tbuckley/cabot-search huggingface dataset:
Prospective evaluation of neuromediators during treatment with docetaxel in castration resistant prostate cancer.
Authors: Jost von Hardenberg, Maike Schwartz, Christian Bolenz, Christel Weiss, Thorsten Werner, Stefan Fuxius, Markus Mueller, Thomas Frangenheim, Elmar Heinrich
Journal: Journal of Clinical Oncology (2016)

e16609 Background: Small-cell/neuroendocrine (SCNC) transformation in castration resistant prostate cancer (CRPC) treated with highly effective AR axis inhibitors has been observed. Similarly, it has been suggested that treatment with Docetaxel significantly impairs the AR axis. We investigated whether treatment with Docetaxel influences the transformation to SCNC. Methods: We conducted a multi-institutional prospective non-interventional trial in five german centers in CRPC patients with clinical or radiographic progression of disease. 53 patients were included. We repeatedly evaluated the circulating neuroendocrine markers chromogranin A (CGA), neuron specific enolase (NSE) and pro-gastrin releasing peptide (Pro-GRP). Serum samples were obtained before and during treatment with Docetaxel. Statistical analyses were performed to test if neuromediator levels increase during treatment with Docetaxel and if PSA response and survival, median follow-up 8.3 months; correlate with neuromediator levels. Results: 53 patients (median age 73, median PSA = 125 ng/ml, clinical manifestation of SCNC n = 46 (87 %)) were included. Before study inclusion 26 (51 %) patients had received Abiraterone Acetate, 7 (13 %) Enzalutamide and 4 (7 %) Docetaxel. CGA and NSE levels before treatment with Docetaxel were above the upper limit of normal in 31 (63 %) and 21 (43 %) patients, respectively. An increase of ≥ 25 % in CGA levels compared to baseline was observed in 28 (58 %; missing n = 5) patients (p = 0.037). An increase of NSE levels compared to baseline was seen in 22 (46 %; missing = 5) patients (p = 0.043). CGA and NSE level increases did not correlate with PSA decline at 12 weeks (p = 0.994; p = 0.931) or PSA nadir (p = 0.948; p = 0.848). CGA increase ≥ 25 % and NSE increase did not correlate with time of survival (p = 0.239, HR 1.00; p = 0.805, HR 1.00). Conclusions: During the treatment with Docetaxel a significant increase of the circulating neuromediators CGA and NSE was observed. Docetaxel may influence the transformation to SCNC but a clinically relevant marker cutoff value still needs to be established. Sequential biopsies of metastatic lesions will add significant information on molecular pathways of SCNC transformation. Clinical trial information: DRKS00004797.
The impact of second-line chemotherapy on advanced pancreatic cancer: A retrospective study in Reggio Emilia Clinical Cancer Centre.
Authors: Licia Baldi, Michele Panebianco, Paolo Giorgi Rossi, Pamela Mancuso, Tiziana Cassetti, Romano Sassatelli, Carmine Pinto
Journal: Journal of Clinical Oncology (2017)

e15732 Background: There is currently no standard second-line treatment for metastatic pancreatic adenocarcinoma. The aim of this study is to evaluate the impact of a second-line therapy prior to the introduction of nab-paclitaxel. Methods: From 01/2009 to 12/2014, 204 patients were treated for pancreatic cancer. 166 (81.3%) received first(I)-line chemotherapy. Patients treated in second(II)-line were evaluated in two different periods, before and after FOLFIRINOX introduction. Results: 99 patients (59.6% treated in I line) received II line therapy. The main regimens used in I line were gemcitabine during the period 2009-2011 and FOLFIRINOX from 2012 to 2014 (some patients were treated with nab-paclitaxel/gemcitabine approved before AIFA registration). We observed that the increased use of gemcitabine in the second period was related to a reduction in I line use (52.1% patients after 2012 vs 21.4% before 2012). Considering the different therapeutic regimens employed in I and II line, no statistically significant differences in overall survival were observed over the two periods (Table). The probability of receiving II line chemotherapy did not change in the two groups (HR 0.6; p=0.2). Conclusions: Within the limits of a retrospective analysis, all II line regimens used showed the same effectiveness, regardless of I line treatment employed. It is likely that the large number of patients treated with effective therapies in II line have concealed the impact of front-line schemes. In an ongoing study we are evaluating the impact of introducing nab-paclitaxel in clinical practice. [Table: see text]
Non-invasive analysis of three disease-progression modes in NSCLC patients after taking EGFR-TKIs by next-generation sequencing.
Authors: Yuqing Wei, Yong Song, Qian Zou, Hongbing Liu, Tangfeng Lv
Journal: Journal of Clinical Oncology (2018)

