tbuckley/cabot-search huggingface dataset:
Emerging transporter-targeted nanoparticulate drug delivery systems
Authors: Hongyan Su, Yan Wang, Shuo Liu, Yue Wang, Qian Liu, Guangxuan Liu, Qin Chen
Journal: Acta Pharmaceutica Sinica B (2018)

Transporter-targeted nanoparticulate drug delivery systems (nano-DDS) have emerged as promising nanoplatforms for efficient drug delivery. Recently, great progress in transporter-targeted strategies has been made, especially with the rapid developments in nanotherapeutics. In this review, we outline the recent advances in transporter-targeted nano-DDS. First, the emerging transporter-targeted nano-DDS developed to facilitate oral drug delivery are reviewed. These include improvements in the oral absorption of protein and peptide drugs, facilitating the intravenous-to-oral switch in cancer chemotherapy. Secondly, the recent advances in transporter-assisted brain-targeting nano-DDS are discussed, focusing on the specific transporter-based targeting strategies. Recent developments in transporter-mediated tumor-targeting drug delivery are also discussed. Finally, the possible transport mechanisms involved in transporter-mediated endocytosis are highlighted, with special attention to the latest findings of the interactions between membrane transporters and nano-DDS.
HPV circulating tumor DNA as predictive biomarker of sustained response to chemotherapy in advanced anal carcinoma
Authors: A. Bernard-Tessier, E. Jeannot, D. Guenat, M. Michel, C. Proudhon, A. Vincent-Salomon, I. Bièche, J.-Y. Pierga, B. Buecher, E. Francois, S. Kim, T. André, M. Jary, V. Vendrely, E. Samalin, F. El Hajbi, N. Baba-Hamed, A. Meurisse, F.-C. Bidard, C. Borg
Journal: Annals of Oncology (2018)
Preliminary results of the first-in-human (FIH) study of MK-1454, an agonist of stimulator of interferon genes (STING), as monotherapy or in combination with pembrolizumab (pembro) in patients with advanced solid tumors or lymphomas
Authors: K.J. Harrington, J. Brody, M. Ingham, J. Strauss, S. Cemerski, M. Wang, A. Tse, A. Khilnani, A. Marabelle, T. Golan
Journal: Annals of Oncology (2018)
Cetuximab in combination with methotrexate (MTX) as first-line treatment in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): A phase Ib randomized phase II study versus single agent MTX
Authors: J. Ham, E. Meerten, E. Fiets, F. Jeurissen Mc Haaglanden, M. Slingerland, W.T.A. van der Graaf, C.M.L. van Herpen, L.V. Beerepoot
Journal: Annals of Oncology (2018)
OA03.05 Characterization of the Immunologic Intra-Tumor Heterogeneity in Early Stages of Non-Small Cell Lung Cancer by Multiplex Immunofluorescence
Authors: A. Francisco Cruz, E. Parra, M. Jiang, J. Fujimoto, S. Krishnan, S. Barua, A. Rao, C. Chow, C. Behrens, N. Kalhor, A. Weissferdt, J. Heymach, S. Swisher, B. Sepesi, J. Lee, C. Moran, P.A. Futreal, J. Zhang, I. Wistuba
Journal: Journal of Thoracic Oncology (2018)
Hepatic arterial infusion (HAI) of oxaliplatin with capecitabine in first line treatment of patients (pts) with liver limited metastases from colorectal cancer (LLmCRC)
Authors: B.V. Vittrup, H.H. Nørgaard, M. Bergenfeldt, F.O. Larsen, E. Høgdall, J.S. Johansen, J.S. Sidenius Johansen, H.K. Hermann, D.L. Nielsen
Journal: Annals of Oncology (2018)
OA01.01 10-Year Updated Analysis of NRG Oncology/RTOG 0214: A Phase III Comparison of PCI vs. Observation in Patients with LA-NSCLC.
