tbuckley/cabot-search huggingface dataset:
Associations between job supports and job retention among working patients with colorectal cancer.
Authors: Christine Marie Veenstra, Scott E. Regenbogen, Arden M. Morris
Journal: Journal of Clinical Oncology (2016)

6508 Background: Serious illness may cause substantial economic hardship, exacerbated by illness- or treatment-related job loss. Colorectal cancer (CRC) is a common, serious illness with a rising incidence among younger, working-age patients. Job supports may help working patients with CRC retain their jobs and alleviate financial burden. Methods: In 2011-14, we surveyed Stage III CRC patients from Detroit and Georgia SEER registries. Job retention was the outcome measure. Availability of job support benefits (employer-based health insurance, flexible schedule, paid sick leave, extended sick leave, disability, unpaid leave) was the primary independent variable. We assessed associations between social determinants, environment, job supports and job retention, using a multivariate logistic regression model first controlling only for patient-level social and environmental covariates and then adding in job supports. Results: 1301/1901 eligible patients returned completed surveys (68% response rate). Only the 546 patients who were working at the time of diagnosis were included in this study. 45% of working patients reported that they stopped working altogether as a result of cancer diagnosis and treatment. In the individual- and area-level adjusted model, only education and household income were significantly associated with job retention. In the fully adjusted model including job support benefits, education and income were no longer statistically significant and only employer-based health insurance (OR = 2.63; 95% CI = 1.34-5.14; p < 0.01), flexible work schedule (OR = 6.19; 95% CI = 3.56-10.78; p < 0.01) and paid sick leave (OR = 2.26; 95% CI = 1.11-4.61; p = 0.03) were significantly associated with job retention. Conclusions: Nearly half of working patients were unable to retain their jobs due to CRC diagnosis and treatment. Employer-based health insurance, flexible work schedule, and paid sick leave were associated with significantly greater likelihood of job retention. Based on our findings, an investment in job support benefits by employers and government could provide long-term societal dividends by enabling job retention and reducing financial burden, especially among young working patients.
Randomized phase II trial of oral vinorelbine (OV) and cisplatin (P) followed by maintenance with single-agent OV <i>versus (vs)</i> gemcitabine (GEM) and P followed by maintenance with single-agent GEM as first-line chemotherapy (CT) in locally advanced (LA) or metastatic non-small-cell lung cancer (NSCLC) patients (pts) with squamous (sq) histological type.
Authors: Francesco Grossi, Piotr Jaskiewicz, Eric Pichon, Grzegorz Czyzewicz, Dariusz Kowalski, Libero Ciuffreda, Ramon Garcia-Gomez, Salvatore Caruso, Joaquim Bosch-Barrera, Christine Ta Thanh Minh, Sebastien Henriet, Stephanie Gautier, Helene Hervieu, Gilberto Castro
Journal: Journal of Clinical Oncology (2018)

e21058 Background: The doublets OV+P and GEM+P are among standard treatment options in NSCLC. The study aims to assess efficacy, safety of OV+P (Arm A) and GEM+P (Arm B), followed by maintenance with OV or GEM respectively. Methods: Pts were randomised to receive (every 3-week cycles): OV at 80 mg/m² D1 and D8 (60 mg/m² Cycle 1) + P 80 mg/m² D1 or GEM 1250 mg/m² (D1 and D8) + P 75 mg/m² D1. After 4 cycles of combination, pts without progressive disease received single agent OV or GEM respectively as maintenance until progression or unacceptable toxicity. Primary endpoint: Disease Control Rate (DCR) on study treatment period (combination,maintenance). Results: 113 pts were included in intent-to-treat population (ITT): Baseline: 57 pts (Arm A)/ 56 pts (Arm B), median age of 61 and 64.5 years, stage IV 96.5% and 91.1% respectively. In Arm A/ B, 57 pts and 56 were treated in combination period; in maintenance, 29 and 28 pts were treated with OV or Gem. Results (ITT) for study treatment period in Arm A/ B: DCR 73.7% [95%, CI (62.4; 100.0)] and 75% [95%, CI (63.7; 100.0)]. Median duration of treatment 12.1 and 13.2 weeks; objective response 24.6% [14.1; 37.8] and 30.4% [18.8; 44.1]; median [95% CI] duration of disease control in months (mo) 4.8 [4.1-5.7] and 5.2 [4.3-6.6]; median PFS: 4.2 (2.8-4.9) and 4.3 (3.1-5.5) mo; median survival: 10.2 (6.9-12.9) and 8.4 (5.3-11.9) mo. Total of any grades (Gr) of related adverse events (r-AEs) arm A/ B respectively: 87.7% and 92.9%. Any grade of related infections : 1.8% vs 8.9%.Gr 3-4 of selected r-AEs: nausea/vomiting 1.8%/3.5% vs 8.9%/ 5.4%, peripheral neuropathy 0% vs1.8%, renal failure 1.8% vs 3.6%, septic shock 0 vs 1.8%. Grade 1-2 related alopecia (8.8% vs 21.4%). One toxic death in each arm. Biological toxicities of gr 3-4 neutropenia 43.9%/37.5%, anaemia 17.5%/10.7%, thrombocytopenia 1.8%/10.7%. Full results to be presented at the meeting. Conclusions: This study confirms efficacy, safety of OV+P in sq NSCLC with a trend for a better median survival for OV+P. Clinical trial information: 2012-003531-40.
Depth of response and progression free survival in CLL patients on ibrutinib.
Authors: Audrey Sigmund, Ying Huang, Amy S. Ruppert, Fan Ny, Margaret Lucas, Weihong Chase, Kami J. Maddocks, Kerry Anne Rogers, Samantha Mary Jaglowski, Leslie Ann Andritsos, Farrukh Tauseef Awan, Michael R. Grever, John C. Byrd, Jennifer Ann Woyach
Journal: Journal of Clinical Oncology (2018)

