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The treatment of deep-seated tumours with electrons of very high energies (VHEE, 70–150 MeV) has already been explored in the past, suggesting that a dosimetric coverage comparable with state-of-the-art proton (PT) or photon radiotherapy (RT) could be achieved with a large (> 10) number of fields and high electron energy. The technical and economical challenges posed by the deployment of such beams in treatment centres, together with the expected small therapeutic gain, prevented the development of such technique. This scenario could radically change in the light of recent developments that occurred in the compact, high-gradient, electron acceleration technology and, additionally, of the experimental evidence of the sparing of organs at risk achieved in ultra-high dose rate irradiation, also referred to as FLASH. Electrons with the energy required to treat intracranial lesions could be provided, at dose rates compatible with what is needed to trigger the FLASH effect, by accelerators that are a few metres long, and the organ sparing could be exploited to significantly simplify the irradiation geometry, decreasing the number of fields needed to treat a patient. In this paper, the case of two patients affected by a chordoma and a meningioma, respectively, treated with protons in Trento (IT) is presented. The proton plans have been compared with VHEE plans and X-ray intensity-modulated radiotherapy (IMRT) plans. The VHEE plans were first evaluated in terms of physical dose distribution and then assuming that the FLASH regimen can be achieved. VHEE beams demonstrated their potential in obtaining plans that have comparable tumour coverage and organs at risk sparing when benchmarked against current state-of-the-art IMRT and PT. These results were obtained with a number of explored fields that was in the range between 3 and 7, consistent with what is routinely performed in IMRT and PT conventional irradiations. The FLASH regimen, in all cases, showed its potential in reducing damage to the organs placed nearby the target volume, allowing, particularly in the chordoma case where the irradiation geometry is more challenging, a better tumour coverage with respect to the conventional treatments.

Abstract The original article [1] contained an error whereby Fig. 4 displayed incorrect magnification scales.

Abstract   Objectives The optimal treatment for elderly patients (age > 70 years) with glioblastoma remains controversial. We conducted a prospective trial in 32 consecutive elderly patients with glioblastoma who underwent surgery followed by radiotherapy (RT) plus concomitant and adjuvant temozolomide. Patients and Methods 32 patients 70 years of age or older with a newly diagnosed glioblastoma and a Karnofsky performance status (KPS) ≥ 70 were treated with RT (daily fractions of 2 Gy for a total of 60 Gy) plus temozolomide at the dose of 75 mg/m2 per day followed by six cycles of adjuvant temozolomide (150–200 mg/m2 for 5 days during each 28-day cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS) and toxicity. Results The median OS was 10.6 months and the median PFS was 7 months. The 6-month and 12-month survival rates were 91% and 37%, respectively. The 6-month and 12-month PFS rates were 56% and 16%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.01). Adverse effects were mainly represented by neurotoxicity (40%), which resolved in most cases with the use of steroids, and Grade 3–4 hematologic toxicity in 28% of patients. Chemotherapy was stopped in 2 patients, delayed in 9 patients and reduced in 4 patients. Conclusions Standard RT plus concomitant and adjuvant temozolomide is a feasible treatment for elderly patients with newly diagnosed glioblastoma who present with good prognostic factors. [ABSTRACT FROM AUTHOR]

Introduction and Aim: Locally advanced head and neck squamous cell carcinoma (LA-Hnscc) is a true therapeutical challenge in the modern era and the scientific community is trying to face this challenge with new therapeutical strategies, including combinations of monoclonal antibodies and radiation therapy. The aim of this study is to evaluate clinical outcomes in LA-Hnscc patients unfit to receive platinum-based chemotherapy, treated with concurrent simultaneous integrated boost-intensity modulated radiotherapy (Sib-Imrt) + cetuximab (Ctx) in daily clinical practice., Methods: LA-Hnscc patients not included in other prospective studies treated in 4 Italian radiotherapy units (2 Messina, 1 Rome, and 1 Lecce) using Sib-Imrt and Ctx were included in this study. Acute and late toxicities and overall survival (OS) have been evaluated., Results: Data regarding 27 patients with squamous tumour were collected and reviewed. The primary tumour sites were oropharynx in 14 patients (51.9%), oral cavity in 7 (25.9%), larynx in 3 (11%) and other sites in 3(11%). There were 20 (74%) patients had stage IV (16 IVa and 4 IVb). Complete remission was observed in 18 patients (66.7%), a partial remission in 4 (14.8%) whilst 4 had a progression disease (14.8%). After 3 year of follow-up 7/27 patients were deaths. The OS was 95.5%, 62.5% and 52.9% respectively at 1,2 and 3 years. Acute toxicities were observed in all treated patients (mucositis, dermatitis and dysphagia) while 66.7% of patients developed late toxicities. All observed toxicities were grade 1 to 3 and just 1 patient developed a G4 toxicity., Conclusion: The concurrent bio-radiotherapy of Sib-Imrt and cetuximab is feasible in real-life daily clinical practice for LA-Hnscc patients unfit for platinum-based chemoradiotherapy.

