tbuckley/cabot-search huggingface dataset:
Preexistence of CT findings with usual interstitial pneumonia (UIP) pattern correlates to radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients receiving chemoradiotherapy (CRT).
Authors: Junji Koyama, Satoru Kitazono, Ryo Ariyasu, Masafumi Saiki, Tomoaki Sonoda, Yosuke Kawashima, Natsuki Takano, Tomoyo Oguri, Shingo Nishikawa, Noriko Yanagitani, Atsushi Horiike, Fumiyoshi Ohyanagi, Katsunori Oikado, Takuyo Kozuka, Makoto Nishio
Journal: Journal of Clinical Oncology (2017)

e20063 Background: RP is a major toxicity commonly observed in NSCLC patients who receive CRT; RP prediction is a critical issue. Although preexisting interstitial pneumonia (IP) is considered as one of the risk factors of RP, the correlation between interstitial lung shadows (ILSs) in the pretreatment CT scan and RP is not well examined. Methods: We reviewed patients with stage III NSCLC who received CRT at our hospital from January 2011 until December 2014. The pretreatment CT scans were retrospectively evaluated, and preexisting ILSs were classified according to the ATS/ERS/JRS/ALAT statement for idiopathic pulmonary fibrosis (IPF) as follows: UIP pattern, possible UIP pattern, and others (not UIP pattern). The incidence, severity, and features of RP were compared between ILS patterns. Results: In total, 105 patients with stage III NSCLC had received CRT. ILSs in pretreatment CT scans were identified in 16 (15.2%) of 105 patients. Of all the identified patterns, one (0.9%) was UIP pattern, six (5.7%) were possible UIP pattern, and nine (8.6%) were not UIP pattern. Grade 3 or higher RP was observed in 2 of 7 (28.6%) patients with UIP pattern or possible UIP pattern and 1 of 9 (11.1%) patients with not UIP pattern ( P = 0.55). RP that extended outside the irradiation field like an acute exacerbation of IP was observed in 4 of 7 (57.1%) patients with UIP pattern or possible UIP pattern and 1 of 9 (11.1%) patients with not UIP pattern ( P = 0.106). Conclusions: Preexistence of ILSs classified as UIP pattern or possible UIP pattern should be considered as a risk factor for severe or extensive RP after CRT.
TCT-475 Pacemaker dependency at 2-month follow-up after permanent pacemaker implantation caused by transcatheter aortic valve implantation-induced conduction disturbances
Authors: Martijn van Mourik, Nynke Kooistra, Kirsten Kooiman, Jeroen Vendrik, Pieter Stella, Jan Baan, Jose PS. Henriques, Marije Vis
Journal: Journal of the American College of Cardiology (2018)
Association of loss of tumor suppressor ZFP36 with lethal prostate cancer.
Authors: Christopher Sweeney, Travis Gerke, Himisha Beltran, Andrea Sboner, R. Jeffrey Karnes, Eric A. Klein, Elai Davicioni, Kasra Yousefi, Ashley Ross, Lorelei Mucci, Bruce J. Trock
Journal: Journal of Clinical Oncology (2017)

5062 Background: Inflammation has been linked to prostate cancer (PCa) progression which may be mediated by the transcription factor nuclear factor kappa B (NFκB). Using a bioinformatic screen focused on NFκB pathway activation in lethal PCa, we identified the tumor suppressor ZFP36 as a key node of the NFκB network. We also showed in vitro that ZFP36 expression was inversely associated with both NFκB-controlled gene levels and proliferation and sensitivity to enzalutamide. We examined the role of ZFP36 and PCa progression in patient cohorts. Methods: The association between low mRNA expression of ZFP36 (levels in the lower quartile) and lethal PCa (defined as metastatic disease or death) was assessed with logistic regression among men with localized PCa in two independent cohorts treated with radical prostatectomy (RP). The discovery cohort was RP samples from Health Professional Follow-up Study and Physicians Health Study and the validation cohort was RP samples from Cleveland Clinic, Mayo Clinic, Johns Hopkins and MSKCC. In a third cohort from Cornell University, ZFP36 expression levels were assessed in RP samples from patients with localized PCa and biopsies of metastatic castration resistant prostate cancer (mCRPC). Results: Table 1 shows men with localized PCa and lower quartile of tumor ZFP36 expression had a nearly 2-fold higher risk of lethal PCa after adjusting for known clinical and histological prognostic features (age, RP Gleason score, T-stage); an association confirmed in the validation cohort. ZFP36 gene expression was also significantly lower in mCRPC (n=53) compared with a localized RP cohort (n=68) (p-value &lt;0.0001). Conclusions: In humans lower ZFP36 in RP specimens is associated with clinically significant risk of lethal PCa after treatment with curative intent and lower ZFP36levels are found in metastatic tissue. [Table: see text]
Evaluating year 1 of NCI's experimental therapeutics clinical trials network (ETCTN).
Authors: Grace Miskin, S. Percy Ivy, Jennifer Huang, Lauren Greenberg, Amy Gravell, Martha Kruhm, Jenny R Hopkins, James A. Zwiebel, Jeffrey Moscow, Jeffrey S. Abrams, Andrea Denicoff, Karen E Martier, Holly A. Massett
Journal: Journal of Clinical Oncology (2016)