Authors: A. Sun, C. Hu, E. Gore, S. Wong, G. Videtic, S. Dutta, M. Suntharalingam, Y. Chen, L. Gaspar, H. Choy
Journal: Journal of Thoracic Oncology (2018)
A multicenter phase II trial of paclitaxel, carboplatin and cetuximab (PCE) followed by chemoradiotherapy in patients with unresectable locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: T. Enokida, T. Ogawa, A. Homma, K. Okami, S. Minami, S. Iwae, A. Nakanome, Y. Shimizu, A. Motegi, D. Maki, Y. Ueda, T. Fujisawa, S. Nomura, S. Okano, M. Tahara
Journal: Annals of Oncology (2018)
MA13.03 Heterogeneity Analysis of EBUS-TBNA-Derived Specimens for Evaluation of PD-L1 Expression and Copy Number Alterations in Patients with NSCLC
Authors: K. Yoshimura, Y. Inoue, K. Tsuchiya, M. Karayama, Y. Iwashita, T. Kahyo, A. Kawase, M. Tanahashi, H. Ogawa, K. Yokomura, N. Inui, K. Funai, K. Shinmura, H. Niwa, T. Suda, H. Sugimura
Journal: Journal of Thoracic Oncology (2018)
OA13.03 Anlotinib as Third-Line or Further-Line Treatment in Relapsed SCLC: A Multicentre, Randomized, Double-Blind Phase 2 Trial
Authors: Y. Cheng, Q. Wang, K. Li, J. Shi, L. Wu, B. Han, G. Chen, J. He, J. Wang, H. Qin, X. Li
Journal: Journal of Thoracic Oncology (2018)
The Promise and Pitfalls of Pragmatic Clinical Trials for Improving Health Care Quality
Authors: Nancy Haff, Niteesh K. Choudhry
Journal: JAMA Network Open (2018)

Jennifer K. Carroll, MD, MPH; Gerald Pulver, PhD; L. Miriam Dickinson, PhD; Wilson D. Pace, MD; Joseph A. Vassalotti, MD; Kim S. Kimminau, PhD; Brian K. Manning, MPH; Elizabeth W. Staton, MSTC; Chester H. Fox, MD
A randomized, open label, phase II study of prophylactic octreotide (OCT) to prevent/reduce the frequency and severity of diarrhea in patients (pts) receiving lapatinib (LAP) with capecitabine (CAP) for the treatment of metastatic breast cancer (mBC)
Authors: P. Krivorotko, B. Karaszewska, S. Chan, M. Wieczorek-Rutkowska, T. Sarosiek, M.V. Shomova, E. Ovchinnikova, J.P. Zarate, C. Babanrao Pisal, L. Smith, A. Manikhas
Journal: Annals of Oncology (2018)
P3.01-94 Safety and Efficacy of First-Line Pemetrexed Versus Bevacizumab-Containing Regimens in Advanced Non-Small Cell Lung Cancer
Authors: K. Syrigos, A. Charpidou, D. Grapsa, D. Vassos, S. Tsimpoukis, S. Tsagouli, I. Gkiozos
Journal: Journal of Thoracic Oncology (2018)
P3.01-78 The Cytology Samples and Plasma Specimens were Feasible for the EGFR Molecular Testing.