7514 Background: While it has been established that attainment of a complete response (CR) after chemoimmunotherapy improves progression free survival (PFS), this has not been proven with the BTK inhibitor ibrutinib (IB). Most patients (pts) receiving IB achieve a partial response (PR) at best, and multiple trials have focused on deepening responses. Here we investigate the association of depth of response at one year and PFS in CLL pts on IB. Methods: This was a retrospective study of pts with CLL enrolled in 4 sequential clinical trials of IB as a single agent or in combination with ofatumumab at the Ohio State University. Response was evaluated by two independent investigators using International Workshop on CLL 2008 guidelines if bone marrow was available; if no marrow was available, clinical response was used. A landmark analysis was performed at response assessment at 12 +/- 2 months. PFS was calculated from this response assessment to progression or death. The method of Kaplan-Meier and Cox models were used to estimate PFS. Results: The cohort was comprised of 237 pts enrolled between July 19, 2010 and March 24, 2014 with median number of prior therapies 3 (range 0-13). Median age was 65; 82% IGVH unmutated, 36% with del(17p), and 54% with complex karyotype. At month 12 assessment, 5% of pts had CR, 3% CR with incomplete marrow recovery (CRi), 77% PR, 12% PR with lymphocytosis, and 3% stable disease. With a median follow-up of 48 months, the median PFS was 52 months (95% CI: 42-70) with no significant difference among response groups (p = 0.23). However, PR pts with lymph nodes (LN) ≥3cm had significantly higher risk of progression than pts with LN < 3cm (median PFS 42 vs. 68 months; hazard ratio = 1.6, p = 0.03 from multivariable model). Conclusions: There was no significant difference in PFS between CR and other response groups. However, a significant difference was found in PR pts with LN ≥3cm vs. LN < 3cm. This suggests that, unlike with chemoimmunotherapy, attainment of a CR with IB is not critical, however, those patients with significantly enlarged nodes after 1 year of therapy have shorter PFS. Combination therapy studies without the goal of therapy discontinuation may focus on elimination of bulky nodal disease rather than attainment of CR for all patients.
Justification for deployment of peripherally inserted central catheter (PICC).
Authors: João Raphael Maia, Flavia Torrecillas, Marcio Borella
Journal: Journal of Clinical Oncology (2017)

