tbuckley/cabot-search huggingface dataset:
Differences of TILs, hormone receptor, and HER2 status between primary and metastatic tumors.
Authors: Makiko Ono, Tomo Osako, Shinichiro Taira, Tomoko Shibayama, Kokoro Kobayashi, Takayuki Kobayashi, Naoya Gomi, Takuji Iwase, Takayuki Ueno, Yoshinori Ito, Shinji Ohno, Futoshi Akiyama, Shunji Takahashi
Journal: Journal of Clinical Oncology (2018)

1075 Background: Tumor-infiltrating lymphocytes (TILs) are reported to be associated with response to chemotherapy in early breast cancer. However, it is uncertain whether immunological microenvironment alters when tumors recur. The purpose of this study is to compare TILs and HR and HER2 status between paired primary and recurrent tumors. Methods: The patients were eligible if they had primary surgery at our institute and their breast cancer recurred, and specimens of recurrent disease were available. High TILs were defined as ≥10%. Results: Among 173 recurrent tumors, specimens were metastatic lesion to liver, lung, bone, skin or soft tissue, lymph nodes, and others in 19%, 27%, 16%, 15%, 14%, and 8%, respectively. In primary tumors, 89% were HR positive and 11% were HER2 positive. ER, PgR and HER2 status changed from positive in primary tumors to negative in recurrent tumors in 8%, 40%, and 6%, and changed from negative to positive in 15%, 15%, and 7%, respectively. Accordingly, breast cancer subtype change between primary and recurrent tumors was seen in 13%. High TILs in primary tumors were seen in 22% of patients and significantly associated with breast cancer subtype; HR+HER2-, HR+HER2+, HR-HER+, and HR-HER- in 16%, 36%, 67%, and 62%, respectively (p < 0.001). On the other hand, high TILs in recurrent tumors were not correlated with breast cancer subtype, but the site of metastasis; high TILs in 6%, 39%, 12%, 8% and 19% of liver, lung, bone, skin or soft tissue, and lymph node metastases, respectively (p = 0.002). In 71% of recurrent tumors, TILs did not change or decreased compared with primary tumors, whereas in 29% TILs increased in recurrent tumors. Among recurrent tumors with increased TILs, most frequent metastatic lesions were lung (40%), and bone metastases were less likely to have tumors with increased TILs (7%). High TILs in recurrent tumors were a positive prognostic marker after recurrence, whereas those in primary tumors were not. Conclusions: TILs as well as hormone and HER2 status altered between primary and metastatic tumors. Immunological tumor microenvironment may depend on the site of recurrence and evaluation of recurrent tumors is required in the immunotherapy era.
Effect of trastuzumab on the antiproliferative effects of PI3K inhibitors in HER2+ breast cancer cells with de novo resistance to trastuzumab.
Authors: Estefania Espin, Jose Alejandro Perez-Fidalgo, Eduardo Tormo, Begona Pineda, Juan Miguel Cejalvo, MohammadA Sabbaghi, Elisa Alonso, Ana Rovira, Federico Rojo, Joan Albanell, Begona Bermejo, Octavio Burgues, Pilar Eroles, Ana Lluch
Journal: Journal of Clinical Oncology (2015)

e11592 Background: Despite the therapeutic success of trastuzumab, only 30% of tumors that overexpress HER2 respond. The PI3K/AKT pathway appears to be an important mechanism of resistance. It is known that HER2 receptor and PI3K pathways can be modulated by different miRNAs. The purpose of this study was to investigate the mechanisms of PI3K in resistance to trastuzumab by the evaluation of inhibitory drugs and relevant microRNAs in the context of de novo resistance. Methods: The cell line HCC1954, with de novo resistance to trastuzumab, was treated with the inhibitors BKM120 (PI3K), MK2206 (Akt1/2/3), everolimus (mTOR) and GDC-0980 (dual PI3K-mTOR) alone or in combination with trastuzumab. Cell viability was determined by the colorimetric assay MTT. The expression of miR-21, miR-221, miR-26a and mi-R30b was also evaluated after treatments by quantitative PCR. The transfection of mimetic microRNAs was performed by internalization with the no liposomal TransIT-X2TM reagent (Mirus). Differences in mean between groups were assessed with t-student test. Results: The inhibitors GCD-0980 or BKM120 had a greater inhibitory effect on HCC1954 cell line when combined with trastuzumab vs. monotherapy (p-value < 0.01 and < 0.001). All inhibitors reduced significantly the expression of miR-21 (p-value < 0.01) alone and when added to trastuzumab. MK2206, everolimus and GDC-0980 combined with trastuzumab significantly reduced miR-221 (p-value < 0.05) vs.either treatment alone. The expression of miR-26a decreased in the combination of the inhibitors with trastuzumab (p-value < 0.01) and miR-30b decreased in the treatment with MK2206, everolimus and GDC-0980 (p-value < 0.05). The overexpression of miR-21, miR-221 and miR-30b by transfection decreased the sensitivity of cells to BKM-120 and to the combination of BKM120 and trastuzumab (p-values < 0.05, < 0.01 and 0.01). Conclusions: PI3K pathway inhibitors in breast cancer cells resistant to trastuzumab are active and their antiproliferative effect is enhanced by combining with trastuzumab. This effect appears to be mediated by miRNAs and suggest a role for trastuzumab in enhancing PI3K inhibitor effects in a context of primary resistance.