This study intends to address the impact of weekly hypofractionated radiation therapy with curative intent for cutaneous squamous cell carcinoma of the head and neck region in the elderly population., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: To evaluate the role of definitive weekly hypofractionated radiotherapy (RT) for the treatment of surgery-ineligible elderly patients with cutaneous squamous cell carcinoma of the head and neck region (cHNSCC)., Methods: Eligible elderly patients (aged ≥75 years) with cHNSCC were included. Patients received definitive weekly hypofractionated RT, using megavoltage electrons, to a total dose of 56-64 Gy (8 Gy per fraction). Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), pain response, tolerability, and safety., Results: A total of 19 patients with 27 lesions were included and treated with definitive weekly hypofractionated RT. All patients received the prescribed total dose. ORR was 92.6%, including 70.4% of lesions with a CR and 22.2% with a PR. Median DOR was 12 months. No severe toxicity occurred., Conclusions: Our study confirmed the satisfying efficacy and acceptable toxicity of definitive weekly hypofractionated RT for cHNSCC in elderly patients. Our results establish weekly hypofractionated scheduleas a promising treatment option for elderly patients with cHNSCC., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

The present white paper, referring to the 4th Assisi Think Tank Meeting on breast cancer, reviews state-of-the-art data, on-going studies and research proposals. <70% agreement in an online questionnaire identified the following clinical challenges: 1: Nodal RT in patients who have a) 1-2 positive sentinel nodes without ALND (axillary lymph node dissection); b) cN1 disease transformed into ypN0 by primary systemic therapy and c) 1-3 positive nodes after mastectomy and ALND. 2. The optimal combination of RT and immunotherapy (IT), patient selection, IT-RT timing, and RT optimal dose, fractionation and target volume. Most experts agreed that RT- IT combination does not enhance toxicity. 3: Re-irradiation for local relapse converged on the use of partial breast irradiation after second breast conserving surgery. Hyperthermia aroused support but is not widely available. Further studies are required to finetune best practice, especially given the increasing use of re-irradiation., Competing Interests: Declaration of Competing Interest On behalf of my co-authors (O. Kaidar-Person, L. Boersma, M. C. Leonardi, B. Offersen, P. Franco, M. Arenas, C. Bourgier, R. Pfeffer, V Kouloulias, Y. Bölükbaşı, I. Meattini, C. Coles, A. Montero Luis, V. Masiello, I. Palumbo, A. Morganti, E. Perrucci, V. Tombolini, M. Krengli, F. Marazzi, L. Trigo, S. Borghesi, A. Ciabattoni, I. Ratoša, V. Valentini, P. Poortmans) I declare there is no conflict of interest in this study and that no funding was received from any source., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Oligometastatic disease has been described as an intermediate clinical state between localized cancer and systemically metastasized disease. Recent clinical studies have shown prolonged survival when aggressive locoregional approaches are added to systemic therapies in patients with oligometastases. The aim of this review is to outline the newest options to treat oligometastatic colorectal cancer (CRC), also considering its molecular patterns. We present an overview of the available local treatment strategies, including surgical procedures, stereotactic body radiation therapy (SBRT), thermal ablation, as well as trans-arterial chemoembolization (TACE) and selective internal radiotherapy (SIRT). Moreover, since imaging methods provide crucial information for the early diagnosis and management of oligometastatic CRC, we discuss the role of modern radiologic techniques in selecting patients that are amenable to potentially curative locoregional treatments., Competing Interests: Declaration of Competing Interest The authors disclose no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background Recent consensus statements and clinical trials have assessed the value of MRI-guided focused ultrasound surgery for pain palliation of bone metastases; however, a comparison