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Background/aim: The present study aimed to investigate radiomics features derived from magnetic resonance imaging (MRI) in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT)., Patients and Methods: We retrospectively evaluated data of 53 patients (32 males, 21 females) with T3/T4 or N+ rectal cancer who underwent MRI before and after CRT. Twenty-seven texture radiomics features were extracted from regions of interest, delimiting the tumor on T2-weighted images., Results: All 27 radiomics features extracted before CRT showed a statistically significant association with the tumor regression grade (TRG) (p<0.05), whereas, after CRT, only the Cluster Prominence value was the only variable to predict TRG (p=0.037, r=0.291)., Conclusion: All 27 features extracted before CRT were able to predict response to CRT and Cluster Prominence continued to be statistically significant even after CRT. The impact of radiomics features derived from MRI could be further investigated in patients with locally advanced rectal cancer., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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).)

Background/aim: The majority of patients with endometrial cancer (EC) are diagnosed at an early stage and undergo primary surgery, followed by observation or adjuvant therapy according to risk factors on surgical samples. The objective of this study was to assess the correlation between a risk profile represented by the presence of substantial lymph-vascular space involvement (LVSI) and/or p53 overexpression and the clinical outcome of patients with early-stage endometrial cancer (EC) who received adjuvant vaginal brachytherapy (BT)., Patients and Methods: This investigation assessed 79 patients who underwent hysterectomy, bilateral salpingo-oophorectomy, and pelvic and/o aortic lymphadenectomy or sentinel lymph node biopsy followed by hypofractionated (HDR)-vaginal BT, using 192Ir source, for stage I-II endometrioid (n=70) or non-endometrioid (n=9) EC. Thirty-four patients (43.0%) were considered to have an unfavorable risk profile defined by the presence of substantial LVSI and /or p53 overexpression., Results: Five-year disease-free survival (DFS) and five-year overall survival (OS) were 93.7% and 95%, respectively. There was a significant correlation between unfavorable risk-profile and pelvic recurrence rate (p=0.002) and distant recurrence rate (p=0.017). Patients with abnormal p53 had a higher risk of local relapse (p=0.041). Substantial LVSI was strongly associated with pelvic recurrence (p=0.001) and distant metastasis (p<0.001)., Conclusion: The presence of substantial LVSI and/or p53 overexpression strictly correlated with poor outcome of patients with early-stage EC and should be taken into consideration for better planning adjuvant treatment in this clinical setting., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: Stereotactic ablative radiotherapy (SABR) showed increasing survival in oligometastatic patients. Few studies actually depicted oligometastatic disease (OMD) evolution and which patient will remain disease-free and which will rapidly develop a polymetastatic disease (PMD) after SABR. Therefore, apart from the number of active metastases, there are no clues on which proven factor should be considered for prescribing local treatment in OMD. The study aims to identify predictive factors of polymetastatic evolution in lung oligometastatic colorectal cancer patients., Methods: This international Ethical Committee approved trial (Prot. Negrar 2019-ZT) involved 23 Centers and 450 lung oligometastatic patients. Primary end-point was time to the polymetastatic conversion (tPMC). Additionally, oligometastases number and cumulative gross tumor volume (cumGTV) were used as combined predictive factors of tPMC. Oligometastases number was stratified as 1, 2-3, and 4-5; cumGTV was dichotomized to the value of 10 cc., Results: The median tPMC in the overall population was 26 months. Population was classified in the following tPMC risk classes: low-risk (1-3 oligometastases and cumGTV ≤ 10 cc) with median tPMC of 35.1 months; intermediate-risk (1-3 oligometastases and cumGTV > 10 cc), with median tPMC of 13.9 months, and high-risk (4-5 oligometastases, any cumGTV) with median tPMC of 9.4 months (p = 0.000)., Conclusion: The present study identified predictive factors of polymetastatic evolution after SABR in lung oligometastatic colorectal cancer. The results demonstrated that the sole metastases number is not sufficient to define the OMD since patients defined oligometastatic from a numerical point of view might rapidly progress to PMD when the cumulative tumor volume is high. A tailored approach in SABR prescription should be pursued considering the expected disease evolution after SABR, with the aim to avoid unnecessary treatment and toxicity in those at high risk of polymetastatic spread, and maximize local treatment in those with a favorable disease evolution., Competing Interests: 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., (© 2022 The Authors.)

NAVIGATOR is an Italian regional project boosting precision medicine in oncology with the aim of making it more predictive, preventive, and personalised by advancing translational research based on quantitative imaging and integrative omics analyses. The project's goal is to develop an open imaging biobank for the collection and preservation of a large amount of standardised imaging multimodal datasets, including computed tomography, magnetic resonance imaging, and positron emission tomography data, together with the corresponding patient-related and omics-related relevant information extracted from regional healthcare services using an adapted privacy-preserving model. The project is based on an open-source imaging biobank and an open-science oriented virtual research environment (VRE). Available integrative omics and multi-imaging data of three use cases (prostate cancer, rectal cancer, and gastric cancer) will be collected. All data confined in NAVIGATOR (i.e., standard and novel imaging biomarkers, non-imaging data, health agency data) will be used to create a digital patient model, to support the reliable prediction of the disease phenotype and risk stratification. The VRE that relies on a well-established infrastructure, called D4Science.org, will further provide a multiset infrastructure for processing the integrative omics data, extracting specific radiomic signatures, and for identification and testing of novel imaging biomarkers through big data analytics and artificial intelligence., (© 2022. The Author(s) under exclusive licence to European Society of Radiology.)

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.)