ETV6-NTRK3 induces aggressive acute lymphoblastic leukemia highly sensitive to selective TRK inhibition
Authors: Kathryn G. Roberts, Laura J. Janke, Yaqi Zhao, Aman Seth, Jing Ma, David Finkelstein, Steve Smith, Kevin Ebata, Brian B. Tuch, Stephen P. Hunger, Charles G. Mullighan
Journal: Blood (2018)
Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as prognostic markers in patients with HER2pos operable breast cancer treated with neo-adjuvant trastuzumab-containing chemotherapy.
Authors: Deirdre Kelly, Rozana Rahman, Giuseppe Gullo, David William Fennelly, Janice Maria Walshe, John Crown
Journal: Journal of Clinical Oncology (2018)

594 Background: Inflammation plays an important role in cancer development and proliferation.Host systemic markers of inflammation including the neutrophil-to-lymphocyte ratio (NLR) have been associated with a poor prognosis in solid tumours. The objectives of our study were to evaluate NLR and platelets-to-lymphocytes ratio (PLR) in patients (pts) with operable HER2pos breast cancer (BrCa) treated with neo-adjuvant trastuzumab (T)-containing chemotherapy (NACT) and to correlate NLR and PLR with Disease Free Survival (DFS) and Overall Survival (OS). Methods: This was a retrospective, single-center analysis of a prospectively accrued Institutional database (The One-Thousand HER2pos Patients project) of non-metastatic operable HER2pos BrCa pts who received NACT. Pts with confirmed supraclavicular/internal mammary nodes were excluded. NLR and PLR were calculated at baseline prior to HER2 therapy (Tx) initiation. All patients underwent curative surgery (Sx) following T-containing NACT. Results: 156 female patients were included. Pts characteristics: median age 55.6(27-78)yrs, median time from diagnosis to initiation of HER2 Tx 4(1-18)weeks, ER positive 93(60%), cytology-proven positive lymph nodes at diagnosis 41(26%). NACT was: TCH 116(74%), Docetaxel/Cyclophosphamide/T or single-agent taxane/T 20(13%), AC-TH/FEC-TH 7(4%), other regimens 13(8%). Median follow up is 4.3(11-1)yrs. Pts with NLR < 2.5 at baseline had significantly better PFS (HR 0.29 p = 0.03)and OS (HR 0.14 p = 0.07) compared to pts with NLR > 2.5. Baseline PLR < 150 was associated with superior OS (HR 0.15 p = 0.08) compared to PLR > 150. No statistically significant association was observed between PLR and PFS. (HR 0.35 p = 0.07) Conclusions: This study represents one of the largest real-world datasets looking at NLR and PLR as prognostic markers in NACT for HER2pos BrCa. Baseline NLR > 2.5 and PLR > 150 are inexpensive and readily available prognostic markers of adverse outcome and may play a clinically significant role in refinement of risk estimates within disease stages and subgroups and treatment de-escalation.