with external beam radiation therapy (EBRT) has not been performed. Purpose To compare safety and effectiveness data of MRI-guided focused ultrasound and EBRT in the treatment of bone metastases. Materials and Methods Participants with painful bone metastases, excluding skull and vertebral bodies, were enrolled in a prospective open-label nonrandomized phase II study between January 2017 and May 2019 and underwent either MRI-guided focused ultrasound or EBRT. The primary end point was the overall response rate at 1-month following treatment, assessed via the numeric rating scale (NRS) for pain (0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable"). Secondary end points were improvements at 12-month follow-up in NRS and quality of life (QoL) measures, including the Brief Pain Inventory (BPI), QoL-Questionnaire Cancer-15 Palliative Care (QLQ-C15-PAL), and QoL-Questionnaire Bone Metastases-22 (QLQ-BM22) and analysis of adverse events. Statistical analyses, including linear regression, χ 2 test, and Student t test followed the per-protocol principle. Results Among 198 participants, 100 underwent MRI-guided focused ultrasound (mean age, 63 years ± 13 [SD]; 51 women), and 98 underwent EBRT (mean age, 65 years ± 14; 52 women). The overall response rates at 1-month follow-up were 91% (91 of 100) and 67% (66 of 98), respectively, in the focused ultrasound and EBRT arms ( P < .001), and complete response rates were 43% (43 of 100) and 16% (16 of 98) ( P < .001). The mean baseline NRS score was 7.0 ± 2.1 for focused ultrasound and 6.6 ± 2.4 for EBRT ( P = .16); at 1-month follow-up, they were reduced to 3.2 ± 0.3 and 5.1 ± 0.3 ( P < .001), respectively. QLQ-C15-PAL for physical function ( P = .002), appetite ( P < .001), nausea and vomiting ( P < .001), dyspnea ( P < .001), and QoL ( P < .001) scores were lower in the focused ultrasound group. The overall adverse event rates were 15% (15 of 100) after focused ultrasound and 24% (24 of 98) after EBRT. Conclusion MRI-guided focused ultrasound surgery and external beam radiation therapy showed similar improvements in pain palliation and quality of life, with low adverse event rates. © RSNA, 2023 Supplemental material is available for this article . See also the editorial by Kelekis in this issue.

Background/aim: To evaluate the outcome and toxicities in patients with locally advanced cervical cancer (LACC) treated with radiochemotherapy and intracavitary brachytherapy., Patients and Methods: This study included 67 patients with LACC treated between 2010 and 2018. The most represented stage was FIGO IIB. The patients were treated with external beam radiotherapy (EBRT) to the pelvis and boost to the cervix and parametrials. Concomitant chemotherapy (CHT) with cisplatin (CDDP) 40 mg/mq was planned. Subsequently, the patients underwent CT-based endouterine brachytherapy (BT). The response was evaluated at 3 months with PET-CT and/or pelvic magnetic resonance imaging (MRI). Since then, the patients have been followed with clinical instrumental controls every 4 months for the first 2 years and every 6 months for the following 3 years. Local response was assessed with pelvic MRI and/or PET-CT scan at the end of intracavitary BT) according to RECIST 1.1 criteria., Results: The median duration of treatment was 55 days (range=40-73 days). The prescription dose to the planning target volume (PTV) was delivered in 25 to 30 (median 28) daily fractions. The EBRT median dose to the pelvis and gross tumor volume were 50.4 Gy (range=45-56.25) and 61.6 Gy (range=45-70.4), respectively. The 1-year, 2-year, 3-year, and 5-year overall survival rates were 92.44%, 80.81%, 78.84%, and 76.45% respectively. The actuarial 1-year, 2-year, 3-year, and 5-year disease-free survival rates were 89.5%, 83.6%, 81%, and 78.2% respectively., Conclusion: This study analyzed acute and chronic toxicity, survival, and local control in cervical cancer patients treated with IMRT followed by CT-planned high dose rate-brachytherapy. Patients demonstrated satisfactory outcomes and incidence of acute and late toxicities., Competing Interests: The Authors have no conflicts of interest to declare in relation to this study., (Copyright 2023, International Institute of Anticancer Research.)

