Rosenthal DI, Harari PM, Giralt J, Bell D, Raben D, Liu J, et al. Validation of NRG oncology/RTOG-0129 risk groups for HPV-positive and HPV-negative oropharyngeal squamous cell cancer: implications for risk-based therapeutic intensity trials. įakhry C, Zhang Q, Gillison ML, Nguyen-Tan PF, Rosenthal DI, Weber RS, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.Īng KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, et al. WNT pathway extranodal extension intratumoral heterogeneity lymph node metastasis oropharyngeal cancer. Clonal evolution analysis of primary and metastatic LNs showed that, in some cases, each metastatic LN originated from a different primary tumor sub-clone. Somatic mutations acquired in the WNT pathway during metastasis showed a significant relationship with ENE. Somatic mutations from metastatic LNs showed a different pattern than the primary tumor. Somatic mutations in HPV-positive OPSCC samples showed APOBEC-related signatures. Somatic mutations in CDKN2A and TP53 were frequently detected in HPV-negative OPSCC. Mutation profiles of HPV-positive OPSCC and HPV-negative OPSCC were similar to those reported previously. Among 40 metastatic LNs, 22 showed extranodal extension (ENE). We performed high-depth whole-exome sequencing (200×) of 76 samples from 18 patients with OPSCC (10 HPV-positive and 8 HPV-negative), including 18 primary tumor samples, 40 metastatic LN samples, and 18 normal tissue samples. Here, we compared the somatic mutational profiles and clonal evolution of primary and metastatic LNs using multiregion sequencing of human papilloma virus (HPV)-positive OPSCC and HPV-negative OPSCC. All rights reserved.Lymph node (LN) metastasis is an important factor in determining the treatment and prognosis of oropharyngeal squamous cell carcinoma (OPSCC). Maximally tolerable dose (MTD) Monotherapy Polytherapy Sequential pharmacotherapy Total drug load (TDL).Ĭopyright © 2019 Elsevier B.V. At present, lamotrigine(LTG) and valproate(VPA) combination regimen is the only well documented synergistic regimen, but there are a long-list of candidate regimens requiring future trials in appropriate designs. It is likely that a significant improvement in the outcome of current AEDs therapy is feasible by earlier employment of polytherapy as well as identification of combination drug regimens carrying synergistic interactions. Current evidence stresses the importance of combining drugs having synergistic interactions for better outcome of polytherapy, which has not been considered in previous clinical investigations comparing monotherapy and polytherapy. Previous claims about the advantages of monotherapy over polytherapy are not supported but gradually losing its ground by the introduction of a large number of drugs carrying pharmacological advantages for combination therapy. We conducted a brief comparative overview between monotherapy and polytherapy to provide clues for earlier employment of polytherapy in each steps of sequential drug trials. However, each mode of pharmacotherapy may have both advantages and disadvantages, which are different and variable related to individual case scenario. Although monotherapy has been established as the preferred mode of AEDs therapy in both newly diagnosed and drug resistant epilepsies, there are still lack of evidence to favor either monotherapy or polytherapy in epilepsy, which has generated continuing controversies on the preferred mode of pharmacotherapy. Modern pharmacotherapy for epilepsy consists of orderly, sequential drug trials, in which antiepileptic drugs (AEDs) are chosen under the concept of individual patient-oriented (or - tailored) pharmacotherapy.
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