tbuckley/cabot-search huggingface dataset:
Early, molecular detection of cancer utilizing circulating cell-free DNA assay with ultra high accuracy and sensitivity.
Authors: Stefanie Mortimer, Katharine Dilger, Diana Abdueva, Darya Chudova, Ankit Sarin, Chloe Evelyn Atreya, Jim Leng, Jeeyun Lee, Helmy Eltoukhy, Pamela N. Munster, AmirAli Talasaz
Journal: Journal of Clinical Oncology (2016)

11540 Background: Analysis of cell-free circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) is a promising method for early detection of cancer. Applications include screening high risk populations and detection of post-operative residual disease for adjuvant therapy decision-making and early detection of cancer recurrence. However, to be applicable, tests must cover a broad enough genomic footprint to not require a priori knowledge of mutations to have clinical sensitivity higher than conventional methods Methods: We developed a 20kb panel ctDNA capture panel based on the landscape of genomic alterations in ctDNA of over 10,000 advanced cancer patients, with high theoretical clinical sensitivity for: colorectal (96%), ovarian (95%), lung (90%), and pancreatic cancers (90%). Analytical sensitivity of 0.01% for single nucleotide variants (SNVs) and indels was achieved. We used the panel to monitor advanced cancer patients (n = 120pts with longitudinal samples) and then applied it to a clinical study of 14 early stage (II/III) CRC patients with both pre- and post-tumor resection blood draws (up to 7 days post surgery). A subset (6 patients) also had tumor samples collected at the time of the surgical resection. Results: Overall, the detection rate of ctDNA in pre-op blood draws was 93%. In the post-op blood draws ctDNA was detectable in 43% of cases. When tumor tissue was available and used as a reference, the clinical sensitivity, specificity, and accuracy in pre-op blood samples were 83%, 99.995%, and 99.99%, respectively. The clinical specificity of variants detected in post-op blood samples using pre-op samples as the reference is 99.996%. Cohort expansion of CRC and recently diagnosed ovarian cancer patients is ongoing. Conclusions: In conclusion, we have leverage emerging knowledge of the cancer genome to educate the development of a non-invasive multigene cfDNA NGS test with ultra-high sensitivity and high accuracy for the early detection of ctDNA across many of the most deadly and difficult to detect cancers.
P14 Detection of EGFR/T790M Mutation in Advanced NSCLC Post TKI Treatment: First Experience of Liquid Biopsy in Argentina
Authors: M.C. Mosqueira, S. Anchordoqui, R. Martínez Correa, E. Pichelbauer, A. Trinchero, M. Bianchini, I. Bravo, G. Bramuglia, I. Diaz Perez, L. Sganga, S. Goncalves
Journal: Journal of Thoracic Oncology (2018)
A meta-analysis to indirectly compare the safety and efficacy of PD-1 and PD-L1 antibodies across solid tumors using a Bayesian hierarchical model.
Authors: Mythili Koneru, Amita Patnaik, Jingyi Liu, Shivani Nanda, Zachary M Thomas, Ji Lin
Journal: Journal of Clinical Oncology (2018)