Objective: To investigate the predictive role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the assessment of response to total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC)., Methods: In this single-center retrospective study, patients with LARC who underwent staging MRI and TNT were enrolled. MRI-based staging, tumor volume, and DWI-ADC values were analyzed. Patients were classified as complete responders (pCR) and non-complete responders (non-pCR), according to post-surgical outcome. Pre-treatment ADC values were compared to pathological outcome, post-treatment downstaging, and reduction of tumor volume. The diagnostic accuracy of DWI-ADC in differentiating between pCR and non-pCR groups was calculated with receiver operating characteristic (ROC) analysis., Results: A total of 36 patients were evaluated (pCR, n = 20; non-pCR, n = 16). Pre-treatment ADC values were significantly different between the two groups (p = 0.034), while no association was found between pre-TNT tumor volume and pathological response. ADC values showed significant correlations with loco-regional downstaging after therapy (r = -0.537, p = 0.022), and with the reduction of tumor volume (r = -0.480, p = 0.044). ADC values were able to differentiate pCR from non-pCR patients with a sensitivity of 75% and specificity of 70%., Conclusions: ADC values on pre-treatment MRI were strongly associated with the outcome in patients with LARC, both in terms of pathological response and in loco-regional downstaging after TNT, suggesting the use of DW-MRI as a potential predictive tool of response to therapy., Key Points: • ADC values of pre-TNT MRI examinations of patients with LARC were significantly associated with a pathological complete response (pCR) and with post-treatment regression of TNM staging. • An ADC value of 1.042 ×10 -3 mm 2 /s was found to be the optimal cutoff value for discriminating between pCR and non-pCR patients, with a sensitivity of 75% and specificity of 70%. • DW-MRI proved to have a potential predictive role in the assessment of response to therapy in patients with LARC, throughout the analysis of ADC map values., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: To develop a predictive index model, integrating both clinical and high-resolution anoscopy (HRA) features to further personalize the decision making process in anal canal carcinoma in COVID19 era., Methods and Materials: We assess HRA parameters after definitive chemoradiotherapy in patients with anal canal malignant lesions., Results: HRA features could be important to assess the effect of CRT and a risk stratification system should be introduced in clinical practice to better allocate therapeutic interventions., Conclusion: To our knowledge this is the first proposal for HRA findings in anal canal cancer after definitive CRT. We believe that a risk score can be useful to estimate the risk of treatment failure (in term of persistence disease and/or recurrence) and its clinical relevance should not to be underestimated., 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. Published by Elsevier Inc.)

Background/aim: Intensity modulated radiotherapy (IMRT) is the standard of care for oropharyngeal cancer management. IMRT can be applied using either the sequential boost or simultaneous integrated boost (SIB-IMRT) techniques. The purpose of the study was to assess the efficacy of sequential boost technique or SIB-IMRT) in locally advanced p16-negative oropharyngeal squamous cell carcinoma., Patients and Methods: Baseline characteristics and treatment outcomes were compared between patients with locally advanced p16-negative oropharyngeal squamous cell carcinoma, who received sequential RT (n=40) and those who received SIB-IMRT (n=38)., Results: In total, 78 patients with locally advanced p16-negative oropharyngeal cancer were identified. Mean age was 63 years. Patients treated with SIB-IMRT had better 5-year overall survival (OS; 78.7% vs. 52.5%, p=0.023) and 5-year disease-free survival (DFS; 87.4% versus 63.5%, p=0.046) compared to sequential group. There was no difference of total severe acute and late toxicity (grade ≥3) incidences. Patients treated with SIB technique had higher rates of mild to moderate late xerostomia (73.7% vs. 52.5%), dysgeusia (63.2% vs. 20%), and dysphagia (44.7% vs. 17.5%)., Conclusion: Compared to sequential technique, SIB-IMRT improved both OS and DFS, but higher mild to moderate late toxicity was observed. As long as RT dose constraints to surrounding normal organs can be maintained, SIB technique should be the technique of choice for locally advanced p16-negative oropharyngeal squamous cell carcinoma treatment., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To report long-term survival results after trimodal approach for locally advanced rectal cancer (LARC) in the Covid-19 era. We herein illustrate a clinical application of Covid-death mean-imputation (CoDMI) algorithm in LARC patients with Covid-19 infection., Patients and Methods: We analyzed 94 patients treated for primary LARC. Overall survival was calculated in months from diagnosis to first event (last follow-up/death). Because Covid-19 death events potentially bias survival estimation, to eliminate skewed data due to Covid-19 death events, the observed lifetime of Covid-19 cases was replaced by its corresponding expected lifetime in absence of the Covid-19 event using the CoDMI algorithm. Patients who died of Covid-19 (DoC) are mean-imputed by the Kaplan-Meier estimator. Under this approach, the observed lifetime of each DoC patient is considered as an "incomplete data" and is extended by an additional expected lifetime computed using the classical Kaplan-Meier model., Results: Sixteen patients were dead of disease (DoD), 1 patient was DoC and 77 cases were censored (Cen). The DoC patient died of Covid-19 52 months after diagnosis. The CoDMI algorithm computed the expected future lifetime provided by the Kaplan-Meier estimator applied to the no-DoC observations as well as to the DoC data itself. Given the DoC event at 52 months, the CoDMI algorithm estimated that this patient would have died after 79.5 months of follow-up., Conclusion: The CoDMI algorithm leads to "unbiased" probability of overall survival in LARC patients with Covid-19 infection, compared to that provided by a naïve application of Kaplan-Meier approach. This allows for a proper interpretation/use of Covid-19 events in survival analysis. A user-friendly version of CoDMI is freely available at https://github.com/alef-innovation/codmi., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Only a minority of patients with platinum refractory head and neck squamous cell carcinoma (PR/HNSCC) gain some lasting benefit from immunotherapy., Methods: The combined role of the comprehensive genomic (through the FoundationOne Cdx test) and immune profiles of 10 PR/HNSCC patients treated with the anti-PD-1 nivolumab was evaluated. The immune profiles were studied both at baseline and at the second cycle of immunotherapy, weighing 20 circulating cytokines/chemokines, adhesion molecules, and 14 soluble immune checkpoints dosed through a multiplex assay. A connectivity map was obtained by calculating the Spearman correlation between the expression profiles of circulating molecules., Results: Early progression occurred in five patients, each of them showing TP53 alteration and three of them showing a mutation/loss/amplification of genes involved in the cyclin-dependent kinase pathway. In addition, ERB2 amplification (1 patient), BRCA1 mutation (1 patient), and NOTCH1 genes alteration (3 patients) occurred. Five patients achieved either stable disease or partial response. Four of them carried mutations in PI3K/AKT/PTEN pathways. In the only two patients, with a long response to immunotherapy, the tumor mutational burden (TMB) was high. Moreover, a distinct signature, in terms of network connectivity of the circulating soluble molecules, characterizing responder and non-responder patients, was evidenced. Moreover, a strong negative and statistically significant ( p -value ≤ 0.05) correlation with alive status was evidenced for sE-selectin at T1., Conclusions: Our results highlighted the complexity and heterogeneity of HNSCCs, even though it was in a small cohort. Molecular and immune approaches, combined in a single profile, could represent a promising strategy, in the context of precision immunotherapy.

Purpose: A single-institution prospective pilot study was conducted to the assess correlation between salivary amylase and xerostomia in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiotherapy (IMRT)., Methods and Materials: Serum saliva amylase, clinician-reported xerostomia (using Common Terminology Criteria for Adverse Events), and patient-reported xerostomia (using 8-item self-reported xerostomia-specific questionnaire) were prospectively collected at baseline, during treatment and thereafter. Correlations between variables were assessed by correlation matrices., Results: Twelve patients with locally advanced HNSCC formed the cohort. Eighty-three percent were male, 75% were smokers, 100% had clinical positive lymph nodes at diagnosis, and 42% received induction chemotherapy. All patients received IMRT with concurrent cisplatin-based chemotherapy. No grade ≥4 xerostomia was observed. Severe (G3) acute and late xerostomia occurred in five cases (41.7%) and two cases (16.7%), respectively. Patient-reported xerostomia scores were highly correlated with the clinician-reported scores (ρ = 0.73). A significant correlation was recorded between the concentration of amylase and the acute (ρ = -0.70) and late (ρ = -0.80) xerostomia., Conclusion: Preliminary results are encouraging. Prospective clinical trials are needed to define the value of salivary amylase in the management of HNSCC tumors.

