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Abstract Purpose Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale (“Cuneo score”). Methods We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients’ information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. Results Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). Conclusions In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

In questo lavoro vengono riportati i risultati a breve termine di uno studio prospettico, finalizzato alla valutazione strumentale della funzionalità deglutitoria in pazienti affetti da tumore del rinofaringe e orofaringe sottoposti a trattamento radio o radiochemioterapico con tecnica ad intensità modulata (IMRT). L’ IMRT è stata finalizzata, oltre che al miglioramento della conformazione della dose radiante al volume tumorale, alla riduzione della stessa alle strutture responsabili della deglutizione (SWOARs). I criteri dello studio hanno previsto in tutti i pazienti la valutazione strumentale della deglutizione con Videofluoroscopia (VFS), Fibroscopia Endoscopica della deglutizione (FEES) e Scintigrafia Orofaringea (OPES) prima dell’inizio del trattamento e ad 1 mese dal termine dello stesso. Ogni esame è stato eseguito rispettivamente in seguito all’assunzione di un bolo liquido (L) e semiliquido (SL) e per ognuno sono stati calcolati i seguenti valori strumentali: presenza o meno di caduta pre-deglutitoria, presenza o meno di aspirazione, tempo di transito faringeo (PTT) ed indice di ritenzione ipofaringeo (HPRI). Dal Gennaio 2012 al Giugno 2013, un totale di 20 pazienti ha terminato il trattamento ed ha eseguito la valutazione strumentale a 1 mese dal termine della radioterapia. Il confronto tra i valori dell’HPRI prima e dopo il trattamento radiante ha mostrato un peggioramento significativo sia alla FEES-L (p = 0,021) e SL (p = 0,02) che alla VFS-L (p = 0,008) che SL (p = 0,005). Inoltre è stata riscontrata una significativa correlazione tra i valori dell’HPRI basale ed a 1 mese alla FEES-L e SL (p = 0,005) così come alla VFS-L e SL (p < 0,001). Diversamente, il tempo di transito faringeo (PTT) non è risultato essere influenzato dalla radioterapia (p > 0,2). Solo in pochi pazienti è stata riscontrata la comparsa di caduta pre-deglutitoria ( 1 paziente con tumore della base linguale alla FEES-L e SL) e la presenza di aspirazione (1 paziente con tumore del rinofaringe alla OPES-L e FEES-SL). Nel complesso i risultati iniziali del nostro studio mostrano che l’ IMRT, finalizzata al risparmio delle SWOARs, determina soltanto un significativo incremento della ritenzione di bolo a livello del distretto ipofaringeo. Un follow-up più lungo sarà necessario per valutare se tale incremento sia associato o meno ad un maggior rischio di sviluppare fenomeni di aspirazione tardivi.