Authors: T. Ohira, W. Hamanaka, Y. Shimada, S. Maehara, J. Maeda, M. Hagiwara, M. Kakihana, T. Okano, N. Kajiwara, N. Ikeda
Journal: Journal of Thoracic Oncology (2018)
Prospective cohort study of real world chemotherapy sequence for metastatic breast cancer (KBCRN A001: E-SPEC study)
Authors: K. Nakatsukasa, Y. Kikawa, T. Kotake, K. Yamagami, S. Tsuyuki, H. Yamashiro, H. Suwa, T. Sugie, T. Okuno, H. Kato, S. Takahara, I. Nakayama, N. Ogura, Y. Moriguchi, M. Takata, E. Suzuki, H. Yoshibayashi, H. Ishiguro, T. Taguchi, M. Toi
Journal: Annals of Oncology (2018)
Key gaps in the HIV cascade of care among men who have sex with men and migrants diagnosed with HIV: findings from a surveillance study in Shanghai
Authors: Joshua Brian Mendelsohn, Hua Cheng, Liviana Calzavara, Susan Wang, Sandra Bullock, Sharmistha Mishra, Ann Burchell, Mona Loutfy, Alan Li, Robert Hogg, Sarah Jane Steele, Rahim Moineddin, Laiyi Kang
Journal: The Lancet (2018)
A phase II study of durvalumab, a PD-L1 inhibitor and olaparib in recurrent ovarian cancer (OvCa)
Authors: J.-M. Lee, C.M. Annunziata, N. Houston, E.C. Kohn, S. Lipkowitz, L. Minasian, E. Nichols, J. Trepel, K. Trewhitt, F. Zia, A.D.S. Zimmer
Journal: Annals of Oncology (2018)
Continuation of Bevacizumab vs Cetuximab Plus Chemotherapy After First Progression in <i>KRAS</i> Wild-Type Metastatic Colorectal Cancer
Authors: Jaafar Bennouna, Sandrine Hiret, Aurelie Bertaut, Olivier Bouché, Gael Deplanque, Christian Borel, Eric François, Thierry Conroy, François Ghiringhelli, Gaëtan des Guetz, Jean-François Seitz, Pascal Artru, Mohamed Hebbar, Trevor Stanbury, Marc G. Denis, Antoine Adenis, Christophe Borg
Journal: JAMA Oncology (2018)

Second-line treatment with chemotherapy plus bevacizumab or cetuximab is a valid option for metastatic colorectal cancer.To evaluate the progression-free survival (PFS) rate at 4 months with chemotherapy plus bevacizumab vs cetuximab for patients with progression of metastatic colorectal cancer after bevacizumab plus chemotherapy.A prospective, open-label, multicenter, randomized phase 2 trial was conducted from December 14, 2010, to May 5, 2015. The main eligibility criterion was disease progression after bevacizumab plus fluorouracil with irinotecan or oxaliplatin in patients with wild-type KRAS exon 2 metastatic colorectal cancer. All analyses were performed on the modified intent-to-treat population.Patients were randomized to arm A (FOLFIRI [fluorouracil and folinic acid combined with irinotecan] or modified FOLFOX6 [fluorouracil and folinic acid combined with oxaliplatin] plus bevacizumab) or arm B (FOLFIRI or modified FOLFOX6 plus cetuximab); the second-line chemotherapy regimen was chosen according to first-line treatment (crossover).The primary end point was the 4-month PFS rate. Secondary end points included safety, objective response rate, overall survival, and PFS.A total of 132 patients (47 women and 85 men; median age, 63.0 years [range, 33.0-84.0 years]; 74 patients with an Eastern Cooperative Oncology Group performance status of 0, 54 patients with a performance status of 1, and 4 patients with unknown performance status) were included at 25 sites. The 4-month PFS rate was 80.3% (95% CI, 68.0%-88.3%) in arm A and 66.7% (95% CI, 53.6%-76.8%) in arm B. The median PFS was 7.1 months (95% CI, 5.7-8.2 months) in arm A and 5.6 months (95% CI, 4.2-6.5 months) in arm B (hazard ratio, 0.71; 95% CI, 0.50-1.02; P = .06), and the median overall survival was 15.8 months (95% CI, 9.5-22.3 months) in arm A and 10.4 months (95% CI, 7.0-16.2 months) in arm B (hazard ratio, 0.69; 95% CI, 0.46-1.04; P = .08). A central analysis of KRAS (exons 2, 3, and 4), NRAS (exons 2, 3, and 4), and BRAF (V600) was performed for 95 tumor samples. Eighty-one patients had wild-type KRAS and wild-type NRAS tumors.The results of the PRODIGE18 (Partenariat de Recherche en Oncologie DIGEstive) study showed a nonsignificant difference but favored continuation of bevacizumab with chemotherapy crossover for patients with wild-type RAS metastatic colorectal cancer that progressed with first-line bevacizumab plus chemotherapy.ClinicalTrials.gov identifier: NCT01442649 and clinicaltrialsregister.eu identifier: EUDRACT 2009-012942-22.