Purpose of Review: Gliomas are the most common primary tumors of the central nervous system. They are characterized by a disappointing prognosis and ineffective therapy that has shown no substantial improvements in the past 20 years. The lack of progress in treating gliomas is linked with the inadequacy of suitable tumor samples to plan translational studies and support laboratory developments. To overcome the use of tumor tissue, this commentary review aims to highlight the potential for the clinical application of liquid biopsy (intended as the study of circulating biomarkers in the blood), focusing on circulating tumor cells, circulating DNA and circulating noncoding RNA., Recent Findings: Thanks to the increasing sensitivity of sequencing techniques, it is now possible to analyze circulating nucleic acids and tumor cells (liquid biopsy)., Summary: Although studies on the use of liquid biopsy are still at an early stage, the potential clinical applications of liquid biopsy in the study of primary brain cancer are many and have the potential to revolutionize the approach to neuro-oncology, and importantly, they offer the possibility of gathering information on the disease at any time during its history., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Background: Glioblastoma (GB) is the most severe form of brain cancer, with a 12-15 month median survival. Surgical resection, temozolomide (TMZ) treatment, and radiotherapy remain the primary therapeutic options for GB, and no new therapies have been introduced in recent years. This therapeutic standstill is primarily due to preclinical approaches that do not fully respect the complexity of GB cell biology and fail to test efficiently anti-cancer treatments. Therefore, better treatment screening approaches are needed. In this study, we have developed a novel functional precision medicine approach to test the response to anticancer treatments in organoids derived from the resected tumors of glioblastoma patients., Methods: GB organoids were grown for a short period of time to prevent any genetic and morphological evolution and divergence from the tumor of origin. We chose metabolic imaging by NAD(P)H fluorescence lifetime imaging microscopy (FLIM) to predict early and non-invasively ex-vivo anti-cancer treatment responses of GB organoids. TMZ was used as the benchmark drug to validate the approach. Whole-transcriptome and whole-exome analyses were performed to characterize tumor cases stratification., Results: Our functional precision medicine approach was completed within one week after surgery and two groups of TMZ Responder and Non-Responder tumors were identified. FLIM-based metabolic tumor stratification was well reflected at the molecular level, confirming the validity of our approach, highlighting also new target genes associated with TMZ treatment and identifying a new 17-gene molecular signature associated with survival. The number of MGMT gene promoter methylated tumors was higher in the responsive group, as expected, however, some non-methylated tumor cases turned out to be nevertheless responsive to TMZ, suggesting that our procedure could be synergistic with the classical MGMT methylation biomarker., Conclusions: For the first time, FLIM-based metabolic imaging was used on live glioblastoma organoids. Unlike other approaches, ex-vivo patient-tailored drug response is performed at an early stage of tumor culturing with no animal involvement and with minimal tampering with the original tumor cytoarchitecture. This functional precision medicine approach can be exploited in a range of clinical and laboratory settings to improve the clinical management of GB patients and implemented on other cancers as well., 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 © 2022 Morelli, Lessi, Barachini, Liotti, Montemurro, Perrini, Santonocito, Gambacciani, Snuderl, Pieri, Aquila, Farnesi, Naccarato, Viacava, Cardarelli, Ferri, Mulholland, Ottaviani, Paiar, Liberti, Pasqualetti, Menicagli, Aretini, Signore, Franceschi and Mazzanti.)

Background: There is an unmet need for new biomarkers able to predict both the outcomes of up-front therapy and the compliance of elderly patients diagnosed with glioblastoma. For this purpose, temporal muscle thickness is a promising tool to be investigated., Methods: Data from 52 glioblastoma patients older than 65 years, treated with post-operative radio or radio-chemotherapy and referred to Pisa University Hospital, were retrieved. The thickness of temporal muscle (TMT) was divided into quartiles and correlated with overall survival (Our primary endpoint). Survival curves were calculated using Kaplan-Meier method, and log-rank test was used to evaluate the differences between curves., Results: Patients in the lower quartile of TMT, with TMT thinner than 7 mm, have survived longer; both univariate and multivariate analyses showed a statistically significant correlation between TMT and overall survival (P = 0.012 and P = 0.003, respectively)., Conclusion: Future prospective and more extensive studies focused on elderly glioblastoma patients are needed to confirm the role of TMT as prognostic value on OS and to help explaining this association., (© 2022. Italian Society of Medical Radiology.)

Objectives: The present study aims to investigate the role of the first magnetic resonances (MRI) following radio-chemotherapy (RT-CT) in patients diagnosed with high-grade glioma., Methods: We retrospectively recorded radiological evaluations following RT-CT, symptoms related to disease progression (avoiding any sign due to radiotherapy or chemotherapy) and the change of therapeutic strategy., Results: In March 2021, at data analysis, the data of 149 patients diagnosed with high-grade glioma and treated between May 2013 and July 2020 were retrieved for the present analysis. Two out of 122 (1.6%), 5 out of 106 (4.7%) and 8 out of 92 (8.6%) asymptomatic patients received the diagnosis of disease recurrence at the time of the first, second and third MRI, respectively. Otherwise, 16 out of 27 (59.2%), 16 out of 24 (66.6%) and 13 out of 16 (82.2%) symptomatic patients changed their therapy after the first, second and third MRI, respectively. Among patients that experienced radiological signs of distant progression, 10 out of 14 were symptomatic and changed their therapy., Conclusions: MRIs performed by 6 months after the end of RT-CT lead to change treatment strategy mostly in symptomatic patients., (© 2022. Italian Society of Medical Radiology.)

Background . Systemic immunity and inflammation indexes (SI) derived from blood cells have gained increasing attention in clinical oncology as potential biomarkers that are associated with survival. Materials and methods . We tested 12 different SI using blood tests from patients with isocitrate dehydrogenase 1 and 2 wild-type glioblastomas, treated with radio-chemotherapy. The primary endpoint was their overall survival. Results . A total of 77 patients, comprising 43 males and 34 females, with a median age of 64 years (age range 26-84), who were treated between October 2010 and July 2020, were included in the present analysis (approved by a local ethics committee). In the univariate Cox regression analysis, all the indexes except two showed a statistically significant impact on OS. In the multivariate Cox regression analysis, neutrophil × platelet × leukocyte/(lymphocyte × monocyte) (NPW/LM) and neutrophil × platelet × monocyte/lymphocyte (NPM/L) maintained their statistically significant impact value. Conclusions . This univariate analysis confirms the potential of systemic inflammation indexes in patients with glioblastoma, while the multivariate analysis verifies the prognostic value of NPW/LM and NPM/L.

Purpose: The aim of this systematic review was to examine efficacy of stereotactic radiotherapy (SRT) in patients with oligometastatic thyroid cancer., Materials and Methods: A systematic search was conducted by means of PubMed, Scopus, and Cochrane library., Clinicaltrials: gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. We analyzed only clinical studies as full text carried out on patients with oligometastatic thyroid cancer treated with SRT. Conference papers, surveys, letters, editorials, book chapters, and reviews were excluded. Time of publication was restricted to the years 1990-2021., Results: The number of evaluated patients was 146 (267 lesions), and the median age was 58 years. The median 1-year local control (LC) was 82% (range 67.0%-97.1%); the median disease-free survival (DFS) was 12 months (range 4-53); the median 1-year overall survival was 72% (range 66.6%-85.0%); the 3-year cancer-specific survival was 75.0%; and the 4-year cancer-specific survival was 37.5%. No grade 3-5 acute toxicity was reported. No late effects were recorded., Conclusions: SRT for oligometastases from thyroid cancer as salvage therapy is well tolerated and yields high rates of LC and prolonged DFS., (© 2022. Italian Society of Medical Radiology.)

