tbuckley/cabot-search huggingface dataset:
Racial differences in abnormalities by FISH in minorities with multiple myeloma: A single-center experience.
Authors: Miguel Gonzalez Velez, Valentina Jaramillo Restrepo, Narjust Duma, Matthew Palascak, Marshall McKenna, Joshua Ryan Richter, David H. Vesole, David Samuel DiCapua Siegel, Noa Biran
Journal: Journal of Clinical Oncology (2017)

8044 Background: Racial disparities of FISH abnormalities in multiple myeloma (MM) have been well described in whites (W) but partially described in minorities (M) (Paulus et al, ASH 2016, 4432). We aimed to explore racial-based differences of FISH abnormalities using the largest cohort of m to date. Methods: CD-138 selected FISH was done on 799 consecutive patients (pts). Pts without symptomatic MM, and biopsy &gt;6 months after diagnosis were excluded. The abnormalities evaluated included standard and intermediate risk: IGH rearrangements (IGH r), t(4;14), t(11;14), and high risk: t(14;20), t(14;16), del13q, del 17p, 1q21. Chi-square was used for statistical analysis. Due to smaller numbers, all m (Hispanic (H), Black (B), Asian (A) and Other (O)) were included into the same group for statistical analysis. Results: 482 pts were eligible, 343 (71%) were W, 52 (10%) H, 50 (10%) B, 19 (3%) A, and 18 (3%) O. Median age was 65 years, 54% were male, and 26% ISS stage 3. There were no were no statistically significant differences in FISH abnormalities between the m (Table1). Overall W had more abnormalities in IGH r, t(4;14), t(11;14), t(14:20), 1q21 gain compared to M. Most notably W had more IGH r (39% vs 28%; p=0.019) and t(11;14) (20% vs 12%; p=0.024). There were no statistically significant differences between W and m in the high risk FISH abnormalities. Conclusions: We had significant differences in FISH compared to M. W had more IGH r and t(11;14) than M, and there was no difference in high risk FISH abnormalities between W and M. This study confirms the biological racial disparities that exist in minorities with MM. Further studies with more inclusion of minorities are needed to elucidate these disparities and its effects on risk stratification and outcomes. [Table: see text]
Cigarette price, smoking behaviors, and lung cancer mortality in Indiana.
Authors: Ryan Nguyen, Nasser H. Hanna
Journal: Journal of Clinical Oncology (2018)

6559 Background: Increasing tobacco costs have been proven to be one of the most effective interventions of decreasing tobacco use. The relationship between tobacco cost and lung cancer mortality has not been as well established. We investigated the relationship of cigarette price with smoking prevalence, cigarette consumption, and lung cancer incidence and mortality in Indiana and nationally. Methods: We obtained average cigarette pack prices, cigarette pack sales, smoking prevalence, and lung cancer incidence and mortality rates in Indiana and nationally from 1995-2015. Average cigarette pack prices were inflation adjusted to 2015 then assessed for Pearson correlation coefficient (r) with cigarette pack sales, smoking prevalence, and lung cancer incidence and mortality. Cigarette price was also correlated with smoking prevalence among state-level characteristics that included gender, age, ethnicity, education, and income. Results: From 1995 to 2015, average cigarette pack price in Indiana rose from $2.29 to $5.41. Increasing cigarette price in Indiana was associated with decreasing cigarette consumption (r= -0.91, p < 0.001) and decreasing overall smoking prevalence (r= -0.72, p < 0.001). However, those in the lowest income level had higher smoking prevalence associated with rising cigarette price (r= 0.67, p = 0.001). Increasing cigarette price correlated with decreasing lung cancer mortality both in Indiana (r= -0.79, p < 0.001) and nationally (r= 0.96, p < 0.001). Conclusions: Increasing tobacco taxes and subsequent increasing cigarette prices were associated with decreased smoking prevalence, cigarette consumption, and lung cancer mortality in Indiana. Lower socioeconomic populations in Indiana may not be as price-responsive as similar populations nationally. Policies aimed at increasing tobacco prices should prioritize diverting revenues towards health programs and tobacco-cessation initiatives for lower-income individuals.
Sipuleucel-T (sip-T) to induce cytolytic T lymphocyte (CTL) activity against target antigens in men with hormone-sensitive and castration-resistant prostate cancer (CRPC).
Authors: Charles G. Drake, Emmanuel S. Antonarakis, Daniel Peter Petrylak, David I. Quinn, Adam S. Kibel, Nancy N. Chang, Erica Dearstyne, Dwayne Campogan, Heather Haynes, Tuyen Vu, Nadeem Anwar Sheikh, Eric Jay Small
Journal: Journal of Clinical Oncology (2017)

