tbuckley/cabot-search huggingface dataset:
Prospective characterization of circulating tumor cells using a nanotechnology-based capture system in oligometastatic patients undergoing definitive radiation therapy.
Authors: Daniel Paul Lindsay, Joseph Michael Caster, Kyle Wang, Ja Hye Myung, Ronald C. Chen, Bhishamjit S. Chera, Gaorav P. Gupta, Ellen Jones, Joel E. Tepper, Mahesh A. Varia, Timothy Zagar, Seungpyo Hong, Andrew Wang
Journal: Journal of Clinical Oncology (2017)

11533 Background: Circulating tumor cells (CTCs) can provide prognostic information in select patients with advanced cancers. We have developed a sensitive and specific CTC capture system (Oncosensor) which may predict clinical outcomes in patients undergoing definitive radiation for head and neck cancers. There is increasing interest in utilizing potentially curative metastasis-directed therapy for patients with oligometastatic solid-tumor malignancies. There is currently no biomarker to predict the success of this approach in most patients. The purpose of this prospective study is to investigate the potential utility of CTCs as a predictive biomarker for patients with oligometastatic cancer undergoing potentially curative therapy. Methods: Eligible patients had a metastatic solid-tumor malignancy with 3 or fewer metastases. All sites of disease were treated with definitive radiation or surgery. Concurrent chemotherapy was allowed. Peripheral blood (7 ml) was collected prior to starting, first week, mid-point, end RT, and every 4 to 12 weeks post RT. CTCs were quantified using the Oncosensor platform. We then assessed correlations between CTCs (baseline, end treatment, and changes during treatment) and clinical outcomes using multivariate analysis. Results: Baseline CTCs were detected in 20/20 enrolled patients with a mean baseline of 32/ml which decreased to a mean of 14/ml at the end of treatment. There was no association between pretreatment CTCs and clinical outcomes (p = 0.81). There was a significant association between post-RT CTCs and PFS (p = 0.039, HR 1.07 per CTC). Our data also suggest that post-treatment CTC monitoring may be able to detect early disease recurrence. Among the 4 patients with documented clinical failures and post-treatment CTC monitoring, all 4 had increases in CTCs with or prior to clinical or radiographic disease progression, with 1.6 to 7.3 fold increase at the time of progression compared to the prior time point. Conclusions: Our pilot data suggest CTCs may provide a predictive biomarker for patients with oligometastatic disease and could potentially provide a novel marker of disease recurrence.
TCT-190 Comparison of Mid-term Clinical Outcomes between Optimal Frequency Domain Imaging-guided and Intravascular Ultrasound-guided Percutaneous Coronary Intervention with 2nd Generation Drug Eluting Stents in Stable Angina Pectoris
Authors: Hiroaki Matsuda, Hirooki Higami, Kazuaki Kaitani
Journal: Journal of the American College of Cardiology (2018)
CARSKIN: Pembrolizumab as first line therapy in patients with unresectable cutaneous squamous cell carcinoma (cSCC).
Authors: Eve Maubec, Sabine Helfen, Isabelle Scheer-Senyarich, Marouane Boubaya, Olivier Schischmanoff, Céline Alloux, Lydia Deschamps, Peter Petrow, Isabelle Lopez, Annick Tibi, Vincent Levy
Journal: Journal of Clinical Oncology (2017)