We report on the third Assisi Think Tank Meeting (ATTM) on breast cancer, a brainstorming project which involved European radiation and clinical oncologists who were dedicated to breast cancer research and treatment. Held on February 2020, the ATTM aimed at identifying key clinical questions in current clinical practice and "grey" areas requiring research to improve management and outcomes. Before the meeting, three key topics were selected: 1) managing patients with frailty due to either age and/or multi-morbidity; 2) stereotactic radiation therapy and systemic therapy in the management of oligometastatic disease; 3) contralateral breast tumour prevention in BCRA-mutated patients. Clinical practice in these areas was investigated by means of an online questionnaire. In the lapse period between the survey and the meeting, the working groups reviewed data, on-going studies and the clinical challenges which were then discussed in-depth and subjected to intense brainstorming during the meeting; research protocols were also proposed. Methodology, outcome of discussions, conclusions and study proposals are summarized in the present paper. In conclusion, this report presents an in-depth analysis of the state of the art, grey areas and controversies in breast cancer radiation therapy and discusses how to confront them in the absence of evidence-based data to guide clinical decision-making., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: This is the case report of a synchronous anal canal cancer and cervical cancer in a patient who underwent definitive chemoradiotherapy (CRT) and radical surgery for anal canal and cervical carcinoma, respectively., Case Report: A 55-year-old woman was diagnosed with cT4a cN1 Mx anal canal squamous cell carcinoma and stage IA2 cervical squamous cell carcinoma, based on biopsy and imaging. Definitive CRT consisted of radiotherapy (total dose of 59.4 Gy) and concomitant mitomycin (10 mg/m 2 ) and 5-fluorouracil (750 mg/m 2 /5 daily continuous infusion) during the first and last week of radiation. The patient exhibited a complete clinical and radiological response. A radical hysterectomy with pelvic lymphadenectomy was then performed. At the last follow-up (30 months), the patient is still disease-free without any treatment-associated complications., Conclusion: There is limited information in the literature regarding treatment strategy and outcome of patients with synchronous anal canal and cervical cancer. A two-step treatment, including CRT and radical hysterectomy, is likely to be accepted as valid option., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: To evaluate the diagnostic performance of a Machine Learning (ML) algorithm based on Texture Analysis (TA) parameters in the prediction of Pathological Complete Response (pCR) to Neoadjuvant Chemoradiotherapy (nChRT) in Locally Advanced Rectal Cancer (LARC) patients. Methods: LARC patients were prospectively enrolled to undergo pre- and post-nChRT 3T MRI for initial loco-regional staging. TA was performed on axial T2-Weighted Images (T2-WI) to extract specific parameters, including skewness, kurtosis, entropy, and mean of positive pixels. For the assessment of TA parameter diagnostic performance, all patients underwent complete surgical resection, which served as a reference standard. ROC curve analysis was carried out to determine the discriminatory accuracy of each quantitative TA parameter to predict pCR. A ML-based decisional tree was implemented combining all TA parameters in order to improve diagnostic accuracy. Results: Forty patients were considered for final study population. Entropy, kurtosis and MPP showed statistically significant differences before and after nChRT in patients with pCR; in particular, when patients with Pathological Partial Response (pPR) and/or Pathological Non-Response (pNR) were considered, entropy and skewness showed significant differences before and after nChRT (all p < 0.05). In terms of absolute value changes, pre- and post-nChRT entropy, and kurtosis showed significant differences (0.31 ± 0.35, in pCR, −0.02 ± 1.28 in pPR/pNR, (p = 0.04); 1.87 ± 2.19, in pCR, −0.06 ± 3.78 in pPR/pNR (p = 0.0005); 107.91 ± 274.40, in pCR, −28.33 ± 202.91 in pPR/pNR, (p = 0.004), respectively). According to ROC curve analysis, pre-treatment kurtosis with an optimal cut-off value of ≤3.29 was defined as the best discriminative parameter, resulting in a sensitivity and specificity in predicting pCR of 81.5% and 61.5%, respectively. Conclusions: TA parameters extracted from T2-WI MRI images could play a key role as imaging biomarkers in the prediction of response to nChRT in LARC patients. ML algorithms can be used to efficiently combine all TA parameters in order to improve diagnostic accuracy.