The retrospective analysis of nephrotoxicity for cisplatin dose of CRT compared 100 mg/m2 to 80 mg/m2 for head and neck cancer (HNC) patients
Authors: T. Oguri, K. Nakano, N. Fukuda, K. Kawaguchi, T. Urasaki, M. Nishizawa, M. Yunokawa, M. Ono, S. Taira, J. Tomomatsu, T. Toshiyasu, H. Mitani, S. Takahashi
Journal: Annals of Oncology (2018)
P3.01-96 Clinical Characteristics of Non–Small Cell Lung Cancer Harboring Mutations in Exon 20 Of EGFR or HER2
Authors: M. Takeda, K. Sakai, H. Hayashi, K. Tanaka, J. Tanizaki, T. Takahama, K. Haratani, K. Nishio, K. Nakagawa
Journal: Journal of Thoracic Oncology (2018)
P3.03-14 Downregulation of FOXM1 Inhibits Tumor Proliferation, Colony Formation and Spheroid Formation of Non-Small Cell Lung Cancer
Authors: Y. Otaki, P. Yenerall, B. Gao, M. Peyton, K. Avila, L. Girard, L.S. Li, A. Das, K. Huffman, B. Timmons, H. Park, D. Deb, J. Minna
Journal: Journal of Thoracic Oncology (2018)
P3.01-54 A Historical Comparison of Patients with Advanced NSCLC Harboring Uncommon EGFR Mutations Before and After the Approval of Afatinib in Japan
Authors: T. Kawamura, H. Murakami, H. Kobayashi, K. Nakashima, S. Omori, K. Wakuda, A. Ono, H. Kenmotsu, T. Naito, M. Endo, T. Takahashi
Journal: Journal of Thoracic Oncology (2018)
Primary efficacy results from B-F1RST, a prospective phase II trial evaluating blood-based tumour mutational burden (bTMB) as a predictive biomarker for atezolizumab (atezo) in 1L non-small cell lung cancer (NSCLC)
Authors: E.S. Kim, V. Velcheti, T. Mekhail, T.A. Leal, J.E. Dowell, M.L. Tsai, C.S.R. Dakhil, P. Stella, V. Shen, S. Hu, S.M. Paul, D.S. Shames, E. Schleifman, D.A. Fabrizio, C. Yun, S. Phan, M.A. Socinski
Journal: Annals of Oncology (2018)
Risk of secondary hematological malignancies and hematological toxicities in recurrent ovarian cancer patients treated with poly adenosine diphosphate ribose polymerase (PARP) inhibitors maintenance
Authors: K.Z. Thein, A. Sultan, M.H. Zaw, M.M. Han, R. Yendala, M.M. Zin, S. Awasthi, N. D'Cunha, F. Hardwicke, C. Jones
Journal: Annals of Oncology (2018)
P3.01-21 Metastatic Lung Carcinoma —An Institutional Experience from Eastern India
Authors: S. Mishra, D. Das, S. Dhar, N. Begum, S. Das, S. Patra, S. Mohakud, P. Mohapatra, D. Parida, S. Das Majumdar
Journal: Journal of Thoracic Oncology (2018)
Abstract 14363: Thrombogenicity of Platinum-chromium Everolimus-eluting Stent is Comparable Low to that of Cobalt-chromium Everolimus-eluting Stent in the Subacute Phase of Acute Myocardial Infarction
Authors: Takayuki Ishihara, Osamu Iida, Masashi Fujita, Masaharu Masuda, Shin Okamoto, Kiyonori Nanto, Takashi Kanda, Akihiro Sunaga, Takuya Tsujimura, Shota Okuno, Yasuhiro Matsuda, Koji Yanaka, Takuya Ohashi, Hiroyuki Kawai, Aki Tsuji, Yosuke Hata, Masaaki Uematsu
Journal: Circulation (2016)

Introduction: Population science has shown similar outcomes between the cobalt-chromium everolimus-eluting stent (CoCr-EES) and the platinum-chromium everolimus-eluting stent (PtCr-EES). CoCr-EES d...
