tbuckley/cabot-search huggingface dataset:
Does time to progression (TTP) influence post-progression survival (ppOS)?: Analyses from the PointBreak, ECOG 4599, and ARIES studies of bevacizumab in non–small cell lung cancer (NSCLC).
Authors: Corey J. Langer, Antoinette J. Wozniak, Mark A. Socinski, Larry Leon, Shiyao Liu, Sebastien Hazard, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2015)

e19019 Background: In oncologic trials, it is common to observe progression-free survival benefits that do not translate into comparable OS benefits. In exploratory analyses, we examined the effect of slow vs fast first-line (1L) TTP on ppOS in 3 studies in NSCLC: the ECOG 4599 (E4599) and PointBreak (PB) randomized phase 3 trials, and the ARIES observational cohort study (OCS). Methods: Patients (pts) randomized to the paclitaxel-carbopaltin (PC) + bevacizumab (BV) arms of the E4599 and PB trials received P 200 mg/m2, C area under the curve (AUC) 6, and BV 15 mg/kg every 3 weeks (q3w) for up to 6 (E4599) or 4 (PB) cycles. Eligible pts received maintenance BV q3w until disease progression (PD) or unacceptable toxicity. The ARIES OCS prospectively enrolled pts in the US from 2006 to 2009 receiving 1L BV with various chemotherapy (CT) regimens. Post hoc analyses were conducted to assess the association of slow (TTP ≥ 6 mo) vs fast (TTP < 6 mo) progression on ppOS within treatment groups. A landmark analysis was used to compare slow vs fast 1L TTP in pts who did and did not receive second-line (2L) treatment within 45 days after 1L PD (restricted to pts who survived > 45 days post 1L PD). Cox proportional hazards models were used to adjust for differences in pt baseline characteristics. Results: Median ppOS and hazard ratios (HRs) for ppOS (slow vs fast TTP) are shown in the table. All HRs were statistically significant, except for E4599 pts who received 1L PC but no 2L therapy. Conclusions: Advanced NSCLC pts who experienced longer TTP with 1L therapy had improved ppOS compared with those who experienced shorter 1L TTP, regardless of the receipt of 2L therapy. Results suggest a correlation between 1L TTP and subsequent OS. Clinical trial information: NCT00388206, NCT00021060, NCT00762034. Study (1L Therapy) 2L Therapy Median ppOS, mo HR (95% confidence interval) Slow TTP Fast TTP E4599 (PC) Yes n = 63 9.4 n = 135 6.2 0.66 (0.47–0.93) No n = 28 6.9 n = 48 7.0 0.64 (0.37–1.10) E4599 (PC-BV) Yes n = 92 8.8 n = 78 5.4 0.55 (0.39–0.77) No n = 39 10.7 n = 31 7.3 0.54 (0.31–0.94) PB (PC-BV) Yes n = 73 11.3 n = 95 7.3 0.53 (0.36–0.77) No n = 69 10.3 n = 54 7.2 0.40 (0.26–0.63) ARIES (CT-BV) Yes n = 505 11.4 n = 412 6.9 0.64 (0.56–0.75) No n = 220 10.5 n = 149 4.1 0.44 (0.34–0.56)
Resistance to neoadjuvant chemotherapy in triple-negative breast cancer mediated by a reversible drug-tolerant state
Authors: Gloria V. Echeverria, Zhongqi Ge, Sahil Seth, Xiaomei Zhang, Sabrina Jeter-Jones, Xinhui Zhou, Shirong Cai, Yizheng Tu, Aaron McCoy, Michael Peoples, Yuting Sun, Huan Qiu, Qing Chang, Christopher Bristow, Alessandro Carugo, Jiansu Shao, Xiaoyan Ma, Angela Harris, Prabhjot Mundi, Rosanna Lau, Vandhana Ramamoorthy, Yun Wu, Mariano J. Alvarez, Andrea Califano, Stacy L. Moulder, William F. Symmans, Joseph R. Marszalek, Timothy P. Heffernan, Jeffrey T. Chang, Helen Piwnica-Worms
Journal: Science Translational Medicine (2019)