3065 Background: Many PD-1/PD-L1 mAb are in development across a broad range of tumors. The expanded literature provided an opportunity to address a critical question: if PD-1 mAbs targeting the receptor have a different safety/efficacy profile than the PD-L1 mAbs targeting the ligand. Direct comparison of these mAb would be ideal but highly unlikely. Methods: We performed a meta-analysis using a Bayesian model to provide indirect comparison based on data in the public domain including PubMed and key medical conference abstracts (eg ASCO, ESMO etc.). Key inclusion/exclusion criteria include patients 1) with any specific solid tumor, 2) PD-L1 status if tested using one of the approved assays, 3) received one of the five approved mAbs as a monotherapy, and 4) with disclosure date between June 4th, 2013 and June 6th, 2017. The search resulted in about 70 clinical trials in 31 tumors and 12,025 patients. The endpoints include ORR, PFS for efficacy and the overall G3/4 AE rate for safety. Results: For efficacy, in all solid tumors except for HNSCC, ORR is slightly greater for PD-1 than PD-L1 mAb, with the largest odds ratio (OR) in 2L+ NSCLC favoring the PD-1 mAb [ORRPD-1= 19.8% vs ORRPD-L1= 16.5%, OR = 1.27, 95% CI = (0.96, 1.70)] and the smallest OR in 1L HNSCC favoring the PD-L1 mAb [ORRPD-1= 27.4% vs. ORRPD-L1= 28.7%, OR = 0.975, 95% CI = (0.38, 1.50)]. Overall, there is 81% posterior probability that ORRs are equivalent for PD-1 and PD-L1 mAb. For safety, the Gr 3/4 AE rate (e.g. pneumonitis) is numerically higher for PD-1 than PD-L1 mAb [OR = 1.48, 95% CI = (0.19, 12.39)] across tumors. Overall, there is 79% posterior probability that the safety profile in terms of G3/4 AE rate is equivalent for PD-1 and PD-L1 mAb. Conclusions: There was no significant difference between PD-1 and PD-L1 mAb across tumor types for ORR, PFS and Gr 3/4 AE rate. Moreover, when the information was analyzed across tumor types, the small magnitude of the difference relative to the variability across tumor types suggests strong interchangeability of efficacy and safety profile of the antibodies targeting either PD-1 or PD-L1. Ultimately, the variability within this class of antibodies is not likely to be clinically meaningful.
Clinical benefit of continuing apatinib beyond progression in advanced or metastatic gastric cancer.
Authors: Shukui Qin, Lu Wen, Junsheng Wang, Wenying Deng, Guifang Zhang, Tongfu Jia, Yi Ba, Haijun Zhong, Jianwei Yang, Xiaoyan Lin, Yu-Xian Bai, Yifu He, Zhong Xie, Tienan Yi, Xiangyuan Wu, Feng Ye, Likun Liu, Yong Huang, Mei Wang, Jin Li
Journal: Journal of Clinical Oncology (2018)

e16020 Background: Apatinib has been approved in China for patients (pts) with advanced or metastatic gastric and gastro-esophageal junction adenocarcinoma after at least two lines of systemic chemotherapy. This indication is being evaluated worldwide. However, there is limited option for fourth- or later-line treatment for pts with gastric cancer. Herein, we aimed to assess whether pts could still benefit from continuing apatinib treatment after failure of apatinib as third-line or beyond therapy. Methods: Data were collected from a post-marketing Phase IV study (Ahead-G201) in China, in which pts were planned to receive apatinib until disease progression, death or unacceptable toxicity. Pts who had radiographic or clinical progression were included in the present analysis. Results: As of 12/21/2017, 1229 pts enrolled in the Ahead-G201 study were evaluable for efficacy. Following the scheduled apatinib treatment, there were 336 pts with radiographic progression and 82 pts with clinical progression. Among them, 60 (14.4%) pts chose to continue apatinib monotherapy or in combination with other systemic treatment (defined as apatinib continued group), whereas 358 (85.6%) pts received treatment other than apatinib (defined as no apatinib group). There was no significant difference between the two groups in baseline characteristics, including age, gender, ECOG PS and treatment lines. Compared with no apatinib group, apatinib continued group showed a significantly longer overall survival (OS) (8.84 [95%CI, 7.29–11.89) vs. 6.47 [95%CI, 5.59–7.06] months; p= 0.0270). Radiographic data were only available for 40 pts in the apatinib continued group. No pts achieved complete or partial response. The disease control rate was 42.5%. The median progression-free survival was 1.91 (95%CI, 1.68–2.83) months. Conclusions: For cases with advanced or metastatic gastric cancer who received apatinib as third- or later-line treatment, continuing apatinib monotherapy or in combination with other drugs beyond initial progression still bring survival benefit. This analysis provides evidence for further clinical trials. Clinical trial information: NCT02426034.
Improved urine samples collection for DNA/RNA purification and its application in bladder cancer detection.
Authors: Michiko Suwoto, Paolo Piatti, Xiaojing Yiang, Xi Yu Jia, Yap Ching Chew
Journal: Journal of Clinical Oncology (2016)

