequencing (42%), while 17% suggest next generation sequencing. While analysis and use of MGMT methylation status has become routine in the clinico-pathological setting, there is still controversy regarding the best laboratory method and the clinically relevant cut-off level. Most respondents suggest that an international consensus on both method and cut-off should be established.
Treatment completion and tolerability of women with cervical cancer with and without HIV in Botswana.
Authors: Surbhi Grover, Memory Fadziso Bvochora-Nsingo, Emily MacDuffie, Sarah Ratcliffe, E. Paul Wileyto, Rohini Bhatia, Alyssa Yeager, Sebathu Phillip Chiyapo, Ponatshego A Gaolebale, Anthony Henry Russell, Remigio Makufa, Talkmore Karunmekayi, Dawn Balang, Mukendi Kayembe, Doreen Ramogola-Masire, Scott Dryden-Peterson, Akila N. Viswanathan, Erle Robertson, Nicola Mario Zetola, Lilie L. Lin
Journal: Journal of Clinical Oncology (2016)

5526 Background: Cervical cancer is the leading cause of cancer death for women in Sub-Saharan Africa. HIV increases risk for cervical cancer and concurrent antiretroviral treatment (ART) could increase risk for toxicity of chemoradiation. In the current analysis, we aim to identify differences in treatment toxicities and completion between HIV+ vs. HIV- cervical cancer patients in Botswana treated with radiotherapy (RT). Methods: We prospectively enrolled cervical cancer patients treated with curative RT (+/- chemotherapy). Patients were seen weekly for toxicity monitoring using CTCAE 4 grading. Treatment completion was defined as receiving full dose external beam RT and brachytherapy as prescribed and 4 weekly cycles of cisplatin in < 8 weeks. Results: 190 women were enrolled between 7/2013 and 1/2015. 181 women with complete treatment and HIV data were included in the analysis. 66% (121) of women were HIV+ and presented at a younger age compared to HIV- (median 44 vs. 56 years; p<0.001) and at an earlier stage (HIV- 39% stage II and 47% stage III vs. HIV+ 55% stage II and 31% stage III, p=0.02). Median CD4 count for HIV+ was 469 (range 118-941). 94% of HIV+ patients were on ART. There were no differences between HIV+ vs. HIV- in treatment received and toxicities except renal toxicity in univariate analyses. Only 25% HIV+ vs. 28% HIV- completed treatment. See Table 1. Conclusions: The majority of cervical cancer patients in Botswana are women with well-controlled HIV infection. No significant differences were detected in treatment completion, but HIV+ patients seemed to be at increased risk of renal toxicity. We are further exploring reasons for poor treatment completion in both groups. Treatment and toxicity in patients with cervical cancer in Botswana. Treatment HIV- (N=61) HIV+ (N=115) P value Treatment duration 46.4 days +/- 10 days 45.7 days +/- 8.9 days 0.79 Completed all treatment 17 (28%) 30 (25%) 0.26 Completed 4 cycles of chemotherapy 24 (40%) 55 (50%) 0.23 Completed all RT 36 (61%) 62 (52%) 0.23 RT dose (EQD2) ≥80Gy (recommended): 30 (50%) 59 (49%) 0.48 Toxicities Neutrophil count <1500/mm3 5 (9%) 14 (14%) 0.31 Creatinine elevation >1.5mg/dl 30 (56%) 87 (84%) <0.0001
An internet-based survey of factors influencing patients’ satisfaction score and factors leading to discontinuation of treatment in lung cancer patients in China.
Authors: Weini Qiu, Sai-Hong Ignatius Ou
Journal: Journal of Clinical Oncology (2018)

e18871 Background: China instituted health insurance coverage in 2017 that covers targeted therapy drug gefitinib but not crizotinib. We analyzed factors that influence lung cancer patients' satisfaction & decision to discontinue treatment in patients with or without common actionable driver mutations (EGFR/ALK/ROS1). Methods: We conducted an internet-based survey on patient’s community web-based forum in China on the satisfaction & cost in lung cancer patient’s care from 11/2017 to 1/2018. These 21 questions include age, sex, household income, histologies, molecular sub-type (EGFR/ALK/ROS1 driver mutation or not), money spent on treatment, preference on drug choice & price & satisfaction level of their oncology care. Results: 485 completed lung cancer patient surveys from 25 provinces & regions were analyzed. 73% of the patients had EGFR/ALK/ROS1 driver mutations (Table 1). There is a positive correlation between household incomes & mean patient satisfaction score. Inadequate time with MDs (25.7%) is the leading dissatisfaction factor for monthly household income > 50,000 RMB while treatment cost (23.4%) is the leading dissatisfaction factor for monthly household income < 5,000 RMB. High treatment cost is universally the primary reason for treatment discontinuation. No difference was observed between adenoCA patients with/without actionable driver mutations (EGFR/ALK/ROS1). Conclusions: Strategies to improve patient satisfaction & lower treatment cost may lead to improved lung cancer outcome in China. Table 1 Total AdenoCA (EGFR/ALK/ROS1 positive) AdenoCA (non-EGFR/ALK/ROS1) Squamous cell Small cell Mixed N 466 340 64 30 24 8 Median household income/month 5,000-8,000 RMB 5,000-8,000 RMB 5,000-8,000 RMB < 5,000 RMB 5,000-8,000 RMB 5,000-8,000 RMB Mean Satisfaction Score (1 lowest-10 highest) 5.99 6.04 5.92 6.00 6.17 4.25 Primary reason for dissatisfaction (%) Inadequate time with MDs (24.3) Inadequate time with MDs (24.7) Inadequate time with MDs (26.9) High treatment cost (25.0) Long waiting time (31.6) No good treatment plan provided (23.0) Treatment cost as primary reason for treatment discontinuation (%) 89.2 87.5 89.4 96.7 75.0 79.2