Resistance to neoadjuvant chemotherapy in triple-negative breast cancer can be mediated by a reversible chemotherapy-tolerant state.
Letter to the Editor: Comment on Qiao et al.
Authors: Helene Gilgenkrantz, Christine Perret
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: We read with great interest the article entitled "Axin1 deletion induced hepatocarcinogenesis requires intact β‐Catenin but not Notch cascade in mice" by Qiao et al. published in the February issue of Hepatology.1 The findings of this study corroborate our previous data that the in vivo deletion of Axin1 in hepatocytes using conditional knockout (KO) mice does not result in classical activation of the Wnt/β‐catenin pathway, but leads to development of hepatocellular carcinomas (HCCs).2 Thanks to a 23‐genes signature including LGR5, we also demonstrated, using, in particular, the TGCA database, that 80% of AXIN1‐mutated human tumors do not activate this Wnt/β‐catenin program. Although the definition of the Wnt/β‐catenin program may be difficult, the important point was to highlight that AXIN1‐mutated HCCs do not express the same program as CTNNB1‐mutated HCC and cannot be classified in the same group, as it was often reported. In this new publication, Qiao et al. claim that the development of Axin1‐deleted tumors require an intact β‐catenin pathway. However, the investigators used a very different mouse model, in which Axin1 inactivation, induced by CrispR/Cas9 methodology, was combined with c‐Met overexpression. Given this very specific model and that β‐catenin– and MET‐mediated signaling pathways are known to cooperate in hepatocyte proliferation,3 their conclusion can only apply to tumors mutated for Axin1 and induced for the c‐Met pathway that represent a little bit less than half of AXIN1‐mutated human HCC.1 We agree that our data do not prove that HCCs induced by Axin1 deficiency develop independently of β‐catenin because we did not use Ctnnb1 KO mice. However, the work of Qiao et al. does not either "unequivocally prove that loss of Axin1‐driven HCC requires an intact β‐catenin." In contrast, it elegantly demonstrates that it was the case in a Met activation context, likely representing AXIN1‐mutated HCCs for which we showed a weak activation of the β‐catenin signaling.2 It will thus be particularly interesting in the future to establish to what extent the integrity of β‐catenin pathway is or is not required for AXIN1‐mutated HCCs that do not activate the Met pathway.
Clinical and treatment features associated with improved 5-year survival rate in ALK-positive lung cancer treated with ALK-TKIs
Authors: A. Passaro, A. Prelaj, G. Spitaleri, E. Del Signore, G. Rossi, E. Guerini-Rocco, M. Barberis, C. Catania, F. de Marinis
Journal: Annals of Oncology (2019)

Background: ALK rearrangement predicts for prolonged survival in pts with metastatic NSCLC treated with ALK TKIs. Long-term survival, however, remains undefined in a real-world population. The objective of this study was to determine the 5-years survival in these patients and identify clinical factors associated with OS improvement. Methods: Pts with ALK-rearranged metastatic NSCLC who had been treated with ALK TKIs at European Institute of Oncology between 2013 and 2018 were retrospectively reviewed and analyzed for efficacy outcomes. Results: Among 105 pts, mPFS and mOS were 13.6 mos (95% CI: 9.8 – 17.3) and 40.4 mos (95% CI: 33.6 – 47.1), respectively. 5-year survival rate was 21%, and more than half of overall pts population (51.4%) were treated with different ALKis for more than 3 yrs. The 55.2%, 42.8% and 2% of pts received one, two or three TKIs, respectively. In 99 pts, crizotinib was the first ALKi used with a mPFS of 13.6 (9.8 - 17.3) mos. Univariate analysis showed a positive correlation between mOS and age (< vs ≥ 65 yrs) (42.9 vs 36.3 mos; HR = 0.58, 95% CI: 0.34 – 0.98, p = 0.042), ECOG PS 0/1 vs 2 (44.4 vs 18.4 mos; HR = 0.23, 95% CI: 0.12 – 0.44, p < 0.001) and absence of baseline brain metastases (44.5 vs 22.9 mos; HR = 0.59, 95% CI: 0.35 – 0.97, p = 0.04). Multivariate analysis, adjusted for age, sex, smoking status and ECOG PS, showed that over young age (< 65) and good ECOG PS (0/1), the number of the metastatic sites (< 3 vs ≥ 3) (54.1 vs 36.3 mos; HR = 0.58, 95% CI: 0.34 – 0.98, p = 0.045) and the use of RT for oligoprogression/palliative management (48.4 vs 36.3 mos; HR = 0.58, 95% CI: 0.35 – 0.95, p = 0.033) were significantly associated with prolonged OS. Median IC-PFS was 40 (23.6 – 56.3) mos. Pts without baseline brain metastases reported a significantly longer IC-PFS (55.0 vs 17.3 mos, IC95% HR 0.51, p = 0.029). Conclusions: In this broad real-world population, the clinical benefit was consistent with a 5-year survival of 21%. The absence of brain metastases, the use of palliative RT and the tumour burden resulted as independent positive prognostic factors associated with a statistically significant improvement of prolonged survival. Based on these findings, clinicians can gain an enhanced estimation of long-term outcomes in this population. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Bone Bioprinting: Advancing Frontiers in Bone Bioprinting (Adv. Healthcare Mater. 7/2019)
Authors: Nureddin Ashammakhi, Anwarul Hasan, Outi Kaarela, Batzaya Byambaa, Amir Sheikhi, Akhilesh K. Gaharwar, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2019)