Background: The management of multiple myeloma is challenging because the disease is incurable and unexpected relapses can threaten a patient's survival. Several assessment systems are currently available, but they often require invasive or costly procedures (e.g., instrumental bone marrow and whole-body examinations) or rely on non-specific markers in blood and urine that may not be sufficient to assess and monitor the disease., Aims: To address some of these limitations, the aim of this study was to evaluate the potential use of soluble B-Cell Maturation Antigen (BCMA), a promising new serum biomarker, as a toll for moniting multiple myeloma patients., Materials & Methods: An unselected cohort of 57 newly diagnosed or relapsed myeloma patients was followed up for 6 months after starting a new therapy. Soluble BCMA levels were measured in peripheral blood using a simple and inexpensive ELISA assay., Results: Soluble BCMA was detectable in peripheral blood by a simple and inexpensive assay in all patients, even in non-secretory disease or during BCMA-targeted therapies, and significant changes in its levels were observed over time. The analysis showed that the decrease in sBCMA at 1 and 6 months reflects the quality of the clinical response to anti-myeloma regimens., Discussion & Conclusion: The data provide interesting insights into the usefulness of sBCMA as a non-invasive tool for early assessment of treatment efficacy. Its simple and cost-effective detection in peripheral blood could provide clinicians with an addiotional resource for monitoring disease progression and tailoring treatment strategies., (© 2025 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: To investigate changes of objective instrumental measures and correlate with patient reported outcomes (PROs) of radiation-induced dysphagia (RID) after swallowing organs at risk (SWOARs)-sparing IMRT., Methods: Patients (pts) underwent Fiberoptic Endoscopic Evaluation of Swallowing (FEES), Videofluoroscopy (VFS) and M.D. Anderson Dysphagia Inventory (MDADI) questionnaire at baseline, 6 and 12 months after treatment. They were categorized in two groups: MDADI-C ≥ 80 and MDADI-C < 80. Pharyngeal residue (PR) and penetration (P) or aspiration (A) were considered as surrogate of RID., Results: Between 2016 and 2022 we enrolled 75 pts, 40 (53 %) MDADI-C ≥ 80 and 35 (47 %) MDADI-C < 80 at baseline. Among MDADI-C ≥ 80 the mean baseline PR score at FEES was 0,42 rising to 1,36 at 6 months (p = 0,001) and stabilizing to 1,15 at 12 months (p = 0,21); indeed, the mean baseline PR score at VFS was 0,55 rising to 1 at 6 months (p = 0,069) and slightly dropping to 0,7 at 12 months (p = 0,069). Among MDADI-C < 80 the mean baseline PR score at FEES was 0,56 rising to 1,07 at 6 months (p = 0,012) and stabilizing to 1,07 at 12 months (p = 0,99); indeed the mean baseline PR score at VFS was 0,67 rising to 1,19 at 6 months (p = 0,04) and dropping to 0,78 at 12 months (p = 0,04). No correlation was found between PROs and objective measures., Conclusion: Our results show optimal acceptable deglutition preservation from major complications after SWOARs-sparing IMRT by means of low objective scores in both MDADI-C groups. Lack of correlation between PROs and objective measures suggest that referred RID is likely associated to persistence of SWOARs inflammation rather than to a real impairment of function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The role of the wound care nurse is identified as a key element in the management of patients with venous leg ulcers (VLUs). However, the literature offers fragmented knowledge of the outcomes associated with their practice., Aims: To identify, summarize, and map all available evidence based on the wound care nurses practice for the treatment of VLUs., Methods: A scoping review was conducted in May 2024 on PubMed, CINAHL, Scopus, and Cochrane Library databases. Observational or experimental studies related to patients affected by VLUs and cared for by wound care nurse specialists were included., Results: Of the 1562 articles reviewed, 9 studies met the inclusion criteria. The most frequently measured outcomes were clinical responses and included healing rate and ulcer recurrence. Less frequent outcomes were patient-reported and resource utilization measures., Conclusion: This review indicates a general predominance of outcomes related to objective clinical responses. Future studies should broaden the types of outcomes by also including patient-reported parameters (eg, pain, quality of life, stress) in order to gain greater evidence on the impact of wound care nurse specialists in the care of patients affected by VLUs., Competing Interests: The authors report no conflicts of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Regular physical activity is crucial in preventing chronic diseases. International health authorities recommend that children and adolescents engage in at least 60 minutes of moderate to vigorous physical activity per day to achieve health benefits. Offering regular exercise opportunities to young people can promote the development of healthy lifestyles. In 2021, a new regu-lation introduced up to two compulsory hours of Physical Education per week in Italy and established that Physical Education should be entrusted to adequately trained teachers. The present study aimed to assess, from the perspective of the new teachers, the resources available for Physical Education in Italian primary schools., Methods: A questionnaire-based cross-sectional study was conducted among primary school Physical Education teachers during the year 2022-2023. Their opinion about the school resources were analyzed in light of their demographic characteristics and work experience., Results: Out of the 118 participating teachers, 96 (81.3%) reported the presence of a gym in their school. Participants expressed satisfaction with the size and windows of the gym, particularly for the schools of the North, as well as the adequacy of outdoor spaces. However, lower levels of satisfaction for locker rooms and gym small equipment emerged, especially among those teachers with less work experience., Conclusions: The introduction of the Physical Education teacher figure in Italian primary schools was an important step for health promotion in our country. However, some aspects related to the structural resources should be considered in future policies.

Purpose: Treatment de-intensification for p16 + oropharyngeal squamous cell carcinoma (OPSCC) is an area of active research to reduce the side effects and improve patients' quality of life (QoL). In this paper we evaluated the Overall Survival (OS), the Disease-Free Survival (DFS) and the QoL of patients affected by p16 + OPSCC according to their prognostic stage group (PSG) and different treatments., Methods: Patients were selected retrospectively through our Electronic Tumor Board Database according to prespecified inclusion criteria. Basic data of eligible patients were recorded and analyzed. Then, OS and DFS were evaluated according to the PSG and the treatments performed. Patients alive completed three questionnaires: the QoL Questionnaire Core 30 (QLQ-C30), the QoL Questionnaire Head & Neck 43 (QLQ-HN43) and the MD Anderson Dysphagia Inventory (MDADI) questionnaire., Results: Sixty-one patients were included in this study. Eight patients died from the disease and the remaining 53 patients completed the 3 questionnaires. Fifteen (25%) patients were treated with upfront surgery, 6 (10%) patients with definitive radiotherapy and 40 (65%) patients with concomitant chemoradiotherapy. Comparing the DFS and the OS of PSG I patients by the different treatments performed, no statistically significant difference was identified. Patients treated with upfront surgery showed better outcomes in some aspects of their QoL., Conclusion: For p16 + OPSCC PSG I patients, upfront surgery can be considered a valid alternative to radiotherapy or chemoradiotherapy while maintaining a comparable DFS and OS and giving patients better results in terms of specific aspects of their QoL., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Radiotherapy (RT) is performed in approximately 75% of patients with cancer, and its efficacy is often hampered by the low tolerance of the surrounding normal tissues. Recent advancements have demonstrated the potential to widen the therapeutic window using "very short" radiation treatment delivery (from a conventional dose rate between 0.5 Gy/min and 2 Gy/min to more than 40 Gy/s) causing a significant increase of normal tissue tolerance without varying the tumor effect. This phenomenon is called "FLASH Effect (FE)" and has been discovered by using electrons. Although several physical, dosimetric, and radiobiological aspects need to be clarified, current preclinical " in vivo " studies have reported a significant protective effect of FLASH RT on neurocognitive function, skin toxicity, lung fibrosis, and bowel injury. Therefore, the current radiobiological premises lay the foundation for groundbreaking potentials in clinical translation, which could be addressed to an initial application of Low Energy Electron FLASH (LEE) for the treatment of superficial tumors to a subsequent Very High Energy Electron FLASH (VHEE) for the treatment of deep tumors. Herein, we report a clinical investigational scenario that, if supported by preclinical studies, could be drawn in the near future., Competing Interests: FM received personal support for attending meetings from SIT-Sordina. FP received personal support for attending meetings from SIT-Sordina and from Thema Sinergie. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ursino, Gadducci, Giannini, Gonnelli, Fuentes, Di Martino and Paiar.)