Background/aim: A much-debated topic relating to patients at risk of local prostate cancer recurrence, but with post-operative leveIs of prostate-specific antigen (PSA) lower than 0.2 ng/ml, concerns the best timing of postoperative radiotherapy (RT), adjuvant or salvage? The present monocentric, retrospective study aimed to investigate the best PSA value at which to plan salvage RT for patients with recurrent prostate cancer., Patients and Methods: From January 2011 to December 2019, 158 patients were treated with adjuvant RT at Pisa University Hospital, whilst 91 patients underwent salvage RT. We grouped the patients treated with salvage RT using their PSA values at the time of salvage RT: PSA >0.5 ng/ml, PSA between 0 and 0.5 ng/ml, and PSA ≤0.2 ng/ml. The median follow-up was 63 months. Biochemical recurrence-free survival (BFS) measured from surgery was the primary endpoint., Results: Salvage RT led to shorter BFS compared to adjuvant RT considering the whole cohort of patients, with a hazard ratio of 3.195 (95% confidence interval=1.534-6.655, p=0.002). However, analysing only the group of patients with PSA ≤0.2 ng/ml at the time of salvage RT, salvage RT led to BFS similar to that achieved with adjuvant RT (p=0.35)., Conclusion: Our results suggest that when scheduled for patients with a PSA ≤0.2 ng/ml, salvage RT results in equivalent biochemical control to that with adjuvant RT., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The impact of different patterns of glioblastoma (GBM) recurrence has not yet been fully established in patients suitable for a second surgery. Through the present observational study carried out at Pisa University Hospital, we aimed to investigate how different patterns of GBM failure influence second surgery outcomes. Overall survival (OS) and post-recurrence survival (PRS) were assessed according to clinical characteristics, including pattern of recurrence, in a prospective cohort of recurrent GBM patients. Survival curves were calculated using the Kaplan-Meier method and the log-rank test was applied to evaluate the differences between curves. Patients with local recurrence had better OS than patients with non-local one, 24.1 versus 18.2 months, respectively [P = 0.015, HR = 1.856 (1.130-3.050)]. The second surgery conferred an advantage in OS respect to non-operated patients, however, this advantage was more evident in patients with local recurrence [P = 0.002 with HR 0.212 (95% CI 0.081-0.552) and P = 0.029 with HR = 0.522 (95% CI 0.291-0.936), respectively]. The recurrence pattern can influence the outcome of patients with recurrent GBM suitable for a second surgery., (© 2021. Belgian Neurological Society.)

Background/aim: Uveal melanoma (UM) is the most common primary intraocular malignant tumor. This malignancy is frequently treated using brachytherapy, stereotactic radiotherapy, or proton therapy. The objective of this study was to assess the role of stereotactic radiosurgery in the treatment of large and posterior UM., Patients and Methods: From January 2014 to July 2021, we treated 65 patients (median age=71 years; range=31-89 years) affected by UM. Inclusion criteria were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2, life expectancy >6 months, tumor thickness >10 mm, diameter >16 mm or posterior UM. The treatment was delivered with a True Beam™ LINAC with arc modulation technique. All patients received 27 Gy in one fraction (biological effective dose ≈100 Gy, assuming an α/β of 10)., Results: The median follow-up was 36 (range=3-90) months. Acute toxicities were reported in 14 patients, whereas late toxicity occurred in 45 (69.2%). Fifteen patients (23.0%) underwent enucleation: eight (12.3%) for failure of local control and seven (10.7%) for late treatment co-morbidities. The 5-year local control, and progression-free, metastasis-free, enucleation-free, and overall survival rates were 80%, 43%, 62%, 65% and 56%, respectively. In multivariate analysis, tumor dimensions significantly influenced survival [larger basal diameter: progression-free [hazard ratio (HR)=2.42] and overall (HR=2.61) survival; greater thickness: overall survival (HR=2.36)]. In multivariate analysis, patients without local control had a higher risk of distant metastasis (HR=3.25)., Conclusion: Stereotactic radiosurgery offers an effective and safe approach for selected cases of UM due to the satisfactory results in terms of local control, eye conservation and survival., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

About 60-90% of cancer patients are estimated to develop bone metastases, particularly in the spine. Bone scintigraphy, computed tomography (CT ) and magnetic resonance imaging (MRI ) are currently used to assess metastatic bone disease; positron emission tomography/computed tomography (PET-CT ) has become more widespread in clinical practice because of its high sensitivity and specificity with about 95% diagnostic accuracy. The most common and well-known radiotracer is 18F-fluorodeoxyglucose ( 18 FDG); several other PET-radiotracers are currently under investigation for different solid tumors, such as 11 C or 18 FDG-choline and prostate specific membrane antigen (PSMA)-PET/CT for prostate cancer. In treatment planning, standard and investigational imaging modalities should be registered with the planning CT so as to best define the bone target volume. For target volume delineation of spine metastases, the International Spine Radiosurgery Consortium (ISRC ) of North American experts provided consensus guidelines. Single fraction stereotactic radiotherapy (SRT ) doses ranged from 12 to 24 Gy; fractionated SRT administered 21-27 Gy in 3 fractions or 20-35 Gy in 5 fractions. After spine SRT, less than 5% of patients experienced grade ≥ 3 acute toxicity. Late toxicity included the extremely rare radiation-induced myelopathy and a 14% risk of de novo vertebral compression fractures., Competing Interests: Conflicts of interest The authors have no conflict of interest to declare., (© 2022 Greater Poland Cancer Centre.)

The purpose of this study was to investigate the effect of image preprocessing on radiomic features estimation from computed tomography (CT) imaging of locally advanced rectal cancer (LARC). CT images of 20 patients with LARC were used to estimate 105 radiomic features of 7 classes (shape, first-order, GLCM, GLDM, GLRLM, GLSZM, and NGTDM). Radiomic features were estimated for 6 different isotropic resampling voxel sizes, using 10 interpolation algorithms (at fixed bin width) and 6 different bin widths (at fixed interpolation algorithm). The intraclass correlation coefficient (ICC) and the coefficient of variation (CV) were calculated to assess the variability in radiomic features estimation due to preprocessing. A repeated measures correlation analysis was performed to assess any linear correlation between radiomic feature estimate and resampling voxel size or bin width. Reproducibility of radiomic feature estimate, when assessed through ICC analysis, was nominally excellent (ICC > 0.9) for shape features, good (0.75 < ICC ≤ 0.9) or moderate (0.5 < ICC ≤ 0.75) for first-order features, and moderate or poor (0 ≤ ICC ≤ 0.5) for textural features. A number of radiomic features characterized by good or excellent reproducibility in terms of ICC showed however median CV values greater than 15%. For most textural features, a significant ( p < 0.05) correlation between their estimate and resampling voxel size or bin width was found. In CT imaging of patients with LARC, the estimate of textural features, as well as of first-order features to a lesser extent, is appreciably biased by preprocessing. Accordingly, this should be taken into account when planning clinical or research studies, as well as when comparing results from different studies and performing multicenter studies., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Stefania Linsalata et al.)