5046 Background: Sip-T is an FDA-approved autologous cellular immunotherapy for patients with asymptomatic or minimally symptomatic metastatic CRPC (mCRPC), manufactured from peripheral blood mononuclear cells (PBMCs) cultured with the immunogen PA2024 (prostatic acid phosphatase [PAP] conjugated to granulocyte macrophage colony-stimulating factor). Treatment with sip-T induces cellular and humoral immune responses to both PA2024 and PAP (Antonarakis, ASCO 2015; Petrylak, ECC 2015; Small Clin Cancer Res 2015). To further elucidate the mechanism of sip-T–induced immune responses, we evaluated proliferative and cytolytic characteristics of PA2024- and PAP-specific T cells. Methods: Antigen-specific proliferation of CD4 (T helper [T H ]) and CD8 (CTL) T cells was quantified using flow cytometry. To assess CTL lytic activity, cell-surface CD107a expression, indicating lysosomal fusion with the cell membrane and expulsion of lytic enzymes, was measured after stimulation with PAP or PA2024. CTL lytic activity was assessed in 13 patients (from 3 sip-T trials [NCT01431391, NCT01981122, and NCT01487863] in hormone-sensitive PC and mCRPC patients) and 1 healthy donor (control). Results: In sip-T–treated patients, a significant increase in proliferation of both CTLs and T H cells was detected in response to PA2024 (p &lt; 0.05) and PAP (p &lt; 0.10) at week 6 compared with baseline. Increased PA2024-specific proliferation was maintained in T H cells through week 26 (p &lt; 0.05). CTL CD107a expression increased in sip-T patient samples stimulated with PAP and PA2024 but not in the healthy donor control. Preliminary analyses suggest that patients with longer overall survival (OS) may have greater CTL CD107a activity. Conclusions: Sip-T treatment was associated with well-maintained antigen-specific cellular responses, including robust CTL responses, demonstrating sip-T induces antigen-specific tumor lysis and providing a biologic basis for OS benefit in mCRPC patients. Ongoing work will examine whether patients with longer OS display greater CTL activity. Clinical trial information: NCT01431391; NCT01981122; NCT01487863.
Real-world treatment patterns and survival of BRAF V600-mutated metastatic non-small cell lung cancer patients.
Authors: Leora Horn, Joshua Bauml, Patrick M. Forde, Keith L. Davis, Nathaniel James Myall, Medha Sasane, Anand Dalal, Kenneth W. Culver, Antoinette J. Wozniak, Christina S. Baik, Alex Mutebi, Pingkuan Zhang, Heather A. Wakelee, Bruce E. Johnson
Journal: Journal of Clinical Oncology (2018)

9096 Background: There is limited evidence on clinical outcomes in patients with BRAF-mutated non-small cell lung cancer (NSCLC) treated outside the controlled environs of clinical trials. To address this gap, we described treatment patterns and survival in such patients evaluated and treated at selected US academic cancer centers in 2009 -2016. Methods: This was a cross-sectional, retrospective medical record review of BRAF V600-mutated metastatic NSCLC patients from 7 centers. Participants in current/ previous BRAF-related clinical trials were excluded. Onset of metastatic NSCLC defined the index date, which was required to occur ≥6 months before the record abstraction date. We described treatment patterns and used Kaplan-Meier analyses for overall survival (OS). Results: The study included 72 patients. At index, median age [range] was 65 [44 to 90] years, 61.1% were female, 66.7% were current/former smokers, and 70.8% had Stage IV NSCLC at diagnosis. Fifty-two patients received ≥1 line of systemic therapy for metastatic disease. Platinum-based doublet chemotherapy was the most common first-line (1L) regimen (76.9% of 1L recipients); no patient received 1L targeted therapy (TT). Of the 33 second-line (2L) treatment recipients 30.3% received TT, and 10 patients received TT in ≥3 lines. At time of review, 38 patients were deceased. Median (95%CI) OS from the index date was 31.0 (14.5, 63.8) months for all patients, and 45.9 (16.1, 62.4) months from 1L initiation among 1L recipients. Median (95%CI) OS was 56.5 (13.4, 89.1) months from metastatic onset for TT recipients and 27.2 (10.6, 64.6) months in those not treated with TT. Patients (26) who had a BRAF test result < 3 months from metastatic onset had substantially shorter median survival (14.1 months) than patients (21) who had a test result ≥3 months after onset (52.7 months). Conclusions: These findings indicate that survival expectations of BRAF V600-mutated metastatic NSCLC patients may be higher than metastatic NSCLC patients without an oncogenic driver. The data also show patients who received TT had numerically longer OS from metastatic onset than patients receiving usual care, adding to the evidence on the importance of TT in BRAF V600-mutant NSCLC.
TCT-506 Cut-off value of malapposition volume on resolution of acute incomplete stent apposition at one month using serial optical coherence tomography after cobalt- chromium everolimus-eluting stent implantation in patients with stable coronary artery disease.
Authors: Yohei Uchimura, Tomonori Itoh, Hideto Oda, Wataru Sasaki, Yuya Taguchi, Kyosuke Kaneko, Tsubasa Sakamoto, Iwao Goto, Masafumi Sakuma, Masaru Ishida, Yoshihiro Morino, Daisuke Terashita, Hiromasa Otake, None Yoshiro Tsukiyama, Toshiro Shinke
Journal: Journal of the American College of Cardiology (2018)
P05.57 Health-related quality of life in patients with large skull base benign meningiomas treated with proton therapy
Authors: D Amelio, D Scartoni, I Giacomelli, M Amichetti
Journal: Neuro-Oncology (2018)