In article numbre 1801048 by Nureddin Ashammakhi, Ali Khademhosseini, and co-workers, it is explored that by using 3D bioprinting, it is possible to print bone in situ using bioinks that contain patient derived cells and carrier matrices, and necessary osteoconductive materials and osteoinductive molecules. This procedure can also be carried out in a minimally-invasive manner. This will help to reduce the need for bone grafting and associated problems.
Pathological response and surgical outcome with neoadjuvant chemotherapy (NACT) in Saudi Arabian breast cancer (BC) patients.
Authors: Hossam A. Abdelrahman, Deena Hadedeyah, Habib Ur-Rehman, Syed Mustafa Karim
Journal: Journal of Clinical Oncology (2015)

e12033 Background: NACT for BC is an effective approach for patients with locally advanced and patients with large operable BC to allow for resection with negative margins and to facilitate breast conservation when appropriate. The aim of the study is to assess the impact of NACT on breast cancer, and to evaluate the variables associated with improved NACT outcome in Saudi population. Methods: A retrospective review of BC patients who received NACT at our institution in the period between 2004 and 2013. Patients’ clinical data and tumor characteristics were abstracted from patients’ charts and were correlated with outcome measures. Results: Between 2004 and 2013 a total of 97 breast cancer patients were treated with NACT. The median age was 46 years (ranging from 22-72). 71% of the patients were premenopausal. 77.3% had Tumors larger than 5 cm and 56.7% had palpable axillary nodes. Pathology revealed hormone receptor (HR) +, Her2/neu (Her2) +, and triple negative disease in 61.8%, 42.3%, and 17.5% respectively. The NACT received was Taxane, Anthracycline, and Platinum based in 66%, 79%, 11.3% of the patients respectively. 29% of the patients underwent breast conserving surgery (BCS) and 88.7% had negative resection margins. Overall response rate was 80.4% with 22.7% complete pathological response (pCR). 31 patients had recurrence, of which 12 were local and 19 were distant recurrences, with median recurrence free survival (RFS) of 22 months. In univariate analysis, the rate of pCR in HR negative patients vs HR + was 37.5% vs 15.5% (p = 0.019). Also, patients with Her2 + disease had significantly higher rate of pCR vs Her2 negative 34.1% vs 14.6%, (p = 0.028). Patients with history of oral contraceptive (OCP) use had significantly lower pCR rate (p = 0.015). In multivariate analysis, only HR negative status was associated with higher pCR rate. pCR did not correlate with improved RFS or overall survival (OS). Conclusions: Patients receiving NACT for breast cancer had excellent response rate of 80.4% enabling resection with negative margins in 88.7% and BCS in 29% of patients. HR negative and Her2 + tumors were associated with higher pCR rate. However, the achievement of pCR did not correlate with RFS or OS advantage.
THU-499-Angiotensin receptor blockade attenuates cholangiocarcinoma cell growth by inhibiting the oncogenic activity of Yes-associated protein
Authors: Yuki Tsuji, Kosuke Kaji, Soichiro Saikawa, Kenichiro Seki, Shinya Sato, Keisuke Nakanishi, Hideto Kawaratani, Mitsuteru Kitade, Kei Moriya, Tadashi Namisaki, Hitoshi YOSHIJI
Journal: Journal of Hepatology (2019)
SAT-488-Both ALBI/delta ALBI grade are good predictive parameters for prognosis in chc/hcc patients with transarterial chemoembolization treatment
Authors: Wei Teng, Rachel Wen-Juei Jeng, Yi-Chung Hsieh, Chien-Hao Huang, Chun-yen Lin, I-Shyan Sheen
Journal: Journal of Hepatology (2019)
Design of Idiopathic Pulmonary Fibrosis Clinical Trials in the Era of Approved Therapies
Authors: Robert J. Kaner, Ednan K. Bajwa, Moustapha El-Amine, Eduard Gorina, Renu Gupta, Howard M. Lazarus, Tracy R. Luckhardt, Majd Mouded, Kaity Posada, Luca Richeldi, John Stauffer, Ahmet Tutuncu, Fernando J. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

