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Annals of Oncology: Official Journal of the European Society for Medical Oncology

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https://www.readbyqxmd.com/read/30219896/advanced-basal-cell-cancer-concise-review-of-molecular-characteristics-and-novel-targeted-and-immune-therapeutics
#1
M Nikanjam, P R Cohen, S Kato, J K Sicklick, R Kurzrock
Metastatic basal cell carcinoma is an ultra-rare manifestation of a common disease, appearing in 0.0028% to 0.5% of basal cell carcinomas. Initial therapeutic efforts focused on cytotoxic chemotherapy administration. However, it is now known that the Hedgehog signaling pathway is crucial for basal cell proliferation and Hedgehog pathway mutations may lead to tumorigenesis; thus, small molecule inhibitors of alterations in the components of this pathway, including smoothened (SMO) and GLI, have been the focus of recent therapeutic developments...
September 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30219915/safety-and-clinical-activity-of-atezolizumab-in-head-and-neck-cancer-results-from-a-phase-i-trial
#2
A D Colevas, R Bahleda, F Braiteh, A Balmanoukian, I Brana, N G Chau, I Sarkar, L Molinero, W Grossman, F Kabbinavar, M Fassò, C O'Hear, J Powderly
Background: Head and neck cancer (HNC) has a poor prognosis at advanced stages. Given the immunosuppressive tumor microenvironment in HNC, inhibition of the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling pathway represents a promising therapeutic approach. Atezolizumab (anti-PD-L1) is efficacious against many tumor types. Here we report the clinical safety and activity from the HNC cohort of the phase Ia PCD4989g clinical trial. Patients and methods: Patients with previously-treated, advanced HNC received atezolizumab intravenously every 3 weeks for 16 cycles, up to 1 year or until loss of clinical benefit...
September 13, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30219886/9-weeks-vs-1-year-adjuvant-trastuzumab-in-combination-with-chemotherapy-final-results-of-the-phase-iii-randomized-short-her-study
#3
P Conte, A Frassoldati, G Bisagni, A A Brandes, M Donadio, O Garrone, F Piacentini, L Cavanna, F Giotta, M Aieta, V Gebbia, A Molino, A Musolino, A Ferro, R Maltoni, S Danese, C Zamagni, A Rimanti, K Cagossi, A Russo, P Pronzato, F Giovanardi, G Moretti, L Lombardo, A Schirone, A Beano, L Amaducci, E A Bajardi, R Vicini, S Balduzzi, R D'Amico, V Guarneri
Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment for HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The Short-HER study was aimed to assess the non-inferiority of 9 weeks vs 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT > 2cm, G3, lympho-vascular invasion, Ki-67>20%, age ≤35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9-weeks trastuzumab (arm B, short)...
September 13, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30215684/reply-to-the-letter-to-the-editor-on-body-mass-index-and-20-specific-cancers-re-analyses-of-dose-response-meta-analyses-of-observational-studies-by-g-markozannes-i-kalliala-m-kyrgiou-m-and-kk-tsilidis
#4
E K Choi, M Eisenhut, H J van der Vliet, K H Lee, J I Shin
No abstract text is available yet for this article.
September 12, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30215682/escat-a-step-in-the-right-direction
#5
A J Silver, J L Warner
No abstract text is available yet for this article.
September 12, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30215677/assessment-of-nivolumab-exposure-and-clinical-safety-of-480-mg-every-4-weeks-flat-dosing-schedule-in-patients-with-cancer
#6
G V Long, S S Tykodi, J G Schneider, C Garbe, G Gravis, M Rashford, S Agrawal, E Grigoryeva, A Bello, A Roy, L Rollin, X Zhao
Background: A nivolumab monotherapy flat-dosing regimen of 480 mg every 4 weeks (Q4W) has been approved in the United States, Canada, and European Union as an alternative dosing regimen for several indications. Approvals of this Q4W regimen were based on population pharmacokinetic (PK) analyses, established flat exposure-response relationships, and clinical safety. The objective of this study was to compare the PK exposure of 480 mg Q4W with 3 mg/kg every 2 weeks (Q2W) and 240 mg Q2W using modeling and simulation, and to evaluate clinical safety of the Q4W regimen...
September 12, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30215676/alectinib-versus-crizotinib-in-treatment-na%C3%A3-ve-anaplastic-lymphoma-kinase-positive-alk-non-small-cell-lung-cancer-cns-efficacy-results-from-the-alex-study
#7
S Gadgeel, S Peters, T Mok, A T Shaw, D W Kim, S I Ou, M Pérol, A Wrona, S Novello, R Rosell, A Zeaiter, T Liu, E Nüesch, B Balas, D R Camidge
Background: The phase III ALEX study in patients with treatment-naïve advanced anaplastic lymphoma kinase mutation-positive (ALK+) non-small-cell lung cancer (NSCLC), met its primary endpoint of improved progression-free survival (PFS) with alectinib versus crizotinib. Here we present detailed central nervous system (CNS) efficacy data from ALEX. Patients and methods: Overall, 303 patients aged ≥18 years underwent 1:1 randomization to receive twice-daily doses of alectinib 600 mg or crizotinib 250 mg...