e18199 Background: Urine represents an extremely important body fluid for the sensitive and non-invasive detections of multiple diseases including urinary tract infections and cancers. Recently, urine nucleic acids based biomarkers has gained popularity as the preferred diagnostic methods. However, DNA and RNA in urine are prone to degradation and conventional urine storage (i.e. sample freezing and the addition of additives) have limited positive impacts on the nucleic acids quality. Therefore, to ensure the robust urinalysis, a well-standardized procedure of urine sample collection, storage, and nucleic acid purification should be developed and streamlined. Methods: We developed a novel technology, Urine Conditioning Buffer (UCB) which effectively preserves total DNA and RNA in urine samples for at least 1 month at ambient temperatures, abating the high costs of cold chain. Importantly, UCB inhibits microbial growth, reducing the risk of biohazard exposure. Additionally, the combination of UCB and Quick-DNA Urine Kit (Zymo Research) allows the isolation of either cellular, cell-free, or total DNA from urine samples. Results: We further validated our technology by conducting a pre-clinical study. The DNA methylation level of the 13 unique bladder cancer biomarkers (developed at Zymo Research) was analyzed in a cohort of 53 individuals (33 bladder cancer patients and 20 healthy individuals). Collected urine samples were preserved in UCB and total urine DNA was isolated using Quick-DNA Urine Kit. Urine DNA was analyzed in parallel using two different approaches: a bisulfite conversion based assay and a non-bisulfite based assay. Despite the methodology differences, both assays perfectly discriminated bladder cancer from control samples. This study indicates that UCBpreserves the urine DNA integrity, a prerequisite for the successful urine DNA and RNA based testing. Conclusions: Here, we present a successful application of our unique technology in bladder cancer diagnosis, which is the 5th most common cancer in US. Furthermore, it demonstrates that we have developed a total solution for urine based molecular testing covering sample collection, stabilization, purification, and detection platform.
Impact of race on surgical management of pancreatic neuroendocrine tumors.
Authors: Jamii St. Julien, Jinhai Huo, Ya-Chen T. Shih, Elizabeth Gardner Grubbs, Paul Graham, Nancy D Perrier, Matthew H. G. Katz, James C. Yao, Jeffrey Edwin Lee
Journal: Journal of Clinical Oncology (2016)

e18081 Background: Pancreatic neuroendocrine tumors (PNETs) are uncommon neoplasms with a 5-year survival of approximately 30%. Surveillance, Epidemiology, and End Results data suggest a historical trend towards improved survival for White patients with PNET, but no studies have investigated disparities in this patient population. This study evaluates whether race/ethnicity affects treatment choice, and assesses the impact of socioeconomic factors on outcome. Methods: All patients with non-metastatic PNETs (Stages 1-3) were identified in the National Cancer Database during the period 2004-2013. Clinical, neighborhood socioeconomic (SES), and facility data were collected. Multivariable logistic regression was used to determine if race was associated with receiving surgical treatment. Differences in overall survival were compared using a Cox proportional hazards model. Results: We identified 4,579 patients who met the inclusion criteria, of which 4,302 (94%) underwent surgical resection and 277 (6%) did not. The majority of patients were White (75.7%), with 13.4% Black, 5.9% Hispanic, and 5% other races. There were no significant differences in the likelihood of surgery by race, SES, or facility type. Increasing age and higher stage were associated with decreased likelihoods of surgery (p < 0.05). Medicare patients were almost half as likely to undergo surgery than those with private insurance (OR 0.59, p = 0.042). Patients residing in areas with the highest quartile of median household income (OR 2.3, p = 0.013) and those with a travel distance > 250 miles (OR 3.8, p = 0.018) were significantly more likely to undergo surgery. Overall 5-year survival was 80%. Race did not affect survival, but surgery, female gender, age < 45, private insurance, academic cancer center, travel distance > 50 miles, lower comorbidity index, lower stage, and lower grade were all independently associated with improved survival. Conclusions: For patients with non-metastatic PNETs, race was not associated with treatment choice or survival. Insurance type and SES were associated with treatment choice; gender, insurance type, and income affected survival in unexpected ways. Further detailed study is needed to better understand the etiology of these disparities.
Therapeutic yield of an NGS pan-cancer panel utilizing joint AMP/ASCO/CAP classification guidelines.
Authors: Gregory Lewis, Andrew Hesse, Pavalan Selvam, Matthew Prego, Bridgette Sisson, Kevin Kelly, Honey Reddi
Journal: Journal of Clinical Oncology (2018)