The approval of nintedanib and pirfenidone for treatment of idiopathic pulmonary fibrosis has introduced complexity into the design of clinical trials for new drugs on many levels. Placebo-controlled trials excluding background therapy may have issues with feasibility. Those that allow background therapy must consider the possibility of drug-drug interactions with existing therapies, as well as the narrower therapeutic window available to demonstrate incremental slowing of lung function decline with a new agent. While many trial participants will already be on background therapy, a significant number will not, complicating the study design and analysis. Various approaches to improve the efficiency of IPF clinical trials include attempts to validate new endpoints and biomarkers that reflect functional status or quality of life as well as the use of pragmatic and adaptive trial designs.
SAT-085-Selective improvement by rifaximin of changes in the inmunophenotype in patients who improve minimal hepatic encephalopathy
Authors: María Pilar Ballester, Juan José Gallego, Alba Mangas-Losada, Raquel Garcia-Garcia, Paola Leone, Andrea Cabrera-Pastor, Amparo Urios, Desamparados Escudero-García, Joan Tosca, María Pilar Rios, Cristina Montón, Lucía Durbán, Vicente Felipo, Carmina Montoliu
Journal: Journal of Hepatology (2019)
PS-208-Impact of successful DAA therapy at 3 years of follow-up in liver transplant recipients with hepatitis C recurrence and moderate/severe fibrosis
Authors: Silvia Martini, Marco Sacco, Giulia Testa, Federica Calvo, Stefano Mirabella, Donatella Cocchis, Giorgio Maria Saracco, Renato Romagnoli
Journal: Journal of Hepatology (2019)
Association of Systemic Inflammation Index and Body Mass Index with Survival in Patients with Renal Cell Cancer Treated with Nivolumab
Authors: Ugo De Giorgi, Giuseppe Procopio, Diana Giannarelli, Roberto Sabbatini, Alessandra Bearz, Sebastiano Buti, Umberto Basso, Manfred Mitterer, Cinzia Ortega, Paolo Bidoli, Francesco Ferraù, Lucio Crinò, Antonio Frassoldati, Paolo Marchetti, Enrico Mini, Alessandro Scoppola, Claudio Verusio, Giuseppe Fornarini, Giacomo Cartenì, Claudia Caserta, Cora N. Sternberg
Journal: Clinical Cancer Research (2019)