A phase II/III trial of hafnium oxide nanoparticles activated by radiotherapy in the treatment of locally advance soft tissue sarcoma of the extremity and trunk wall
Authors: S. Bonvalot, P.L. Rutkowski, J. Thariat, S. Carrere, M.-P. Sunyach, E. Saada, P. Agoston, A. Hong, A. Mervoyer, M. Rastrelli, C. Le Pechoux, V. Moreno, R. Li, B. Tiangco, A. Casado Herraez, A. Gronchi, L. Mangel, P. Hohenberger, M. Delannes, Z. Papai
Journal: Annals of Oncology (2018)
Recombinant humanized anti-PD-1 monoclonal antibody (JS001) in patients with refractory/metastatic nasopharyngeal carcinoma: Preliminary results of an open-label phase II clinical study
Authors: R. Xu, F.H. Wang, F.J. Feng, Q. Li, N. Xu, X.C. Hu, W.J. Liao, Y. Jiang, X. Lin, Q.Y. Zhang, X.L. Yuan, H.X. Huang, Y. Chen, G.H. Dai, J.H. Shi, L. Shen, C. Ren, H. Wu, H. Feng, S. Yao
Journal: Annals of Oncology (2018)
Training oncologists and preparing patients for shared decision making about palliative systemic treatment: Results from the randomized controlled CHOICE study
Authors: H.W.M. van Laarhoven, I. Henselmans, P. van Maarschalkerweerd, H. de Haes, D.W. Sommeijer, P.B. Ottevanger, H.-B. Fiebrich, S.E. Dohmen, G.-J.M. Creemers, F.Y.F.L. De Vos, E.M. Smets
Journal: Annals of Oncology (2018)
P2.15-16 Clinical Economic Impact of Improved Genotyping in Patients with Advanced Non-Small Cell Lung Adenocarcinoma (NSCLC)
Authors: G. Lopes, V. Raymond, J. Scott, C. Matthews, S. Doshi, E. Wang, S. Skrzypczak, R. Lanman, D. Gandara
Journal: Journal of Thoracic Oncology (2018)
CBFβ-MYH11 interferes with megakaryocyte differentiation via modulating a gene program that includes GATA2 and KLF1
Authors: Guoqiang Yi, Amit Mandoli, Laura Jussen, Esther Tijchon, Maaike G. J. M. van Bergen, Gaëlle Cordonnier, Marten Hansen, Bowon Kim, Luan N. Nguyen, Pascal W. T. C. Jansen, Michiel Vermeulen, Bert van der Reijden, Emile van den Akker, Jonathan Bond, Joost H. A. Martens
Journal: Blood Cancer Journal (2019)

Abstract The inv(16) acute myeloid leukemia-associated CBFβ-MYH11 fusion is proposed to block normal myeloid differentiation, but whether this subtype of leukemia cells is poised for a unique cell lineage remains unclear. Here, we surveyed the functional consequences of CBFβ-MYH11 in primary inv(16) patient blasts, upon expression during hematopoietic differentiation in vitro and upon knockdown in cell lines by multi-omics profiling. Our results reveal that primary inv(16) AML cells share common transcriptomic signatures and epigenetic determiners with megakaryocytes and erythrocytes. Using in vitro differentiation systems, we reveal that CBFβ-MYH11 knockdown interferes with normal megakaryocyte maturation. Two pivotal regulators, GATA2 and KLF1, are identified to complementally occupy RUNX1-binding sites upon fusion protein knockdown, and overexpression of GATA2 partly induces a gene program involved in megakaryocyte-directed differentiation. Together, our findings suggest that in inv(16) leukemia, the CBFβ-MYH11 fusion inhibits primed megakaryopoiesis by attenuating expression of GATA2/KLF1 and interfering with a balanced transcriptional program involving these two factors.