TPS9596 Background: Treatment options are limited for patients (pts) with locally advanced or metastatic cSCCs. Cisplatin-based combinations have some efficacy but their toxicity often prohibits their use, particularly for the elderly. New therapeutic options are needed. Tumors divert the programmed death receptor 1 (PD-1) pathway suppressing immune control. Pembrolizumab (MK-3475) is a high-affinity humanized monoclonal anti-PD-1 antibody. It leads to dual PD-1 ligand (PD-L1 and PD-L2) blockade that may reactivate the immune surveillance and elicit anti-tumor response. It has antitumor activity in several tumors including head and neck SCCs. Moreover, an efficacy of pembrolizumab in cSCCs has been reported recently in a series of 6 cases. Methods: CARSKIN (ClinicalTrials.gov, NCT02883556) is a French multicenter, open-label, nonrandomized phase 2 trial, designed to evaluate the efficacy and safety of pembrolizumab in 39 pts with unresectable and/or metastatic cSCCs, naive of chemotherapy and of EGFR inhibitors. Pembrolizumab is administered (200 mg IV Q3W) for up to 24 months or until disease progression or unacceptable toxicity. Eligible pts must undergo a baseline biopsy of the tumor prior to treatment for PD-L1 evaluation. Response is to be assessed at baseline, wk 9, 15 and 24, and thereafter Q12W by central radiology review per RECIST 1.1 and per modified RECIST v1.1. The primary objective is response rate (RR) at wk 15 per RECIST 1.1. Secondary efficacy objectives are to assess whether patients with PD-L1+ tumors have a better RR than the whole sample at wk 15 and to assess in the whole sample and in PD-L1+ pts, disease control rate (DCR) at wk15, RR at wk 24, best RR, overall survival (OS), progression free survival (PFS), duration of response / control and time to disease progression. A Simon optimal two-stage design will be used. Four responders among 19 pts will be needed in the 1 st step to continue the trial. Overall 9 responses will be needed to conclude the effectiveness. Kaplan-Meier statistics will assess PFS and OS. Adverse events (AEs) will be assessed throughout the study and for 30 d thereafter (6 m for serious AEs) and graded per NCI CTCAE v4.0. Clinical trial information: NCT02883556.
Monocytes and neutrophils as a predictive marker of response to immune checkpoint inhibitors (ICI) in metastatic non-small cell lung cancer (mNSCLC).
Authors: Kaushal Parikh, Arun Kumar, Jibran Ahmed, Asad Anwar, Carmelo Puccio, Hoo Geun Chun, Michael Paul Fanucchi, Seah Lim
Journal: Journal of Clinical Oncology (2018)

e21165 Background: PD-L1 expression and mutational load in tumor cells have been found to predict response to ICI in patients with mNSCLC. These parameters, however, are not readily available clinically. Identification of parameters easily measured in the clinics will help select NSCLC patients most likely to benefit from ICI. Methods: We carried out a retrospective cohort study on patients with mNSCLC to identify clinical and laboratory factors associated with response to ICI. Results: Of the 37 consecutive patients identified, only 32 patients were analyzed as 5 patients were not evaluable for response. There were 17 males and 15 females. Their median age was 64.5 years (range 20-84). History of smoking was present in 25/32 (78%) patients. Non-squamous cell tumors were by far the commonest histologic subtype (27/32, 84%). 12 patients received pembrolizumab, 19 patients nivolumab, and one patient received nivolumab followed by pembrolizumab. Responses were observed in 19 (59%) of these 32 patients. All 19 patients had partial response. There was no difference in the distribution of sex, age, smoking status, and histologic subtypes between responders and non-responders. The median time to response (TTR) in this cohort of patients was 12 weeks (range 6-24) and the median duration of response (DoR) was 24 weeks (range 7-112). Higher pre-therapy absolute monocyte counts (AMC) correlated to shorter TTR (R = -0.50; 95% CI -0.79 – -0.05) (p = 0.03) but not DoR. Patients with AMC > 700/mm3 had a significantly shorter median TTR than those with AMC ≤ 700/mm3 (8 weeks vs 12 weeks; p = 0.048). Lower absolute neutrophil counts (ANC) after dose #1 predicted response to ICI (p = 0.02). Patients with ANC ≤ 4200/mm3 after dose #1 were more likely to respond than those with ANC > 4200/mm3 (OR = 6.8; 95% CI 1.1 – 41.8) (p = 0.05). Pre- and post-therapy lymphocyte counts, platelet counts, or hemoglobin did not predict responses or DoR. Conclusions: Higher pre-therapy AMC and lower post-dose #1 ANC in mNSCLC treated with ICI were correlated to improved probability of response. Analysis of AMC and ANC before and during therapy may provide an easy method to identify those mNSCLC patients most likely to respond to ICI.
Describing the value of the most common first line NSCLC regimens in a real world setting.
Authors: Lee N. Newcomer, Stacey DaCosta Byfield, Benjamin Chastek, Stephanie Korrer, Thomas Horstman, Jennifer Malin
Journal: Journal of Clinical Oncology (2017)