The sensitivity of ELISA-based devices strongly depends on the right orientation of antibodies on the sensor surface. The aim of this work was to increase the analytical performance of a commercial ELISA-based medical device (VIDAS®), thanks to the specific orientation of antibodies on gold nanostructured disposables. For this purpose, fPSA VIDAS® assay was used as model and the disposable providing the antigen binding surface (SPR®) was functionalized with gold nanostructures coated with monovalent half-fragment antibodies (reduced IgG, rIgG). The functionalization of polystyrene SPRs® with gold nanostructures was achieved through a one-step incubation of gold dispersions in a mixture of non-toxic solvents. Five different concentrations of gold nanoparticles (NPs) were tested with a maximum fluorescence enhancement for NPs density around 3-8 *10 3 NPs/μm 2 (752 ± 11 RFV vs 316 ± 5 RFV of bare SPRs®). The comparison of the dose-response curve obtained with commercial and gold coated-SPRs® revealed a significant improvement (p < 0.0001) of the analytical sensitivity of the VIDAS® system using nanostructured disposables. This improved version of SPRs® allows to distinguish small variations of fPSA concentrations opening the way to the application of this biomarker to other kinds of cancer as recently described in the literature., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: The present study examined the longitudinal trajectories, through hierarchical modeling, of quality of life among patients with head and neck cancer, specifically symptoms burden, during radiotherapy, and in the follow-up period (1, 3, 6, and 12 months after completion of radiotherapy), through the M.D. Anderson Symptom Inventory Head and Neck questionnaire, formed by three factors. Furthermore, analyses were conducted controlling for socio-demographic as well as clinical characteristics., Methods: Multi-level mixed-effects linear regression was used to estimate the association between quality of life and time, age, gender, household, educational level, employment status, ECOG performance status, human papilloma virus (HPV) status, surgery, chemotherapy, alcohol intake, and smoking., Results: Among the 166 participants, time resulted to be a predictor of all the three questionnaire factors, namely, general and specific related symptoms and interference with daily life. Moreover, regarding symptom interference with daily activities factor, HPV-positive status played a significant role. Considering only HPV-negative patients, only time predicted patients' quality of life. Differently, among HPV-positive patients, other variables, such as gender, educational level, alcohol use, surgery, age at diagnosis, employment status, and ECOG status, resulted significant., Conclusion: It was evident that quality of life of patients with head and neck cancer declined during RT, whereas it slowly improved after ending treatment. Our results clarified the role of some socio-demographic and clinical variables, for instance, HPV, which would allow to develop treatments tailored to each patient., (© 2023. The Author(s).)

Objectives: To prospectively investigate changes in M.D. Anderson Dysphagia Inventory (MDADI) scores in patients affected by naso- and oropharynx cancer after definitive radiochemotherapy (ChemoRT) using swallowing organs at risk (SWOARs)-sparing IMRT., Methods: MDADI questionnaires were collected at baseline and at 6 and 12 months after treatment. MDADI scores were categorized as follows: ≥ 80 "optimal," 80-60 "adequate," < 60 "poor" deglutition-related quality of life (QoL) group, and dichotomized as "optimal" vs "adequate/poor" for the analysis. A mean MDADI composite (MDADI-C) change of 10 points was considered as minimal clinically important difference (MCID)., Results: Sixty-three patients were enrolled of which 47 were considered for the analysis. At baseline, 26 (55%) were "optimal" and 21 (45%) were "adequate/poor." The mean baseline MDADI-C score was 93.6 dropping to 81 at 6 months (p = 0.013) and slightly rising to 85.5 at 12 months (p = 0.321) for the "optimal" group. Indeed, the mean baseline MDADI-C score was 64.3 rising to 77.5 at 6 months (p = 0.006) and stabilizing at 76 at 12 months (p = 0.999) for the "adequate/poor" group. A statistically significant but not clinically relevant worsening of the MDADI-C score was reported for the "optimal" group, whereas both a statistically significant and clinically meaningful improvement of the MDADI-C score were reported for the "adequate/poor" group from before to post-treatment., Conclusion: Our results suggest a doubly clinical benefit of dose optimization to SWOARs to minimize the RT sequalae in patients with a baseline "optimal" deglutition-related QoL and to recover from cancer dysphagia in those with a baseline "adequate/poor" deglutition-related QoL., (© 2022. The Author(s).)