e14049 Background: NCI launched the ETCTN in April 2014 to conduct early phase cancer studies via a network using team science principles. NCI committed to a 3 year process evaluation of the new program to assess performance and participant satisfaction and identify course corrections. We report on the findings for Year 1. Methods: Three methods were employed: 1) analysis of archival data (1/2010-1/14) to establish baseline (BL) measures; 2) analysis of year 1 (Yr1) data; 3) satisfaction survey of ETCTN investigators (PIs, N = 105; response rate 81%) and staff (N = 119; response rate 67%). Results: LOI approval rates increased from 23% at BL to 33% in Yr1 (23 LOIs were approved in Yr1). ETCTN LOIs are solicited via new multi-disciplinary project teams (PTs; n = 5 PTs in Yr1) or are unsolicited. Participants in PTs had high satisfaction (mean = 4.2 on 5 pt-scale; 5 = very satisfied). Time from IDSC review to first LOI approval for PTs took 348 days (median, n = 3), compared to 526 days for past mass solicitations (n = 5). For unsolicited LOIs, PIs were most satisfied with submission process transparency (mean = 3.6) and least satisfied with number of drugs available (3.0). There were 36 accruals in Yr1 to 6 available ETCTN trials and 452 accruals to pre-ETCTN trials. Overall PI satisfaction with Yr1 and the ETCTN trial portfolio was moderate (3.0 for both). PIs were most satisfied with the portfolio's lack of duplication with other studies (3.6) but least satisfied with the number of trials (2.4). 50% of PIs solidly agreed (score of 4 or 5 on 5 pt-scale) that their concerns would get worked out over the grant and 71% agreed that their center now has a team-based approach for early phase trials. Among staff, Yr1 involvement was low (44% little or no involvement), but users were satisfied with most services (means >3.5/5). Conclusions: PI satisfaction with ETCTN Yr1 was modest, with concerns raised about too few trials. The transition and start-up processes of Yr1 resulted in a small number of trials available and limited ETCTN participation by sites and staff. PIs viewed the team approach as a strength of the program. NCI has made numerous changes in response to Yr1 feedback, and as the number and rate of approved LOIs increases, more trials and greater involvement are expected.
New Approaches to the Management of Adult Acute Lymphoblastic Leukemia
Authors: Renato Bassan, Jean-Pierre Bourquin, Daniel J. DeAngelo, Sabina Chiaretti
Journal: Journal of Clinical Oncology (2018)

Traditional treatment regimens for adult acute lymphoblastic leukemia, including allogeneic hematopoietic cell transplantation, result in an overall survival of approximately 40%, a figure hardly comparable with the extraordinary 80% to 90% cure rate currently reported in children. When translated to the adult setting, modern pediatric-type regimens improve the survival to approximately 60% in young adults. The addition of tyrosine kinase inhibitors for patients with Philadelphia chromosome-positive disease and the measurement of minimal residual disease to guide risk stratification and postremission approaches has led to additional improvements in outcomes. Relapsed disease and treatment toxicity-sparing no patient but representing a major concern especially in the elderly-are the most critical current issues awaiting further therapeutic advancement. Recently, there has been considerable progress in understanding the disease biology, specifically the Philadelphia-like signature, as well as other high-risk subgroups. In addition, there are several new agents that will undoubtedly contribute to additional improvement in the current outcomes. The most promising agents are monoclonal antibodies, immunomodulators, and chimeric antigen receptor T cells, and, to a lesser extent, several new drugs targeting key molecular pathways involved in leukemic cell growth and proliferation. This review examines the evidence supporting the increasing role of the new therapeutic tools and treatment options in different disease subgroups, including frontline and relapsed or refractory disease. It is now possible to define the best individual approach on the basis of the emerging concepts of precision medicine.
The role of endomyocardial biopsy in cardiac tumors diagnosis.
Authors: Dana Ionescu, Danielle Stone, James Stone, Jean-Bernard Durand, Jose Banchs, Cezar Iliescu
Journal: Journal of Clinical Oncology (2017)