Neoadjuvant chemotherapy based on dose-dense epirubicin (E) plus cyclophosphamide (C) followed by docetaxel (D) plus trastuzumab (T), DT plus carboplatin (CBDCA), or DT plus HER2 double blockade in HER2-positive breast cancer patients.
Authors: Lucia Ceniceros, Laura Murillo Jaso, Natalia Rodríguez-Spiteri, Eduardo Castanon Alvarez, Leyre Zubiri Oteiza, Patricia Martin, Pablo Sala, Itziar Gardeazabal, Ignacio Gil-Bazo, Jaime Espinós, Jose M. Aramendia, Oscar Fernández-Hidalgo, Marta Santisteban
Journal: Journal of Clinical Oncology (2015)

e11617 Background: Amplification of the HER-2 gene occurs in 20% of breast cancer (BC) patients (pts). Trastuzumab administered concurrently with chemotherapy (CT) is the standard of care in the neoadjuvant setting. Moreover, the use of a combination of antiHER2 therapies with CT are related to an increased pCR, which could be a surrogate marker for survival. Methods: We retrospectively analyzed three historic cohorts with overexpressing HER2 BC. They received neoadjuvant CT based on dose dense anthracyclines followed by three schedules of antiHER2 therapy: 1) docetaxel plus trastuzumab (DT; n = 33 pts); 2) DT plus CBDCA (DTP; n = 17 pts); and 3) DT plus double blockade with triweekly pertuzumab or daily L (750mg/day; n = 12) (DTD; n = 14) before surgery. Study endpoints were safety, pCR (breast + axilla) based on Miller&Payne criteria and DFS. Results: Sixty-four pts with HER2 overexpressing BC were studied since 2005. Baseline characteristics were well balanced. The median age was 48 (range 23-80). Coexpression of ER and HER2 in each cohort was 48% in DT, 53%% in DTP and 57% DTD (p = 0.855) as well as initial BC stages (p = 0.64). Grade 3-4 toxicity in DT, DTP and DTD were respectively: asthenia 0%, 5.8% and 0% (p = 0.71), hand-foot syndrome 3%, 5.8% and 0% in DT, DTP and DTD (p = 0.719), anemia 0%, 5.8% and 0% (p = 0.71) leukopenia 6%, 11.7% and 0% in DTD (p = 0.60) and diarrhea in 35.7% in DTD (p = 0.002). We did not find differences in pCR (42.4% in the DT, 29.4%% in the DTP and 42.8% in DTD cohorts; p = 0.67), axillar response (type D) was significantly superior in the DTD cohort with the followed distribution of 51.1%, 52.9% and 85.7% respectively (p = 0.04). However breast responses were similar in the three cohorts (p = 0.9). With a median follow-up of 72, 90 and 21 months respectively, the number of pts who progressed were 12.1%, 11.7% and 0% in DT, DTP and DTD. Conclusions: We did not find differences in pCR in any cohort. The best significant axillary responses were in the DTD cohort, however this fact did not impact in total pCR. DTD cohort has more gastrointestinal toxicity. To date, median survival has not been reached.
Abstract 19880: High Failure Rate of Linox Defibrillator Leads
Authors: Sophie C Van Malderen, Tamas Szili-Torok, Sing C Yap, Rohit Bhagwandien, Sip Wijchers, Dominic A Theuns
Journal: Circulation (2015)

Introduction: Recent lead failures have resulted in large recalls with a significant global impact, not only financially, but also physically and mentally for those carrying an implantable cardiac defibrillator (ICD). Following the introduction of the ‘Linox S’ and ‘Linox SD’ ICD leads in 2006 by manufacturer ‘Biotronik’, we observed several cases with early failure. The objective of this study was to determine the failure rate of ‘Biotronik Linox’ leads implanted at our centre, and to compare them with the performance of two comparators, the Durata (St. Jude Medical) and the Endotak (Boston Scientific) lead. Methods: As of 2012, all ‘Linox S or SD’ (n=408), Durata (model 7122, n=340) and Endotak (model 0125, 0138 and 0158, n=343) leads were identified form the Erasmus MC prospective ICD registry. Lead failure was defined by low/high-voltage impedance, failure to capture, sense or defibrillate, or the presence of non-physiological signals not due to external interference. Results: A total of 1091 high-voltage defibrillation leads were implanted between April 2000 and May 2012 in 1066 patients (78% males, median age 62 years). The median time from implantation to lead failure was 3.6 years (IQR, 1.5 to 4.8 years). ‘Linox’ leads demonstrated a sudden increase in failure at 3-3.5 years after implantation and their estimated failure rates were 5.5% and 10.1%, at 5 and 8 years after implantation, respectively. Durata and Endotak demonstrated gradual malfunction and failure rates were 2.1% and 2.1%, and 0.4% and 0.8%, at 5 and 8 years, respectively. The mechanism of failure was noise in the majority of failed leads (50%) followed by impedance out-of-range (29%). Conclusions: ‘Linox S/SD’ leads demonstrate a significant high failure rate. Remote monitoring is reasonable as electrical dysfunction (noise or impedance out-of-range) is observed in the majority of cases. National device safety and advisory committees worldwide might be facing a new challenge.
