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Background: In many European countries, short-term 5 x 5 Gy radiotherapy has become the standard preoperative treatment of patients with resectable rectal cancer. Individualized risk assessment might allow a better selection of patients who will benefit from postoperative treatment and intensified follow-up. Patients and methods: From patient's data from three European rectal cancer trials (N=2881), we developed multivariate cox nomograms reflecting the risk for local recurrence (LR), distant metastases (DM) and overall survival (OS). Evaluated variables were age, gender, tumour distance from the anal verge, the use of radiotherapy, surgical technique (total mesorectal excision/conventional surgery), surgery type (low anterior resection/abdominoperineal resection), time from randomization to surgery, residual disease (R0 versus R1 + 2), pT-stage, pN-stage and surgical complications. Results: Pathological T- and N-status are of vital importance for an accurate prediction of LR, DM and OS. Short-course radiotherapy reduces the rate of LR. The developed nomograms are capable of predicting events with a validation c-index of 0.79 (LR), 0.76 (DM) and 0.75 (OS). The proposed stratification in risk groups allowed significant distinction between Kaplan-Meier curves for outcome. Conclusion: The developed nomograms can contribute to better individual risk prediction for LR, DM and OS for patients operated on rectal cancer. The practicality of the defined risk groups makes decision support in the consulting room feasible, assisting physicians to select patients for adjuvant therapy or intensified follow-up. [ABSTRACT FROM AUTHOR]

Background: Transanal endoscopic microsurgery (TEM) after radiochemotherapy (RCT) has been reported in selected cases of locally advanced rectal cancer as an alternative to traditional radical resection with total mesorectal excision with a curative intent or as diagnostic tool to confirm a pathological complete response of the primary tumor. No study has evaluated functional outcome after TEM in preoperatively irradiated patients. Methods: This study was designed to evaluate short-term morbidity (according to Clavien's classifications) and establish (by a questionnaire) continence and evacuative function after RCT and TEM, at 1 year from surgery, analyzing the impact of RCT on postoperative outcomes. Patients with locally advanced rectal cancer treated by RCT and TEM (group 1) or with early T1 or adenomas treated only by TEM (group 2) entered this cohort comparative study. Results: Twenty-two patients entered the study as group 1 and 25 as group 2. No postoperative mortality occurred. The morbidity rate was 36.4 % in group 1 vs. 16 % in group 2 ( p = 0.114). The rate of suture dehiscence was 22.7 % in group 1 vs. 4 % in group 2 ( p = 0.068). No grade III complications, reoperation, or hospital readmission within 30 days was recorded in either group. One year after surgery, continence and evacuative scores in group 1 were 1.05 ± 1.25 and 24.72 ± 2.79, respectively, which were similar to group 2 ( p = 0.081 and 0.288, respectively). Conclusions: TEM after RCT in selected rectal cancer patients has an acceptable morbidity and functional results at 1 year from surgery. Preoperative irradiation could increase postoperative short-term morbidity, but it does not seem to influence evacuative or sphincter function after 1 year from surgery. [ABSTRACT FROM AUTHOR]

Abstract: The effects of lycopene-enriched extenders on motility, viability, osmotic resistance, DNA integrity and lipid peroxidation of rabbit sperm were examined after both chilled and frozen storage. Five pools of semen diluted in extenders containing 0, 0.05 or 0.1mg/mL of lycopene were refrigerated at 5°C for 48h or cryopreserved. Sperm quality was generally compromised after storage, especially post-freezing, however lycopene limited the amount of sperm lipid peroxidation after chilling and freezing. In chilled sperm, the highest dose of lycopene was provided to maintain the viability, acrosome and DNA intactness similar to that of fresh semen and contained the reduction of sperm motility, whereas in cryopreserved semen lycopene protected the DNA integrity of sperm, even if not in a dose-dependent way. So lycopene diminished sperm lipid peroxidation during refrigeration and cryopreservation, prolonging the survival of rabbit sperm after liquid storage, but it had a limited effect on sperm cryosurvival. [Copyright &y& Elsevier]

A letter to the editor is presented about the clinicopathological findings in a patient with the LRRK2-G2019S mutation and an atypical tauopathy.

