Nodal Elective Volume Selection and Definition during Radiation Therapy for Early Stage (T1-T2 N0 M0) Perianal Squamous Cell Carcinoma: A Narrative Clinical Review and Critical Appraisal.

Distinction between anal canal and perianal squamous cell carcinomas (pSCCs) is essential, as these two subgroups have different anatomical, histological, and lymphatic drainage features. Early-stage true perianal tumors are very uncommon and have been rarely included in clinical trials. Perianal skin cancers and aCCs are included in the same tumor classification, even though they have different lymphatic drainage features. Furthermore, pSCCs are treated similarly to carcinomas originating from the anal canal. Radiation therapy (RT) is an essential treatment for anal canal tumors. Guidelines do not differentiate between treatment volumes for perianal tumors and anal cancers. So far, in pSCC, no study has considered modulating treatment volume selection according to the stage of the disease. We conducted a narrative literature review to describe the sites at higher risk for microscopic disease in patients with early-stage perianal cancers (T1-T2 N0 M0) to propose a well-thought selection of RT elective volumes.

The Prognostic Role of Baseline Eosinophils in HPV-Related Cancers: a Multi-institutional Analysis of Anal SCC and OPC Patients Treated with Radical CT-RT.

BACKGROUND AND AIM: Anal squamous cell carcinoma (SCC) and oropharyngeal cancer (OPC) are rare tumors associated with HPV infection. Bioumoral predictors of response to chemoradiation (CT-RT) are lacking in these settings. With the aim to find new biomarkers, we investigated the role of eosinophils in both HPV-positive anal SCC and HPV-related oropharyngeal cancer (OPC). METHODS: We retrieved clinical and laboratory data of patients with HPV-positive anal SCC treated with CT-RT in 5 institutions, and patients with locally advanced OPC SCC treated with CT-RT in 2 institutions. We examined the association between baseline eosinophil count (the best cutoff has been evaluated by ROC curve analysis: 100 × 10^9/L) and disease-free survival (DFS). Unadjusted and adjusted hazard ratios by baseline characteristics were calculated using the Cox proportional hazards model. RESULTS: Three hundred four patients with HPV-positive anal SCCs and 168 patients with OPCs (122 HPV-positive, 46 HPV-negative diseases) were analyzed. In anal SCC, low eosinophil count (< 100 × 10^9/L) correlates to a better DFS (HR = 0.59; p = 0.0392); likewise, in HPV-positive OPC, low eosinophil count correlates to a better DFS (HR = 0.50; p = 0.0428). In HPV-negative OPC, low eosinophil count confers worse DFS compared to high eosinophil count (HR = 3.53; p = 0.0098). After adjustment for age and sex, eosinophils were confirmed to be independent prognostic factors for DFS (HR = 4.55; p = 0.0139). CONCLUSION: Eosinophil count could be used as a prognostic factor in anal HPV-positive SCC. The worse prognosis showed in HPV-positive patients with high eosinophil count is likely to derive from an unfavorable interaction between the HPV-induced immunomodulation and eosinophils, which may hamper the curative effect of RT.

Concurrent Chemoradiation in Anal Cancer Patients Delivered with Bone Marrow-Sparing IMRT: Final Results of a Prospective Phase II Trial.

We investigated the role of the selective avoidance of haematopoietically active pelvic bone marrow (BM), with a targeted intensity-modulated radiotherapy (IMRT) approach, to reduce acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. We designed a one-armed two-stage Simon's design study to test the hypothesis that BM-sparing IMRT would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05; ß = 0.20). A minimum of 21/39 (54%) with G0-G2 toxicity represented the threshold for the fulfilment of the criteria to define this approach as 'promising'. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. From December 2017 to October 2020, we enrolled 39 patients. Maximum observed acute HT comprised 20% rate of ≥G3 leukopenia and 11% rate of ≥G3 thrombocytopenia. Overall, 11 out of 39 treated patients (28%) experienced ≥G3 acute HT. Conversely, in 28 patients (72%) G0-G2 HT events were observed, above the threshold set. Hence, 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in this clinical setting.

Bone Marrow-Sparing IMRT in Anal Cancer Patients Undergoing Concurrent Chemo-Radiation: Results of the First Phase of a Prospective Phase II Trial.

PURPOSE: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with 18FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. METHODS: a one-armed two-stage Simon's design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the ß = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0-G2 acute HT to further proceed with the trial. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. RESULTS: from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0-G2 events, way above the threshold set by the trial design. CONCLUSION: 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial.

Prospective assessment of taste impairment and nausea during radiotherapy for head and neck cancer.

Dysgeusia and nausea are common side effects observed in head and neck cancer patients treated with either exclusive radiotherapy or combined modality treatment. The aim of the present study was to prospectively evaluate dysgeusia, during treatment and follow-up, using the chemotherapy-induced taste alteration scale (CiTAS), a metrics based on 18-items exploring three dimensions (quantitative and qualitative changes in taste perception, and diet-related issues) identified through a four-factor analysis: decline in basic taste, discomfort, phantogeusia-parageusia, and general taste alterations. Moreover, we scored, according to Common Toxicity Criteria Adverse Events, nausea and other treatment-related toxicities. Since, ginger is traditionally used to prevent and/or treat nausea and vomiting, we prophylactically employed a ginger-based supplement named Naumix/Naugin (Gamfarma, Milan, Italy), to potentially mitigate both nausea and taste impairment. Using the CiTAS scale, we highlighted a progressive increase in all dysgeusia dimensions, peaking at the VII week of treatment and a subsequent partial late recovery. In particular, we observed a recovery for discomfort, phantogeusia-parageusia, and general taste alterations at 6 months. Grade 2 nausea, observed to be as low as 12.9% potentially due to the use of ginger, peaked at the III week of treatment. Finally, for patients experiencing nausea, the dysgeusia dimension of discomfort was also relevant.