Thanks to their distinct physical properties proton therapy (PT) offers a superior dose distribution than photon radiation therapy. For benign skull base tumors such dose sparing can be harnessed to minimize the risk of side effects ultimately reducing the possible detrimental effect on quality of life (QoL). Aim of this report is to describe QoL in patients (pts) with large skull base benign meningiomas treated with PT. Thirty-three pts with large skull base meningiomas were treated with PT between January 2015 and February 2018. Median age was 53 years (range, 28–82) while KPS ranged between 60 and 100 (median 90). All patients received PT for residual, progressive or non-operable lesions. Newly diagnosed tumors received total dose of 50 GyRBE (RBE: relative biologic effectiveness) while progressing meningiomas 54 GyRBE, in 2 GyRBE per fraction. Health-related (HR) QoL was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)--C30 and EORTC Quality of Life Questionnaire Brain Cancer Module (QLQ-BN20). Subscales within the EORTC QLQ-C30 include five functional scales (physical, role, emotional, cognitive, and social), three symptoms scales (nausea, vomiting, and fatigue), six single-item scales (insomnia, appetite loss, constipation, diarrhea, dyspnea, and financial effect of tumor/treatment) and global QoL. The BN20 is specifically developed for brain patients and assessed visual disorders, motor function, communication deficit, various disease symptoms, treatment, toxicity and future uncertainty. The patients completed the EORTC questionnaires before starting PT, the last day of PT and every follow-up consult until progression of disease. At median follow-up time of 9 months (range, 3–37), all pts completed the questionnaires at baseline as well as thereafter. Currently all pts are free of disease progression. The treatment was associated with improvement or stability in most of the preselected HRQoL domains. Global health improved over time with a maximum difference between baseline and 9-months follow-up. Also social functioning and motor dysfunction improved over time. Cognitive and emotional functioning, as well as fatigue remained stable during the analysis. PT is a safe treatment with a favourable effect on HRQoL in pts with large skull base benign meningiomas
Efficacy of niraparib on progression-free survival (PFS) in patients (pts) with recurrent ovarian cancer (OC) with partial response (PR) to the last platinum-based chemotherapy.
Authors: Mansoor Raza Mirza, Bradley J. Monk, Marta Gil-Martin, Lucy Gilbert, Ulrich Canzler, Philippe Follana, Justin S. Waters, Frederic Kridelka, Tally Levy, Benedict B. Benigno, Kathrine Woie, Diane M. Provencher, Hans-Joachim Lueck, Antonio Casado Herraez, Anne Lesoin, Joseph Buscema, Kristina Hellman, Bj Rimel, Sebastien Hazard, Ursula A. Matulonis
Journal: Journal of Clinical Oncology (2017)