September 12, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30204845/a-centralised-multidisciplinary-clinic-approach-for-germ-cell-tumours
#8
S M Crawford
No abstract text is available yet for this article.
September 11, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30204839/neoadjuvant-rectal-score-run-with-the-hare-and-hunt-with-the-hounds
#9
F Sclafani, E Kalaitzaki, D Cunningham, D Tait, G Brown, I Chau
No abstract text is available yet for this article.
September 11, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30204835/oncogenes-expand-during-evolution-to-withstand-somatic-amplification
#10
X Wang, X Li, L Zhang, S H Wong, M H T Wang, G Tse, R Z W Dai, G Nakatsu, O O Coker, Z Chen, H Ko, J Y K Chan, T Liu, C H K Cheng, A S L Cheng, K F To, D Plewczynski, J J Y Sung, J Yu, T Gin, M T V Chan, W K K Wu
Background: Cancer-related genes are under intense evolutionary pressure. We conjectured that gene size is an important determinant of amplification propensity for oncogenes and thus cancer susceptibility and therefore could be subject to natural selection. Patients and Methods: Gene information, including size and genomic locations, of all protein-coding genes were downloaded from Ensembl (release 87). Quantification of gene amplification was based on GISTIC scores obtained from available The Cancer Genome Atlas studies...
September 11, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30203045/immunological-differences-between-primary-and-metastatic-breast-cancer
#11
B Szekely, V Bossuyt, X Li, V B Wali, G A Patwardhan, C Frederick, A Silber, T Park, M Harigopal, V Pelekanou, M Zhang, Q Yan, D L Rimm, G Bianchini, C Hatzis, L Pusztai
Background: Little is known about how the immune microenvironment of breast cancer evolves during disease progression. Patients and methods: We compared tumor infiltrating lymphocyte (TIL) count, PD-L1 protein expression by immunohistochemistry and mRNA levels of 730 immune-related genes using Nanostring technology in primary and metastatic cancer samples. Results: TIL counts and PD-L1 positivity were significantly lower in metastases. Immune cell metagenes corresponding to CD8, T-helper, T-reg, Cytotoxic T, Dendritic and Mastoid cells, and expression of 13 of 29 immuno-oncology therapeutic targets in clinical development including PD1, PD-L1, and CTLA4 were significantly lower in metastases...
September 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30202945/development-and-validation-of-a-prognostic-model-for-overall-survival-in-chemotherapy-na%C3%A3-ve-men-with-metastatic-castration-resistant-prostate-cancer
#12
A J Armstrong, P Lin, C S Higano, C N Sternberg, G Sonpavde, B Tombal, A J Templeton, K Fizazi, D Phung, E K Wong, A Krivoshik, T M Beer
Background: Prognostic models are needed that reflect contemporary practice for men with metastatic castration-resistant prostate cancer (mCRPC). We sought to identify predictive and prognostic variables for overall survival (OS) in chemotherapy-naïve men with mCRPC treated with enzalutamide. Patients and methods: Patients from the PREVAIL trial database (enzalutamide versus placebo) were randomly split 2:1 into training (n=1159) and testing (n=550) sets. Using the training set, 23 predefined variables were analyzed and a multivariable model predicting OS was developed and validated in an independent testing set...
September 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30202942/programmed-death-ligand-1-expression-in-uncommon-epidermal-growth-factor-receptor-mutation-positive-non-small-cell-lung-cancer
#13
Y Taniguchi, M Takeda, A Tamiya, T Kasai, S Atagi
No abstract text is available yet for this article.
September 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30202892/design-and-conduct-of-early-clinical-studies-of-immunotherapy-agent-combinations-recommendations-from-the-task-force-on-methodology-for-the-development-of-innovative-cancer-therapies
#14
M Smoragiewicz, J Bogaerts, E Calvo, A Marabelle, A Perrone, L Seymour, A Shalabi, L L Siu, J Tabernero, G Giaccone
The Methodology for the Development of Innovative Cancer Therapies Task Force considered aspects of the design and conduct of early studies of combinations of immunotherapy agents during their 2018 meeting. The Task Force defined the relevant data to justify combination clinical trials, which includes a robust hypothesis for the combination, pre-clinical data with evidence of efficacy and an understanding of the pharmacodynamics effects of each agent, and ideally evidence of single agent activity. Evaluation of pharmacodynamic biomarkers is critical in early phase combination trials, and should be incorporated into trial objectives and go/no-go decisions...