Orthodontic miniscrews: an experimental campaign on primary stability and bone properties.

OBJECTIVE: To evaluate the primary stability of different shaped miniscrews through the acquisition of data regarding maximum insertion torque, pullout force, and a radiodiagnosic evaluation of bone characteristics. MATERIALS AND METHODS: Sixty fresh porcine bone samples were scanned by computed tomography (CT) and cone-beam computed tomography (CBCT). By means of a dedicated software, CT and CBCT images were analysed to measure the insertion-site cortical thickness, cortical density, and marrow bone density. Sixty miniscrews of 12 different types were implanted with no predrilling pilot hole in the bone samples. Every device was tightened by means of a digital torque screwdriver and torque data were collected. Subsequently, pullout tests were performed. Spearman and Pearson correlations were employed to compare any relationship between continuous variables. RESULTS: Different types of miniscrews did not show statistically significant differences in their torque value (P = 0.595), instead a significant difference was revealed by considering their load measures (P = 0.039). Cortical bone thickness resulted strongly correlated both with value of load (P < 0.001), and modestly with torque measures (P = 0.004). A strong positive correlation was found between CT and CBCT both for cortical density (P < 0.001) and marrow bone density (P < 0.001). CONCLUSION: Bone characteristics play the major role in miniscrews primary stability.

Promotion of Förster resonance energy transfer in a saponite clay containing luminescent polyhedral oligomeric silsesquioxane and rhodamine dye.

A new hybrid photostable saponite clay with embedded donor-acceptor dyes was prepared and characterized in this work. The saponite is intercalated with a luminescent polyhedral oligomeric silsesquioxane, which transfers the photoexcitation energy directly to an acceptor dye (rhodamine B). The obtained composite material was characterized by means of XRD, TEM microscopy, and UV/Vis and photoluminescence spectroscopy. A physicochemical study showed that the system behaved as an efficient Förster resonance energy transfer pair, owing to the very good spectral overlap of donor emission (λem =510-540 nm) and acceptor absorption in the λ=530-570 nm range. The hybrid material represents the first example of a photonic antenna based on a synthetic saponite clay and can be considered a step forward in the search for new, efficient, and stable materials suitable for light-harvesting applications.

Flow cytometry evidence of human granulocytes interaction with polyhedral oligomeric silsesquioxanes: effect of nanoparticle charge.

Nanoparticles (NPs) entering the human body are immediately confronted with the innate part of human immune system. In particular, monocyte and neutrophil granulocytes readily clear particles by phagocytosis, even if in the case of NPs the uptake mechanism may be classified as macropinocytosis. Among engineered nanoparticles, in the last years, siliceous materials have emerged as promising materials for several applications ranging from catalysis to biomedical. The polyhedral oligomeric silsesquioxanes (POSS) are nanodimensional, easily synthesizable molecular compounds and POSS-based systems are promising carriers for biological molecules. In this work, the ability of human granulocytes to uptake positively and negatively charged POSS was measured using a simple flow cytometry analysis based on cell size modifications. The data obtained showed that after a 30 min exposure only positive NPs were uptaken by human granulocyte using both macropinocytosis and clathrin-mediated mechanisms as demonstrated by uptake inhibition mediated by amiloride and chlorpromazine.

A novel electroluminescent PPV copolymer and silsesquioxane nanocomposite film for the preparation of efficient PLED devices.

Polymer light-emitting diodes (PLEDs) have attracted growing interest in recent years for their potential use in displays and lighting fields. Nevertheless, PLED devices have some disadvantages in terms of low optoelectronic efficiency, high cost, short lifetimes and low thermal stability, which limit their final applications. Huge efforts have been made recently to improve the performances of these devices. The addition of inorganic or hybrid organic-inorganic nanoparticles to the light-emitting polymers, for example, allows their thermal stability and electroluminescent efficiency to be increased. Following this approach, novel PLED devices based on composite films of PPV-derivative copolymer (commercial name Super Yellow, SY) and octaisobutil POSS, were developed in this study. The device containing Super Yellow loaded with 1 wt% of POSS showed higher efficiency (ca. +30%) and improved lifetime in comparison to PLED prepared with the pure electroluminescent polymer. The PLED devices developed in this study are suitable candidates for automotive dashboards and, in general, for lighting applications.

A novel luminescent bifunctional POSS as a molecular platform for biomedical applications.

A novel luminescent polyhedral oligomeric silsesquioxane (POSS) containing in the structure a fluorescein derivative molecule and a carboxylic functionality, suitable to anchor different organic compounds (dyes, markers, drugs, contrast agents, …), was successfully synthesized and characterized in this manuscript by a multidisciplinary approach. An emission enhancement of the dye of ca. four times was found after reaction with POSS, rendering this new hybrid compound a promising contrast agent for optical imaging. In vitro tests on tumoral HeLa cells demonstrated that the luminescent POSS (namely POSS_F), here described, is able to be taken up in the cell cytosol by an efficient and selective process. Its high chemical versatility and peculiar properties could render this novel bifunctional POSS a molecular platform for biomedical applications.