e18257 Background: Is not practical in countries of Latin America the use of Central Venous Catheters - CL in Oncology due the difficulty of financing of this procedure. The PICC is a vascular access device inserted in peripheral vein infusion drugs with Center for a cost of no more than 20% when compared to use of a catheter fully deployed. Methods: We conducted a cross-sectional study, retrospective and quantitative data were collected from complication and pharmacovigilance of a private oncology outpatient clinic in Rio de Janeiro, in the care of patients undergoing treatment for breast cancer with Paclitaxel weekly in the Jan 2016 period the Dec 2016. Results: The study were performed with 98 patients, peripheral venous access 75.5% and 24.5% central venous access. Of patients with peripheral venous access, 47.3% had exclusive member to puncture. Of this group, 21.6% of patients achieved success on first CL in all infusions performed in the period and 78.4% needed more than one CL for Administration of paclitaxel in at least an infusion. 182 Pharmacovigilance notifications were made, being 38.5% for the flebogênicidade symptoms after use of paclitaxel. Conclusions: The study highlights the relationship between venous access safe and successful outpatient antineoplasic therapy. The data observed in analyzed period justifies the creation of deployment Protocol of PICC for patients with breast cancer to treatment with Paclitaxel weekly. It is hoped with this Protocol added convenience and safety for the patient, ensuring fast start of infusional therapy often delayed by the difficulty in accessing the patient's venous network, reducing and avoiding delays in cycles, with low rates of complications for the same and lower costs.
Impact of liquid-biopsy in the therapeutic decision making process in a Peruvian institution.
Authors: Luis Schwarz, Henry Leonidas Gomez, Paola Catherine Montenegro, Claudio J. Flores, María Requena, Jhajaira M Araujo, I. Tirado-Hurtado, Victoria M. Raymond, Alfredo Aguilar, Carlos Vallejos Sologuren
Journal: Journal of Clinical Oncology (2018)

e18761 Background: Liquid biopsy is a non-invasive method that allows us to understand the molecular changes occurring in the tumor in real time due to heterogeneity and/or therapeutic pressure. In the present work we sought to elucidate the ability of liquid biopsy to re-shape treatment decisions in our institution. Methods: A total of 25 patients (pts) with advanced gastric (AGC; n = 5), colorectal (ACC; n = 5) and non-small cell lung cancers (ALC; n = 15) in second or third line of treatment were analyzed by a commercially available plasma cell-free DNA (cfDNA) next generation sequencing (NGS; Guardant360®). The comprehensive -cfDNA NGS panel evaluates point mutations, amplifications, fusions, and insertion-deletion alterations in up to 73 genes. Type of genomic alterations and concordance with tissue testing were examined. Results: Ninety-two percent of patients (23/25) had ≥1 ctDNA alteration(s). AGC showed the highest somatic alteration burden (17.4%; [1.4%-49%]), followed by ACC (10.84%; [0%-22.3%]) and ALC (2.74%; [0.1%-23%]). The most common alterations detected by plasma cfDNA were TP53 (72%), EGFR (36%) and KRAS (24%). In our cohort, 20% (5/25) of pts changed treatment for a FDA-approved drug available at our institution due to the plasma cfDNA results; among these cases, we had EGFR and ERBB2 mutations not detected in initial biopsy of two ALC pts (744_K745insKIPVAI [Exon 19 Insertion] and L755P, respectively) changing therapeutic indication in both pts (2/15, 13.3%). Two ERBB2 amplifications in AGC pts were detected by ctDNA, but not at initial biopsies (2/5, 40%). KRAS alterations (mutation/ amplification) were present in 3 out of 5 cases of ACC by ctDNA, one KRAS mutant was not detected at initial tissue biopsy, allowing change in therapeutic decision (1/5, 20%). Response rates (RR) in pts with ALC (2) and ACC (1) who started treatment based on Guardant360 results was 100%, reducing time to start of treatment by 50% compared to NGS in FFPE. Conclusions: In our cohort, 20% of pts evaluated by plasma cfDNA have a treatment change, allowing early identification of biomarkers of response / resistance to targeted therapies, corroborated by a significative RR.
Management of breast cancer in a small Charity Hospital Cancer Center in Brazil: Ten years of a single institution´s experience.
Authors: Sabina B. Aleixo, Jose Zago Pulido, Narelle Parmanhane, Jose A. G. Aleixo
Journal: Journal of Clinical Oncology (2018)