Introduction: The optimal definitive radiotherapy (RT) scheme in cutaneous squamous cell carcinoma (cSCC) remains controversial, especially in elderly patients., Methods: Data of elderly patients with cSCC lesion(s) treated with weekly hypofractionated RT (8 Gy per week per 7-8 weeks) were analyzed., Results: Eighteen patients (median age 89 years) with 23 cSCC lesions have been identified including nine males (50%) and nine females (50%). The most common tumor localization was the head and neck region (n = 21; 91.3%), and the majority of lesions (n = 15; 65.2%) was stage ≥ III. At diagnosis, pain and bleeding were ascribed in 13 (56.5%) and eight (34.8%) cSCC, respectively. Compliance with weekly hypofractionated RT was excellent. The overall response rate at 12 weeks after treatment was 95.7%. Bleeding and pain relief were achieved in all cases. Severe toxicity was not recorded. The 1-year overall survival was 66.0%. The 1-year progression-free survival was 58.7%., Conclusions: Weekly hypofractionated RT provides a safe, efficient, and cost-effective treatment in elderly cSCC patients with minimal side effects., (© 2021 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Background/aim: A single-institution prospective study was conducted to evaluate hearing loss rate after intensity modulated radiotherapy with concomitant cisplatin-based chemotherapy (CRT) for locally advanced head and neck cancer and identify cochlear dosimetric parameters associated with hearing loss risk., Patients and Methods: Hearing assessment, patients' characteristics, tumor-related variables, and cochlear quantitative dosimetric factors for adults with locally advanced head and neck cancer treated with CRT were prospectively collected. Each patient repeated audiometry at baseline (pre-CRT), 1 month after CRT, and then every 3 to 6 months. For each cochlea minimum dose (D min ), mean dose (D mean ), and maximum dose (D max ) were extracted from treatment plans. Logistic analysis was used for multivariate modeling. The relation between cochlear dosimetric factors and significant hearing loss was also analyzed with receiver operating characteristic (ROC) curves., Results: Between January 2016 and December 2018, 35 patients (70 cochleae) were included. Most patients (n=29; 82.9%) had primary cancer in a low-risk region (oral cavity, oropharynx, larynx). All patients completed the programmed CRT. During follow-up, significant hearing loss was recorded in 13 cases (37.1%). The ROC areas for significant hearing loss in relation to D min , D mean , and D max were 0.70, 0.66, and 0.66, respectively. A dose-dependent relationship was noted between cochlear D min and significant hearing loss., Conclusion: D min <14.4 Gy is associated with reduced rates of significant hearing loss after concomitant cisplatin-based CRT in patients with locally advanced head and neck cancer., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Squamous-cell carcinoma of the anus (ASCC) is a rare disease. Barriers have been encountered to conduct clinical and translational research in this setting. Despite this, ASCC has been a prime example of collaboration amongst researchers. We performed a bibliometric analysis of ASCC-related literature of the last 20 years, exploring common patterns in research, tracking collaboration and identifying gaps. The electronic Scopus database was searched using the keywords "anal cancer", to include manuscripts published in English, between 2000 and 2020. Data analysis was performed using R-Studio 0.98.1091 software. A machine-learning bibliometric method was applied. The bibliometrix R package was used. A total of 2322 scientific documents was found. The average annual growth rate in publication was around 40% during 2000-2020. The five most productive countries were United States of America (USA), United Kingdom (UK), France, Italy and Australia. The USA and UK had the greatest link strength of international collaboration (22.6% and 19.0%). Two main clusters of keywords for published research were identified: (a) prevention and screening and (b) overall management. Emerging topics included imaging, biomarkers and patient-reported outcomes. Further efforts are required to increase collaboration and funding to sustain future research in the setting of ASCC.