Results For discriminating high risk category vs the other categories one random forest model from the radiomics features (radiomics model), and two logistic regression models from clinical and ultrasound features (clinical-ultrasound model), and from clinical, ultrasound and radiomics features (mixed model) were created. Aim of this study was to develop and validate ultrasound-based radiomics models, aiming to differentiating high risk category, as defined by ESMO-ESGO-ESTRO in 2016, vs the remaining categories of risk. OC10.01: *Developing and validating ultrasound-based radiomics models for predicting high-risk category in endometrial cancer patients. [Extracted from the article]

The aim of this study was to prospectively define and measure evacuation and continence disorders after preoperative radiochemotherapy and total mesorectal excision (TME) for rectal cancer 1 year after surgery. We submitted 100 patients, who underwent neoadjuvant treatment and anterior resection with TME from 1996 to 2003, to a questionnaire on postoperative continence and evacuation. Anal sphincter function was further assessed by the Memorial Sloan–Kettering score. Factors influencing anorectal function were examined in univariate and multivariate analysis. Median evacuation score was 16.12 ± 5.12 (range 0–28). Sensation of incomplete evacuation was reported in 58% of cases, necessity to return to the bathroom <15 min in 37% and inability to evacuate completely <15 min in 35%. Median continence score was 13.7 ± 4.79 (range 0–20). Incontinence to flatus was reported in 46% of cases. Colonic J-pouch allows better evacuation and continence. Continence was also better in absence of postoperative complications. Sphincter function resulted excellent or good in 75% of patients according to the Memorial Sloan–Kettering score. The most frequent symptoms in our series are the sensation of incomplete evacuation, the incontinence to flatus, and the necessity to return to the bathroom <15 min. Colonic J-pouch warrants a better function. Postoperative complications compromise good functional results. [ABSTRACT FROM AUTHOR]

Background: The antiepidermal growth factor receptor (antiEGFR) monoclonal antibodies cetuximab and panitumumab have good clinical activity in about 10% of patients with metastatic colorectal cancer that is resistant to chemotherapy. The molecular mechanisms underlying clinical response or resistance to these agents are unknown.Methods: Tumours from 31 patients with metastatic colorectal cancer who had either an objective response (n=10) or stable disease or progressive disease (n=21) after treatment with cetuximab or panitumumab were screened for genetic changes in EGFR or its immediate intracellular effectors. Specifically, we assessed the EGFR copy number and the mutation profile of the EGFR catalytic domain and of selected exons in KRAS, BRAF, and PIK3CA.Results: Eight of nine of patients with objective responses who were assessable by fluorescence in-situ hybridisation (FISH) had an increased EGFR copy number. By contrast, one of 21 non-responders assessable by FISH had an increased EGFR copy number (p<0.0001 for responders vs non-responders, Fisher's exact test). The mutation status of the EGFR catalytic domain and its immediate downstream effectors PIK3CA, KRAS, and BRAF did not correlate with disease response. In colorectal-cancer cell lines, the concentration of cetuximab that completely inhibited proliferation of cells with amplified EGFR copy number did not affect proliferation of cells with unamplified EGFR.Interpretation: We propose that the response to antiEGFR treatment has a genetic basis and suggest that patients might be selected for treatment on the basis of EGFR copy number. [ABSTRACT FROM AUTHOR]

Vertemati M, Sabatella G, Minola E, Gambacorta M, Goffredi M&Vizzotto L(2005)Histopathology46,451–459Morphometric analysis of primary graft non-function in liver transplantation: Primary graft non-function (PNF) is a life-threatening condition that is thought to be the consequence of microcirculation injury. The aim of the present study was to assess, with a computerized morphometric model, the morphological changes at reperfusion in liver biopsy specimens from patients who developed PNF after liver transplantation.: Biopsy specimens were obtained at maximum ischaemia and at the end of reperfusion. Morphology included many stereological parameters, such as volumes of all parenchymal components, surface density, size distribution and mean diameter of hepatocytes. Other variables examined were intensive care unit stay, degree of steatosis, serum liver function tests and ischaemic time. In the postoperative period, the PNF group showed elevated serum levels of alanine transferase, decreased daily rate of bile production and prothrombin activity. Blood lactates were significantly higher in the PNF group than in a control group. When comparing groups, the volumetric parameters related to hepatocytes and sinusoids and the surface densities of the hepatic cells showed an inverse relationship. At the end of reperfusion, in PNF group the volume fraction of hepatocyte cytoplasm was decreased; in contrast, the volume fraction of sinusoidal lumen was markedly increased. The cell profiles showed the same inverse trend: the surface density of the parenchymal border of hepatocytes was decreased in PNF when compared with the control group, while the surface density of the vascular border was increased. In the PNF group, the surface density of the sinusoidal bed was directly correlated with alanine transferase, daily rate of bile production, prothrombin activity and cold ischaemic time.: The alterations in hepatic architecture, as demonstrated by morphometric analysis in liver transplant recipients that developed PNF, provide additional information that may represent useful viability markers of the graft to complement conventional histological analysis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented discussing the antitumor effect of allogeneic hematopoietic stem cell transplantation (SCT) in metastatic medulloblastoma.