e13600 Background: The aim of this retrospective study was to describe the clinical characteristics of patients with breast cancer (BC) treated at the Oncology Unit of the Hospital Evangélico, a Charity Hospital of Cachoeiro de Itapemirim, Brazil and take a look on the elderly population treated because treatment decisions are often challenging in this population since evidence-based survival data according to staging and treatment progressively declines with increasing age. Methods: All cases were identified from the Charity Hospital cancer registry database and an observational retrospective cohort study was done with 538 patients treated from January 2002 to December 2012. Results: : Stage at diagnosis : In situ – 11, I – 127, II – 214, III – 151, IV – 35. Median age was 54 years (25 - 91). Hormonal expression : ER expression 385 cases and PR expression 341, HER2 positive in 83 cases and triple negative in 61 cases . The procedures performed were mastectomy 48%, lumpectomy 45% , did not operate 3% , without information on surgery 2%, radiotherapy 75%, hormonal therapy 73% and chemotherapy 76%. Chemotherapy intention at diagnosis was neoadjuvant 21%, adjuvant 53% and palliative 2%; the preferred regimens were CMF, FAC, ACT. Of the 83 cases that needed access to trastuzumab, only 9 patients received it. Patients above 70 years represented 16% of the population with varied stage groups: I – 3, II – 23, III – 16 and IV – 4; out of these patients 57 % had mastectomy, 35 % lumpectomy, 51% chemotherapy, 30% radiotherapy and 73% hormonal therapy. In December of 2012, 49% of the patients were alive in follow-up, 15% had medical release, 23% died of breast cancer and 35% were lost to follow-up. Conclusions: The breast patient profile of the Charity Hospital is a woman with a median age of 54 years, mostly with stage II or III, has access to surgery, chemotherapy and hormonal therapy but does not have access do monoclonal antibody therapy. Interestingly, the elderly have more mastectomies, less chemotherapy and radiotherapy, with the same percentage of hormonal therapy.
Cardiac effects of chimeric antigen receptor (CAR) T-cell therapy in children.
Authors: Danielle S. Burstein, Shannon L. Maude, Stephan A. Grupp, Heather Griffis, Joseph W. Rossano, Kimberly Y. Lin
Journal: Journal of Clinical Oncology (2017)

10531 Background: Treatment with CAR T-cells targeting CD19 for pediatric leukemia has demonstrated significant efficacy with the principal toxicity being cytokine release syndrome (CRS). However, the cardiac effects related to CAR T-cell therapy have not been systematically evaluated. Methods: A retrospective chart review was performed on a large cohort who received CAR T-cell therapy from April 2012 through September 2016. Baseline oncologic and cardiac characteristics were recorded. Cardiomyopathy was defined as an ejection fraction &lt; 55%, shortening fraction &lt; 28%, or diastolic dysfunction. Primary outcome was cardiac event, defined as need for inotropic support or echocardiographic decline in function. Descriptive and univariate analyses were performed. Results: 93 patients were included [55% male, mean age 11.8 yrs (range 1.7-27.1)]; 98% had B cell ALL. Prior to treatment, 15% had cardiomyopathy and 1 patient had single ventricle Fontan palliation. Cardiac events occurred in 34 (36%) with mean onset 4.8 days (range 1-9) after CAR T-cell infusion, of whom 12 (35%) had abnormal systolic or diastolic function on echocardiogram and 6 (18%) required milrinone for cardiac support. 21 (22%) patients had CRS requiring tocilizumab and vasoactive infusions; there were no cardiac-related deaths. Factors associated with cardiac events included higher pre-treatment blast % on bone marrow biopsy [OR 10.45 (95% CI 3.87-28.22) for blast &gt; 10%; p &lt; 0.001] but not cardiomyopathy (p = 0.356), total body irradiation (p = 0.717) or anthracycline dose (p = 0.711). At discharge, 7 (7.5%) patients had worse cardiac function than at baseline, but only 2 (2%) had persistent cardiac dysfunction by 6 months post-infusion. Pre-treatment factors were not associated with persistent dysfunction. Conclusions: This is the first study to describe the cardiac effects of CAR T-cell therapy in children. CAR T-cell therapy appears to be safe, even in patients with cardiomyopathy. Although one-third experienced a cardiac event, persistent cardiac dysfunction is rare. Children with a pre-treatment blast &gt; 10% were most at risk for cardiac events, a finding that may help identify patients who warrant close observation and early intervention with pressor support.
Pharmacodynamic and clinical activity of RGX-104, a first-in-class immunotherapy targeting the liver-X nuclear hormone receptor (LXR), in patients with refractory malignancies.
Authors: Monica M. Mita, Alain C. Mita, Bartosz Chmielowski, Erika Paige Hamilton, Shubham Pant, Roger J. Waltzman, Eric Keith Rowinsky, Michael Szarek, Foster Gonsalves, Isabel Kurth, Celia Andreu, Robert Busby, David Martin Darst, Sohail S. Tavazoie, Masoud Tavazoie, Michael A. Postow
Journal: Journal of Clinical Oncology (2018)