e22536 Background: Pathologic examination is essential for definite diagnosis of both primary and secondary (metastatic) cardiac tumors. Limited data exists on the risks and benefits of catheterization with endomyocardial biopsy (EMB) of cardiac tumors. The present study aims to assess the safety of EBM in diagnosing cardiac tumors. Methods: We retrospectively reviewed therecords of cancer patients who presented with cardiac masses at MD Anderson Cancer Center between 2011 and 2016. Clinical presentation, transthoracic/transesophageal echocardiogram and pathology laboratory results for patients who underwent cardiac catheterization &amp; EMB were reviewed. Results: Out of 8 patients with cardiac tumors (4 females, 4 men, average age of 59.7 y.o.), 5 patients had cardiac catheterization with EMB (5.4 French with Jaw Volume of 2.2, specimens are typically 5 to 20 mg per sample). Clinical presentation included shortness of breath and dyspnea (3 patients), syncope and palpitations (1 patient), and fatigue and slurred speech, as result of a hemispheric stroke (1 patient). Diameter of the cardiac tumors ranged between 4 – 6.5 cm, with no wall abnormalities or hemodynamic compromise as identified by echocardiography. Right atrium (RA) was the most common location (4 patients). One patient had extension of bronchus squamous cell tumor extending into a coronary artery bypass graft (LIMA). Review of the pathological specimens obtained from EMB performed under TEE and fluoroscopic guidance identified 2 patients with cardiac sarcomas in the RA, 1 patient with atrial metastatic melanoma (RA) and 1 patient with lymphoma (right ventricle). EMB was performed with minimal blood loss in all patients. During procedure, one patient developed rapid accumulation of fluid in the pericardial space requiring emergent echo-guided pericardiocentesis. Conclusions: EMB is suggested for the diagnosis of selected cardiac tumors, if the potential benefits from the procedure outweighs the risks. A more invasive approach for rapid histological diagnosis allows appropriate therapy to be promptly initiated. To ensure the safety, EMB should be performed by an experienced operator with fluoroscopy and with transthoracic, transesophageal or intra-cardiac echocardiography guidance.
EGFR mutation detection on lung cancer cytological specimens by the rapid and fully integrated Idylla molecular diagnostics system.
Authors: Caterina de Luca, Gianluca Gragnano, Umberto Malapelle, Giancarlo Troncone
Journal: Journal of Clinical Oncology (2016)

e20542 Background: In everyday practice, EGFR testing is centralized in referral laboratories that receive paucicellular cytologic specimens. Ideally, EGFR testing should be carried out in the center where the patient is diagnosed, such that the most cellular slide can be selected from in-house cytological material. However, available techniques are little standardized and difficult to be implemented in settings with little expertise in molecular testing The Idylla EGFR prototype assay is a rapid and fully automated test which may easily be adopted by a wider number of pathological centers. However, the assay has been designed to process paraffin-embedded tissue sections, rather than cytology. This study assessed whether an Idylla EGFR prototype assay can be reliably applied to cytological lung cancer specimens. Methods: The limit of detection (LOD) of the Idylla EGFR prototype assay was assessed by cell line dilution studies. A quantity of DNA ranging from 1.75 ng/μl to 60 ng/μl was extracted from 76 lung cancer cytological samples and a total of 10 ng was directly placed inside an Idylla EGFR prototype assay cartridge. Idylla results were compared to fragment length (exon 19 del) and Taqman assays. In addition, in 17 cases, scraped cytological material was directely inserted in the cartridge, rather than extracted DNA. Results: The Idylla EGFR prototype assay showed an LOD of 1% mutant allele. Idylla yielded valid results in 74/76 (97,3%) samples, detecting all the mutant cases (n = 36) identified by standard techniques; in addition, two low abundance EGFR mutations were found by Idylla and missed by the fragment length assay. The subset of cases processed by directly analysing scraped material gave a mutant rate concordant with those detected by standard techniques. Conclusions: Our data suggest that the Idylla EGFR prototype assay is sensitive on extracted DNA and can reliably be applied on cytological samples, enabling implementation of EGFR testing even in diagnostic units without molecular expertise. Investigation is required to further validate this test on scraped cytological material. These data make the Idylla test an attractive option to standardize and to widespread EGFR testing.
Outcomes of single port access surgical staging for twenty-one endometrial cancer patients.
Authors: Yoon Kyung Elena Lee, Keun Ho Lee
Journal: Journal of Clinical Oncology (2016)