e21168 Background: Most of the non-small cell lung cancer(NSCLC) patients experienced good clinical responses to an EGFR- TKIs will inevitably develop disease-progression .Herein we aimed to investigate three different disease-progression modes (progression of primary foci,progression of metastatic foci,progression of both in primary and metastatic foci) of NSCLC patients after taking EGFR-TKIs by NGS. Methods: 41 NSCLC patients with sensitive EGFR-mutations who acquired resistance to EGFR-TKIs and underwent post-progression NGS were enrolled.The clinical characteristics, progression-free survival(PFS), genomic alteration and the expressions of exon 19 deletions (Del 19), L858R mutation and T790M mutation between the above three disease-progression modes were analyzed. Results: Sites of disease progression were as follows: primary foci in 19.5%(8/41)(Mode 1), metastatic foci in 31.7%(13/41)(Mode 2),both primary and metastatic foci in 48.8%(20/41)(Mode3).Median PFS of three modes were 6 months(95%CI,1-8),11months(95%CI,8-14),10 months(95%CI,3-16),respectively,which had statistical difference (p = 0.0084).The expressions of Del19 showed a significant difference between three modes(p = 0.02),while L858R and T790M mutation had no statistical difference.Mutations in the TP53 tumor suppressor gene were the most frequent genetic alteration in our study,which account for 48.8%(20/41).TP 53 mutation of Mode 1 mainly in the exon 6 and exon 8,Mode 2 and Mode 3 all located from exon 4 to exon 8.The numbers and species of mutant genes in Mode 3 were obviously more than Mode 1 and Mode 2,and there was no gene amplification in Mode 3.In addition,we can clearly see that mutation of genes such as CCND1、CCNE1、CDK4 can promote cancer cell proliferation and mutation of genes such as ERBB2、ERBB4、PTEN、MYC、MET that can promote cancer cell proliferation and metastasis. Conclusions: Our findings provided insights into three different disease-progression modes after taking EGFR-TKIs and had significant value in the design of future therapeutic strategies.
Impact of complete molecular response (CMR) on survival in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
Authors: Nicholas James Short, Elias Jabbour, Jorge E. Cortes, Rebecca Garris, Susan Mary O'Brien, Keyur Patel, Koji Sasaki, Ghayas C. Issa, Guillermo Garcia-Manero, Deborah A. Thomas, Hagop M. Kantarjian, Farhad Ravandi
Journal: Journal of Clinical Oncology (2016)

7034 Background: Minimal residual disease (MRD) assessment can identify patients with ALL at increased risk for relapse and death. However, the impact of achieving CMR in Ph+ ALL remains undefined. Methods: Between 4/2001 and 12/2015, 202 adult patients with Ph+ ALL received frontline chemotherapy plus a tyrosine kinase inhibitor at our institution. Of these, 196 achieved CR and 122 had MRD assessments for BCR-ABL1 by RQ-PCR both at CR and at 3-month time points; 37 patients underwent stem cell transplant (SCT) and were excluded, leaving 85 patients evaluable for this analysis. Patients received hyperCVAD plus imatinib (n = 23), dasatinib (n = 39) or ponatinib (n = 23). Major molecular response (MMR) was defined as a BCR-ABL1/ABL1 ratio < 0.1% standardized to the international scale, and CMR was defined as the absence of a quantifiable BCR-ABL1 transcript. Results: Median duration of survivor follow-up was 30 months. Molecular response rates at CR and at 3 months and their respective 3-year OS and RFS rates are summarized in the Table. Overall, MRD status at 3 months had better discrimination for OS and RFS than did MRD status at CR. At CR, no difference in OS or RFS was observed between patients achieving CMR and those with lesser responses (P = 0.26 and P = 0.15, respectively). At 3 months, achievement of CMR was associated with longer median OS and RFS compared to those with lesser responses (127 vs. 38 months, P = 0.009; and 126 vs. 18 months, P = 0.007, respectively). Patients with CMR at 3 months also had superior OS and RFS compared to those who achieved MMR at the same time point (P = 0.04 and P = 0.05, respectively). Among the 51 patients who achieved CMR at 3 months, there was no impact of molecular response at CR on either OS or RFS (P = 0.79 and 0.48, respectively). Conclusions: Patients with Ph+ ALL who achieve CMR at 3 months have superior outcomes compared to those with lesser molecular responses. PCR response at CR. N (%) 3-year OS rate (%) P 3-year RFS rate (%) P CMR 29 (34) 81 73 MMR 22 (26) 74 0.04 65 0.01 No MMR 34 (40) 56 40 PCR response at 3 months. N (%) 3-year OS rate (%) P 3-year RFS rate (%) P CMR 51 (60) 79 69 MMR 23 (27) 56 0.006 42 0.002 No MMR 11 (13) 45 36
Characteristics of successful fertility preservation programs for cancer patients.
Authors: Patrick Heiser, Stephanie Wei, Roxanne Dutia, Jane Ruman
Journal: Journal of Clinical Oncology (2016)