Gene expression profiles of glomerular endothelial cells support their role in the glomerulopathy of diabetic mice
Authors: Jia Fu, Chengguo Wei, Weijia Zhang, Detlef Schlondorff, Jinshan Wu, Minchao Cai, Wu He, Margaret H. Baron, Peter Y. Chuang, Zhihong Liu, John Cijiang He, Kyung Lee
Journal: Kidney International (2018)
A RB-1 loss of function gene-signature (RBsig) as a tool to predict response to neoadjuvant chemotherapy (CT) plus anti-HER2 agents (H): A substudy of the NeoALTTO trial (BIG 1-06).
Authors: Emanuela Risi, Chiara Biagioni, Matteo Benelli, Ilenia Migliaccio, Amelia McCartney, Martina Bonechi, Cristina Guarducci, Florentine Hilbers, Serena Di Cosimo, Jose Baselga, Dario Romagnoli, Giulia Boccalini, Stefania Vitale, Andrea Grilli, Silvio Bicciato, Christos Sotiriou, Laura Biganzoli, Angelo Di Leo, Luca Malorni
Journal: Journal of Clinical Oncology (2018)

570 Background: CT added to H is the treatment of choice in HER2+ early breast cancer (BC) patients (pts). However HER2+ tumors are clinically and biologically heterogeneous and treatment response varies significantly by hormone receptor (HR) status and molecular subtype. Predictive biomarkers are needed in this context. We have previously shown that RBsig expression correlates with pathological complete response (pCR) rate following CT +/− H in ER+/HER2+ BC pts within a metadataset of 10 neoadjuvant clinical trials. The present study assessed whether RBsig is predictive of response to neoadjuvant CT in combination with H, within the NeoALTTO trial. Methods: We collected RNA-sequencing data from pre-treatment biopsies derived from NeoALTTO, a trial randomizing pts with HER2+ early BC to receive lapatinib, trastuzumab or both together with weekly paclitaxel. RBsig expression was computed retrospectively and correlated with pCR using receiving-operating characteristic (ROC) curves.The RBsig was dichotomized as High/Low in correspondence to the 25th percentile. The distribution of RBsig expression was evaluated within PAM50 molecular subtypes. Reported p-values resulted from Fisher exact test. Results: Of 455 NeoALTTO pts, 245 had available RNA-sequencing data (HR+ n = 129 HR− n = 116). Overall, pCR rate was significantly higher in pts with RBsig High tumors, than those with RBsig Low (36% vs 18% respectively p = 0.01). The area under the ROC curve (AUC) was 0.60 (95% CI 0.52-0.67). A remarkably low pCR rate of 11% was seen in HR+/ RBsig Low pts vs 28% in HR+/RBsig High. HER2-enriched (HER2e) tumors were the predominant molecular subtype in both HR+ (n = 65) and HR− (n = 89) subsets. RBsig could further stratify HER2e tumors, with RBsig High and Low showing a pCR rate of 44% and 21% respectively (p = 0.02).The pCR rate of HR+/ HER2e/ RBsig High pts was 37% vs 7% for HR+/ HER2e/ RBsig Low (p = 0.04). The ROC curve AUC was 0.65 (95% CI 0.50-0.79). Conclusions: RBsig Low expression identifies a subset of HER2+ pts less likely to respond to CT + H. This is particularly notable in HER2e tumors thus indicating RBsig may add significant information to molecular subtypes.
