A functional gene expression analysis in epithelial sinonasal cancer: Biology and clinical relevance behind three histological subtypes

Epithelial sinonasal cancers (SNCs) are rare diseases with overlapping morphological features and a dismal prognosis. We aimed to investigate the expression differences among the histological subtypes for discerning their molecular characteristics. We selected 47 SNCs: (i) 21 nonkeratinizing squamous cell carcinomas (NKSCCs), (ii) 13 sinonasal neuroendocrine cancers (SNECs), and (iii) 13 sinonasal undifferentiated cancers (SNUCs). Gene expression profiling was performed by DASL (cDNA-mediated annealing, selection, extension, and ligation) microarray analysis with internal validation by quantitative RT-PCR (RT-qPCR). Relevant molecular patterns were uncovered by sparse partial-least squares discriminant analysis (sPLS-DA), microenvironment cell type (xCell), CIBERSORT, and gene set enrichment (GSEA) analyses. The first two sPLS-DA components stratified samples by histological subtypes. xCell highlighted increased expression of immune components (CD8 + effector memory cells, in SNUC) and \u201cother cells\u201d: keratinocytes and neurons in NKSCC and SNEC, respectively. Pathway enrichment was observed in NKSCC (six gene sets, proliferation related), SNEC (one gene set, pancreatic \u3b2-cells), and SNUC (twenty gene sets, some of them immune-system related). Major neuroendocrine involvement was observed in all the SNEC samples. Our high-throughput analysis revealed a good diagnostic ability to differentiate NKSCC, SNEC, and SNUC, but indicated that the neuroendocrine pathway, typical and pathognomonic of SNEC is also present at lower expression levels in the other two histological subtypes. The different and specific profiles may be exploited for elucidating their biology and could help to identify prognostic and therapeutic opportunities

Long-term outcome of re-irradiation for recurrent or second primary head and neck cancer: A multi-institutional study of AIRO-Head and Neck working group

Background To report the long-term outcome of patients undergoing re-irradiation (re-RT) for a recurrent or second primary head and neck cancer (RSPHNCs) in seven Italian tertiary centers, while testing the Multi-Institution Reirradation (MIRI) recursive partitioning analysis (RPA) recently published. Methods We retrospectively analyzed 159 patients. Prognostic factors for overall survival (OS) selected by a random forest model were included in a multivariable Cox analysis. To externally validate MIRI RPA, we estimated the Kaplan-Meier group-stratified OS curves for the whole population. Results Five-year OS was 43.5% (median follow-up: 49.9 months). Nasopharyngeal site, no organ dysfunction, and re-RT volume <36 cm(3) were independent factors for better OS. By applying the MIRI RPA to our cohort, a Harrell C-Index of 0.526 was found indicating poor discriminative ability. Conclusion Our data reinforce the survival benefit of Re-RT for selected patients with RSPHNC. MIRI RPA was not validated in our population

Preliminary epi-diode characterization for HDR brachytherapy quality assurance

High Dose Rate vaginal brachytherapy for endometrial cancer has evolved from simple single-channel (i.e. cylindrical applicator) deliveries to treatments involving several channels (i.e. multichannel applicator) for the radiotherapy source to dwell, increasing the complexity of the dose distribution, and allowing more space for potential errors. For this reason real-time treatment verification has gained a greater importance than ever before, and more methods need to be developed in order to provide assurance that the dose delivery has been carried out as intended by the hospital staff. P-type silicon epi diodes have been designed at the Centre for Medical Radiation Physics (CMRP) in Australia to suit the specific needs of HDR BT, and characterized in the clinical BT facility of the Fondazione IRCCS (INT) in Italy. They have shown great potential for BT treatment verification in real time due to their radiation hardness, dose rate independence, flexibility in physical design, and ability to monitor the treatment at a 1-kHz readout frequency. Their dynamic range has been determined as ± 17 to ± 20 mm and dwell time calculation accuracy of \u3e 0.1 s has been shown. If placed on the same longitudinal plane of a treatment accessory, these detectors would enable coverage of about 40 mm for source position and dwell time tracking. Respective detector positioning at (0, +3, -3 mm) would extend this range to 45-50 mm, depending on the catheter location, proving to be sufficient for the majority of treatment cases. Further studies are encouraged to develop diodes with a wider dynamic range