9046 Background: We aim to describe clinical and economic outcomes of common chemotherapy regimens for first line therapy of metastatic non-small cell lung cancer (mNSCLC).The data are intended to help clinicians and patients understand the real world results for patients like themselves. Methods: This retrospective analysis used clinical data obtained from a prior authorization (PA) program for chemotherapy linked with administrative claims data from 6/1/2015 to 5/31/2016 from a large national managed care organization. Clinical data included cancer type, stage at diagnosis, biomarkers, treatment line and evidence of progression/relapse. Eligible patients were commercially insured members with a PA request for commonly used NCCN recommended regimens for first line therapy of mNSCLC. Outcomes, including duration of therapy, % of patients hospitalized and total cost of care were tracked from first claim for chemotherapy until end of treatment due to discontinuation, death or start of a second line, with remaining patients censored at 5/31/2016 or end of enrollment. Results: Of 830 mNSCLC patients, 498 (60%) completed first line therapy during the study period. 345 initiated one of the following: Carbo/cisplatin + pemetrexed (CA), Carbo/cisplatin + paclitaxel (CP), Carbo/cisplatin + bevacizumab + pemetrexed (CBA), nivolumab (N), and docetaxal (D). Outcomes are summarized in the Table. Conclusions: Patients treated with the five most commonly prescribed first line therapies for mNSCLC have much shorter duration of therapies (52-76 days) than reported in published clinical trials with a significant risk of hospitalization (18% -30%) and at substantial cost ($34,971 - $108,100). These data are an important consideration for the patient and clinician making treatment decisions in routine clinical practice and will become more valuable as the database grows over time. [Table: see text]
Prevalence of herbal medicine (HM) use among breast cancer patients treated with chemotherapy, hormone therapy, or targeted therapy.
Authors: Helene Langin, Gautier Lefebvre, Emmanuelle Tresch-Bruneel, Marie-Cecile Le Deley, Guillaume Marliot, Ilyes Sakji, Marie Vanseymortier, Michel Reich, Eric Lartigau, Jacques Bonneterre
Journal: Journal of Clinical Oncology (2018)

e13108 Background: Complementary and alternative medicine (CAM) are widely used by cancer patients during their antineoplastic treatment. Potential drug interactions are still unknown. Few data are available about security of biological CAM. The aim of this study was to evaluate the prevalence and knowledge of phytotherapy among patients (pts) undergoing anti-cancer treatment for breast cancer (BC). Methods: From June to September 2017, 93 patients treated in our comprehensive cancer center, were asked to fulfill a standardized questionnaire regarding use of HM. Clinico-pathological characteristics were recorded, as well as the antineoplastic treatment (TT). HM were defined as plants used for their therapeutic properties. Results: Our population was: 34 BC localized, 28 BC with axillary lymphadenopathy, 31 BC advanced. 60.9% (95%CI: 50.1-70.9) used one or more CAM during TT. Most popular CAM were respectively, homeopathy, HM, acupuncture. 58.7% (95%CI: 48-68.9) knew HM, and 30 patients used it (32.6% (95%CI: 23.2-43.2)). HM use was more prevalent in localized cancer pts (p = 0,020). 7 started it during TT. 4 thought HM had synergistic effect on TT. No pts thought HM was more efficient than TT. Main reasons for CAM use were to improve health condition (19) or reduce TT's adverse effects (17). Half of them believed HM is harmless, 33.3% (10/30 95%CI: 17.3-52.8) had informed their oncologist; 28 would appreciate information on herbs. Conclusions: Prevalence of CAM use in cancer pts is high. However, herbs are likely to interact with conventional drugs. Pts have to be educated and further works are needed in this field.
Mouse Models to Disentangle the Hallmarks of Human Aging
Authors: Alicia R. Folgueras, Sandra Freitas-Rodríguez, Gloria Velasco, Carlos López-Otín
Journal: Circulation Research (2018)