The identification of breast cancer by Near-Infrared fluorescence imaging with methylene blue.
Authors: Chong Zhang, Yamin Mao, Kun Wang, Jie Tian
Journal: Journal of Clinical Oncology (2018)

e12591 Background: Breast cancer lacks an effective means to determine tumor boundaries. Most patients choose radical mastectomy to reduce the recurrence rate. However, with the pursuit of life quality, breast-conserving surgery is accepted by more and more patients. For breast-conserving surgery, we need an effective assessment to identify the tumor boundary, so as to detect the lesion area accurately and reduce the resection range. Methods: As a clinically approved dye, methylene blue(MB) is commonly used as a blue dye for sentinel node biopsy in breast cancer. Besides the visible characteristic, MB also has the near-infrared (NIR) fluorescence properties (excitation: 668 nm, emission: 688nm). Recently MB was confirmed to detect the breast tumors through intravenous injection with NIR fluorescence imaging. Up to now, we have enrolled 12 patients with radical mastectomy in Liaoning Cancer Hospital. 3 of them were injected with 0.5 mg / kg MB intravenously, and the remaining 9 were 1 mg / kg. The injection time was about 3 hours before surgery. Results: After the radical mastectomy, we detected the fluorescence signal in the resected specimen. The results of 3 cases with injection dose of 0.5mg/kg were failed. 7/9 cases with injection dose of 1mg/kg were able to be detected fluorescence signal in the breast tumors. The average tumor-to-background ratio (TBR) was 1.578±0.36. Conclusions: As a safe dye approved by FDA, Methylene Blue with NIR fluorescence imaging is a feasible way to detect breast tumors. It has the potential to real-time detect residual tumors and tumor boundaries for breast-conserving therapy.
Quality of life and current needs of cancer survivors enrolled in Humanitas Research Hospital's survivorship care model.
Authors: Elena Lorenzi, Lucia Morello, Laura Giordano, Elisa Agostinetto, Camille Grosso, Matteo Nicolosi, Isabella Maria Giovanna Garassino, Raffaele Cavina, Rita Mazza, Carmelo Carlo-Stella, Armando Santoro
Journal: Journal of Clinical Oncology (2018)

170 Background: While there are different studies investigating the quality of life (QoL) of cancer patients (pts) during active treatment, few studies report QoL of cancer survivors (CS) after at least 5 years (yrs) from achieving complete remission. We have investigated QoL and concerns about physical\psychological symptom of CS enrolled in our survivorship program from April 2015 to December 2016. Methods: We included pts &gt; 18 yrs affected by hematologic or solid tumors after at least 5 yrs from achieving complete remission. A cross-sectional survey was carried out using validated scales: Cancer Survivors Survey of Needs subscale and a single-item measure of global QoL perception. Results: We analyzed data from 178 CS. The median age was 62 yrs (52 yrs at diagnosis), 70% were females. The most frequent histological types were breast (50%), colorectal (11%) and hematologic tumors (16%). Most pts received both chemotherapy and radiation therapy. With a median observation time of 139 months, the 10-yrs cumulative incidence of second neoplasm and cardiac adverse event was 8% and 7% respectively. 133 pts (65%) reported a good QoL (score &gt; 3). The most frequent symptoms reported were weight changes (77%), memory\concentration deficit (65%), dental\mouth problems (61%). The most common physical\psychological symptoms were fear of relapse (83%), genetic counseling (68%), living with uncertainty (66%). A positive statistically significant association (p &lt; 0.05) was observed between previous hormonal therapy and the following concerns (score ≥2): sleep disturbance (42% vs 35%); weight gain (31% vs 24%), osteoporosis (35% vs 18%), living with uncertainty (44% vs 38%). Female reported more fear of relapse (p 0.023) and sense of uncertainty (p 0.006) than males. 92% of pts have fully or partially adhered to the survivorship care plan. Conclusions: Most CS have a good QoL perception but we observed a high percentage of pts with a low score indicating different needs to be addressed. Pts treated with hormonal therapy are at higher risk of having both physical and psychological concerns. So far, the compliance of pts with the program was high.