Development and internal validation of a predictive nomogram of progression-free survival in well-differentiated stage IV gastroenteropancreatic neuroendocrine tumours treated with somatostatin analogues: GETNE-TRASGU study
Authors: R. Garcia-Carbonero, V. Alonso, J. Capdevila, M. Sanchez Canovas, T. Alonso, M. Benavent, A. Custodio, G. Crespo Herrero, C. Lopez, J. Hernando, M.C. Riesco Martinez, P. Escudero, J. Gallego Plazas, M. Marazuela, J.A. Diaz, M. Llanos-Munoz, A. La Casta, J.C. Percovich, P. Jimenez-Fonseca, A. Carmona-Bayonas
Journal: Annals of Oncology (2018)
Intermittent short course enzalutamide in biochemically recurrent prostate cancer: Analysis of PSA recovery, testosterone levels and tolerability
Authors: M. Al Harthy, H. Singh, F. Karzai, P. Arlen, M. Theoret, J. Marte, M. Bilusic, A. Couvillon, H. Owens, A. Hankin, L. Cordes, I. Rosner, J. Strauss, W.D. Figg, J. Schlom, W. Dahut, J. Gulley, R. Madan
Journal: Annals of Oncology (2018)
Outcomes by prior transarterial chemoembolization (TACE) in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC)
Authors: T. Yau, A.-L. Cheng, T. Meyer, B.-Y. Ryoo, J.-W. Park, H.-J. Klümpen, H.Y. Lim, S. Kim, J. Knox, M. Patel, A.B. El-Khoueiry, R.K. Kelley, G.K. Abou-Alfa
Journal: Annals of Oncology (2018)
P2.16-12 Expanded Data Confirm Molecular Testing Identifies Lung Adenocarcinoma Patients, Including Stage IA, Who Benefit from Adjuvant Chemotherapy
Authors: G. Woodard, S. Wang, J. Kratz, G. Haro, M. Gubens, C. Blakely, T. Jahan, K. Jones, M. Mann, D. Jablons
Journal: Journal of Thoracic Oncology (2018)
Factors Associated With Efficacy of Cognitive Behavior Therapy vs Education for Patients With Irritable Bowel Syndrome
Authors: Jeffrey M. Lackner, James Jaccard, Rebecca Firth, Susan Krasner, Frank Hamilton, Laurie Keefer, Chang-Xing Ma, Chris Radziwon, Michael Sitrin, Darren Brenner, Gregory Gudleski, Ann Marie Carosella, Len Katz
Journal: Clinical Gastroenterology and Hepatology (2018)

Among patients with irritable bowel syndrome (IBS), it would be helpful to identify those most likely to respond to specific treatments, yet few factors have been identified that reliably predict positive outcome. We sought to identify pretreatment baseline characteristics that associate with gastrointestinal symptom improvement in patients who received empirically validated regimens of cognitive behavior therapy (CBT) or IBS education.
Comparison of tissue-based and liquid biopsy genomic tests to guide lung cancer therapy: Asian experience
Authors: M.-L. Nairismägi, K.-C. Tung, Y.-T. Yang, Y.-J. Lu, R.-S. Jhou, P.-N. Yu, Y.-T. Liu, Y.-L. Hsieh, S.L. Poon, S.-J. Chen, K.T. Tan
Journal: Annals of Oncology (2018)
Antitubulin sulfonamides: The successful combination of an established drug class and a multifaceted target
Authors: Alba Vicente‐Blázquez, Myriam González, Raquel Álvarez, Sara del Mazo, Manuel Medarde, Rafael Peláez
Journal: Medicinal Research Reviews (2018)

Abstract Tubulin, the microtubules and their dynamic behavior are amongst the most successful antitumor, antifungal, antiparasitic, and herbicidal drug targets. Sulfonamides are exemplary drugs with applications in the clinic, in veterinary and in the agrochemical industry. This review summarizes the actual state and recent progress of both fields looking from the double point of view of the target and its drugs, with special focus onto the structural aspects. The article starts with a brief description of tubulin structure and its dynamic assembly and disassembly into microtubules and other polymers. Posttranslational modifications and the many cellular means of regulating and modulating tubulin’s biology are briefly presented in the tubulin code. Next, the structurally characterized drug binding sites, their occupying drugs and the effects they induce are described, emphasizing on the structural requirements for high potency, selectivity, and low toxicity. The second part starts with a summary of the favorable and highly tunable combination of physical–chemical and biological properties that render sulfonamides a prototypical example of privileged scaffolds with representatives in many therapeutic areas. A complete description of tubulin‐binding sulfonamides is provided, covering the different species and drug sites. Some of the antimitotic sulfonamides have met with very successful applications and others less so, thus illustrating the advances, limitations, and future perspectives of the field. All of them combine in a mechanism of action and a clinical outcome that conform efficient drugs.