A large pooled analysis of liver oligometastases, classified accordingly to the ESTRO/EORTC recommendations, treated by stereotactic radiotherapy (SBRT) and Radiosurgery (SRS) was carried out. The clinical and dosimetric data of patients who underwent SBRT/SRS for liver metastases were analysed in terms of efficacy and toxicity profile. In particular, the Local Control (LC), the Distant Metastases Free Survival (DMFS), the Disease-Free Survival (DFS), the Overall Survival (OS), and the Next Systemic Therapy Free Survival (NEST-FS) rates were analysed. 113 patients (M/F: 49/64), accounting for a total of 150 hepatic lesions (March 2006-February 2023) in two Italian radiotherapy Institutions were evaluated. Median age was 67 years old (36-92) and 48 (42.5%) patients had at least one comorbidity. The majority of the lesions were induced (30.7%) or repeated oligoprogressive (12.7%) metastases. 98 lesions were treated with more than one daily fraction (mainly 50 Gy in 5 fractions), while 52 were radiosurgery treatments (mainly 32 Gy). The treatment response at 3-4 months was evaluable in 147 lesions: complete response was 32.0%, partial response 17.0%, and stable disease 32.0%. Actuarial LC, DMFS, DFS, OS, and NEST-FS at 1 year were 75.8%, 37.7%, 34.9%, 78.7%, and 59.4% respectively; while actuarial LC, DMFS, DFS, OS, and NEST-FS at 2 years were 52.1%, 24.9%, 21.9%, 51.3%, and 36.8%, respectively. The achievement of complete response, synchronous oligometastases, and no treatment interruptions correlated with a more favorable outcomes. As per the toxicity profile, we registered only two acute and one late toxicity cases higher than grade 2. Stereotactic treatment for liver metastases seems to be a safe and promising option in terms of local control. The best results in term of outcomes have been obtained in patients with complete response, synchronous oligometastases, favorable histology, and no treatment interruptions., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Aims: To report toxicity profile, outcomes and quality of life (QoL) data in patients with recurrent gynaecological cancer who underwent stereotactic body radiotherapy (SBRT) retreatment., Materials and Methods: Data from patients' folders were retrospectively extracted, focusing on the primary neoplasm, previous systemic therapies and previous radiotherapy. Concerning SBRT, the total dose (five daily fractions) was delivered with a linear accelerator using intensity-modulated radiotherapy techniques. Acute and late toxicities were assessed by the CTCAE 4.03 scale. QoL was evaluated according to the Cancer Linear Analogue Scale [CLAS1 (fatigue), CLAS2 (energy level), CLAS3 (daily activities)]., Results: Between December 2005 and August 2021, 23 patients (median age 71 years, range 48-80) with 27 lesions were treated. Most patients had endometrial (34.8%), ovarian (26.1%) and cervical cancer (26.1%) as the primary tumour. The most common SBRT schedules in five fractions were 30 Gy (33.3%), 35 Gy (29.6%) and 40 Gy (29.6%). The median follow-up was 32 months (range 3-128). There were no patients reporting acute or late toxicities higher than grade 2, except for a bone fracture. One- and 2-year local control was 77.9% and 70.8%, respectively. One- and 2-year overall survival was 82.6% and 75.1%, respectively. The overall response rate was 96.0%. Regarding QoL, no statistically significant difference was identified between the baseline and follow-up values: the median CLAS1, CLAS2 and CLAS3 scores for each category were 6 (range 4-10) at baseline and 6 (range 3-10) 1 month after SBRT., Conclusions: This preliminary experience suggests that SBRT retreatment for recurrent gynaecological cancer is a highly feasible and safe treatment with limited side-effects and no short-term QoL impairment., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The glioblastoma's bad prognosis is primarily due to intra-tumor heterogeneity, demonstrated from several studies that collected molecular biology, cytogenetic data and more recently radiomic features for a better prognostic stratification. The GLIFA project (GLIoblastoma Feature Analysis) is a multicentric project planned to investigate the role of radiomic analysis in GB management, to verify if radiomic features in the tissue around the resection cavity may guide the radiation target volume delineation., Materials and Methods: We retrospectively analyze from three centers radiomic features extracted from 90 patients with total or near total resection, who completed the standard adjuvant treatment and for whom we had post-operative images available for features extraction. The Manual segmentation was performed on post gadolinium T1w MRI sequence by 2 radiation oncologists and reviewed by a neuroradiologist, both with at least 10 years of experience. The Regions of interest (ROI) considered for the analysis were: the surgical cavity ± post-surgical residual mass (CTV&#95;cavity); the CTV a margin of 1.5 cm added to CTV&#95;cavity and the volume resulting from subtracting the CTV&#95;cavity from the CTV was defined as CTV&#95;Ring. Radiomic analysis and modeling were conducted in RStudio. Z-score normalization was applied to each radiomic feature. A radiomic model was generated using features extracted from the Ring to perform a binary classification and predict the PFS at 6 months. A 3-fold cross-validation repeated five times was implemented for internal validation of the model., Results: Two-hundred and seventy ROIs were contoured. The proposed radiomic model was given by the best fitting logistic regression model, and included the following 3 features: F&#95;cm&#95;merged.contrast, F&#95;cm&#95;merged.info.corr.2, F&#95;rlm&#95;merged.rlnu. A good agreement between model predicted probabilities and observed outcome probabilities was obtained ( p -value of 0.49 by Hosmer and Lemeshow statistical test). The ROC curve of the model reported an AUC of 0.78 (95% CI: 0.68-0.88)., Conclusion: This is the first hypothesis-generating study which applies a radiomic analysis focusing on healthy tissue ring around the surgical cavity on post-operative MRI. This study provides a preliminary model for a decision support tool for a customization of the radiation target volume in GB patients in order to achieve a margin reduction strategy., 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. The handling editor declared a shared parent affiliation with the authors SC, RR, FB, GS, MC, RG, SL, HT, LB, ND, CV, FP, GD, GD’A, AO, MB, CC, MG, VV, and SG at the time of review., (Copyright © 2023 Chiesa, Russo, Beghella Bartoli, Palumbo, Sabatino, Cannatà, Gigli, Longo, Tran, Boldrini, Dinapoli, Votta, Cusumano, Pignotti, Lupattelli, Camilli, Della Pepa, D’Alessandris, Olivi, Balducci, Colosimo, Gambacorta, Valentini, Aristei and Gaudino.)