e17123 Background: Single port access (SPA) surgery could be utilized in staging for gynecologic oncology. We are to report outcomes of endometrial cancer patients with SPA surgical staging. Methods: From Nov 2011 to Dec 2015, 21 cases of endometrial cancer with SPA surgical staging were reviewed retrospectively. All the operative procedures of hysterectomy ± pelvic or peri-aortic lymphadenectomy (including 3 sentinel lymph node biopsy) were done by conventional laparoscopic instruments with Octoport platform. Results: Ninteen stage I , 1 stage II and 1 stage IVB endometrial cancer were included in this study. There was no case of conversion to laparotomy or multi-port surgery. Mean age of the patients was 57 years old. Thirteen patients received pelvic lymphadenectomy and 11 had peri-aortic lymphadenectomy. Three had sentinel lymph node biopsy and 5 omitted lymphadenectomy. Two premenopausal patients preserved the ovaries. Mean operative time was 182 minutes (SD, 69) and mean 20 pelvic lymph nodes and 13 peri-aortic lymph nodes were retrieved. One patient who had bone metastasis showed positive peri-aortic lymph node metastasis. One showed post-operative ileus subside with conservative treatment and post-operative hospital stage was 3 days (range, 1-15). Conclusions: SPA surgery can be applicable to surgical staging for endometrial cancer with safety and efficacy. Operative outcomes and complications are comparable to conventional laparoscopic staging.
Does training oncologists to have goals of care discussions affect healthcare utilization among patients with advanced cancer?
Authors: Nina A. Bickell, Kerin B. Adelson, Jason Parker Gonsky, Jenny J. Lin, Rebeca Franco, Natalia Egorova, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2018)

6595 Background: Aggressive treatment near the end of life is a measure of poor quality care. Goals of Care (GoC) discussions may affect healthcare utilization among patients with advanced cancer. We coached oncologists to improve communication skills (CS) & report the effect of CS coaching on hospital, ER, hospice & ICU admission in the last month of life. Methods: We randomized solid tumor oncologists at 4 academic, community, municipal and rural hospitals to participate in a RCT of communication skills training & recruited their newly diagnosed advanced cancer patients with < 2 year prognosis. Ten CSs were assessed via checklist review of audiotaped visits. Charts were abstracted, patients or their caregivers were surveyed at 6 months to assess utilization of: chemotherapy, ICU, hospitalizations, ER visits and hospice in the last 30d of life and over the 6 months enrolled in the study. A GoC discussion included discussion of prognosis, treatment preferences, and what’s important to patients given their cancer diagnosis. We enrolled 22 of 25 eligible oncologists (88%). 263 patients were recruited & surveyed to assess whether a GoC discussion occurred. 250 (95%) had charts abstracted and were resurveyed at 6 months to assess utilization at other hospitals. Results: Patients’ mean age was 63 yrs (20-89), 60% male, 53% white, 29% black & 19% Latino. 35 patients (13%) died within 6 months of baseline survey with no difference between patients of intervention (INT) or control (CNTL) oncologists. Compared to CNTLs, INT oncologists’ skills improved with coaching (1.63 vs -0.09; p = .04). 43% INT and 46% CNTL patients reported a GoC discussion. The average rate of hospitalization/ pt = 0.32 (0-3) and ER visits = 0.44 (0-4) with no difference between INT & CNTL. Rates of aggressive treatment in the last 30d of life varied: chemotherapy = 21%; ICU stay = 7% with no difference between INT & CNTL patients. Hospice enrollment occurred 2 weeks prior to death; no difference in INT vs CNT (13.5d vs 14d). Conclusions: Despite improving oncologists’ communication skills to conduct GoC discussions, there was no impact on rates of hospitalization, receipt of aggressive treatments or enrollment in hospice at the end of life. Clinical trial information: NCT02374255.
Monitoring pharmacodynamic response to nucleoside analogs targeting DNMT1 using p16/INK4a re-expression in circulating tumor cells.
Authors: Robert J. Kinders
Journal: Journal of Clinical Oncology (2018)