Evidence on the efficacy of postoperative radiotherapy (PORT) in low-intermediate risk squamous cell carcinoma of the oral cavity (OSCC) remains inconclusive. Members of a task force from two national radio-oncology Associations (AIRO and GORTEC) defined 14 clinically relevant questions to identify "gray areas" pertinent to the indication for PORT in this clinical setting. Consequently, a literature review was performed on the topic. The resulting statements were then rated by an Expert Panel (EP) using a modified Delphi method. Only radiation oncologists were part of the discussion and voting on the scenarios. There was agreement on the 14 statements at the first round of voting. The task force then decided to propose clinical cases for the two more controversial statements that had received a lower agreement to better capture the Experts' attitudes. The clinical cases highlighted a more significant decisional heterogeneity. However, the good level of consensus reached among the two Associations gives relevant support in informing clinical choices while acknowledging general indications cannot fit all clinical situations and do not replace multidisciplinary discussion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The free electron fraction is the fraction of electrons, produced inside the cavity of an ionization chamber after irradiation, which does not bind to gas molecules and thereby reaches the electrode as free electrons. It is a fundamental quantity to describe the recombination processes of an ionization chamber, as it generates a gap of positive charges compared to negative ones, which certainly will not undergo recombination. The free electron fraction depends on the specific chamber geometry, the polarizing applied voltage and the gas thermodynamic properties. Therefore, it is necessary to evaluate such fraction in an accurate and easy way for any measurement condition. In this paper, a simple and direct method for evaluating the free electron fraction of ionization chambers is proposed. We first model the capture process of the electrons produced inside an ionization chamber after the beam pulse; then we present a method to evaluate the free electron fraction based on simple measurements of collected charge, by varying the applied voltage. Finally, the results obtained using an Advanced Markus chamber irradiated with a Flash Radiotherapy dedicated research Linac (ElectronFlash) to estimate the free electron fraction are presented. The proposed method allows the use of a conventional ionization chamber for measurements in ultra-high-dose-per-pulse (UHDP) conditions, up to values of dose-per-pulse at which the perturbation of the electric field due to the generated charge can be considered negligible., Competing Interests: Declaration of Competing Interest F. Galante, G. Mariani, M. Pacitti and G. Felici are SIT employees; G. Felici is a SIT shareholder; A. Gasparini received a grant for a post doc position funded by SIT S.p.A. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Workplace violence (WV) is a significant occupational hazard for nurses. Previous studies have shown that WV has a reciprocal relationship with occupational stress. Headaches and sleep problems are early neuropsychological signs of distress. This cross-sectional study aims to ascertain the frequency of physical or verbal assaults on nurses and to study the association of WV with headaches and sleep problems. During their regular medical examination in the workplace, 550 nurses and nursing assistants (105 males, 19.1%; mean age 48.02 ± 9.98 years) were asked to fill in a standardized questionnaire containing the Violent Incident Form (VIF) concerning the episodes of violence experienced, the Headache Impact Test (HIT-6) regarding headaches, and the Pittsburgh Sleep Quality Inventory (PSQI) on sleep quality. Occupational stress was measured using the Effort/Reward Imbalance questionnaire (ERI). Physical and non-physical violence experienced in the previous year was reported by 7.5% and 17.5% of workers, respectively. In the univariate logistic regression models, the workers who experienced violence had an increased risk of headaches and sleep problems. After adjusting for sex, age, job type, and ERI, the relationship between physical violence and headaches remained significant (adjusted odds ratio aOR = 2.25; confidence interval CI95% = 1.11; 4.57). All forms of WV were significantly associated with poor sleep in a multivariate logistic regression model adjusted for sex, age, job type, and ERI (aOR = 2.35 CI95% = 1.44; 3.85). WV was also associated with the impact of headaches and with sleep quality. WV prevention may reduce the frequency of lasting psychoneurological symptoms, such as headaches and poor sleep quality, that interfere with the ability to work.