Objective: The objective of this study is to find a contrast-enhanced CT-radiomic signature to predict clinical incomplete response in patients affected by hepatocellular carcinoma who underwent locoregional treatments., Patients and Methods: 190 patients affected by hepatocellular carcinoma treated using focal therapies (radiofrequency or microwave ablation) from September 2018 to October 2020 were retrospectively enrolled. Treatment response was evaluated on a per-target-nodule basis on the 6-months follow-up contrast-enhanced CT or MR imaging using the mRECIST criteria. Radiomics analysis was performed using an in-house developed open-source R library. Wilcoxon-Mann-Whitney test was applied for univariate analysis; features with a p-value lower than 0.05 were selected. Pearson correlation was applied to discard highly correlated features (cut-off=0.9). The remaining features were included in a logistic regression model and receiver operating characteristic curves; sensitivity, specificity, positive and negative predictive value were also computed. The model was validated performing 2000 bootstrap resampling., Results: 56 treated lesions from 42 patients were selected. Treatment responses were: complete response for 26 lesions (46.4%), 18 partial responses (32.1%), 10 stable diseases (17.9%), 2 progression diseases (3.6%). Area-Under-Curve value was 0.667 (95% CI: 0.527-0.806); accuracy, sensitivity, specificity, positive and negative predictive values were respectively 0.66, 0.85, 0.50, 0.59 and 0.79., Conclusions: This contrast-enhanced CT-based model can be helpful to early identify poor responder's hepatocellular carcinoma patients and personalize treatments.