Inflammation indexes and body mass index (BMI) are easily evaluated, predict survival, and are potentially modifiable. We evaluated the potential association of inflammatory indexes and BMI with the clinical outcome of patients with renal cell carcinoma (RCC) undergoing immune checkpoint inhibitor therapy.A prospective cohort of patients with metastatic RCC treated with nivolumab enrolled in the Italian Expanded Access Program from July 2015 through April 2016 was examined. Reference measures of inflammation were identified for neutrophil-to-lymphocyte ratio (NLR) </≥ 3, systemic immune inflammation index (SII) </≥ 1,375, and platelet-to-lymphocyte ratio (PLR) </≥ 232. Patients were classified as high BMI (≥25 kg/m2) versus normal BMI (<25 kg/m2).Among 313 evaluable patients, 235 (75.1%) were male, and median age was 65 years (range, 40-84 years), with 105 (33.69%) ≥70 years. In univariate analysis, age, performance status, BMI, SII, NLR, and PLR were able to predict outcome. In multivariate analyses, SII ≥1,375, BMI <25 kg/m2, and age ≥70 years independently predicted overall survival [OS; HR = 2.96, 95% confidence interval (CI), 2.05-4.27; HR = 1.59, 95% CI, 1.10-2.30; and HR = 1.65, 95% CI, 1.07-2.55, respectively). A patient with both SII ≥1,375 and BMI <25 kg/m2 was estimated to have much worse OS (HR, 3.37; 95% CI, 2.29-4.95; P <0.0001) than a patient with neither or only one risk factor. SII changes at 3 months predicted OS (P <0.0001).Normal BMI combined with inflammation tripled the risk of death, suggesting that these biomarkers are critical prognostic factors for OS in patients with RCC treated with nivolumab.
Disease burden of varicella versus other vaccine-preventable diseases before introduction of vaccination into the national immunisation programme in the Netherlands
Authors: Alies van Lier, Brechje de Gier, Scott A McDonald, Marie-Josée J. Mangen, Maarten van Wijhe, Elisabeth A.M. Sanders, Mirjam E. Kretzschmar, Hans van Vliet, Hester E. de Melker
Journal: Eurosurveillance (2019)

Introduction Estimating burden of disease (BoD) is an essential first step in the decision-making process on introducing new vaccines into national immunisation programmes (NIPs). For varicella, a common vaccine-preventable disease, BoD in the Netherlands was unknown. Aim To assess national varicella BoD and compare it to BoD of other vaccine-preventable diseases before their introduction in the NIP. Methods In this health estimates reporting study, BoD was expressed in disability-adjusted life years (DALYs) using methodology from the Burden of Communicable Diseases in Europe (BCoDE)-project. As no parameters/disease model for varicella (including herpes zoster) were available in the BCoDE toolkit, incidence, disease progression model and parameters were derived from seroprevalence, healthcare registries and published data. For most other diseases, BoD was estimated with existing BCoDE-parameters, adapted to the Netherlands if needed. Results In 2017, the estimated BoD of varicella in the Netherlands was 1,800 (95% uncertainty interval (UI): 1,800–1,900) DALYs. Herpes zoster mainly contributed to this BoD (1,600 DALYs; 91%), which was generally lower than the BoD of most current NIP diseases in the year before their introduction into the NIP. However, BoD for varicella was higher than for rotavirus gastroenteritis (1,100; 95%UI: 440–2,200 DALYs) and meningococcal B disease (620; 95%UI: 490–770 DALYs), two other potential NIP candidates. Conclusions When considering the introduction of a new vaccine in the NIP, BoD is usually estimated in isolation. The current approach assesses BoD in relation to other vaccine-preventable diseases’ BoD, which may help national advisory committees on immunisation and policymakers to set vaccination priorities.
The pulmonary haemodynamics during exercise – research network (PEX-NET) ERS Clinical Research Collaboration: investigating the prognostic relevance of exercise haemodynamics
Authors: Gabor Kovacs, Philippe Herve, Horst Olschewski
Journal: European Respiratory Journal (2019)

<b>PEX-NET is likely to provide answers regarding the prognostic relevance of pulmonary haemodynamics during exercise and will stimulate further research on the underlying pathophysiology, diagnosis and treatment of exercise pulmonary hypertension</b>http://ow.ly/VThP30o2Anl
Impact of antibiotic treatment and host innate immune pressure on enterococcal adaptation in the human bloodstream
Authors: Daria Van Tyne, Abigail L. Manson, Mark M. Huycke, John Karanicolas, Ashlee M. Earl, Michael S. Gilmore
Journal: Science Translational Medicine (2019)