Ultra-High dose-per-pulse regimens (UHDP), necessary to trigger the "FLASH" effect, still pose serious challenges to dosimetry. Dosimetry plays a crucial role, both to significantly improve the accuracy of the radiobiological experiments necessary to fully understand the mechanisms underlying the effect and its dependencies on the beam parameters, and to be able to translate such effect into clinical practice. The standard ionization chamber in UHDP region is significantly affected by the effects of the electric field generated by the enormous density of charges produced by the dose pulse. This work describes the theory and the conceptual design of a gas chamber (the ALLS chamber) which overcomes the above-mentioned problems., Competing Interests: Declaration of Competing Interest F. Galante, G. Mariani, M. Pacitti and G. Felici are SIT employees; G. Felici is a SIT shareholder; A. Gasparini received a grant for a post doc position funded by SIT S.p.A. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

The purpose of this multi-centric work was to investigate the relationship between radiomic features extracted from pre-treatment computed tomography (CT), positron emission tomography (PET) imaging, and clinical outcomes for stereotactic body radiation therapy (SBRT) in early-stage non-small cell lung cancer (NSCLC). One-hundred and seventeen patients who received SBRT for early-stage NSCLC were retrospectively identified from seven Italian centers. The tumor was identified on pre-treatment free-breathing CT and PET images, from which we extracted 3004 quantitative radiomic features. The primary outcome was 24-month progression-free-survival (PFS) based on cancer recurrence (local/non-local) following SBRT. A harmonization technique was proposed for CT features considering lesion and contralateral healthy lung tissues using the LASSO algorithm as a feature selector. Models with harmonized CT features (B models) demonstrated better performances compared to the ones using only original CT features (C models). A linear support vector machine (SVM) with harmonized CT and PET features (A1 model) showed an area under the curve (AUC) of 0.77 (0.63-0.85) for predicting the primary outcome in an external validation cohort. The addition of clinical features did not enhance the model performance. This study provided the basis for validating our novel CT data harmonization strategy, involving delta radiomics. The harmonized radiomic models demonstrated the capability to properly predict patient prognosis.

Background: tumor recurrence after NSCLC surgical resection is the most common cause of treatment failure that sharply reduces the patient's life expectancy. The optimal treatment strategy for loco-regional recurrences developing after surgical resection in patients with non-small-cell lung cancer (NSCLC) is not established yet. This report aims to describe the pattern of relapse, PFS, and OS in patients treated with radio-chemotherapy and durvalumab for loco-regional relapse after surgery., Methods:  We conducted a multicenter, retrospective study including subjects who underwent surgical resection for NSCLC and were treated with Pacific protocol after loco-regional relapse., Results: Twenty-four patients met the inclusion criteria. At the time of diagnosis mean age was 65 years (range 47-78), the majority being male (58.3%). The 12-month progression-free survival rate was 68.7%, the 18-month progression-free survival rate was 45.8%, and the 24-month progression-free survival rate was 34.3%. There were three deaths: the 12-month survival rate was 91%, and the 18-month survival rate was 82.8%., Conclusions: In this article, we propose a treatment strategy that might prolong post recurrence survival in patients with good performance status experiencing loco-regional relapse after surgery., (© 2022. The Author(s).)