Objective: The aim of our systematic review was to assess the role of interventional radiotherapy (IRT, brachytherapy) in the management of primary and/or recurrent vulvar carcinoma., Evidence Acquisition: A systematic research using PubMed, Scopus and Cochrane library was performed. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Only full-text English-language articles related to IRT for treatment of primary or recurrent VC were identified and reviewed. Conference paper, survey, letter, editorial, book chapter and review were excluded. Time restriction (1990-2018) as concerns the years of the publication was considered., Evidence Synthesis: Primary disease: the median 5-year LC was 43.5% (range 19-68%); the median 5-year DFS was 44.5% (range 44-81%); the median 5-year OS was 50.5% (range 27-85%). Recurrent disease: the median 5-year DFS was 64% (range 56-72%) and the median 5-year OS was 45% (range 33%-57%). Acute ≥ grade 2 toxicity was reported in three patients (1.6%). The severe late toxicity rates (grade 3-4) ranged from 0% to 14.3% (median 7.7%)., Conclusion: IRT as part of primary treatment for primary and/or recurrent vulvar cancer is associated with promising clinical outcomes.

Objective: From a clinical point of view, Kimura's disease is typically characterized by a subcutaneous mass occurring predominantly in the head and neck region. It occurs predominantly in young men of Asian descent, with a peak incidence in the second and third decades of life. However, KD has been also reported in other ethnic groups and in children. The most frequently used local treatments are surgical excision, radiotherapy, and surgical excision followed by radiotherapy. The aim of this multicenter systematic review is to highlight the available literature evidence about the outcome of RT in this setting., Materials and Methods: A systematic review of any relevant literature in the principal medical databases, such as PubMed, Scopus and Cochrane library, was conducted. The inclusion criteria were original articles specifically reporting about KD and RT, including both prospective and retrospective studies., Results: We were able to identify 11 studies, published from 1989 to 2021, eligible for inclusion in this review. Overall, data on 124 patients were recorded and are presented in this systematic review. The median recurrence rate, considering all patients, was 11% (ranging from 0% to 41.2%). In seven out of 11 studies, the relapse rate was less than 20%. Moreover, the relapse rate was 0% in four studies., Conclusions: The results of this multicenter systematic literature review show that evidence on RT of KD is limited and derives only from retrospective studies. In this setting RT seems to be well-tolerated and able to produce very high response rates in unresected lesions and reasonable results in terms of local control both as an exclusive and adjuvant treatment.

Objective: The aim of this paper is to provide an update about the current clinical indications of RT in this poorly explored field outside the traditional oncological setting., Materials and Methods: We performed a literature search on the main databases, including PubMed, Scopus and Cochrane from their inception until 31st December 2020. An additional manual check of scientific meeting proceedings and books was conducted in order to identify all the potentially useful sources. Only essays published in English have been considered for the purposes of this analysis. The searched items included: "Radiotherapy or Radiation Therapy" and "Benign disorder or Benign disease"., Results: We provided a list of current clinical indications for benign disorders based on the latest international surveys available, including major sites: eye, bone, head and neck, skin, brain, heart and peripheral vascular system., Conclusions: Radiotherapy for benign diseases is still a feasible therapeutic strategy, which may allow to treat several invalidating conditions, especially after medical therapies have failed thus avoiding potentially invalidating major surgical procedures. A careful evaluation in selecting the indication is essential and all the choices should be thoroughly discussed with the patients.

Objective: This review aimed at examining efficacy of interventional radiotherapy (brachytherapy-IRT) alone or combined with external beam radiotherapy (EBRT) in stage I esophageal cancer as exclusive treatment., Materials and Methods: A systematic research using PubMed, Scopus, and Cochrane library was performed. 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 study as full-text publication, reporting on patients with stage I esophageal cancer treated with IRT alone or in combination with other treatments (e.g., EBRT). Conference paper, survey, letter, editorial, book chapter, and review were excluded. Patients who underwent previous surgery were excluded. Time restriction (1990-2018) was applied for years of the publication., Results: Twelve studies have been selected. The number of evaluated patients was 514; the median age was 69 years. In the IRT group, the median: local control (LC) was 77% (range 63%-100%), disease-free survival (DFS) was 68.4% (range 49%-86.3%), the overall survival (OS) was 60% (range 31%-84%), the cancer specific survival (CSS) was 80% (range 55-100%), and grade 3-4 toxicity range was 0%-26%., Conclusions: IRT alone or combined to EBRT is an effective and safe treatment option for patients with stage I esophageal cancer. Definitive radiation therapy could be an alternative to surgery in patients with superficial cancer.