The European Society for Medical Oncology (ESMO) suggests the use of chemotherapy as neoadjuvant, adjuvant, and concomitant to surgery and radiotherapy for the treatment of oral carcinoma by depending on the cancer stage. The usual drug of choice belongs to the platinum compounds. In this context, the evaluation of the cancer behavior associated with the administration of standard or emerging cisplatin compounds supports the establishment of optimal cancer management. Here, we have assessed and compared the performance of cisplatin alone and contained in biodegradable nanocapsules on standardized chorioallantoic membrane (CAM) tumor models. The vascularized environment and optimized grafting procedure allowed the establishment of solid tumors. The treatments showed antitumor and anti-angiogenic activities together with deregulation of pivotal genes responsible of treatment resistance and tumor aggressiveness. This study further supports the significance of CAM tumor models in oncological research for the comprehension of the molecular mechanisms involved in tumor treatment response., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Background: The role of image-derived biomarkers in recurrent oligometastatic Prostate Cancer (PCa) is unexplored. This paper aimed to evaluate [ 18 F]FMCH PET/CT radiomic analysis in patients with recurrent PCa after primary radical therapy. Specifically, we tested intra-patient lesions similarity in oligometastatic and plurimetastatic PCa, comparing the two most used definitions of oligometastatic disease., Methods: PCa patients eligible for [ 18 F]FMCH PET/CT presenting biochemical failure after first-line curative treatments were invited to participate in this prospective observational trial. PET/CT images of 92 patients were visually and quantitatively analyzed. Each patient was classified as oligometastatic or plurimetastatic according to the total number of detected lesions (up to 3 and up to 5 or > 3 and > 5, respectively). Univariate and intra-patient lesions' similarity analysis were performed., Results: [ 18 F]FMCH PET/CT identified 370 lesions, anatomically classified as regional lymph nodes and distant metastases. Thirty-eight and 54 patients were designed oligometastatic and plurimetastatic, respectively, using a 3-lesion threshold. The number of oligometastic scaled up to 60 patients (thus 32 plurimetastatic patients) with a 5-lesion threshold. Similarity analysis showed high lesions' heterogeneity. Grouping patients according to the number of metastases, patients with oligometastatic PCa defined with a 5-lesion threshold presented lesions heterogeneity comparable to plurimetastic patients. Lesions within patients having a limited tumor burden as defined by three lesions were characterized by less heterogeneity., Conclusions: We found a comparable heterogeneity between patients with up to five lesions and plurimetastic patients, while patients with up to three lesions were less heterogeneous than plurimetastatic patients, featuring different cells phenotypes in the two groups. Our results supported the use of a 3-lesion threshold to define oligometastatic PCa., (© 2021. The Author(s).)

Aim: Pancreatic adenocarcinoma is a life-threatening disease with a rising frequency and the fourth leading cause of cancer death. This review aimed to assess the impact of postoperative radiotherapy through a meta-analysis of prospective randomized studies., Materials and Methods: Six studies met the inclusion criteria and were analyzed to calculate the cumulative risk of death (hazard ratio) in patients affected by pancreatic cancer treated with or without radiotherapy. Higgins' index was used to determine heterogeneity in between-study variability and, subsequently, the random-effects model was applied according to DerSimonian and Laird., Results: Eight hundred and thirty-seven patients were analyzed (418 in the control arm and 419 in the treatment one), the hazard ratio for death after randomization was 0.92 (p=0.560, 95% confidence interval=0.70-1.22). When scrutinizing these studies, only one out of six showed a statistically significant benefit due to the addition of radiotherapy in the postoperative setting., Conclusion: We conclude that the use of adjuvant radiotherapy is not beneficial in treating all patients affected by pancreatic cancer but only for a subset of cases with potential residual local disease., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

This study reports the results of a monocentric prospective analysis conducted with the aim of evaluating the impact of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms (SNP) on patients with high-grade glioma treated with concomitant radio-chemotherapy. From October 2010 to August 2019, a total of 75 patients aged ≥18 years, with histological diagnosis of high-grade glioma, isocitrate dehydrogenase (IDH) 1/2 wild type and treated with radio-chemotherapy and sequential chemotherapy with temozolomide (TMZ) were prospectively recruited. The local ethic committee approved this study (Comitato Etico di Area Vasta Nord Ovest [CEAVNO]; protocol 3304/2011). After a median follow up of 25 months (range: 7-98 months), median progression-free survival (PFS) and overall survival (OS) were 11 months (CI95%: 8-14 months) and 18 months (CI95%: 15-21 months), respectively. In univariate and multivariate Cox regression analysis, a statistically significant association with PFS and OS was found with XRCC3 rs1799794 SNP. The study suggests that XRCC3 rs1799794 SNP can be associated with different PFS and OS in glioblastoma patients treated with radio-chemotherapy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Objective: Despite recent advances in diagnosis and treatment of the disease, the prognosis of patients with glioblastoma multiforme (GBM) remains poor. While the value of molecular pattern profiles at first diagnosis has been demonstrated, only few studies have examined these biomarkers at the time of recurrence. The aim of this study was to explore the impact of extent of resection at repeated craniotomy on overall survival (OS) of patients with recurrent GBM. In addition, we investigated the molecular pattern profiles at first and second surgery to evaluate possible temporal evolution of these patterns and to assess the effect of these modifications on OS., Methods: We conducted a retrospective cohort study of 63 patients (mean age 59.2 years) surgically treated at least two times for recurrent GBM between 2006 and 2020., Results: Median OS and progression-free survival (PFS) were 22 months (range 2-168 months) and 10 months (range 1-96 months), respectively. The OS following gross-total resection (GTR) at recurrence for patients with initial GTR (GTR/GTR) was significantly increased (42.6 months) compared with sub-total resection (STR) at reoperation after initial GTR (GTR/STR) (19 months) and with GTR at reoperation after initial STR (STR/GTR) (17 months) (p = 0.0004). Overall surgical morbidity resulted 12.7% and 11.1% at first and at second surgery, respectively. Changes in genetic profiles between first and second surgery of 1p/19q co-deletion, MGMT promoter methylation and p53 mutations occurred in 5.6%, 1.9% and 9.3% of cases, respectively. MGMT promoter methylation appeared to affect OS in univariate analysis at first (p = 0.038) and second surgery (p = 0.107), whereas p53 mutation appeared to affect OS only at second surgery (p = 0.01). In a multivariate analysis female sex (HR = 0.322, 95% CI 0.147-0.705; p = 0.005), PFS (HR = 0.959, 95% CI 0.934-0.986; p = 0.003), GTR at first and second surgery (HR = 0.195, 95% CI 0.091-0.419; p < 0.0001) and adjuvant chemotherapy at recurrence (HR = 0.407, 95% CI 0.206-0.809; p = 0.01) were associated with longer OS., Conclusions: This study confirmed the role of extent of resection (EOR) at first and at recurrence as a significant predictor of outcome in patients with recurrent GBM. In addition, this study highlighted the concept of a dynamic evolution of GBM genome after initial surgical resection, supporting the need of further studies to investigate the clinical and therapeutic implications of the changes in genetic profiles after initial surgery., (Copyright © 2021 Elsevier B.V. All rights reserved.)

PRIMAGE is a European Commission-financed project dealing with medical imaging and artificial intelligence aiming to create an imaging biobank in oncology. The project includes a task dedicated to the interoperability between imaging and standard biobanks. We aim at linking Digital imaging and Communications in Medicine (DICOM) metadata to the Minimum Information About BIobank data Sharing (MIABIS) standard of biobanking. A very first integration model based on the fusion of the two existing standards, MIABIS and DICOM, has been developed. The fundamental method was that of expanding the MIABIS core to the imaging field, adding DICOM metadata derived from CT scans of 18 paediatric patients with neuroblastoma. The model was developed with the relational database management system Structured Query Language. The integration data model has been built as an Entity Relationship Diagram, commonly used to organise data within databases. Five additional entities have been linked to the "Image Collection" subcategory in order to include the imaging metadata more specific to the particular type of data: Body Part Examined, Modality Information, Dataset Type, Image Analysis, and Registration Parameters. The model is a starting point for the expansion of MIABIS with further DICOM metadata, enabling the inclusion of imaging data in biorepositories.