High-dose daptomycin in patients with infective endocarditis or sternal wound infections
Authors: N. Peiffer-Smadja, S. Abbara, N. Rizk, M. Pogliaghi, E. Rondinaud, C. Tesmoingt, L. Massias, J.C. Lucet, S. Alkhoder, L. Armand-Lefèvre, F.X. Lescure
Journal: Clinical Microbiology and Infection (2018)
The impact of site of care (office clinic versus hospital outpatient) on treatment patterns in HER2-positive breast cancer.
Authors: Anju Parthan, Deepa Lalla, Art Small, Melissa Brammer
Journal: Journal of Clinical Oncology (2012)

e11077 Background: This study examines treatment (tx) patterns in patients (pts) with breast cancer (BC) receiving trastuzumab (T) in a physician clinic (MD) &amp; outpatient hospital (HOSP) setting. Methods: Pts ≥18 yrs with BC (≥2 claims with ICD-9-CM 174.xx, ≥30 days apart) and ≥2 T claims from 1/1/2006 to 12/31/2010 were identified from a large US commercial insurance claims database. Pts continuously enrolled for ≥ 6mths before &amp; after index date (date of 1 st T claim) were included. Pts receiving T at both sites of care, receiving T before the index date &amp;/or pts with &gt; 1 primary cancer were excluded. Metastatic (mBC) vs. early stage (ESBC) tx was identified by presence of ≥2 claims of metastases after index date. Pts were followed from index date to 30 days after the last infusion prior to a gap of ≥ 90 days, death, disenrollment, or end of study period. Pts were stratified by site of care- MD or HOSP. Descriptive &amp; multivariate analyses were conducted to examine differences in tx patterns (duration and doses/mo) &amp; number of missed doses during the tx period. Results: 2,823 BC pts receiving T were identified; 480 (17%) were treated for mBC. Most patients received T in the MD setting (94% ESBC pts and 87% of MBC pts). Compared to the MD setting, pts treated in the HOSP were more likely to be older (ESBC: 61 vs 53 yrs; MBC: 64 vs 54 yrs; each p &lt;0.001) &amp; have Medicare benefits (ESBC: 54% vs 7%; MBC: 63% vs 9%; each p &lt;0.001). There was no difference in mean baseline Charlson comorbidity index in any group. Mean T duration in HOSP was significantly shorter vs MD among ESBC pts (303 &amp; 333 days, p&lt;0.05) but not MBC pts (313 for HOSP vs 355 days for MD, p&gt;0.05). Compared to the MD setting, HOSP treated patients had more treatment gaps of 30-59 days (ESBC: 58% vs 25%; MBC 56% vs 27%; each p&lt;0.001) and fewer infusions/month (ESBC: mean 1.45 vs 1.99; MBC 1.54 vs 2.07; each p&lt;0.001). In multivariate analyses, infusion counts remained lower among HOSP treated patients (ESBC: IRR 0.74, CI 0.67-0.79; MBC: IRR 0.76, CI 0.66-0.87). Conclusions: MBC and ESBC pts treated in the MD setting were younger and received more infusions with fewer treatment gaps than HOSP pts. Further research assessing the impact of these differences in tx patterns on clinical outcomes is needed.
Early life travelling does not increase risk of asthma, allergies and atopy until 15 years: results from GINIplus and LISAplus
Authors: I. Markevych, M. Standl, S. Koletzko, I. Lehmann, C.-P. Bauer, B. Hoffmann, A. von Berg, D. Berdel, J. Heinrich
Journal: Allergy (2016)
Colorectal endoscopic submucosal dissection using a clip-on-clip traction method
Authors: Tatsuma Nomura, Akira Kamei, Shinya Sugimoto, Jun Oyamada
Journal: Endoscopy (2018)

To safely and efficiently perform colorectal endoscopic submucosal dissection (ESD), clear visualization of the submucosal layer is important. Therefore, various traction methods have been developed to date [1] [2] [3]. However, there are few reports of using special devices other than clips, and traction methods that are generally used have not been reported. Recently, we developed a new clip-on-clip closure method to close the mucosal defect after ESD using clips only [4]. Here, we describe a new traction method: clip-on-clip traction method (CCTM).