Aim: Recommendations for managing patients with nasopharyngeal carcinoma (NPC) in non-endemic areas are largely derived from studies conducted in endemic areas. We analysed the impact of treatment approaches on survival in non-endemic areas., Methods: In an international, multicentre, retrospective study, we analyse consecutive patients with NPC diagnosed between 2004 and 2017 in 36 hospitals from 11 countries. Treatment was categorised as non-intensive (NIT), including radiotherapy alone or concomitant chemoradiotherapy (cCRT), and intensive (IT) including cCRT preceded by and/or followed by chemotherapy (CT). The impact of IT on overall survival (OS) and disease-free survival (DFS) was adjusted for all the available potential confounders., Results: Overall, 1021 and 1113 patients were eligible for overall survival (OS) and disease-free survival (DFS) analyses, respectively; 501 and 554 with Epstein Barr-encoded RNA (EBER) status available. In the whole group, 5-year OS was 84% and DFS 65%. The use of NIT was associated with a risk of death or recurrence 1.37 times higher than patients receiving IT. Patients submitted to NIT and induction CT + concurrent concomitant chemo and three-dimensional Conformal Radiation Therapy (3DCRT) had a risk of death or recurrence 1.5 and 1.7 times higher than patients treated with induction CT + cCRT with intensity-modulated radiotherapy (IMRT), respectively. The IT had no impact on OS in neither patients with EBER+ nor in patients with EBER-; IT showed better DFS in EBER+ but not in patients with EBER-., Conclusions: In low-incidence areas, patients with NPC treated with induction CT followed by concurrent IMRT cCRT achieved the highest DFS rate. The benefit of IT on DFS was restricted to patients with EBER+, suggesting that additional therapy offers no advantages in EBER- cases., Competing Interests: Conflict of interest statement Bossi reports personal fees from Merck, Sanofi Regeneron, BMS, MSD, GSK, Astrazeneca, Sunpharma, Angelini and grants from GSK and Sunpharma, outside the submitted work. Buglione reports personal fees from Meck Serono, outside the submitted work. Cirauqui Cirauqui reports congress support from MSD, Merck, BMS and Roche, and personal fees from BMS and Roche, outside the submitted work. Ursino reports grants from Merck Serono, Nestlé, Kyowakirin and Astra Zeneca, outside the submitted work. D'angelo reports personal fees from Astra Zeneca, Nestlé and Merck Spa, outside the submitted work. Licitra reports personal fees and grants from Astra Zeneca, Bayer, BMS, Boehringer ingelheim, Debiopharm International SA, EISAI, Merck Serono MSD, Novartis, Roche; Personal fee from Bayer, SOBI, IPSEN, GSK, Doxa Pharma srl, Incyte Biosciences Italy srl, Amgen, Nanobiotics Sa; Grants from Celgene International, Exelixis inc, grants Hoffmann-La Roche ltd, IRX Therapeutics incMedpace inc, grants Pfizer, outside the submitted work. Mesia reports Consulting and advisory role for Merck, MSD, Roche, Asta Zeneca, BMS and speaker's Bureau for Merck, MSD, BMS, Roche. All the other authors have nothing to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The standard treatment of locally advanced rectal cancers (LARC) consists on neoadjuvant chemoradiotherapy followed by total mesorectal excision. Different data in literature showed a benefit on tumor downstaging and pathological complete response (pCR) rate using radiotherapy dose escalation, however there is shortage of studies regarding dose escalation using the innovative techniques for LARC (T3-4 or N1-2)., Aim: To analyze the role of neoadjuvant radiotherapy dose escalation for LARC using innovative radiotherapy techniques., Methods: In December 2020, we conducted a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane library. The limit period of research included articles published from January 2009 to December 2020. Screening by title and abstract was carried out to identify only studies using radiation doses equivalent dose 2 Gy fraction (EQD2) ≥ 54 Gy and Volumetric Modulated Arc Therapy (VMAT), intensity-modulated radiotherapy or image-guided radiotherapy (IGRT) techniques. The authors' searches generated a total of 2287 results and, according to PRISMA Group (2009) screening process, 21 publications fulfil selection criteria and were included for the review., Results: The main radiotherapy technique used consisted in VMAT and IGRT modality. The mainly dose prescription was 55 Gy to high risk volume and 45 Gy as prophylactic volume in 25 fractions given with simultaneous integrated boosts technique (42.85%). The mean pCR was 28.2% with no correlation between dose prescribed and response rates ( P value ≥ 0.5). The R0 margins and sphincter preservation rates were 98.88% and 76.03%, respectively. After a mean follow-up of 35 months local control was 92.29%. G3 or higher toxicity was 11.06% with no correlation between dose prescription and toxicities. Patients receiving EQD2 dose > 58.9 Gy and BED > 70.7 Gy had higher surgical complications rates compared to other group ( P value = 0.047)., Conclusion: Dose escalation neoadjuvant radiotherapy using innovative techniques is safe for LARC achieving higher rates of pCR. EQD2 doses > 58.9 Gy is associated with higher rate of surgical complications., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Abstract: Out of 38,282 passengers entering Italy at a major seaport, submitted to SARS-CoV-2 rapid antigenic test, 272 (0.6%) resulted positive and 212 (93.4%) were confirmed positive by qRT-PCR, leaving a 0.6% of false positive. Those resident in the area under control of the same Local Health Authority of the seaport were immediately submitted to isolation and investigated for contact tracing, the others notified to their Local Health Authority which did the same in the following day. This procedure was made possible by a full-time dedication of the local healthcare workers who managed all the passengers disembarking around the clock along the months of the emergency.

Purpose: Head and neck cancer (HNC) patients are likely to develop severe side effects, which may persist long after the end of treatment and may be responsible for decrease patient's quality of life. The M.D. Anderson Symptom Inventory- Head and Neck Module (MDASI-HN) is a questionnaire developed to detect patient's symptom burden. To conduct an Italian language psychometric validation of MDASI-HN among Italian HNC patients on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Head and Neck Working Group., Method and Materials: To assess construct validity, it was performed a confirmatory factor analysis (CFA) with both a five-factor solution and three-factor solution, which were compared by a chi-square difference test. The concurrent validity was evaluated by the correlation with EORTC QLQ-C30 and HN35, and it was also assessed known-group validity. The internal consistency was tested using Cronbach's alpha coefficient., Results: In total 166 patients (71.7% male) were included in the study, most of patients (56.2%) had an oropharynx cancer and received definitive chemoradiotherapy (51.2%). The chi-square difference test was significant and indicated that the five-factor solution fits the data better than the other one. Regarding CFA, all items had a significant saturation with their respective factors; besides, significant and strong correlations were found among factors. Most of the correlations between MDASI-HN factors and EORTC QLQ-C30 and HN35 were significant. It was found a good internal consistency., Conclusion: The MDASI-HN is a valid, short, and easy patient-reported outcome questionnaire which would be useful and efficient in clinical setting., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