e13513 Background: Treating tumors with therapies that target specific molecular aberrations is the hallmark of personalized medicine. Genomic sequencing can provide information to guide these choices and recent guidelines have been published to establish consistency of cancer variant classification. Methods: We performed retrospective analysis of 62 solid tumor cases to assess the yield of reported FDA therapies, investigational drug trials and overall classification profile of the JAX ActionSeq™ test (targeted panel of 212 cancer related genes). Actionability was based on the joint AMP/ASCO/CAP variant interpretation guidelines, which included 3 reportable tiers; 2 clinically significant (Tier I, Tier II) and 1 clinical significance unknown (Tier III). Benign/likely benign variants (Tier IV) were not reported. Results: In total, 331 variants were reported [Avg: 5.3 per patient (pt)] with mean target coverage 1037x. Clinically significant Tier I/II mutations were identified in 90% (56/62) of cases. Considering all tiers, the most frequently mutated genes were TP53, APC, KRAS, and PIK3CA. Genomic alterations that were associated with one or more FDA-approved targeted therapies (indicated or off label) were reported in 61% of pts (38/62) with an average of 6.5 drugs per pt. For these 38 pts, 48 unique targeted drugs across 19 drug classes were identified. The ratio of FDA drugs approved in the patient’s tumor versus approved for a different indication was 1 to 6 (1:6). MEK, PARP, mTOR and multi-kinase inhibitors were the most frequently reported FDA therapies. 83% of patients (54/62) were potentially eligible for gene and/or variant-specific clinical trials, with ~12 reported per patient on average. These trials generated > 60 unique investigational therapies with WEE1, AKT and ERK inhibitors being a few of the most frequent experimental drugs. Conclusions: Our implementation of AMP/ASCO guidelines using a large pan-cancer genomic panel proved effective in generating a variety of targeted therapeutic considerations with sound biological rationale, however reporting may benefit from an additional classification tier to better stratify the range of variants that bin into tier II (Tier II ~35.5%, Tier I ~4.5%).
Activity of components of plasminogen activation system in dynamics of transplantable B16/F10 melanoma development.
Authors: Valeria Bandovkina, Oleg Ivanovich Kit, Elena Mikhaylovna Frantsiyants, Maria I. Maksimova, Maria G. Ilchenko, Natalia A. Maksimova, Yulia A. Pogorelova, Natalia D. Cheryarina, Yury Valentinovich Przhedetskiy
Journal: Journal of Clinical Oncology (2016)

e21062 Background: Melanomas are capable of metastasis and invasion due to breaking of basal membrane and extracellular matrix by tumor-associated proteases. Our purpose was to study the activity of plasminogen activation system in skin, tumor and its perifocal zone in dynamics of experimental В16/F10 melanoma growth. Methods: The study included female С57ВL/6 mice (n = 40) bearing subcutaneously transplanted В16/F10 melanoma. 10% cytosolic fractions were obtained from the tumor, perifocal zone and skin in weeks 1, 2 and 3 of melanoma growth; levels of plasmin (PAP) and content and activity of uPA, t-PA and PAI-I were determined by ELISA. Results: PAP content increased by 1.3 times on day 7, uPA and tPA levels – by 5.2 and 10 times, respectively, PAI-I activity and content – by 4.1 and 6.9 times, respectively. Tumors appeared on day 10 after melanoma transplantation, and it changed priorities between tPA and uPA: uPA activity increased by 1.5-2.1 times in weeks 2-3 of the experiment, while tPA activity decreased by 1.4 times as compared to the values on day 7. Content of uPA increased by 12.8%, tPA – decreased by 1.6-2.1 times. PAI-I activity did not change during the second week, but its content increased more than twice; by the third week both activity and content of PAI-I decreased by 4.1 and 2.8 times, respectively. PAP level increased by 1.8 times and remained as high till the end of the experiment. PAP level in tumor in all stages was 3.4 times higher than the norm, uPA content and activity increased by 1.8 and 11.2 times, and tPA content and activity increased by 36 and 4.5 times, respectively. Activity and content of PAI-I increased maximally by the second week – by 5.4 and 16.3 times, respectively. Perifocal zone showed an increase in PAP level by 1.8 times and an increase in uPA activity by 1.6 times in later stages with its high content (5.9 times higher than the norm). tPA activity in perifocal zone was within the norm in spite of its high content. Conclusions: Plasmin formation system is activated in skin before the tumor appears, and it reaches its maximum directly in melanoma spreading to perifocal zone.
Impact of apolipoprotein E (APOE) genotype on neurocognitive function (NCF) in patients with brain metastasis (BM): An analysis of NRG Oncology’s RTOG 0614.
Authors: Jeffrey Scott Wefel, Snehal Deshmukh, Paul D. Brown, David R Grosshans, Erik P. Sulman, Jane H. Cerhan, Minesh P. Mehta, Deepak Khuntia, Wenyin Shi, Mark Vikas Mishra, John H. Suh, Nadia N. Laack, Yuhchyau Chen, Amarinthia Curtis, Joanna Laba, Rex B. Mowat, Anu Thakrar, Stephanie L Pugh, Deborah W Bruner
Journal: Journal of Clinical Oncology (2018)