Model organisms have provided fundamental evidence that aging can be delayed and longevity extended. These findings gave rise to a new era in aging research aimed at elucidating the pathways and networks controlling this complex biological process. The identification of 9 hallmarks of aging has established a framework to evaluate the relative contribution of each hallmark and the interconnections among them. In this review, we revisit these hallmarks with the information obtained exclusively through the generation of genetically modified mouse models that have a significant impact on the aging process. We discuss within each hallmark those interventions that accelerate aging or that have been successful at increasing lifespan, with the final goal of identifying the most promising antiaging avenues based on the current knowledge provided by in vivo models.
Geographic distribution and survival outcomes for rural cancer patients treated in clinical trials.
Authors: Joseph M. Unger, Anna Moseley, Banu Symington, Mariana Chavez-MacGregor, Scott David Ramsey, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2018)

6569 Background: Studies show that cancer patients from rural areas have worse cancer outcomes than their urban counterparts. But studies relying on cancer population data are unable to account for differences in access to care. In contrast, clinical trial patients receive protocol-directed care by design, so large clinical trial databases are ideal for examining the impact of residency on outcomes. Methods: We compared the geographic distribution and survival outcomes for rural versus urban cancer clinical trial patients. We examined 36,995 patients from all 50 states enrolled in 44 phase III or II-III SWOG treatment trials from 1986-2012, comprising 17 different cancer-specific analysis cohorts. We examined overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS) for patients by rural/urban status to determine if residency – based on Rural-Urban Continuum Codes (RUCCs) – was associated with outcome. We used multivariate Cox regression to estimate the association of residency and survival outcomes, controlling for major disease-specific prognostic factors and demographic variables and stratifying by study. Different definitions of rurality were examined. The distribution of rural vs. urban patients by geographic region was described. Results: Overall, 19% of patients were from rural locations, the same as the rate of rural individuals in the U.S. Rural patients were older (≥65 years, 31% vs. 27%, p < .01) and less likely to be African American (5% vs. 12%, p < .01), but were similar with respect to sex (40% each) and were well represented within major geographic regions. Clinical prognostic factors were very similar. In multivariable regression, rural patients with adjuvant-stage ER-/PR- breast cancer had worse OS (HR = 1.27, p = .008) and CSS (HR = 1.26, p = .02). No other statistically significant differences were found. Results were consistent regardless of the definition of rurality. Conclusions: Rural and urban patients with uniform access to cancer care through participation in a trial had similar outcomes. This finding suggests that improving access to uniform treatment strategies for cancer patients may help resolve the rural/urban disparity in cancer outcomes.
Avelumab-cetuximab-radiotherapy (RT) versus standards of care (SoC) in locally advanced squamous cell carcinoma of the head and neck (SCCHN): Safety phase of the randomized trial GORTEC 2017-01 (REACH).
Authors: Yungan Tao, Anne Auperin, Xu Shan Sun, Christian Sire, Laurent Martin, G Bera, Alexandre Coutte, Jessica Miroir, Cedrik Lafond, Natacha Colin-Batailhou, Aline Maillard, Laurent Gibel, Cécile Michel, Joel Guigay, Jean Bourhis
Journal: Journal of Clinical Oncology (2018)