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.

Objectives: The objective of the paper was to assess real-life experience in the management of head and neck cancer (HNC) patients during the COVID-19 pandemic in radiotherapy departments and to evaluate the variability in terms of adherence to American Society of Radiation Oncology (ASTRO) and European Society for Radiotherapy and Oncology (ESTRO) recommendations., Materials and Methods: In May 2020, an anonymous 30-question online survey, comparing acute phase of outbreak and pre-COVID-19 period, was conducted. Two sections exploited changes in general management of HNC patients and different HNC primary tumors, addressing specific statements from ASTRO ESTRO consensus statement as well., Results: Eighty-eight questionnaires were included in the demographic/clinical workflow analysis, and 64 were analyzed for treatment management. Forty-eight percent of radiotherapy departments became part of oncologic hubs. First consultations reduced, and patients were addressed to other centers in 33.8 and 18.3% of cases, respectively. Telematic consultations were used in 50% of follow-up visits and 73.9% of multidisciplinary tumor board discussions. There were no practical changes in the management of patients affected by different primitive HNCs. Hypofractionation was not favored over conventional schedules., Conclusions: Compared to pre-COVID era, the clinical workflow was highly re-organized, whereas there were no consistent changes in RT indications and schedules.

Aim of the Study: The aim of this retrospective study was to analyse tumour control, toxicity, and aesthetic outcome of patients affected by non-melanoma skin cancer (NMSC) treated with 192 Ir high-dose-rate (HDR)-brachytherapy (BT) at the Division of Radiotherapy, University of Pisa., Material and Methods: From January 2014 to December 2019 we treated 37 patients (median age 79 years; range 31-91 years) affected by NMSC, with the following histological subtypes: 62.2% basal cell carcinoma and 37.8% squamous cell carcinoma. We analysed 40 lesions with a depth ≤ 5 mm, located in 40.0% scalp, 17.5% nose, 25.0% face, and 17.5% ear, all treated with 192 Ir-based HDR-BT, using tailored custom moulds, with a median of 5 catheters (range, 1-9) spaced 1 cm apart. The most common fractionation scheme was 40 Gy in 8 daily fractions; the biological effective dose was 60 Gy., Results: The median follow-up was 25 months (range, 3-70 months). The 2-year local control rate was 90%. Common terminology criteria for adverse event (CTCAE vs. 5.0) G1 toxicities were dermatitis (52%), pain (25%), and ulceration (22%). The only G2 acute toxicities were dermatitis and ulceration. The most common G1 late toxicities were fibrosis (17%), atrophy (15%), and hypopigmentation (12%). No G3 or higher acute or late toxicity was reported. Excellent cosmetic results were observed in 65.0% of the lesions; only 1 case (2.5%) reported a poor cosmetic result., Conclusions: Surface mould HDR-BT is a safe, effective, and well tolerated treatment modality for NMSC and can be considered a good alternative, especially for elderly patients who are often unfit for surgery., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Termedia.)

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.

Purpose: This study describes the long-term survival and toxicity outcomes of a multicenter randomized phase 2 trial comparing radiation therapy (RT) plus cisplatin (CDDP) or cetuximab (CTX) as first line treatment in locally advanced head and neck cancer (LASCCHN)., Methods and Materials: Between January 2011 and August 2014, 70 patients were enrolled and randomized to receive RT plus weekly CDDP (40 mg/m 2 ) or CTX (250 mg/m 2 plus a loading dose of 400 mg/m 2 ). This updated series focuses on late toxicities (graded by using Common Terminology Criteria for Adverse Events version 4.0) and long-term survival outcomes in terms of local control, overall survival, cancer-specific survival, and metastasis-free survival (MFS). A supplementary analysis based on human papilloma virus (HPV) status was also performed., Results: No statistically significant difference was found in terms of late effects (xerostomia, fibrosis, mucosal atrophy, weight loss). In the CDDP arm and the CTX arm, 5-year local control rates were 67% and 48%; 5-year MFS rates were 83% and 97%; 5-year overall survival rates were 61% and 52%; and 5-year cancer-specific survival rates were 70% and 59%, respectively. None of these differences reached statistical significance. A subgroup analysis by HPV status and anatomic subsites revealed that in HPV+ oropharyngeal carcinoma, better survival was obtained in the CDDP arm (although statistical tests were not performed owing to the small sample size). Conversely, no statistically significant differences were observed in HPV- oropharyngeal carcinoma and other anatomic subsites, except for the confirmed better MFS rates of the CTX arm., Conclusions: Long-term results are in line with current literature suggesting that RT + CTX is inferior to RT + CDDP for the definitive treatment of LASCCHN. However, if not as an alternative to CDDP, CTX might still play a role in LASCCHN, particularly in HPV- cases., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Background: In the last years, functional imaging has given a significant contribution to the clinical decision-making of biochemically relapsed prostate cancer (PCa). Hereby, we present a prospective study aiming to validate the role of [ 18 F]Fluoro-Methyl Choline ([ 18 F]FMCH) PET/CT in the selection of PCa patients suitable for stereotactic body radiotherapy (SBRT)., Methods: Patients with biochemical recurrence limited up to three lesions revealed by [ 18 F]FMCH PET/CT were enrolled in the present study and treated with SBRT on all active lesions. Systemic therapy-free survival since the [ 18 F]FMCH PET/CT was considered as the primary endpoint., Results: Forty-six patients were evaluated, and a total of 67 lesions were treated. After a median follow-up of 28.9 months, systemic therapy was started in 30 patients (65.2%) and median systemic therapy-free survival was 39.1 months (95% CI 6.5-68.6); 6, 12, and 24-month ratios were 93.5%, 73.9%, and 63.1%, respectively. At univariate Cox regression analysis, Delta PSA demonstrated an impact on systemic therapy-free survival (p < 0.001)., Conclusions: Based on our findings, [ 18 F]FMCH PET/CT can identify oligometastatic prostate cancer patients suitable for SBRT, resulting in a systemic therapy-free survival of 39.1 months.

Purpose: Herein, we report the clinical outcomes of a multicenter study evaluating the role of SBRT in a cohort of patients affected by oligoprogressive castration-resistant prostate cancer (CRPC)., Materials and Methods: This is a retrospective multicenter observational study including eleven centers. Inclusion criteria of the current study were: (a) Karnofsky performance status > 80, (b) histologically proven diagnosis of PC, (c) 1-5 oligoprogressive metastases, defined as progressive disease at bone or nodes levels (detected by means of choline PET/CT or CT plus bone scan) during ADT, (d) serum testosterone level under 50 ng/ml during ADT, (e) controlled primary tumor, (f) patients treated with SBRT with a dose of at least 5 Gy per fraction to a biologically effective dose (BED) of at least 80 Gy using an alpha-to-beta ratio of 3 Gy, (g) at least 6 months of follow-up post-SBRT., Results: Eighty-six patients for a total of 117 lesions were treated with SBRT. The median follow-up was 30.7 months (range 4-91 months). The median new metastasis-free survival after SBRT was 12.3 months (95% CI 5.5-19.1 months). One- and two-year distant progression-free survival was 52.3% and 33.7%, respectively. Twenty-six out of 86 patients underwent a second course of SBRT due to further oligoprogressive disease: This resulted in a median systemic treatment-free survival of 21.8 months (95% CI 17.8-25.8 months). One-year systemic treatment-free survival was 72.1%., Conclusion: SBRT appears to be a promising approach in oligoprogressive castration-resistant prostate cancer. Further investigations are warranted.