3095 Background: RGX-104 is a small-molecule LXR agonist that modulates innate immunity via transcriptional activation of the ApoE gene. RGX-104 depletes myeloid derived suppressor cells (MDSCs) and stimulates dendritic cells (DCs), activating cytotoxic lymphocytes (CTLs) with anti-tumor activity as monotherapy and in combination with checkpoint blockade in murine models. Methods: We are conducting a Phase 1 dose escalation and expansion study of RGX-104 in patients with refractory solid tumors. Safety, PK, PD, and efficacy are being assessed. Results: RGX-104 was dosed orally in 23 patients with a broad array of tumors on 5 cohorts at doses ranging from 120 mg QD for 3 of 4 weeks to 200 mg BID continuously. Following single dosing, PK analysis demonstrated high inter-patient variability with t1/2 from 6 – 8 hr. ApoE gene expression measured in whole blood leukocytes correlated with RGX-104 dose and exposure, demonstrating robust LXR target engagement. Peripheral immune-cell monitoring revealed substantial MDSC depletion (CD33+CD15+HLA-DR-/low; median 78% decrease), DC stimulation (HLA-DR+Lin-; median 34% increase in PD-L1) and CTL activation (median 257% increase in PD-1+GITR+ CD8+ T-cells) in 10/12 evaluable patients. Peak PD effects began ~2 weeks after RGX-104 initiation. Three patients experienced grade 3-4 neutropenia and 1 patient had grade 3 elevated cholesterol, reversible with a statin, likely on-target adverse events. A patient with a platinum-refractory, high-grade neuroendocrine carcinoma with small cell features had a 53% reduction in index hepatic metastases--a partial response pending confirmation, and 5 patients had stable disease at 8 weeks. Conclusions: Proof of principle has been demonstrated for immunologic and anti-tumor activity of the first-in-class LXR-agonist RGX-104 in advanced cancer patients. RGX-104 was well tolerated at doses up to 160mg BID and demonstrated robust PD effects on ApoE expression and relevant immune cell populations. Dose escalation with a PD-1 inhibitor has begun with plans to study RGX-104 both as monotherapy and in combination with a PD-1 inhibitor in select malignancies. Clinical trial information: NCT02922764.
Life expectancy and early detection of neoplasia: One stop screening for multiple cancer types—11 year (2006-2017) experience of an integrated cancer prevention center (ICPC).
Authors: Nadir Arber, Ari Leshno, Menachem Moshkowitz, Amira Harlap-Gat, Miri Sror, Rafi Alon, Dana Feldman, Bar Chikman, Arye Blachar, Eyal Gur, Vadim Reiser, Gustavo Melinger, Ada Kessler, Galit Aviram, Nicola J Mabjeesh, Lior Galazan, Maayan Jean, Shiran Shapira, Ido Wolf, Ravit Geva
Journal: Journal of Clinical Oncology (2018)

e13553 Background: Cancer is the leading cause of mortality worldwide. Methods: Screening of healthy individuals (20-80 years) at the ICPC included 11 most common cancer types. Extensive clinical and epidemiological data was obtained. Peripheral blood DNA was genotyped for APC I1307K and E1317Q. Subjects were examined by specialists in internal medicine, surgery, plastic surgery, OBGYN, urology, oncology, oral surgery, gastroenterology, and others when indicated. Women (all ages) underwent vaginal US and pap smear and (40 yr) mammography and US/MRI when indicated. PSA and free PSA for Men ( > 40 yr). LDCT for heavy smokers. Colonoscopy to all subjects ( > 40 yr). Results: 7067 (49.4%) men and 7240 women mean age 46.69±11.5 years. 647 new lesions were detected among 602 (4.21%). Over half of them were malignant (366, 56.6%). Skin (105, 0.73%), breast (44, 0.31%), prostate (35, 0.24%), thyroid (31, 0.22%), CRC (24, 0.17%), ovarian (19, 0.13%), urinary (17, 0.12%), lung (15, 0.10%), hematology (15, 0.10%), cervical (14, 0.10%) and oropharynx (11, 0.08%). Patients with newly diagnosed cancers began screening at a significantly older age (55±13 years, P < 0.0001). In 23 (0.16%) more than one cancer was detected. Among cancer patients 6.0% died after 33±26 months at a mean age of 69±13 years. Their survival rate was similar to the general population. The APC I1307K and E1317Q variants were detected in 572 (4.8%) and 182 (1.5%) subjects respectively. First-degree family member with cancer (OR = 1.8), I1307K carriership (OR = 1.4), female gender (OR = 1.3) and advanced age (OR = 1.1) were all associated with statistically significant (P < 0.05) increased cancer risk. Advanced age and first degree family history were also associated with detection of more than one cancer types. Conclusions: One stop shop screening for 11 common cancers is feasible. It can significantly improve morbidity and mortality. The I1307K APC carries an overall increase cancer risk. The life expectancy of cancer patients diagnosed at the ICPC is similar to the general population