6076 Background: Based on the hypothesis of a synergistic effect of the anti-PDL1 avelumab when combined with cetuximab (cetux) and RT, this new combination is tested in a large scale randomized trial against two well established SoC in LA SCCHN. Methods: This randomized multicenter phase III trial comprises cohorts of pts deemed fit (Cohort 1) to receive high dose cisplatin (CDDP 100 mg/m², Q3W) or unfit (Cohort 2) to receive CDDP. The SoC is IMRT (69.96 Gy, 33 fractions) combined with CDDP in cohort 1 and with cetux in Cohort 2 (400 mg/m² Day-7 and 250 mg/m² weekly). In both cohorts, experimental (exp) arms are IMRT concomitant with cetux (same as in SoC) and avelumab (10 mg/kg Day-7 and every 2 weeks) followed by avelumab 10 mg/kg bi-monthly for 12 months. The primary objective is to test whether exp arm is superior to SoC for progression-free survival in each cohort, with 400 and 268 pts to be randomized to Cohort 1 and 2 respectively. Monitoring of grade ≥ 4 acute adverse events in both exp arms was planned with null and alternative hypotheses of 15% and 35%. Overall 1-sided alpha error of 0.10, Lan-DeMets alpha spending function, 95% power. This safety phase was approved by the study Data and Safety Monitoring Committee
Cancer of unknown primary: Experience at University Hospital Waterford.
Authors: Abdul Rehman Farooq
Journal: Journal of Clinical Oncology (2018)

e24011 Background: Cancers of unknown primary (CUP) site account for 3-5% of all malignancies and represent tumours with metastases for which workup fails to identify a primary site. This study presents the data for a selection of identified CUP patients presenting to University Hospital Waterford over last 5 years. Methods: A list of patients who presented with CUP in the last 5 years was assembled. The patients’ demographics and clinical data was retrieved from patient records and electronic patient databases. Results: 38 patients with a diagnosis of CUP were identified from 2013 -2017, of which 21 were female and 17 male. The majority (65%) were > 65 years of age. 71% had an ECOG of > 2, 29% were ECOG 0-1. 47% (18) had adenocarcinoma, 15% (6) squamous cell or poorly / undifferentiated cancer, 1 patient had small cell cancer, 1 neuroendocrine cancer and histological confirmation was not available in 6. The majority of patients had multiple metastases at diagnosis. 44% (17) patients had treatment: chemotherapy in 12, surgery in 5 and radiation therapy in 3 cases.Median overall survival was 3 months with values ranging from 1 month to 58 month.4 patients who were treated as ovarian and breast cancer had a median OS of 34 months. 16 patients had LDH levels tested, with 10 having elevated LDH levels. Patients with elevated LDH had a median OS of 2 months as compared to 8 months for those with normal LDH. Patients with ECOG PS of 0-1 had a significantly improved OS of 9 months as compared to 2 months for those with ECOG PS of 2 or more Conclusions: CUP’s have a poor prognosis. This was evident in our patients with a median overall survival of 3 months. A subset of patients who were able to receive directed therapy performed better. LDH and ECOG PS were found to be good prognostic factors and this is consistent with international data. The first study for CUP is expected to open in Ireland in 2018 and will allow us to use molecular testing of actionable targets to direct therapy decisions.
Survival of elderly patients with advanced hepatocellular carcinoma with distant metastasis in pre- and post- sorafenib era: A population based study.
Authors: Nibash Budhathoki, Binay Kumar Shah
Journal: Journal of Clinical Oncology (2017)