Introduction: This survey describes Italian RTTs' involvement and opinions in research activities related to radiation oncology. Primary aim was to assess the degree of involvement of the national RTTs community in research and to describe how RTTs can integrate their skills collaborating with other professionals., Materials and Methods: A ten-items multiple-choice questionnaire, with 2-8 possible responses, was developed by a steering committee and generated on a survey platform. Links were sent via email to Italian RTTs.The questions were divided in 3 domains: demographic data; scientific research and activity; opinions about RTTs role in scientific research. The survey started on October 1, 2018 and ended on January 31, 2019., Results: One hundred thirty-five out of 509 (26.5%) RTTs responded to the questionnaire at its expiring date; 97.73% think to be valid contributors in radiation oncology research, expressing clear interest in "data collection" tasks (52.71%); 38.64% feel unsupported by other professionals in the research team and 59.85% of the respondents are not members in any scientific society., Conclusions: The role of Italian RTTs in research is heterogeneous. Mainly RTTs in the age range from 30 to 40 years responded to the survey showing their interest in scientific research. This might be related to different informatics and educational skills as well as to personal attitudes. RTTs particular skills, like data management and technical hypothesis generation abilities, are of benefit to realize research projects. Therefore, engaging RTTs in research activities is strongly suggested., 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., (© 2020 The Authors.)