A genomics analysis shows how a gut commensal adapts rapidly to bloodstream infection, resisting both antibiotics and host innate immune pressure.
The survival rate at 5 years in Turkish metastatic melanoma patients treated with ipilimumab: Final analysis of MIPI-TURK.
Authors: Alper Sevinc, Hande Turna, Mustafa Ozdogan, Suleyman Buyukberber, Nil Molinas Mandel, Gokhan Demir, Erhan Gokmen, Semra Paydas, Hakan Akbulut, Ismail Celik
Journal: Journal of Clinical Oncology (2015)

e20072 Survival rate at 5 years in Turkish metastatic melanoma patients treated with ipilimumab: final analysis of MIPI-TURK. Background: Ipilimumab has been shown to improve immune responses and overall survival in metastatic melanoma patients. This study aimed to provide national data on metastatic melanoma patients treated under an expanded access program in 13 centers in Turkey. Methods: Patients were treated with ipilimumab 3 mg/kg every 3 weeks for 4 doses. Response evaluation was performed at week 12. Patients with complete response (CR), partial response (PR), and stable disease (SD) were eligible for retreatment. Results: Of 97 patients enrolled, 77 were evaluable. Ipilimumab was given as second-, third-, and fourth-line treatments in 20.0%, 64.3%, and 15.7% of patients, respectively. Ipilimumab was given at 1, 2, 3, and 4 doses in 5.2%, 11.7%, 16.9%, and 62.3% of patients, respectively. Seven patients were eligible for retreatment. Grade 1 and 2 adverse events (AEs) were reported in 23.4%, grade 3 and 4 in 14.3%, and grade 5 in 2.6% of patients. The most common grade 1 and 2 immune-related AEs were rash (14.3%), muscle weakness (10.0%), and gastrointestinal AEs (8.6%). Seven patients had grade 3 AEs (diarrhea in 4, muscle weakness in 1, hypothyroidism in 1, and gastrointestinal bleeding in 1) and 4 patients had grade 4 AEs (thrombocytopenia in 1, diarrhea in 1, sinus tachycardia in 1, and multiple organ failure in 1). Two deaths (grade 5) were associated with hepatic AEs. There was no CR within 16 months of follow-up and the median progression-free survival was 2 months (95% CI:1.6–2.5). The disease control rate was 38.8% (PR = 16.3% and SD = 22.5%). Median time to progression was 2 months (95% CI:1.8–3.1). Of patients, 31.9%, 22.2%, and 19.2% survived to 12, 24, and 30 months of follow-up, respectively, and median overall survival was 6 months (95% CI:3.5–8.5). According to current status, 5.2% of patients (n = 4) were lost to follow-up and 14.2% of patients (n = 11) survived. Conclusions: Ipilimumab treatment resulted in favorable clinical benefit for metastatic melanoma patients. Data from 13 centers revealed an efficacy and safety profile consistent with the currently available ipilimumab trials.
FRI-189-HBcrAg decline in JNJ-56136379-treated chronic hepatitis B patients: Results of a phase 1 study
Authors: Oliver Lenz, Thierry Verbinnen, Moana Hodari, Willem Talloen, Joris Vandenbossche, Umesh Shukla, Françoise Berby, Caroline Scholtes, David Blue, Jeysen Yogaratnam, Sandra De Meyer, Fabien Zoulim
Journal: Journal of Hepatology (2019)
FRI-496-Recurrence of hepatocellular carcinoma in patients with complete response treated with direct acting antivirals in clinical practice
Authors: Christie Perelló, Elba Llop, Inmaculada Fernández Vázquez, Ana M Matilla, Francisco Gea, Francisco Javier Garcia-Samaniego Rey, Ana Martin, Araceli Garcia-Sanchez, Rafael Bañares, Agustin Albillos, José Luis Calleja Panero
Journal: Journal of Hepatology (2019)
Guide to presenting clinical prediction models for use in clinical settings
Authors: Laura J Bonnett, Kym I E Snell, Gary S Collins, Richard D Riley
Journal: BMJ (2019)

Clinical prediction models estimate the risk of existing disease or future outcome for an individual, which is conditional on the values of multiple predictors such as age, sex, and biomarkers. In this article, Bonnett and colleagues provide a guide to presenting clinical prediction models so that they can be implemented in practice, if appropriate. They describe how to create four presentation formats and discuss the advantages and disadvantages of each format. A key message is the need for stakeholder engagement to determine the best presentation option in relation to the clinical context of use and the intended users