e18008 Background: ~1 in 10 cancer cases occur in adults of reproductive age.* ASCO guidelines encourage oncologists to discuss the possibility of infertility with patients of reproductive age or with guardians of children treated for cancer; yet, communication about fertility preservation (FP) options and resultant referrals remain low. Methods: The Ferring HeartBeat program provides access to select fertility medications at no cost to US women with a new cancer diagnosis who wish to undergo FP prior to starting cancer treatment. An average of 83 patients per month have used the program since its inception in 2012. Online surveys were sent to the top 100 (of 530) reproductive endocrinologists (REs) utilizing the HeartBeat program to collect information on their successful FP practices. Results: 54 REs responded. The majority have been in clinical practice for > 10 years and were from either large practices ( ≥ 5 physicians) and/or university-based academic centers, and responsible for ≥ 500 in-vitro fertilization cycles per year. Over 50% of respondents see 2-5 FP patients per month. Patients with a diagnosis of breast cancer were most frequently referred, followed by those with hematologic malignancies and gynecologic cancers. 56% report that patients are typically referred ≤ 14 days of diagnosis and 57% of patients are fully staged prior to referral. Greater than 96% of patients are seen by an RE ≤ 2 days of referral. 70% of respondents are able to complete FP treatment cycles ≤ 2 weeks of referral, as 83% of respondents utilize menstrual cycle-independent protocols. 98% report that they communicate the FP treatment plan to the referring oncologist prior to the start of treatment. 94% of REs discount FP cycle cost for patients whose insurance does not provide coverage; of these, 51% cut the cost of a cycle by more than half. Respondents felt concerns over delay in cancer treatment and lack of awareness of advances in assisted reproductive technology (e.g. oocyte vitrification, tissue cryopreservation, etc.) were the most important obstacles limiting oncology referrals. Conclusions: The majority of successful FP programs provide the referred cancer patient with rapid and discounted access to treatment. * Adams E. Br J Cancer; (2013)108, 1602–15.
Parenchymal sparing surgery for colorectal liver metastases: The need for a common definition.
Authors: Marie Desjardin, Serge Evrard, Véronique Brouste, Gregoire Desolneux, Marianne Fonck, Dominique Bechade, Benjamin Bonhomme, Yves Becouarn
Journal: Journal of Clinical Oncology (2017)

e15013 Background: Colorectal cancer metastases (CRLM) are major public health issue. Recently, surgeons have advocated the use of parenchymal sparing surgery (PSS) however, a common definition of the concept is lacking.To clarify and try to validate the concept of PSS to treat CRLM through the available retrospectives studies, including ours. Methods: Retrospective analysis of a cohort of patients treated by combined resections and intra-operative ablation (IOA) based on PSS, prospectively recorded in a database from 2003 to 2015 in a regional referral cancer center. All the patients benefited from the same strategy, constituting a homogenous series.PSS consists of using resection or IOA in order to spare the healthy parenchyma. One-stage is favored over two-stage surgery and use of portal vein embolization was restricted to the minimum.Post-operative complications were the primary endpoint with a special focus on post-operative liver failure. Liver toxicities and overall survival were also scrutinized. Results: Three hundred and eighty-seven patients underwent a PSS out of which 348 patients received a median of 9 pre-operative cycles of oxaliplatin or irinotecan with targeted therapies for half of them. Resection was major in 128 patients, combined with IOA in 137 patients and IOA alone in 50 cases. Thirty-eight patients had a PVO by strict necessity. The 5yr-overall survival was 50.3%. Seventy-eight patients had a complication &gt; grade 3 out of which 10 patients died. Nine patients had a liver failure (LF) grade B and C and four died. There was no difference in post-operative complications comparing minor and major resections, validating our PSS definition. Chemotherapy and liver toxicity were not related to more post-operative complications. Only one patient died from a primitive LF. Conclusions: With PSS, healthy liver is no more a target. Routine use of chemotherapy does not impair the results and severe LFs are rare. PSS is the optimal strategy to treat CRLM. Definition of PSS cannot be based just on the retrived volume but on the ratio Tumor burden/Healthy liver. A major hepatectomy can be a PSS and a minor may not be one. That is why PSS defintion must be clarify especially for further prospective validations.
Case 28-2018: A 39-Year-Old Man with Epistaxis, Pain and Erythema of the Forearm, and Pancytopenia
Authors: Christiana A. Iyasere, Ronald W. Takvorian, F. Joseph Simeone, Bradford J. Siegele
Journal: New England Journal of Medicine (2018)