Radiomics is a process of extraction and analysis of quantitative features from diagnostic images. Liquid biopsy is a test done on a sample of blood to look for cancer cells or for pieces of tumourigenic DNA circulating in the blood. Radiomics and liquid biopsy have great potential in oncology, since both are minimally invasive, easy to perform, and can be repeated in patient follow-up visits, enabling the extraction of valuable information regarding tumour type, aggressiveness, progression, and response to treatment. Both methods are in their infancy, with major evidence of application in lung and gastrointestinal cancer, while still undergoing evaluation in other cancer types. In this paper, the main oncologic applications of radiomics and liquid biopsy are reviewed, and a synergistic approach incorporating both tests for cancer diagnosis and follow-up is discussed within the context of systems medicine. TEACHING POINTS: • Radiomics is a process of extraction and analysis of quantitative features from diagnostic images. • Most clinical applications of radiomics are in the field of oncologic imaging. • Radiomics applies to all imaging modalities. • A cluster of radiomic features is a "radiomic signature". • Machine learning may improve the efficacy of radiomics analysis.

Background and Purpose: A prospective instrumental assessment of late dysphagia using swallowing organs at risk (SWOARs)-sparing IMRT for nasopharyngeal and oropharyngeal cancers., Materials and Methods: Objective instrumental assessment included fiberoptic endoscopic evaluation of swallowing (FEES) and videofluoroscopy (VFS) at baseline, and at 6 and 12 months after treatment. FEES assessed the pharyngeal residue according to the Farneti pooling score (P-score) as follows: 4-5 no dysphagia; 6-7 mild dysphagia; 8-9 moderate dysphagia; 10-11 severe dysphagia. Three different consistencies were tested for the P‑score: liquid (L), semisolid (SS), and solid (S). VFS assessed penetration-aspiration according to the Penetration-Aspiration Scale (PAS) and two different consistencies of the bolus were tested: thin liquid barium (L) and paste barium (S)., Results: 38 patients were evaluable. There was a significant worsening of the P‑score at 6 months both for SS (p = 0.015) and S (p < 0.001), which persisted only for S at 12 months (p < 0.0001). Similarly, there was a significant worsening of the PAS score at 6 and 12 months (p = 0.065 and 0.039, respectively) for the S bolus. Overall, 3-7 and 10-14% aspiration after L and S was observed, respectively., Conclusions: Promising results using a SWOARs-sparing IMRT technique are reported. Therefore, treatment plans should be optimized for reducing doses to these structures.

Background/aim: In the last years, the use of Image Guided Stereotactic Radiotherapy (IG-SBRT) in patients with metastatic prostate cancer has increased. In this study, we aimed to assess the role of IG-SBRT in terms of local control and safety in patients with metastatic prostate cancer., Materials and Methods: Primary and secondary endpoints of this prospective observational study were local control and safety related to IG-SBRT. All lesions were treated with 24 Gy as a single fraction or 27 Gy in 3 fractions. After SBRT, Systemic therapies were administered only after the occurrence of more than three synchronous active lesions in oligometastatic patients (patients with less than 4 active synchronous lesions) or new lesions occurrence in patients with more than 3 synchronous lesions., Results: From April 2011 to June 2017, 78 metastatic lesions (32 bone and 46 node) from 51 patients with prostate cancer were treated. After a median follow-up of 18.5 months (range=3-103 months), only 2 lesions (4%) relapsed inside the radiation field. All local recurrences were located on the bone. Estimated 12 and 24 months local control ratios were 98.7 and 97.4%, respectively. Except for one case, toxicity greater than G2 was not recorded., Conclusion: IG-SBRT is safe and can be considered as a valid therapy in patients with metastatic prostate cancer requiring a long-lasting metastases control., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults and, despite recent advances, the prognosis for this cancer remains dismal. The aims of this study were to test the influence of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms on progression free survival (PFS) and overall survival (OS) in GBM patients treated with radiotherapy (RT) and temozolomide (TMZ). Fifty GBM patients treated with upfront radio-chemotherapy (RT 60 Gy/30 sessions; TMZ 75 mg/m 2 during RT and 200 mg/m 2  days 1 → 5 every 28 days) were enrolled. Survival curves were calculated using the Kaplan-Meier method, and the log-rank test was used to evaluate differences between curves. A trend to a statistically significant association with PFS in univariate and multivariate COX regression analysis was found with GSTP-1 rs1695 polymorphism (p = 0.087 and p = 0.097 on univariate and multivariate analyses, respectively). Conversely, the same GSTP-1 rs1695 SNP revealed a statistically significant association with OS (p = 0.007 and p = 0.042 on univariate and multivariate analysis, respectively). Our pharmacogenetic prospective study suggests that GSTP-1 rs1695 genotypes can be associated with different OS in GBM patients treated with RT and TMZ.

Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled. MC4R gene SNPs (rs17782313, rs489693, rs8087522, rs17700633) were analyzed by a validated TaqMan® SNP genotyping assays. Univariate and multivariate analyses were performed. A P < 0.0125 (Bonferroni's correction) was considered significant ( Clinicaltrial.gov identifier NCT02458508). The median progression-free survival (PFS) and median overall survival (OS) of these patients were 9.54 (95% CI 5.4-14.3) months and 24.9 (95% CI 17.8-34.6) months, respectively. The MC4R rs489693 AA genotype was significantly associated with a shorter PFS and OS. Indeed, with regard to PFS, patients harboring the rs489693 AA genotype had a median PFS of 2.99 months whereas patients with AC/CC genotypes had a median PFS of 10.82 months (P = 0.009). Interestingly, the rs489693 AA patients also had a lower median OS as compared with the median OS of the AC/CC genotypes (10.75 vs. 29.5 months, respectively, P = 0.0001). This study suggests that the MC4R rs489693 AA genotype is significantly associated with a shorter PFS and OS in patients treated with radiotherapy and temozolomide. These findings represent a relevant effort to identify novel clinical markers for RT-CT therapy in GBM to be validated in future pharmacogenetic clinical trials.

Purpose: Dysphagia is one of the most important treatment-related side effects in head and neck cancer (HNC), as it can lead to severe life-threating complications such as aspiration pneumonia and malnutrition. Intensity-modulated radiotherapy (IMRT) could reduce swallowing dysfunction by producing a concave dose distribution and reducing doses to the swallowing-related organs at risk (SWOARs). The aim of this study was to review the current literature in order to compare swallowing outcomes between IMRT and three-dimensional conformal radiotherapy (3DCRT)., Methods: A search was conducted in the PubMed and Embase databases to identify studies on swallowing outcomes, both clinically and/or instrumentally assessed, after 3DCRT and IMRT. Dysphagia-specific quality of life and objective instrumental data are summarized and discussed., Results: A total of 262 papers were retrieved from the searched databases. An additional 23 papers were retrieved by hand-searching the reference lists. Ultimately, 22 papers were identified which discussed swallowing outcomes after 3DCRT and IMRT for HNC. No outcomes from randomized trials were identified., Conclusion: Despite several methodological limitations, reports from the current literature seem to suggest better swallowing outcomes with IMRT compared to 3DCRT. Further improvements are likely to result from the increased use of IMRT plans optimized for SWOAR sparing.