Methodology and technology for the development of a prognostic MRI-based radiomic model for the outcome of head and neck cancer patients

The purpose of this study was to establish a methodology and technology for the development of an MRI-based radiomic signature for prognosis of overall survival (OS) in nasopharyngeal cancer from non-endemic areas. The signature was trained using 1072 features extracted from the main tumor in T1-weighted and T2-weighted images of 142 patients. A model with 2 radiomic features was obtained (RAD model). Tumor volume and a signature obtained by training the model on permuted survival data (RADperm model) were used as a reference. A 10-fold cross-validation was used to validate the signature. Harrel's C-index was used as performance metric. A statistical comparison of the RAD, RADperm and volume was performed using Wilcoxon signed rank tests. The C-index for the RAD model was higher compared to the one of the RADperm model (0.69±0.08 vs 0.47±0.05), which ensures absence of overfitting. Also, the signature obtained with the RAD model had an improved C-index compared to tumor volume alone (0.69±0.08 vs 0.65±0.06), suggesting that the radiomic signature provides additional prognostic information

In vivo rectal wall measurements during HDR prostate brachytherapy with MOSkin dosimeters integrated on a trans-rectal US probe: Comparison with planned and reconstructed doses

Background and purpose: To study if MO. Skin detectors coupled to a trans-rectal ultrasound (TRUS) probe may be used for in vivo dosimetry on the rectal wall surface during US-based HDR prostate brachytherapy and to quantify possible discrepancies between planned and delivered doses. Materials and methods: MO. Skins are a specific type of MOSFET dosimeter optimized to measure dose in steep dose gradients on interfaces. Two MO. Skins were assembled on a TRUS probe used for on-line treatment planning. Measurements of the dose to the rectal wall were performed over 18 treatment sessions and compared to the doses calculated on the pre-treatment plan (DPRE ) and reconstructed on post-treatment images (DPOST ). Results: Averages of the absolute differences between MO. Skin readings and DPRE , MO. Skin readings and DPOST and DPRE and DPOST were 6.7. ±. 5.1%, 3.6. ±. 1.9% and 6.3. ±. 4.7%, respectively. Agreement between measurements and DPOST was significantly better than between measurements and DPRE (p = 0.002) and DPRE and DPOST (p = 0.004). Discrepancy between DPOST and DPRE correlated with the time required for treatment planning. Conclusion: MO. Skin dosimeters integrated to the TRUS probe proved to be an accurate instrument for measuring the dose delivered to the rectal wall in HDR prostate brachytherapy. The delivered doses may differ significantly from those calculated in the treatment plan

Study of the correlation between rectal wall in vivo dosimetry performed with MOSkins and implant modification during TRUS-guided HDR prostate brachytherapy

In transrectal-US guided HDR prostate brachytherapy, modifications of the geometry of the needle implant can arise in the time lapse between image acquisition and dose delivery. The aim of the present study was to investigate whether in vivo dosimetry measurements could be directly correlated to possible intra-fraction modifications of the implants. During 14 HDR prostate brachytherapy treatments, in vivo dosimetry measurements were performed with an array of two MOSkin detectors integrated onto the longitudinal axis of the transrectal-US probe. The implant displacement was quantified as the difference between the barycenters of the needle location on images acquired prior to treatment planning and after treatment delivery (ΔIB). A further parameter that takes into account also the needle distance from the dosimeters and the planned source dwell times was calculated (ΔwIB). Correlation analysis was performed to indicate any possible relationship between measured and calculated dose discrepancies (ΔDDPPvsTPS) and both ΔIB and ΔwIB. ΔDDPPvsTPS, ranged from a minimum of −19.5% to a maximum of 15.8%. Analysis of the implant barycentre shifts demonstrated a clear systematic trend of the needle implant in the direction of the rectum, with a consequent increase of the dose to the rectal wall. A moderate correlation of r = 0.64 was found between ΔDDPPvsTPS and ΔIB in the antero-posterior direction (ΔIBy), with r increasing to 0.74 if ΔwIBy was considered. The modification in dose to the rectal wall, as a consequence of implant migration that possibly happens in the time lapse between image acquisition and dose delivery, was correctly identified by IVD performed with MOSkins. This study is a further demonstration on how the application of IVD systems may facilitate improvements in quality for HDR prostate brachytherapy