A 39-year-old man presented with epistaxis, pain and erythema of the arm, and pancytopenia, with neutropenia and monocytopenia. Imaging studies were notable for splenomegaly and lymphadenopathy. A diagnostic procedure was performed.
Real world clinical outcomes of palbociclib in hormone receptor positive (HR+) metastatic breast cancer (MBC) patients.
Authors: Akaolisa Samuel Eziokwu, Leticia Varella, Megan Lynn Kruse, Xuefei Jia, Halle C. F. Moore, George Thomas Budd, Jame Abraham, Alberto J. Montero
Journal: Journal of Clinical Oncology (2018)

e13034 Background: Palbociclib (PA), a CDK4/CDK6 inhibitor, has been shown in clinical trials to prolong progression free survival (PFS) in HR+/Her-2 negative MBC when combined with an aromatase inhibitor (AI) or fulvestrant (FULV). This study assessed real world outcomes of HR+ MBC patients (pts) treated with PA/endocrine therapy (ET). Methods: This is a retrospective, single institution review of HR+ MBC pts treated with PA plus either an AI or FULV from 2015-2017. The primary outcome was progression-free survival (PFS) as assessed by the clinician based on radiological and/or clinical criteria. Tolerability and observed toxicities with PA and overall survival (OS)—defined as date of initial PA treatment to date of death— were also evaluated as secondary outcomes. Results: 411 women with HR+ MBC who received PA were identified. 94% were HER-2 negative. Median and average follow up duration were 10.2 and 11.3 months, respectively. 55% received PA/letrozole (LTZ), 6% PA/other AI, and 38% PA/FULV. PA/ET was initiated as 1st, 2nd, 3rd, or 4th line and beyond in 36%, 26%, 13%, and 25% of pts, respectively. As of 1/3/2018, 310 patients (76%) were still alive, 186 patients (45%) had progressed on PA with 48% currently on PA. The estimated median PFS for PA/LTZ was 8.92 months (95% CI 6.16-11.0)—similar to that for PA/other AI. For PA/FULV the estimated median PFS was 10.3 months (95% CI 8.16-12.3). Most pts (65%) received PA/LTZ in the 2nd line and beyond. For pts who received PA/LTZ as 1st line therapy, the estimated PFS was 15.1 months (95% CI 12.3-infinity). The median OS could not be calculated because of insufficient number of deaths. In the overall cohort, the 1 and 2 year OS rates were 78% and 53.1%, respectively. PA was dose reduced in 27% of pts due to drug toxicity, most commonly because of neutropenia. Permanent discontinuation of PA due to toxicity was infrequent occurring only in 7% of pts. Conclusions: Among HR+ MBC pts in non-clinical trial setting, the estimated PFS on PA/fulvestrant was comparable to PALOMA-3, however our observed PFS with PA/letrozole as 1st line therapy was shorter than that reported in PALOMA-2. PA was well tolerated with manageable toxicity and low drug discontinuation rate.
P44 Solitary Pulmonary Nodule: Primary or Metastatic Neoplastic Lesion?
Authors: M. Grafino, J. Eurico Reis, M. Felizardo, M.O. Fernandes, A. Catarino, F. Mascaranhas, C. Loewenthal, M. Pantarotto, S. Furtado, F. Martelo
Journal: Journal of Thoracic Oncology (2018)
OS1.1 Role of RNU6-1 isolated from circulating exosomes as a differential biomarker for GBM versus non-neoplasic brain lesions and PCNSL
Authors: M Puigdelloses, M González-Huarriz, B Zandio, S Besora, J Bruna, G Petrirena, M Marigil, R Díez-Valle, S Tejada, J Nuñez, M Alonso, J Gállego Pérez-Larraya
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) is the most common malignant primary brain tumour in adults, and is still associated with a dismal prognosis despite intensive research and therapeutic efforts. The identification of circulating biomarkers for tumor detection and response assessment would be of great clinical help. Recent studies have shown that GBM cells release microvesicles containing a select subset of cellular proteins and RNA. Previously, we demonstrated that exosomes isolated from the serum of GBM patients had an increased expression of the small non-coding RNA RNU6-1 compared to control samples, and hence could serve as a non-invasive diagnostic biomarker for GBM.In this study, we set to investigate the role of RNU6-1 as a differential biomarker of GBM versus other brain diseases with similar radiological features. We analyzed the expression of RNU6-1 in circulating exosomes of GBM patients (n=18), healthy controls (n=28), and patients with different brain lesions that can mimic GBM on Magnetic Resonance Imaging: subacute stroke (n=30), acute-subacute haemorrhage (n=29), acute demyelinating lesions (n=19), brain metastases (n=21) and Primary CNS Lymphomas (PCNSL) (n=12). First, we isolated the exosomes from the serum of healthy subjects and patients with these pathological conditions using an adsorption method (Exoquick). Then, RNU6-1 levels were analyzed by digital droplet PCR (ddPCR). Corroborating our previous results, we found that the expression of RNU6-1 was significantly higher in GBM patients (412 ± 550.48 copies/20µL) than in healthy controls (150 ± 224.35 copies/20µL; p=0.039). In addition, RNU6-1 levels were higher in exosomes from GBM patients than in exosomes from patients with non-neoplasic lesions (stroke [223 ± 709.8 copies/20µL; p=0,067], haemorrhage [127 ± 198.7 copies/20µL; p=0.010], demyelinating lesions [111.5 ± 250.35 copies/20µL; p=0.019]) and PCNSL [18.15 ± 245.7 copies/20µL; p=0.004]). In contrast, RNU6-1 levels were similar between brain metastases and GBM patients [325 ± 632 copies/20µL; p=0.573]. In addition, analyzing whether this small non-coding RNA could be a predictive marker of GBM by ROC curves analysis, we demonstrated that RNU6-1 was a robust diagnostic biomarker of GBM compared to subacute stroke [AUC=0.659; p=0.004], acute/subacute haemorrhage [AUC=0.724; p=0.006], acute demyelinating lesions [AUC=0.728; p=0.011] and PCNSL [AUC=0.814; p<0.001]; on the contrary, it did not allow differentiating GBM from brain metastases [AUC=0.552; p=0.575]. Our data suggest that RNU6-1 isolated in circulating exosomes could serve as a differential biomarker for GBM versus non-neoplastic brain lesions and PCNSL.(Grant: 42/2015 Dpto. de Salud Gobierno de Navarra)
Lifetime history of sexual and physical abuse among competitive athletics (track and field) athletes: cross sectional study of associations with sports and non-sports injury
Authors: Toomas Timpka, Staffan Janson, Jenny Jacobsson, Örjan Dahlström, Armin Spreco, Jan Kowalski, Victor Bargoria, Margo Mountjoy, Carl Göran Svedin
Journal: British Journal of Sports Medicine (2018)