Objective: The aim of this study was to develop and validate a decision support model using data mining algorithms, based on morphologic features derived from MRI images, to discriminate between complete responders (CR) and non-complete responders (NCR) patients after neoadjuvant chemoradiotherapy (CRT), in a population of patients with locally advanced rectal cancer (LARC)., Methods: Two populations were retrospectively enrolled: group A (65 patients) was used to train a data mining decision tree algorithm whereas group B (30 patients) was used to validate it. All patients underwent surgery; according to the histology evaluation, patients were divided in CR and NCR. Staging and restaging MRI examinations were retrospectively analysed and seven parameters were considered for data mining classification. Five different classification methods were tested and evaluated in terms of sensitivity, specificity, accuracy and AUC in order to identify the classification model able to achieve the best performance. The best classification algorithm was subsequently applied to group B for validation: sensitivity, specificity, positive and negative predictive value, accuracy and ROC curve were calculated. Inter and intra-reader agreement were calculated., Results: Four features were selected for the development of the classification algorithm: MRI tumor regression grade (MR-TRG), staging volume (SV), tumor volume reduction rate (TVRR) and signal intensity reduction rate (SIRR). The decision tree J48 showed the highest efficiency: when applied to group B, all the CR and 18/21 NCR were correctly classified (sensitivity 85.71%, specificity 100%, PPV 100%, NPV 94.2%, accuracy 95.7%, AUC 0.833). Both inter- and intra-reader evaluation showed good agreement (κ > 0.6)., Conclusions: The proposed decision support model may help in distinguishing between CR and NCR patients with LARC after CRT., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background/aim: To compare clinical outcomes following intensified total neoadjuvant therapy (TNT) and intensified neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC)., Patients and Methods: Of the 79 patients with LARC admitted to our department, 51 received intensified neoadjuvant CRT (CRT group) and 28 received intensified TNT (TNT group). Intensified TNT was defined as multi-agent chemotherapy, including FOLFOXIRI regimen plus bevacizumab (mutated Ras-BRAF) or panitumumab/cetuximab (wild-type Ras-BRAF) followed by oxaliplatin-5-fluorouracil-based CRT and surgery. Kaplan-Meier and Log rank test were used for survival analysis. Survival rates of the two groups were compared using propensity score matching., Results: Data from 28 TNT patients and 28 CRT patients were analyzed after a 1:1 propensity matching with replacement. Kaplan-Meier curve showed that overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates with TNT were comparable to those with CRT. The 5-year DMFS rates for TNT and CRT were 61.5% versus 63.0% (p=0.82), respectively. In the TNT group, 32.1% patients (n=9) achieved pathological complete response (pCR), whereas 21.4% patients (n=6) achieved pCR with CRT (p=0.37)., Conclusion: Intensified TNT and CRT resulted in similar survival outcomes, while intensified TNT led to higher pCR, albeit not statistically significant., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Different therapies are adopted for the treatment of deep seated tumours in combination or as an alternative to surgical removal or chemotherapy: radiotherapy with photons (RT), particle therapy (PT) with protons or even heavier ions like 12 C, are now available in clinical centres. In addition to these irradiation modalities, the use of Very High Energy Electron (VHEE) beams (100-200 MeV) has been suggested in the past, but the diffusion of that technique was delayed due to the needed space and budget, with respect to standard photon devices. These disadvantages were not paired by an increased therapeutic efficacy, at least when comparing to proton or carbon ion beams. In this contribution we investigate how recent developments in electron beam therapy could reshape the treatments of deep seated tumours. In this respect we carefully explored the application of VHEE beams to the prostate cancer, a well-known and studied example of deep seated tumour currently treated with high efficacy both using RT and PT. The VHEE Treatment Planning System was obtained by means of an accurate Monte Carlo (MC) simulation of the electrons interactions with the patient body. A simple model of the FLASH effect (healthy tissues sparing at ultra-high dose rates), has been introduced and the results have been compared with conventional RT. The study demonstrates that VHEE beams, even in absence of a significant FLASH effect and with a reduced energy range (70-130 MeV) with respect to implementations already explored in literature, could be a good alternative to standard RT, even in the framework of technological developments that are nowadays affordable., Competing Interests: The 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 © 2021 Sarti, De Maria, Battistoni, De Simoni, Di Felice, Dong, Fischetti, Franciosini, Marafini, Marampon, Mattei, Mirabelli, Muraro, Pacilio, Palumbo, Rocca, Rubeca, Schiavi, Sciubba, Tombolini, Toppi, Traini, Trigilio and Patera.)