COVID-19 pandemic is a dramatic health, social and economic global challenge. There is urgent need to maximize testing capacity. Rapid Antigen Tests (RAT) represent good candidates for point-of-care and mass surveillance testing to rapidly identify SARS-CoV-2-infected people, counterbalancing lower sensitivity vs. gold standard molecular tests with fast results and possible recurrent testing. We describe the results obtained with the testing algorithm implemented at points of entry (airports and ports) in the Lazio Region (Italy), using the STANDARD F COVID-19 Antigen Fluorescence ImmunoAssay (FIA), followed by molecular confirmation of FIA-positive samples. From mid-August to mid-October 2020, 73,643 RAT were reported to the Regional Surveillance Information System for travelers at points of entry in Lazio Region. Of these, 1176 (1.6%) were FIA-positive, and the proportion of RT-PCR-confirmed samples was 40.5%. Our data show that the probability of confirmation was directly dependent from the semi-quantitative FIA results. In addition, the molecularly confirmed samples were those with high levels of virus and that were actually harboring infectious virus. These results support public health strategies based on early mass screening campaigns by RAT in settings where molecular testing is not feasible or easily accessible, such as points of entry. This approach would contribute to promptly controlling viral spread through travel, which is now of particular concern due to the spread of SARS-CoV-2 variants.

The Asian tiger mosquito Aedes albopictus (Skuse 1894) is assuming an ever-increasing importance as invasive species in Europe and consequently as human health and nuisance concern. In Central Italy, the species has been recently involved in a chikungunya outbreak. A 3 yr Ae. albopictus monitoring was carried out in 21 municipalities of the Lazio region (Central Italy), belonging to three provinces. Samplings were performed on a weekly basis using ovitraps, in order to investigate climatic and spatial variables driving egg abundance and Ae. albopictus period of activity. A temperature of 10.4°C was indicated as lower threshold for the onset of egg-laying activity, together with a photoperiod of 13:11 (L:D) h. The whole oviposition activity lasted 8 mo (May-December), with 95% of eggs laid between early June and mid-November and a peak at the end of August. Egg abundance was positively influenced by accumulated temperature (AT) of the 4 wk preceding sampling and negatively by precipitation during the week before. Egg-laying activity dropped with decreasing AT, increasing rainfall, and with a photoperiod below 10:14 (L:D) h. Our results pinpointed the importance of fine-scaled spatial features on egg abundance. Some of these fine-scaled characteristics have been highlighted, such as the presence of vegetation and human footprint index. Our model estimated an almost doubled maximum number of laid eggs for the maximum value of human footprint. Compelling evidence of the relevance of fine-scaled characteristics was reported, describing cases where human-made breeding sites driven the abundance of Ae. albopictus., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America.)

Purpose: To develop a videofluoroscopy-based predictive model of radiation-induced dysphagia (RID) by incorporating DVH parameters of swallowing organs at risk (SWOARs) in a machine learning analysis., Methods: Videofluoroscopy (VF) was performed to assess the penetration-aspiration score (P/A) at baseline and at 6 and 12 months after RT. An RID predictive model was developed using dose to nine SWOARs and P/A-VF data at 6 and 12 months after treatment. A total of 72 dosimetric features for each patient were extracted from DVH and analyzed with linear support vector machine classification (SVC), logistic regression classification (LRC), and random forest classification (RFC)., Results: 38 patients were evaluable. The relevance of SWOARs DVH features emerged both at 6 months (AUC 0.82 with SVC; 0.80 with LRC; and 0.83 with RFC) and at 12 months (AUC 0.85 with SVC; 0.82 with LRC; and 0.94 with RFC). The SWOARs and the corresponding features with the highest relevance at 6 months resulted as the base of tongue (V65 and D mean ), the superior (D mean ) and medium constrictor muscle (V45, V55; V65; D mp ; D mean ; D max and D min ), and the parotid glands (D mean and D mp ). On the contrary, the features with the highest relevance at 12 months were the medium (V55; D min and D mean ) and inferior constrictor muscles (V55, V65 D min and D max ), the glottis (V55 and D max ), the cricopharyngeal muscle (D max ), and the cervical esophagus (D max )., Conclusion: We trained and cross-validated an RID predictive model with high discriminative ability at both 6 and 12 months after RT. We expect to improve the predictive power of this model by enlarging the number of training datasets.