To examine associations between lifetime sexual and physical abuse, and the likelihood of injury within and outside sport in athletes involved in competitive athletics.A cross sectional study was performed among the top 10 Swedish athletics athletes using 1 year prevalence of sports and non-sports injuries as the primary outcome measure. Associations with sociodemographic characteristics, lifetime abuse history and training load were investigated. Data were analysed using simple and multiple logistic regression models.11% of 197 participating athletes reported lifetime sexual abuse; there was a higher proportion of women (16.2%) than men (4.3%) (P=0.005). 18% reported lifetime physical abuse; there was a higher proportion of men (22.8%) than women (14.3%) (P=0.050). For women, lifetime sexual abuse was associated with an increased likelihood of a non-sports injury (OR 8.78, CI 2.76 to 27.93; P<0.001). Among men, increased likelihood of a non-sports injury was associated with more frequent use of alcoholic beverages (OR 6.47, CI 1.49 to 28.07; P=0.013), while commencing athletics training at >13 years of age was associated with a lower likelihood of non-sports injury (OR 0.09, CI 0.01 to 0.81; P=0.032). Lifetime physical abuse was associated with a higher likelihood of sports injury in women (OR 12.37, CI 1.52 to 100.37; P=0.019). Among men, athletes with each parents with ≤12 years formal education had a lower likelihood of sustaining an injury during their sports practice (OR 0.37, CI 0.14 to 0.96; P=0.040).Lifetime sexual and physical abuse were associated with an increased likelihood of injury among female athletes. Emotional factors should be included in the comprehension of injuries sustained by athletes.