Aim: To find diffusion-weighted (DW) magnetic resonance imaging (MRI) parameters predictive for radiation-induced vaginal stenosis (VS) in locally advanced cervical cancer (LACC) treated with neoadjuvant chemoradiation therapy (CRT)., Materials and Methods: Retrospective analysis of 43 patients with LACC who underwent 1.5 T DW-MRI before (baseline), after 2 weeks (early), and at the end of CRT (final). At MRI, vaginal length, thickness, width, and cervical tumour volume (TV) were measured. Vaginal signal intensity at DW-MRI was analysed at final MRI. CRT-induced VS was graded using Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Correlations between DW-MRI and clinical data were made using Wilcoxon's test, Mann-Whitney test, Fisher's exact test, or chi-squared test as appropriate. Receiver operating characteristic (ROC) curves were generated for variables to evaluate diagnostic ability to predict CRT-induced VS using a logistic regression model., Results: Asymptomatic vaginal toxicity (CTCAE Grade 1) was observed in 14 patients and symptomatic CRT-induced VS (CTCAE Grade ≥2) was detected in 29 patients. Baseline TV was higher in Grade 1 than in Grade ≥2 (p=0.013). Median vaginal length, thickness, and width decreased between baseline and final MRI in all patients (p<0.0001) without significant variances between CTCAE grades. Significant differences were observed in DW-MRI patterns (p<0.0001). In Grade ≥2, DWI showed signal loss of vaginal mucosa in 17 patients (63%) and diffuse restricted diffusion of vaginal wall in eight patients (30%). AUC was 0.938 (coefficient=4.72; p<0.001) for DWI and 0.712 (coefficient=-2.623×10 -5 ; p=0.004) for TV., Conclusions: This is the first study using DW-MRI for predicting CRT-induced VS. DWI is useful tool in patients with LACC after CRT for early prevention and management strategies for VS., (Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Introduction: Colorectal cancer is a very common form of cancer worldwide, affecting an increasing number of young women. Standard treatment for locally advanced rectal cancer (LARC) can pose a threat to fertility in these patients., Case Presentation: We present the case of a young woman affected by LARC who expressed a desire for child-bearing. The treatment she was proposed, according to guidelines, was neoadjuvant chemo-radiotherapy (CRT) followed by delayed surgery, carrying with it a high risk for amenorrhea. Counselling was performed before the initiation of treatment, with the aim of preserving fertility by the proposal of GnRH agonist administration, ovarian transposition and ovarian tissue cryopreservation, which the patient accepted. Treatment was then successfully completed. The patient presented regular menstrual period from before the surgery., Discussion: Ovarian tissue is very sensitive to radiations. Transposition of the organ can prevent ovarian insufficiency by placing it outside the radiation field, while ovarian tissue cryopreservation and orthotopic transplantation offers the possibility to restore fertility in the case of organ failure. We performed both of the techniques. GnRH analogs administration allowed to diminish the risk of ovarian cytotoxicity. Radiation treatment plan was optimized in order to minimize the dose to organs at risk (ovary and vagina in particular); position of the uterus, which is quite radiosensitive too, was monitored with daily cone-beam CT (CBCT)., Conclusion: The strategy proposed seemed safe and effective, resulting in radical treatment and persistence of regular menstrual period. Further studies are needed., 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., (© 2019 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Objective/purpose: Extramammary Paget disease (EMPD) is a rare neoplasm of the skin generally affecting the anogenital area. Because of the low-frequency of the disease, no specific guidelines about the treatment strategy are available. Surgery is the recommended therapy for resectable and localized disease, but several other local treatments have been reported such as radiotherapy (RT). Most articles report small retrospective studies, referring to patients treated decades ago with large heterogeneity in terms of RT dose and technique. The aim of this study was to systematically review the main experiences in RT for the treatment of EMPD in the past 30 years., Materials and Methods: A systematic search of the bibliographic databases PubMed and Scopus from January 1986 to January 2017 was performed including studies published in English, Italian, Spanish, French, and German language., Results: According to the search strategy, 19 full-text articles, published from 1991 to 2015, fulfilled inclusion criteria and were included in the final review. All articles were retrospective analyses with no randomized controlled trials. These studies evaluated 195 EMPD patients treated with RT, delivered in several settings. A large variability in terms of RT doses, fractionation, clinical setting, and techniques was found.Radiotherapy was administered as definitive treatment for primary or recurrent disease after surgery in 18 studies with doses ranging from 30 to 80.2 Gy delivered in 3 to 43 fractions. Radiotherapy was administered as postoperative adjuvant treatment in 9 articles with doses ranging between 32 and 64.8 Gy in 20 to 30 fractions. Two studies reported the RT use in preoperative neoadjuvant setting with doses ranging between 40 and 43.30 Gy, and 2 experiences reported the RT treatment for in situ EMPD, using 39.6 to 40 Gy. Adverse events were reported in almost all but 2 articles and were grade 2 or lower.The 18 studies evaluating RT as definitive treatment for primary or recurrent disease after surgery reported a complete response rate ranging from 50% to 100%, with a variable rate of local relapse or persistent disease ranging from 0% to 80% of cases. The 9 studies evaluating RT as postoperative adjuvant treatment reported a local relapse or persistent disease rate of 0% to 62.5%. A dose-response relationship was reported suggesting doses greater than or equal to 60 Gy for gross tumor volume treatment. Local control, disease-free survival, and overall survival at 12, 20, and 60 months have been retrieved for available data, respectively.In patients with EMPD and concurrent underlying internal malignancy, the prognosis was often worsened by the latter. In this setting, literature analysis showed a potential RT palliative role for symptoms control or local control maintenance.Derma tumor invasion greater than 1 mm and lymph node metastases were reported to be important prognostic factors for distant metastases or death., Conclusions: To date, literature highlights the role of RT in the management of EMPD, but with low level of evidences.