Objective: The objective of this study was to assess the role of stereotactic body radiotherapy (SBRT) in the treatment of distantly recurrent, oligometastatic gynecological cancer., Methods: The hospital records of 45 patients with F-fluorodeoxyglucose (F-FDG) positron emission tomography positive, distantly recurrent, oligometastatic gynecological cancer were reviewed. All these patients had a number of target lesions less than 5, with largest diameter less than 6 cm. The treatment was delivered with a TrueBeam LINAC and RapidArc technique, using 10 or 6 MV FFF beams. A total of 70 lesions were treated, and lymph nodes represented the most common site of metastases, followed by lung, liver, and soft tissues. Twenty lesions were treated with one single fraction of 24 Gy and 5 lesions received 27 Gy delivered in 3 fractions, depending on the ability to fulfill adequate target coverage and safe dose/volume constraints for the organ at risk with either regimen., Results: Positron emission tomography scan 3 months after SBRT showed a complete response (CR) in 45 lesions (64.3%), a partial response in 14 (20.0%), a stable disease in 5 (7.1%), and a progressive disease in 6 (8.6%). No lesions in CR after SBRT subsequently progressed. Overall acute toxicity occurred in 13 (28.9%) patients. The most common grade 1 to 2 adverse event was pain (n = 9, 20.0%), followed by nausea and vomiting (n = 5, 11.1%). No grade 3 to 4 acute toxicities occurred, and no late toxicities were observed. Patients who failed to achieve a CR had a 2.37-fold higher risk of progression and a 3.60-fold higher risk of death compared with complete responders (P = 0.04 and P = 0.03, respectively)., Conclusions: Stereotactic body radiotherapy offers an effective and safe approach for selected cases of oligometastatic gynecological cancer.

The aim of the present study is to evaluate the impact of extent of resection at initial and repeat craniotomy on overall survival of patients with recurrent glioblastoma. The authors retrospectively reviewed the records of all adults patients who underwent repeat resection of recurrent glioblastoma following radiation and chemotherapy at an academic tertiary-care institution between 2011 and 2015. We evaluated the survival outcomes with regard to extent of resection considering both the initial and repeat resections. The role of possible prognostic factors that may affect survival after repeat resection, including age, preoperative performance status, tumor location and adjuvant treatment, was evaluated using Cox regression analyses. Forty-eight patients were included in this study. The overall median survival of 14 patients who had subtotal resection at recurrence after initial subtotal resection did not statistically differ from seven patients who had gross-total resection at recurrence after initial subtotal resection (18 months vs. 22 months, p = 0.583). The overall median survival of 13 patients who had gross-total resection at recurrence after initial gross-total resection was significantly increased compared with survival of 13 patients who had subtotal resection at recurrence after initial gross-total resection (47 months vs. 14 months, p = 0.009). A Cox proportional hazards model was created demonstrating that preoperative performance status at recurrence (HR 0.418, p = 0.035) and the extent of repeat resection (HR 0.513, p = 0.043) were independent predictors of survival. Gross-total resection at repeat craniotomy is associated with longer overall survival and should be performed whenever possible in patients with recurrent glioblastoma and in good performance status.

Aim: To assess the outcome of 35 patients with vaginal carcinoma treated with different radiotherapy modalities., Materials and Methods: Thirty-one patients received external-beam irradiation (EBRT) to the entire vagina, para-vaginal area and pelvic nodes (total dose=45-50.4 Gy). Concomitant chemotherapy was used in 22 patients. Nineteen patients received additional 15-25 Gy high-dose-rate brachytherapy (BT) boost and eight received additional EBRT boost to the primary tumor site. Four women received exclusive 30-40 Gy high-dose-rate BT., Results: Median progression-free survival and median overall survival were 22 months and 89 months, respectively. Age <70 years, use of EBRT plus BT, and concomitant chemotherapy were associated with better progression-free (p=0.002, p=0.007, and p=0.02) and overall (p=0.01, p=0.009, p=0.009) survival., Conclusion: Concomitant EBRT and chemotherapy followed by BT is the best treatment for vaginal carcinoma., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: This study was undertaken to evaluate the association of individual parameters and outcome in patients with unresectable locally advanced head and neck cancer treated with radiochemotherapy., Materials and Methods: We retrospectively reviewed data from 126 patients treated in our Institution between 1998 and 2010 for a locally advanced head and neck cancer. Sixteen individual parameters were evaluated for association with specific outcomes such as overall survival, persistence of disease, disease-specific survival and disease-free survival., Results: Six factors influenced overall survival on Kaplan-Meier survival analysis and on univariate Cox regression analysis: smoking, body mass index, site, haemoglobin (Hb) nadir, total dose of radiotherapy and comorbidities. On a multivariate logistic model with stepwise selection, comorbidities, body mass index, total dose and site maintained significance. A significant association for persistence of disease was found with smoking, Hb nadir and site of cancer on univariate and multivariate analysis. Disease-free survival was correlated with performance status, Hb nadir and comorbidities using Kaplan-Meier survival analysis and on univariate Cox regression analysis. Only performance status maintained the significance on multivariate analysis. Disease-specific survival was correlated with five parameters: body mass index, site, Hb nadir, therapy interruption and total dose; on multivariate analysis, Hb nadir, therapy interruption and site maintained a statistically significant association., Conclusions: Hb nadir during treatment, body mass index, smoking, stage, comorbidities and performance status are prognostic factors of outcome and response to radical treatment with radiochemotherapy.

Purpose: The aim of our study was to evaluate the usefulness of the four-dimensional computed tomography (4DCT) in accelerated partial breast irradiation (aPBI) planning., Materials and Methods: At our Institute, we have been treating the index quadrant with external intensity-modulated radiation therapy in a phase III trial. For this study, we selected a sample of 10 patients with right- or left-sided breast cancer and surgical clips at the excision site. Contouring of the target was performed both using three-dimensional computed tomography (3DCT) and 4DCT imaging. On both 3DCT and 4DCT, we recorded the clinical target volume (CTV) and the planning target volume (PTV) and the coordinates of the PTV centroid. We calculated the treatment plans, according to our protocol, using the contours drawn on the 3DCT and 4DCT and evaluated target coverage and sparing of organs at risk (OAR)., Results: Median age of the patients was 63.5 years (range 52-75). The comparison between the 3DCT and 4DCT PTV volumes was not statistically significant (p = 0.79). Concerning centroid coordinates, the average absolute differences were 0.1 mm in the latero-lateral, 0.7 mm in the antero-posterior and 0.3 mm in the supero-inferior direction. No statistically significant differences were observed both in PTV coverage and OAR sparing; the 4D PTV contour is adequately covered when the plan based on the 3D contours is used. Target coverage was reduced on average by 1 % and no statistically significant difference was observed (p = 0.93)., Conclusions: In our experience, no significant differences between PTV volumes, PTV coverage, OAR sparing and centroid position are evidenced when comparing 3DCT and 4DCT plans. Conventional 3DCT-based planning is adequate for aPBI.