5517 Background: Therapeutic paradigms for recurrent OC vary by geography. Maintenance following response to platinum-based chemotherapy (Plat) is standard in Europe, whereas in the US maintenance is considered following complete response (CR) vs treatment for partial response (PR). Niraparib is a highly selective PARP 1/2 inhibitor (PARPi). In preclinical studies it concentrates in the tumor relative to plasma, delivering &gt; 90% durable PARP inhibition and antitumor effects. Niraparib demonstrated significantly longer PFS vs placebo (P) in pts with recurrent OC following a CR or PR to Plat in the randomized, controlled, double-blind phase 3 ENGOT-OV16/NOVA trial. Methods: Pts with recurrent OC, no prior PARPi use, ≥2 prior courses of Plat, and response to most recent Plat were eligible. Pts were assigned to 1 of 2 cohorts on the basis of g BRCA testing (g BRCAmut or non-g BRCAmut) and randomized 2:1 within each cohort to niraparib 300 mg or P qd until progressive disease (PD). Randomization occurred up to 8 weeks after last dose of the most recent Plat. Pts were stratified by time to progression after penultimate Plat (6 to &lt; 12 months or ≥12 months), prior use of bevacizumab (yes/no), and response to most recent Plat (CR or PR). PFS was measured from time of randomization to death or earliest PD as assessed by independent review committee. Results: 49% of pts (niraparib: 67/138; P: 32/65) in the g BRCAmut and ~49% of pts (niraparib: 117/234 [50%]; P: 56/116 [48%]) in the non-g BRCAmut cohorts entered NOVA with a PR following their most recent Plat. At time of unblinding, 30 (45%) niraparib and 23 (72%) P pts in the g BRCAmut and 65 (56%) niraparib and 45 (80%) P pts in the non-g BRCAmut cohorts had PFS events. PFS hazard ratios (95% CI) were 0.24 (0.131–0.441) in g BRCAmut and 0.35 (0.230–0.532) in non-g BRCAmut cohorts for pts who had a PR to their most recent platinum regimen. This compared favorably to the overall NOVA study results, where PFS hazard ratios (95% CI) were 0.27 (0.173–0.410) in g BRCAmut and 0.45 (0.338–0.607) in non-g BRCAmut cohorts. Conclusions: Niraparib treatment provided significant benefit to pts with recurrent OC who achieved a PR following Plat. Clinical trial information: NCT01847274.
Do pancreatic cancer (PDA) stem cell markers predict biologic behavior?
Authors: Ibrahim Halil Sahin, Mesruh Turkekul, Marinela Capanu, Gokce Askan, Breanna McMahon, Kenneth H. Yu, Maeve Aine Lowery, Olca Basturk, Christine Iacobuzio-Donahue, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2016)

4112 Background: Studies indicate heterogeneous clinical behavior arises in part from variant clones and cancer stem cells (CSC) which are CD44 (+) and Epithelial Specific Antigen (ESA) (+) (Lee, 2008). We investigated the impact of CSC markers on survival in PDA patients who had recurrence following surgical resection (SR). Methods: N=69 patients (pts) diagnosed between 01/04 and 12/14 at Memorial Sloan Kettering who had SR followed by lung or liver recurrence, were identified. Pts eligible if they had consented to IRB #00-032/#06-107, permitting research tissue analysis, and if they had primary tumor tissue available. We assessed CD44 and ESA expression by immunohistochemistry (IHC) staining. Staining intensity was scored as weak (1), moderate (2) and strong (3); The number of (+) cells was scored as: few (1), patchy (2) and diffuse (3). IHC staining was considered (+) if total score ≥4. Overall survival (OS) and time from relapse to death (TRD) were evaluated using Wilcoxon signed-rank test Results: Of 69 pts, N=25 primary tissue samples were available to assess CD44 and N=23 samples for ESA. All pts were deceased at the time of analysis. No difference in OS was observed between pts with CD44(+) and CD44(-) (Table1). Pts with ESA (-) had worse OS compared to pts with ESA (+) (P=0.008). TRD was 3.4 and 8.8 mo in CD44(+) and CD4(-) pts respectively (P=0.2). Improved TRD was observed in ESA (+) pts compared to ESA (-) pts(P=0.02). Sub-analysis of CD44 (+) and ESA (-) pts (group1) and CD44 (-) and ESA (+) pts (group2) showed a trend to worse OS and TRD in group1. Conclusions: Observed survival outcomes were improved for pts with ESA (+). Loss of ESA expression and related worse outcomes could be due to epithelial-mesenchymal transition and acquisition of CSC characteristics. The observed trend to worse TRD in CD44 (+) may indicate a potential biomarker role for rapid disease progression following recurrence. Respecting small sample size, these data suggest CSC biomarkers may have prognostic value in PDA and further investigation is warranted. CD44 (+)/CD44 (-) (13/12) ESA (+)/ESA (-) (16/7) CD44 (+) and ESA (-)/CD44 (-) and ESA (+) (4/9) OS (mo) 16.1/17.2 (P=0.5) 34.3/8.74 (P=0.008) 8.7/36.5 (P=0.08) TRD (mo) 3.4/8.8 (P=0.2) 10.7/3.2 (P=0.02) 3.2/19.6 (P=0.13)
A study of REGN3767, an anti-LAG-3 antibody, alone and in combination with cemiplimab (REGN2810), an anti-PD1 antibody, in advanced cancers.
Authors: Kyriakos P. Papadopoulos, Nehal J. Lakhani, Melissa Lynne Johnson, Haeseong Park, Ding Wang, Timothy Anthony Yap, Kathleen N. Moore, Tasha Nicholle Sims, Chetachi Emeremni, Maria Karasarides, Glenn Scott Kroog
Journal: Journal of Clinical Oncology (2018)