Objective: Over the years, evidence-based data and technical improvements have consolidated the central role of radiation therapy (RT) in head and neck cancer (HNC) treatment, even in the elderly. This survey aimed to describe the management of the elderly HNC patients among Italian Radiation Oncology Departments (RODs) and provide possible suggestions for improvement., Methods: An online survey based on 43 questions was sent to RODs via email. For each RODs, a radiation oncologist with expertise in HNC was invited to answer questions addressing his/her demographic data, ROD multidisciplinary unit (MU) organisation and ROD management policy in elderly HNC patients., Results: In total, 68 RODs answered, representing centres located in 16 Italian regions. MU was considered the core of HNC patient management in almost all the entire country. However, in many RODs, there was minimal access to a routinely comprehensive geriatric assessment at diagnosis. Most treatments were reported by respondents as curative (89% on average) and the preferred treatment technique was intensity modulated radiation therapy (IMRT). A considerable variation between RODs was found for RT target volumes. There was a relation between the specialist's years of experience and type of concomitant systemic therapy prescribed., Conclusions: Substantial differences in elderly HNC management have been found, especially concerning patient clinical evaluation and target volume delineation. This survey shows the necessity to design a prospective national trial to provide a uniform treatment strategy and define an effective patient-centred approach., (Copyright © 2020 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background/aim: In 2020, because of coronavirus pandemic, medical activities changed. The aim of this report is to compare the volumes of Pisa radiotherapy activities from March 9 th to May 31 st , 2020, with the same period in 2019., Patients and Methods: We analyzed the activity of our Unit to evaluate how logistics changes, related to the COVID-19 epidemic, impacted on volumes of radiotherapy (RT) activity and on the number of cases of COVID-19 infections observed in healthcare professionals and patients., Results: The total number of first-time visits between March-May 2020 was reduced by 18%, probably due to delays in diagnosis and histological tests as well as the temporary closure of the operating rooms. None of the healthcare professionals and only two patients contracted the infection., Conclusion: We were able to treat all patients referred to our hospital and we were able to reduce risk of infection for both our patients and healthcare staff, guaranteeing continuum of care for our oncological patients., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Management of patients with head and neck cancers (HNCs) is challenging for the Radiation Oncologist, especially in the COVID-19 era. The Italian Society of Radiotherapy and Clinical Oncology (AIRO) identified the need of practice recommendations on logistic issues, treatment delivery and healthcare personnel's protection in a time of limited resources. A panel of 15 national experts on HNCs completed a modified Delphi process. A five-point Likert scale was used; the chosen cut-offs for strong agreement and agreement were 75% and 66%, respectively. Items were organized into two sections: (1) general recommendations (10 items) and (2) special recommendations (45 items), detailing a set of procedures to be applied to all specific phases of the Radiation Oncology workflow. The distribution of facilities across the country was as follows: 47% Northern, 33% Central and 20% Southern regions. There was agreement or strong agreement across the majority (93%) of proposed items including treatment strategies, use of personal protection devices, set-up modifications and follow-up re-scheduling. Guaranteeing treatment delivery for HNC patients is well-recognized in Radiation Oncology. Our recommendations provide a flexible tool for management both in the pandemic and post-pandemic phase of the COVID-19 outbreak.

Platelets contain abundant growth factors and cytokines that have a positive influence on the migration and proliferation of different cell types by modulating its physiopathological processes. As it is known that human umbilical cord blood platelet lysate (UCB-PL) contains a supraphysiological concentration of growth factors, in the present study, we investigated its effectiveness in wound-healing processes. Human UCB-PL was obtained by the freeze/thaw of platelet concentrate (1.1 × 10 9 platelets/L), and its effect was evaluated on human or mouse endothelial cells, monocytes, fibroblasts, and keratinocytes in different concentrations. Human UCB-PL was observed to have high levels of pro-angiogenic growth factor than peripheral blood platelet-rich plasma. Among the cell lines, different concentrations of human UCB-PL were necessary to influence their viability and proliferation. For L929 cells, 5% of total volume was necessary, while for human umbilical vein endothelial cell, it was 10%. Cell migration on monocytes was increased with respect to the positive control, and scratch closure on keratinocytes was increased with respect to serum-free medium with only 10% of human UCB-PL. We concluded that the human UCB-PL may be useful to produce a large amount of standard platelet concentrates sufficient for several clinical-scale expansions avoiding inter-individual variability, which can also be used as a functional tool for clinical regenerative application for wound healing., (© 2019 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Distant Metastases from Head and Neck Squamous cell carcinomas are uncommon (9-11%) and they are usually found in the lung and less frequently in the liver, kidney and adrenals. Central nervous system (CNS) metastases are extremely rare (2-8%), and they are described mainly in patients who already have extracranial metastases. So there's scarcity of data about their optimal management ., Methods and Results: A patient presented CNS metastases after having been successfully treated with induction chemotherapy and definitive radiotherapy for a pyriform sinus carcinoma. The patient's work up, treatment and outcome are described., Conclusions: CNS metastases from Head and Neck carcinomas are exceptionally rare. Nevertheless, clinicians should be alert of neurological symptoms in these patients, in order to set up a timely assessment and treatment. Secondarily, given the rarity of this condition, additional research on this topic is warranted in order to improve therapeutic strategies and outcomes of such patients.