e24069 Background: Nucleoside analogs decitabine, FdCyd [5-fluorodeoxycytidine, administered concurrently with tetrahydrouridine, (THU)], thiodeoxycytidine (TdCyd), and 5-aza-thiodeoxycytidine (Aza-TdCyd) all knock down DNMT1 protein levels in vitro in cultured colon and bladder cancer cell lines, which is followed by re-expression of p16/INK4a within two weeks of culture following continuous drug exposure. The Developmental Therapeutics Clinic at NCI (DTC) is the lead site for Phase 1 trials evaluating oral FdCyd+THU, oral TdCyd, and intravenous FdCyd+THU. A Phase 1 trial of Aza-TdCyd has opened. To provide evidence of target engagement in the Phase 1 studies, we evaluated pharmacodynamic response to treatment by measuring the change in the fraction of circulating tumor cells that are p16/INK4a positive using fluorescence microscopy. Methods: Drug was administered on a QDx5/2 days off/QDx5 schedule every 30 days. Venous blood specimens were collected in CellSave tubes, and handled and processed according to the manufacturer’s instructions. PD sampling occurred at baseline (pre-dose) and at post-dose day 1, post-dose day 2, and post-dose on day 12 . Specimen analysis was performed on a CellSearch instrument, and the fraction of CTCs (identified by tumor marker staining) that are p16 positive at each time point was monitored employing a laboratory-developed 5 channel immunofluorescence assay. Results: Eighty patients were monitored during therapy. Baseline p16 expression in CTCs was detected in ≤15% of patients, and treatment with each drug regimen increased by at least 3-fold the fraction of p16+ CTCs in65% of evaluable patients by the end of cycle 1 (C1D12), indicating successful target engagement and re-expression of this putative tumor suppressor as a consequence of drug administration. Conclusions: p16/INK4a protein re-expression in CTCs is a reliable and robust marker of PD drug response for both FdCyd+THU and TdCyd. P16 expression in CTCs will be tested during the Phase 1 trial of Aza-TdCyd in the DTC trial that has just opened. Funded by NCI Contract No. HHSN261200800001E
Impact of hospital safety-net burden on oncology patterns of care and outcomes.
Authors: Reith Sarkar, Zachary David Guss, Christian Lopez, Michael Brandel, James Don Murphy
Journal: Journal of Clinical Oncology (2018)

6567 Background: Safety-net hospitals serve a vital role in treating underserved populations. These hospitals often receive less funding, which could lead to different patterns of care for patients treated at these facilities. The purpose of this study was to determine the patterns of care and oncologic outcomes among a large cohort of cancer patients treated at safety-net hospitals. Methods: We identified 3,398,962 patients within the National Cancer Database with 10 common cancers including breast, prostate, lung, head and neck, colon, rectal, pancreas, cervix, bladder, and uterus diagnosed between 2004 and 2015. Safety-net burden was defined from the percentage of uninsured or Medicaid patients seen at each facility, and hospitals were then categorized as low (LBH), medium (MBH), or high burden (HBH) hospitals. We evaluated the impact of safety-net burden on patterns of care, as well as other outcomes including surgical margin status, and overall survival using multivariable linear, logistic, and Cox regression models. Results: Cancer patients seen at HBHs were more likely to be young, female, black, Hispanic, and reside in a low-income zip-code. HBHs were more likely to be academic, smaller institutions, and located in the South. After controlling for patient and tumor-related factors HBHs had differing patterns of treatment, and overall were less likely to operate (odds ratio [OR] 0.83; 95% confidence interval [CI] 0.82-0.84; p < 0.0001) and were more likely to provide radiation (OR 1.09; 95% CI 1.08-1.1; p < 0.0001) than LBHs. With respect to surgery, HBHs had higher rates of positive surgical margins (OR 1.08; 95% CI 1.06-1.1; p < 0.0001) than LBHs. HBHs had higher all-cause mortality when compared to LBHs (hazard ratio 1.09; 95% CI 1.08-1.10; p < 0.0001). Conclusions: Oncologic care at safety-net hospitals is associated with different patterns of care, as well as adverse clinical outcomes. Future research should focus on determining the etiology of this disparity, and work to devise strategies to improve outcomes among patients treated at safety-net hospitals.