Aims and Background: We investigated efficacy, safety, and prognostic factors of reirradiation in patients with recurrent or second primary head and neck cancer., Methods: Records of 75 consecutive patients treated with reirradiation between August 2005 and December 2013 were reviewed., Results: Median overall survival (OS) and cancer-specific survival (CSS) were 29.5 and 33.6 months. Median local control (LC) and progression-free survival (PFS) were 21.7 and 16.2 months. Univariate analysis showed that patients younger than 70 years, with a Karnofsky Performance Status (KPS) &gt;90 or with 2 or less comorbidities at time of reirradiation, have a better OS; KPS &gt;90 and biological equivalent dose (BED) &gt;72 Gy positively influenced the PFS. At multivariate analysis, KPS at reirradiation was an independent predictive factor for OS, while BED was an independent predictive factor for CSS and OS. At univariate analysis, patients with planning target volume (PTV) &gt;221 mL had worse LC and PFS rates, with results confirmed at multivariate analysis. The rate of fatal treatment-related adverse events was 6.7% (3 carotid blowout, 1 soft tissue necrosis, and 1 thromboembolic event)., Conclusions: This study confirms the role and outcomes of reirradiation. A careful selection of patients could minimize acute and late side effects and influence survival: elderly patients, with significant medical comorbidities or poor KPS, are worse candidate for reirradiation. Total dose delivered with reirradiation and PTV appear to be other potential prognostic factors. Further studies of dose escalation are needed to establish the total dose that could achieve better LC rates with a safer toxicity profile.

Aim: The aim of this study was to compare surface imaging, portal imaging, and skin marker set-up in radiotherapy of thoracic and pelvic regions, using cone beam computed tomography (CBCT) data as the gold standard., Patients and Methods: Twenty patients were included in this study. CBCT, surface acquisition (SA), and two orthogonal portal images (PI) were acquired during the first four treatment sessions. Patient set-up corrections, obtained by registering the planning CT with CBCT, were used as the gold standard. Registration results of the PI and SA were evaluated and compared with those obtained with CBCT. The advantage derived from using SA or PI verification systems over a skin marker set-up was also quantified., Results: A statistically significant difference between PI and SA (in favour of PI) was observed in seven patients undergoing treatment of the pelvic region and in two patients undergoing treatment of the thoracic region. The use of SA or PI, compared with a skin marker set-up, improved patient positioning in 50% and 57% of the thoracic fractions, respectively. For pelvic fractions, the use of PI was beneficial in 73% of the cases, while the use of SA was beneficial in only 45%. Patient positioning worsened with SA, particularly along longitudinal and vertical directions., Conclusion: PI yielded more accurate registration results than SA for both pelvic and thoracic fractions. Compared with the skin marker set-up, PI performances were superior to SA for pelvic fractions while comparable results were obtained for thoracic fractions.

Purpose: The aim of this study is to evaluate the evolution of supracricoid partial laryngectomy (SCPL) in indications, surgical techniques and outcomes through last decades., Materials and Methods: A retrospective analysis of 146 patients affected by laryngeal cancer treated with SCPL was carried on. We defined: (1) group A, 100 patients treated by cold instruments between 1995 and 2004; (2) group B, 46 patients treated by harmonic scalpel between 2005 and 2010. Complications rate, and functional and oncological results were documented and a comparison between the two groups was made; histopathological analysis of surgical margins was evaluated and correlated with local incidence of recurrence., Results: Significant differences in age mean-value (p=0.02), T classification (p=0.007), and in indication for more advanced-staged patients were found in group B (p=0.001). Surgical procedure was shorter in group B (p<0.001), with shorter swallowing recovery (p=0.003). Oncological outcomes did not report any significant differences. Group B showed a higher incidence of post- operative arytenoid edema (p=0.03) associated with a lower rate of pneumonia (p=0.038). Despite a higher rate of close or positive-margins found in group B no higher incidence of local-recurrence was reported (p=0.02) compared to group A., Conclusions: We documented changing in indications and surgical technique for SCPL because of the development of modern diagnostic techniques and the introduction of low-thermal injury device allowing a more challenging tumor excision as well as with a shorter swallowing recovery in our series., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We have previously shown that a subset of sinonasal intestinal-type adenocarcinomas (ITAC) shows activation of the epidermal growth factor-receptor (EGFR) pathway. In this study we examine the status of the EGFR, KRAS and BRAF genes in a series of sinonasal intestinal (ITAC) and non-intestinal type adenocarcinomas (non-ITAC). Eighteen ITACs and 12 non-ITACs were studied immunohistochemically for EGFR expression. Point mutations were analyzed for EGFR exons 19 and 21, KRAS exon 2 and BRAF exon 15 by direct sequencing. Non-ITACs showed significantly higher expression of EGFR (p = 0.015). Mutation analysis revealed one ITAC with EGFR and one ITAC with KRAS mutation, while two non-ITACs presented mutation of BRAF. We conclude that a subset of sinonasal adenocarcinomas shows overexpression of EGFR, while activating mutations of the signaling cascade downstream of EGFR are rare, suggesting that these tumors could be good candidates for anti-EGFR therapies.

Purpose: The aim of this study was to evaluate disease-free survival (DFS), overall survival and toxicity of patients who underwent preoperative therapy for soft tissue sarcoma., Materials and Methods: The data of 38 consecutive patients affected by soft tissue sarcoma were retrospectively analysed. Six (15.8 %) patients were treated only with neoadjuvant radiotherapy, and 32 (84.2 %) with neoadjuvant chemo-radiation therapy. Surgery was performed within 4-6 weeks after the completion of neoadjuvant treatment., Results: Median follow-up was 4.9 years (range 1-13.7 years). All patients received preoperative external beam radiotherapy (RT). Most patients (84.2 %) underwent neoadjuvant chemotherapy treatment associated with radiotherapy. After neoadjuvant treatment, the majority of patients underwent wide excision (32 out of 38) and five patients had marginal surgery; only one patient underwent amputation. Local recurrence was observed in only two patients (5.2 %). Fourteen (36.8 %) patients experienced metastatic relapse. At the time of our analysis 13 patients (34.2 %) had died due to metastatic spread of the disease. In our series, DFS in relation to distant metastases (DM) showed a significant result for lower limb involvement (p = 0.038) and marginal excision (p = 0.024), both predictors of a worse DFS, histology was statistically significant although it was not possible to evaluate the risk for specific histology due to the small number of events in the different subtypes., Conclusions: The results obtained from our study are encouraging with regard to the feasibility and efficacy of preoperative RT in the treatment of soft tissue sarcoma in view of the results obtained in terms of local control, limb sparing and safety.