September 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30188977/gastrointestinal-stromal-tumours-esmo-euracan-clinical-practice-guidelines-for-diagnosis-treatment-and-follow-up
#15
P G Casali, N Abecassis, S Bauer, R Biagini, S Bielack, S Bonvalot, I Boukovinas, J V M G Bovee, T Brodowicz, J M Broto, A Buonadonna, E De Álava, A P Dei Tos, X G Del Muro, P Dileo, M Eriksson, A Fedenko, V Ferraresi, A Ferrari, S Ferrari, A M Frezza, S Gasperoni, H Gelderblom, T Gil, G Grignani, A Gronchi, R L Haas, A Hannu, B Hassan, P Hohenberger, R Issels, H Joensuu, R L Jones, I Judson, P Jutte, S Kaal, B Kasper, K Kopeckova, D A Krákorová, A Le Cesne, I Lugowska, O Merimsky, M Montemurro, M A Pantaleo, R Piana, P Picci, S Piperno-Neumann, A L Pousa, P Reichardt, M H Robinson, P Rutkowski, A A Safwat, P Schöffski, S Sleijfer, S Stacchiotti, K Sundby Hall, M Unk, F Van Coevorden, W Van der Graaf, J Whelan, E Wardelmann, O Zaikova, J Y Blay
No abstract text is available yet for this article.
September 5, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30184148/adjuvant-treatment-for-high-risk-renal-cell-carcinoma-the-jury-is-still-out
#16
G Procopio, P Sepe, E Verzoni, S Pignata, A Bamias
No abstract text is available yet for this article.
September 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30165555/associations-between-rad51d-germline-mutations-and-breast-cancer-risk-and-survival-in-brca1-2-negative-breast-cancers
#17
X Chen, Y Li, T Ouyang, J Li, T Wang, Z Fan, T Fan, B Lin, Y Xie
Background: RAD51D is involved in DNA double-strand break repair by homologous recombination and plays an important role in the maintenance of genomic stability. The associations between RAD51D germline mutations and breast cancer risk and survival are not fully elucidated. Patients and methods: RAD51D germline mutations were determined using a multi-gene panel in 7657 unselected breast cancer patients who were negative for BRCA1/2 germline mutations. The RAD51D recurrent mutation p...
August 27, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30165423/small-repeated-boluses-are-unreliable-to-provide-rapid-analgesia-with-intravenous-morphine-titration-and-mislead-conversion-ratio-to-oral-morphine
#18
S Mercadente
No abstract text is available yet for this article.
August 27, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30165419/association-between-pd1-mrna-and-response-to-anti-pd1-monotherapy-across-multiple-cancer-types
#19
L Paré, T Pascual, E Seguí, C Teixidó, M Gonzalez-Cao, P Galván, A Rodríguez, B González, M Cuatrecasas, E Pineda, A Torné, G Crespo, S Martin Algarra, E Pérez-Ruiz, Òscar Reig, Marga Viladot, Carme Font, B Adamo, M Vidal, L Gaba, M Muñoz, I Victoria, G Ruiz, N Viñolas, B Mellado, J Maurel, J Garcia, M Á Molina, M Juan, J M Llovet, N Reguart, A Arance, A Prat
Background: We hypothesized that the abundance of PD1 mRNA in tumor samples might explain the differences in overall response rates (ORR) observed following anti-PD1 monotherapy across cancer-types. Patients and Methods: RNASeqv2 data from 10,078 tumor samples representing 34 different cancer-types was analyzed from TCGA. Eighteen immune-related gene signatures and 547 immune-related genes, including PD1, were explored. Correlations between each gene/signature and ORRs reported in the literature following anti-PD1 monotherapy were calculated...
August 27, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30165371/pd-l1-expression-tumor-mutational-burden-and-response-to-immunotherapy-in-patients-with-met-exon-14-altered-lung-cancers
#20
J K Sabari, G C Leonardi, C A Shu, R Umeton, J Montecalvo, A Ni, R Chen, J Dienstag, C Mrad, I Bergagnini, W V Lai, M D Offin, K C Arbour, A J Plodkowski, D F Halpenny, P K Paik, B T Li, G J Riely, M G Kris, C M Rudin, L M Sholl, M Nishino, M D Hellmann, N Rekhtman, M M Awad, A Drilon
Background: MET exon 14 alterations are actionable oncogenic drivers. Durable responses to MET inhibitors are observed in patients with advanced MET exon 14-altered lung cancers in prospective trials. In contrast, the activity of immunotherapy, PD-L1 expression and tumor mutational burden (TMB) of these tumors and are not well characterized. Patients and Methods: Patients with MET exon 14-altered lung cancers of any stage treated at two academic institutions were identified...
August 27, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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