Improving Outcomes in NSCLC: Optimum Dose Fractionation in Radical Radiotherapy Matters.

IntroductionWe analyzed a comprehensive national radiotherapy data set to compare outcomes of the most frequently used moderate hypofractionation regimen (55 Gy in 20 fractions) and conventional fractionation regimen (60-66 Gy in 30-33 fractions).MethodsA total of 169,863 cases of NSCLC registered in England from January 2012 to December 2016 obtained from the Public Health England were divided into cohort 1 (training set) diagnosed in 2012 to 2013 and cohort 2 (validation set) diagnosed in 2014 to 2016. Radiotherapy data were obtained from the National Radiotherapy Dataset and linked by National Health Service number to survival data from the Office of National Statistics and Hospital Episode Statistics, from which surgical data and Charlson comorbidity index were obtained. Of 73,186 patients with stages I to III NSCLC, 12,898 received radical fractionated radiotherapy (cohort 1-4894; cohort 2-8004). The proportional hazards model was used to investigate overall survival from time of diagnosis. Survival was adjusted for the prognostic factors of age, sex, stage of disease, comorbidity, other radical treatments, and adjuvant chemotherapy, and the difference between the treatment schedules was summarized by hazard ratio (HR) and 95% confidence interval. The significance of any difference was evaluated by the log likelihood test.ResultsOf patients with stages I to III NSCLC, 17% to 18% received radical fractionated radiotherapy. After adjustment for independent prognostic factors of age, stage, comorbidity, and other radical and adjuvant treatments, patients in cohort 1 treated with the 2.75 Gy per fraction regimen had a median survival of 25 months compared with 29 months for patients treated with the 2 Gy per fraction regimen (HR = 1.16, p = 0.001). Similarly, in cohort 2, the respective median survival values were 25 and 28 months (HR = 1.10, p = 0.02).ConclusionsBig data analysis of a comprehensive national cohort of patients with NSCLC treated in England suggests that compared with a 4-week regimen of 55 Gy in 20 fractions, a 6-week regimen of conventional daily fractionation to a dose of 60 to 66 Gy at 2 Gy per fraction is associated with a survival benefit. Within the limitations of the retrospective big data analysis with potential selection bias and in the absence of randomized trials, the results suggest that conventional fractionation regimens should remain the standard of care

From graphene and topological insulators to Weyl semimetals

Here we present a short introduction into physics of Dirac materials. In particular we review main physical properties of various two-dimensional crystals such as graphene, sil- icene, germanene and others.We comment on the origin of their buckled two-dimensional shape, and address the issues created by Mermin-Wagner theorem prohibiting the exis- tence of strictly two-dimensional, at crystals. Then we describe main ideas which were leading to the discovery of two and three-dimensional topological insulators and Weyl fermions. We describe some of their outstanding electronic properties which have been originating due to the existence of the Dirac gapless spectrum. We also compare simplest devices made of Dirac materials. Analogies and di erences between Dirac materials and optics are also discussed

Afatinib and radiotherapy, with or without temozolomide, in patients with newly diagnosed glioblastoma: results of a phase I trial.

Funder: Boehringer Ingelheim; doi: http://dx.doi.org/10.13039/100001003BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Amplification or overexpression of the epidermal growth factor receptor gene, part of the ErbB family, occur in approximately 40% and 60% of patients with GBM, respectively. We present data from a dose-finding study of the ErbB inhibitor afatinib in combination with radiotherapy (RT), with or without temozolomide (TMZ), in patients with GBM. METHODS: This was a phase I, open-label, 3 + 3 dose-escalation trial in patients with newly-diagnosed, histologically-confirmed grade 4 malignant glioma and proven O6-methylguanine-DNA methyltransferase gene promoter methylation status. The primary endpoint was the maximum tolerated dose (MTD) of continuous daily afatinib when given in combination with RT, with (regimen M) or without (regimen U) concomitant TMZ treatment. RESULTS: Fifty-five patients were enrolled; 36 received ≥ 1 dose of trial medication (regimen M, n = 20, regimen U, n = 16). Afatinib was discontinued by all patients during the study. Reasons for afatinib discontinuation (regimen M/U) included disease progression (45%/50%), dose-limiting toxicity (10%/0%), and other adverse events (AEs; 35%/38%). The most frequently reported AEs with either regimen were diarrhea and rash, with no new safety signals identified. The MTD was determined as afatinib 30 mg in combination with daily TMZ and RT, and afatinib 40 mg in combination with RT alone. CONCLUSIONS: This study identified the MTD for afatinib in combination with RT, with and without TMZ, in patients with GBM. Further studies of afatinib in patients with GBM are warranted and should be based on appropriate biomarker-based preselection. TRIAL REGISTRATION: NCT00977431 (first posted September 15, 2009)