e15643 Background: Sorafinib was approved for advanced hepatocellular carcinoma in 2007. This study was conducted to study relative survival in elderly patients with advanced hepatocellular carcinoma in presorafinib and sorafinib era. Methods: We selected elderly patients (age ≥ 65 years) with advanced hepatocellular carcinoma (distant metastasis based on SEER’s LRD staging) from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed during January 2000 to December 2013. We calculated one year and five year relative survival rates in pre- (2000-2006) and post- sorafinib (2008-2013) era by sex and ethnicity (Caucasians, African-Americans (AA) &amp; Other) using SEER*Stat software. Results: There were total of 1533 patients in presorafinib era and 1694 patients in postsorafinib era. Of the total population, 71.30% were male and 28.70% female, 71% were Caucasian, 10% African-American and 19% were other race. Median age of patients was 73 years (65-99 years) and medial follow up period was 3 months (0-167 months) Survival rates improved significantly from pre- to post- sorafenib era (1 year RS: 10.60% ±0.80% vs 12.10±0.90%, p value = 0.001; 5 year RS: 1.10%±0.30% vs 1.8%±0.6%, p value = 0.001 ). The survival rate improved significantly for male (1 year RS: 11.60%±1.00% vs 12.30%±1.00%, p value = 0.006; 5 year RS: 1.00%±0.40% vs 1.3%± 0.6% , p value = 0.007) and Caucasian (1 year RS: 10.60%±1.00% vs 12.60%±1.10%, p value = 0.0008; 5 year RS: RS = 1.20%±0.40% vs 1.4%±0.7%, P value = 0.001) patients in post sorafenib era. There was no significant difference in the survival rates among any other cohorts examined.However in black (N = 153 vs 158 , RS = 6.80%±2.10% vs 7.80%±2.40% , p value = 0.77) or other races (N = 311 vs 311, RS = 12.20%±1.90% vs 12.80%±2.10%, p value = 0.30 ) , no significant improvement in survival was noted. Conclusions: Our study showed that relative survival rates of elderly patients with advanced hepatocellular carcinoma with distant metastasis has improved in the post-sorafenib compared to pre-sorafenib era. The improvement in survival is limited to male and Caucasian patients.
Modified FOLFOXIRI regimen as salvage treatment for metastatic colorectal cancer patients: A retrospective study.
Authors: Zhen Wang, Song Zheng, Xifeng Xu, Yuan Qian
Journal: Journal of Clinical Oncology (2018)

e15571 Background: After failure of standard treatment ,objective to evaluate the safety and preliminary efficacy of modified FOLFOXIRI(mFOLFOXIRI) regimen as salvage treatment of patients with unresectable metastatic colorectal cancer (mCRC). Methods: We systematically searched data of all patients with mCRC at Hangzhou First People's Hospital and Hangzhou Cancer Hospital from January 2011 to October 2017. A total of 17 patients who received mFOLFOXIRI (the combination of irinotecan, oxaliplatin, leucovorin and 5-fluorouracil/capecitabine with reducing dosages) treatment were followed up. Our primary outcome was progression-free survival(PFS). Secondary outcomes were overall survival, rates of grade 3 or 4 adverse events, objective remission rate and clinical benefit rate. Results: Median age was 53 (range from 39 to 68) years. All the 17 patients who received median 4(range from 1 to 8) cycles mFOLFOXIRI regimen were evaluated for efficacy and the incidence of toxic effects. Out of 17 cases, 11 cases received more than 4 cycles of the regimen(64.7%). The median progression-free survival was 3.4 months (95%CI, 0.9-5.9). Due to the shorter observation time, 4 patients did not reach OS, the median OS was 10 months (95%CI 4.9-15.1). In all observed data, the objective remission rate was 27.3% and the clinical benefit rate was 81.8%. The most frequent grade 3/4 adverse events ware leukocyte reduction(17.6%), peripheral neuropathy (11.8%), anemia (5.9%), and neutropenia (5.9%), thrombocytopenia (5.9%). No death occurred in association with the treatment. Conclusions: In this study, the mFOLFOXIRI regimen after the failure of the standard treatment is feasible in patients with good performance status, and demonstrates some PFS, OS and clinical benefit. A randomized phase III trial is warranted to confirm the results of this study.