Search

Loco-regional recurrence (LRR) is the predominant pattern of failure in locally-advanced head and neck cancer (HNC), both in squamous cell carcinoma (SCC) and non-squamous histotypes. Despite the proven role of radiotherapy (RT) as primary treatment strategy, there is sparse evidence on the use of reirradiation (ReRT) in recurrent HNC (rHNC). Various regimens of hypofractionation have been described in the literature, without a clear consensus. The aim of our single-centre study is to evaluate the clinical outcome of unresectable rHNC patients treated with Cyberknife-based (CK) hypofractionated reRT. We retrospectively analyzed data from consecutive patients with rHNC who received CK reRT at our institution. All eligible patients had a recurrent, non-metastatic, previously irradiated unresectable HNC. Each case was discussed at a multidisciplinary level before treatment. Local control (LC), progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and log rank test with time measured from the date of last day of reRT to date of local recurrence, progression of disease or death, respectively. [Display omitted] First curatively intended course of RT was delivered from 1997 to 2020, concomitantly with chemotherapy or not. Thirty-five patients received Cyberknife (CK)-based hypofractionated reRT. The majority of patients (22, 63%) had a diagnosis of SCC and 13 patients (37%) had other histotypes than SCC. The median age of the cohort was 62 years at diagnosis. The CK reRT was performed from 2012 to 2022. The most commonly adopted schedules of reRT were 25Gy (57%) and 30Gy (43%) in 5 fractions on alternating days. After a median follow-up of 12 months (range 2-48), 6 out of 35 patients were alive. Causes of death were related to HNC in 12 patients and in 9 to other causes. The median LC and the 1-year LC rate were 10 months (95% CI 6,6-13,4 months) and 42%, respectively. The median PFS and OS and the 1-year PFS and OS rates were 8 months (95% CI 6.1-9,8 months), 18 months (95% CI 11,8-24,1 months) and 15% and 71% (Figure 1), respectively. At univariate analysis, a negative correlation between time to CK reRT < 12 months and LC (p 0.01) was reported. Moreover, a positive trend association between time from first to second irradiation ≥ 12 months and OS (p 0.09) was shown, in line with findings available from the literature. A significantly better OS was found in patients aged < 65 years (p 0.045). From our analysis, hypofractionated ReRT can be viewed as a well-tolerated treatment option for rHNC with potential for prolonged local control in appropriately selected patients. [ABSTRACT FROM AUTHOR]

Excavations in the Etruscan city of Marzabotto, the ancient Kainua, have brought to light a well-developed production structure over time which, especially for the Etruscan world, makes Marzabotto an especially favourable, paradigmatic context for the study of this particular aspect. Thanks to the contributions from the most recent investigations, together with the revision of older excavation data, this theme has in recent years benefitted from a series of updated considerations. The quality and variety of the data collected permits analyses from multiple points of view, not only on an architectural and urban planning level, but also on social, economic and political-institutional levels. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiotherapy (SBRT) has emerged as a novel therapeutic option to improve outcome of patients with locally advanced pancreatic cancer (LAPC). More intensive schedules are often challenging due to proximity of organs at risks (OARs). Local control is closely related to a biologically effective dose (BED) of 100 Gy10, corresponding to a dose of 50 Gy in 5 fractions. An in-silico study was performed to evaluate the feasibility of dose escalation in SBRT treatments of LAPC through inhomogeneous dose prescription, and to identify patients suitable for this strategy, based on anatomical proximity between target volumes and OARs. Materials and methods: We collected dosimetric data from 14 patients treated at our center for LAPC. For each patient, a CyberKnife (CK) Synchrony re-planning for fiducial-guided pancreatic SBRT treatment was developed for a planned dose of 50 Gy and 40 Gy in 5 fractions to gross tumor volume (GTV) and target volume planning (PTV), respectively. Priority was given to OAR constraints. Criteria for acceptable coverage of the target were: a) 50 Gy and 47.5 Gy to ≥90% and ≥95% of the GTV, respectively, and b) 40 Gy to ≥95% of the PTV. For each plan, a Expansion-Intersection Volume (EIV), corresponding to the intersection volume between PTV and OARs expanded by 5 mm, was calculated. The planned doses to the target volumes and the OARs were evaluated and statistically analyzed. Results: Median GTV and PTV sizes were 40.8 (range 22.3-205.3) cc and 73.7 (range 36.1-266.7) cc, respectively. Treatment plans have been optimized to keep a V35 in the duodenum, stomach and intestines below 0.5cc in all cases. Median V50 and V47.5 for GTV was 91.0% (range 82.4% -97.8%) and 96.8% (range 92.5% -99.9%), respectively: GTV coverage was acceptable in 10 out of 14 cases. Median V40Gy for PTV was 96.8% (range 90.0% -99.8%): PTV coverage was acceptable in 11 of 14 cases. Median EIV was 12.9 (3.9- 25.1) cc. Spearman correlation showed a significant association between EIV and V47.5Gy for GTV (rho -0.77228, p<0.001) and V40Gyfor PTV (rho -0.68352, p <0.001), respectively (Figure 1). Conclusions: Inhomogenous dose escalated prescription to a BED≥100Gy10 is a feasible treatment strategy in selected patients with LAPC (Figure 2). EIV represents a simple tool to identify suitable patients for this approach [ABSTRACT FROM AUTHOR]

The spliceosome and the microprocessor complex (MPC) are two important processing machineries that act on precursor (pre)-mRNA. Both cleave the pre-mRNA to generate spliced mature transcripts and microRNAs (miRNAs), respectively. While spliceosomes identify in a complex manner correct splice sites, MPCs typically target RNA hairpins (pri-miRNA hairpins). In addition, pre-mRNA transcripts can contain pri-miRNA-like hairpins that are cleaved by the MPC without generating miRNAs. Recent evidence indicates that the position of hairpins on pre-mRNA, their distance from splice sites, and the relative efficiency of cropping and splicing contribute to determine the fate of a pre-mRNA. Depending on these factors, a pre-mRNA can be preferentially used to generate a miRNA, a constitutively or even an alternative spliced transcript. For example, competition between splicing and cropping on splice-site-overlapping miRNAs (SO miRNAs) results in alternative spliced isoforms and influences miRNA biogenesis. In several cases, the outcome of a pre-mRNA transcript and its final handling as miRNA or mRNA substrate can be frequently closely connected to the functional relationships between diverse pre-mRNA processing events. These events are influenced by both gene context and physiopathological conditions., (© 2014 John Wiley & Sons, Ltd.)