TPS3127 Background: Lymphocyte activation gene 3 (LAG-3) is an immune checkpoint receptor with a biological role in T cell regulation. Analysis of immune-cell infiltrates from human tumors show that a subset of CD4+ and/or CD8+ cells co-express LAG-3 and PD-1 and may be associated with decreased T-cell effector function and tumor escape (Baitsch L et al. J Clin Investig. 2011;121:2350-2360; Jie HB et al. Br J Cancer. 2013;109:2629-2635.). Preclinical models provide evidence that dual inhibition of LAG-3 and PD-1 blockade offer synergistic anti-tumor effects and suggest a promising immunotherapy combination that warrants clinical investigation (Woo SR et al. Cancer Res. 2012;72(4): 917-927). This first in human study will evaluate the safety and efficacy of REGN3767 alone and in combination with cemiplimab in advanced malignancies. Methods: Phase 1 study enrolling patients with advanced malignancies. Dose escalation phase employs a modified 3+3 (4+3) design to assess the tolerability and pharmacokinetics (PK) of REGN3767 monotherapy and in combination with cemiplimab. Monotherapy is exploring 4 escalating REGN3767 dose levels. Combination is exploring 3 escalating REGN3767 dose levels. After tolerability and PK evaluation, doses of REGN3767 will be selected for monotherapy and combination therapy tumor-specific expansion cohorts. Solid tumor expansion cohorts will enroll per Simon’s two-stage design to evaluate safety and preliminary efficacy. Lymphoma expansion cohorts will enroll 15 patients. Patients who are anti-PD-1/PD-L1 therapy naïve and experienced are eligible for separate cohorts. Patients previously exposed to anti-LAG-3 therapy are not eligible. The primary objectives are the determination of the recommended phase 2 dose (RP2D, dose escalation) and ORR (dose expansion). Secondary objectives include characterization of PK and immunogenicity in all patients, as well as anti-tumor efficacy in dose escalation, and safety in dose expansion. This trial is actively enrolling eligible patients in the US, UK, Ireland, and South Korea. Clinical Trial Information: NCT03005782.
Fasting vs. postprandial evaluation of iron deficiency anemia in cancer.
Authors: Satish Maharaj, Karan Seegobin, Marwan Shaikh
Journal: Journal of Clinical Oncology (2018)

e18876 Background: Iron deficiency anemia in patients with cancer is a frequent complication that may be present at diagnosis and worsen with disease. It has been reported in 32-60% of patients with cancer. The severity of anemia correlates with quality of life and can worsen performance status leading to poorer outcome. The accurate investigation of iron status in these patients is key to diagnosis, assessment of severity and treatment (oral or IV iron or ESA’s). National Comprehensive Cancer Network (NCCN) revised guidelines on Cancer- and Chemotherapy-Induced Anemia (2018) state that to prevent falsely elevated levels, serum iron and total iron-binding capacity should be done in the fasting state. In this study, we investigate the hypothesis that post-prandial iron testing results in falsely elevated levels, underestimating iron deficiency. Methods: We identified a cohort of patients who were evaluated for anemia. Each patient had undergone iron studies in both the fasting (overnight) and post-prandial states with a maximum of 30 days between testing. We excluded any patient with transfusion, hemoglobinopathy, iron overload, IV iron administration, hemolysis or bacteremia during the study period. Descriptive statistics were used to analyze data. Results: Our study included 50 patients with anemia (25 cases with active malignancy and 25 controls without malignancy). Surprisingly, there was a significant trend towards higher serum iron levels with fasting studies when compared with post-prandial testing. A review of current research on iron levels provides biological plausibility for this finding. There was variation in transferrin levels between both states but the trend was not significant. Conclusions: As recommended in current NCCN guidelines, most patients with cancer who have anemia undergo testing after overnight fasting. In this study we found that prolonged overnight fasting was in fact associated with higher serum iron concentrations compared with post-prandial testing. This challenges the current recommendations and has implications for accurate diagnosis and management. Further investigation and an evidence-based standardized approach to testing is recommended.