Mutational and inflammatory microenvironment characteristics in primary and matched local recurrent non-small cell lung cancer brain metastases
Authors: A.S. Berghoff, B. Erguener, M.R. Schuster, U. Rajky, G. Ricken, J.M. Frischer, B. Gatterbauer, C. Marosi, K. Dieckmann, G. Widhalm, C. Bock, M. Preusser
Journal: Annals of Oncology (2018)

Background: Tumor heterogeneity in mutational as well as inflammatory characteristics is a proposed major driver of treatment resistance and tumor progression. Given that the majority of patients with brain metastases (BM) develop brain relapse during their clinical course, we aimed to investigate the mutational and immunological heterogeneity in BM. Methods: Patients treated with neurosurgical resection of a newly diagnosed BM from non-small cell lung cancer and subsequent neurosurgical resection of the local BM recurrence were identified from the Vienna Brain Metastasis Registry. Whole exome sequencing and analysis of tumor infiltrating lymphocytes (TILs) using immunohistochemistry was performed. Results: 24 matched BM specimens from 12 patients (9/12 (75%) male; median age 60 years) were available for analysis. A high concordance in CD3+ TIL (p = 0.004) and CD8+ TIL (p = 0.004) density as well as in the tumor mutational burden (TMB; p < 0.001) was evident between the two specimens of the same patient. A single case (1/12 (8.3%)) changed from low CD3+ and CD8+ TIL density to high density although no radiotherapy or immunotherapy was applied in-between. TMB in the first resection specimen (median 39.2 mutations / Mb) correlated with TMB in the second resection specimen (39.3 mutations / Mb; p < 0.001). A single case (1/12 (8.3%)) presented with marked TMB increase (154 mutation/Mb to 217 mutation/Mb) after application of stereotactic radiotherapy to the resection cavity. No correlation of TIL density and TMB was evident in the investigated specimens (p > 0.05). Overall the mutational characteristics were stable between the two specimens at the same location but at different time points of the same patients as 88% (range 80%-93%) of mutations were shared by both samples. Conclusions: High concordance in mutational and immunological characteristics was observed in this homogenous cohort of local non-small cell lung cancer BM recurrences. TIL density as well as TMB were consistent between BM and the matching local recurrence, although radiotherapy might impact the mutational characteristics. Further analysis of the mutational differences might reveal new therapeutic approaches for secondary BM prevention. Legal entity responsible for the study: Medical University of Vienna. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Integrative approach identifies corticosteroid response variant in diverse populations with asthma
Authors: Albert M. Levin, Hongsheng Gui, Natalia Hernandez-Pacheco, Mao Yang, Shujie Xiao, James J. Yang, Samantha Hochstadt, Andrea J. Barczak, Walter L. Eckalbar, Dean Rynkowski, Lesly-Anne Samedy, Pui-Yan Kwok, Maria Pino-Yanes, David J. Erle, David E. Lanfear, Esteban G. Burchard, L. Keoki Williams
Journal: Journal of Allergy and Clinical Immunology (2018)
Gene expression (GE)-based biomarkers associated with nivolumab response in a real-life cohort of patients with metastatic non-small cell lung cancer (mNSCLC)
Authors: N. Radosevic-Robin, S. Ong, S.E. Warren, M. Kossai, C. Godfraind, M. Masson, H. Janicot, P. Merle, P. Dubray-Longueras, X. Durando, P. Morel, A. Cesano, F. Penault-Llorca
Journal: Annals of Oncology (2018)