2065 Background: Whole brain radiotherapy (WBRT) is a common treatment for BM and is associated with decline in NCF. The APOE e4 allele is associated with increased risk of Alzheimer’s disease, and NCF decline after chemotherapy for non-CNS cancer, treatment for primary brain tumor, and in irradiated mouse models. APOE carrier status has not been evaluated as a risk factor for impaired NCF in patients with BM before and after WBRT. Methods: RTOG 0614 treated adult patients with BM with 37.5 Gy of WBRT (+/- memantine), performed NCF testing (HVLT-R, TMT, COWA) at baseline, 8, 16, 24, and 52 weeks, and included an optional blood draw for APOE analysis. APOE alleles were evaluated by real-time PCR based SNP analysis using TaqMan genotyping. NCF test results were compared at baseline and over time with mixed effects models adjusted for baseline score, treatment arm, time, and interaction between time and APOE carrier status. A cause-specific Cox model for time to NCF failure was performed to assess the effects of treatment arm (memantine versus placebo) and APOE carrier status (e4 versus no e4). Results: APOE results were available for 45% (n = 227/508) of patients. No pretreatment differences were detected between patients with APOE available versus not available. APOE e4 carrier status was evenly distributed between treatment arms (e4 positive = 29.5%). NCF test results did not differ by APOE e4 carrier status at baseline, but e4 carriers were less often white and had started WBRT at study entry more often. Mixed effects modeling showed that patients without an APOE e4 allele had better memory after WBRT compared to patients with an APOE e4 allele (HVLT-R Total Recall [estimate = 2.44, p = 0.026], Delayed Recognition [estimate = 1.15, p = 0.024]). For time to NCF failure, treatment arm was significant (HR = 0.715, 95% CI: 0.513-0.998, p = 0.0487) in favor of memantine; however, APOE e4 status was not (HR = 0.865, 95% CI: 0.606-1.233, p = 0.422). Conclusions: Patients with an APOE e4 allele exhibited worse memory function after treatment with WBRT (+/- memantine), but no difference in time to NCF failure. APOE carrier status was not associated with NCF in patients with BM prior to WBRT. Clinical trial information: NCT00566852.
Request for complementary and alternative medicine (CAM) in German patients with breast cancer: A cross-sectional survey.
Authors: Heidemarie Haller, Petra Voiss, Kyung-Eun Choi, Silke Lange, Sabine Felber, Alexander Traut, Anna Paul, Gustav Dobos, Sherko Kümmel
Journal: Journal of Clinical Oncology (2016)

e21604 Background: To improve patient-centered care, this study aimed at investigating breast cancer patients’ request for integrative oncology treatment. Methods: A cohort of patients diagnosed with breast cancer was recruited between 2011 and 2015 at an integrative Breast Care Center in Germany. The N = 710 patients (mean age: 55.8 ± 12.1; 98% female; staging I-III) who gave their informed consent responded to a questionnaire assessing social demographics, medical history, prior CAM use and request for the integration of CAM therapies into conventional cancer care. Analyses included descriptive statistics and logistic regression modeling on characteristics of patients requesting CAM. Results: Prior use of CAM therapies, also including use independent of cancer treatment, was reported by 75.2% of the sample. Overall, 90.6% are interested in integrating at least one CAM therapy into their current cancer treatment. With 32.8%, the offer of integrative cancer care was decisive in their choice of a hospital. The most requested therapies were exercise (71.5%), nutrition advice (68.2%), relaxation (66.8%), and CAM self-help strategies (65.8%), followed by acupuncture (31.8%), yoga (23.4%), mistletoe (14.4%), and massage therapy (13.2%). Herbal medicine, Ayurveda, homeopathy, nutritional supplements, fasting, neural therapy, and hydrotherapy were reported by less than 10%. Characteristics significantly predicting CAM request were younger age (for exercise and yoga), higher education (for hydrotherapy), relapse (for mistletoe, fasting and neural therapy) and higher grading/staging (for acupuncture and mistletoe), prior experience with CAM (for CAM self-help strategies), higher levels of anxiety (for exercise, yoga, relaxation and massage), and less depression (for massage). Conclusions: Many breast cancer patients reported experience with and request for CAM therapies. Given the risk of drug interactions between CAM and conventional cancer therapies on the one hand and possible improvement in symptoms and quality of life by adding CAM to conventional care on the other hand, CAM counseling and CAM therapies should be provided more often already in inpatient settings.