Purpose: The aim of this study is to provide a prospective analysis of post-operative and oncological outcomes in patients affected by locally advanced rectal cancer (LARC), who obtained a major/complete clinical response after pre-operative radio-chemotherapy (RCT) and were treated with local excision (LE) by trans-anal endoscopic microsurgery (TEM) to confirm a pathological complete response (pCR) after to neo-adjuvant RCT., Methods: All patients with LARC treated by pre-operative RCT and full-thickness LE by TEM (2000-2014) were included in the study. If the pathological analysis confirmed near complete or pCR, intensive follow up was proposed. If the pathological response was incomplete, a radical resection with TME was proposed. Post-operative (according to Clavien's classification), functional and long-term oncological outcome were analyzed., Results: 36 patients were treated by TEM. The median post-operative hospital stay was 5 days. The post-operative morbidity was 41.6% (no grade ≥3). At pathological analysis, 23 specimens were ypT0 TRG1, and 4 were ypT1 TRG2. In 9 cases (ypT>1 and/or TRG>2), radical surgery with TME was proposed but 3 refused it. Median follow-up was 68 months. One local recurrence and 4 distant metastases occurred. The 5-yr actuarial local control, overall survival and disease-free survival were 96.0%, 92.0% and 82.8%., Conclusions: In case of major or complete clinical response of LARC after pre-operative RCT, LE by TEM can be used to confirm the pathological response. This avoids the necessity of radical surgery and, in our experience, this approach seems to guarantee oncological safety with the functional advantages of an organ-sparing procedure., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: To compare patterns and rates of early and late complications, and survival outcome in FIGO stage III cervical cancer patients underwent to radical hysterectomy after chemo-radiation (CT-RT) vs. chemo-radiation alone., Methods: Between May 1996 and April 2013 150 FIGO stage III cervical cancer patients were treated. We divide patients according to type of treatment: 77 were submitted to standard treatment (Group A), and 73 to completion hysterectomy after chemo-radiation (Group B)., Results: The baseline characteristics of the 2 groups were superimposable. We observed lower intra-operative and treatment-related early urinary and gastro-intestinal complications in Group B with respect to Group A (p < 0.001). Vascular complications were registered only in Group B (p < 0.001). We found a significantly higher rate of local recurrences in the Group A than in the Group B (p < 0.002). We registered 29 deaths in the Group A and 22 in the Group B (p = 0.021). The 3-years disease-free survival rate in the Group A and in the Group B was 62.9% and 68.3%, respectively (p = 0.686), and the 3-years overall survival rate in the Group A and in the Group B was 63.2% and 67.7%, respectively (p = 0.675)., Conclusions: This study confirms that radical hysterectomy after CT-RT is an effective therapeutic approach for advanced cervical cancer. Further prospective and randomized studies should be performed in order to solve the question about the standard approach, and how the different pattern of complication could impact on the quality of life., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Correlation between pathological response of primary tumour and mesorectal lymph node involvement was prospectively evaluated to assess the role of local excision (LE) in rectal cancer after complete response to neoadjuvant treatment. A series of 272 consecutive rectal cancer, submitted to neoadjuvant radiochemotherapy (RCT) and surgery with total mesorectal excision (TME) were analysed. Tumour downstaging (pT) and tumour regression grade (TRG) together with sex, age, location of the tumour, pre-treatment clinical stage, type of chemoradiation and operation performed entered in an univariate and multivariate analysis. Pathological complete response on primary tumour was found in 56 patients (20.6%). Lymph node metastases were found in 72 patients (26.5%). The rate of positive nodes was 1.8% for pT0 and TRG1 cases, respectively, to go up to 6.3% for pT1 and 24.1% for TRG 2 cases, respectively. At the univariate analysis, factors with a statistically significant correlation with the risk of lymph node metastasis were: clinical pre-treatment N stage (p<0.05), pT stage (p<0.001) and TRG (p<0.001). At the multivariate analysis, the best predictors of pathologic lymph node involvement were pT stage (p=0.0013 ) and TRG (p=0.0011). Because LE is an adequate technique to assess the tumour pathological response and nodal involvement in pT0 or TRG1 cases seems extremely infrequent, radical resection is probably not justified after pathological complete response. Prospective randomized trials are necessary to establish if, in these cases, LE can guarantee the same oncologic results offered by the currently adopted protocols of RCT followed by radical resections.

Purpose: Endocavitary radiation (RT) provides a conservative alternative to proctectomy. Although most suitable for small, mobile lesions, patients with less favorable tumors are often referred if they are poor surgical candidates. Knowing the extent to which radiation can control such tumors can be an important factor in making clinical decisions., Methods and Materials: One hundred ninety-nine patients, who received endocavitary RT with or without external beam RT (EBRT) during 1981 through 1995, were followed for disease status for a median of 70 months, including deaths from intercurrent causes. In the early years of the study, 21 patients were treated with endocavitary RT alone, the remainder of the patients received pelvic EBRT (usually 45 Gy in 25 fractions) 5-7 weeks before endocavitary RT., Results: Overall, 141 patients (71%) had local control with RT alone. Salvage surgery rendered an additional 20 patients disease free, for an ultimate local control rate of 81%. On multivariate analysis for local control (excluding surgical salvage), the most significant factors were mobility to palpation, use of EBRT, and whether pretreatment debulking of all macroscopic disease had been done (generally a piecemeal, nontransmural procedure). Of 77 cases staged by transrectal ultrasonography, the local control rate with RT alone was 100% for uT1 lesions, 85% (90% with no evidence of disease after salvage) for freely mobile uT2 lesions, and 56% (67% with no evidence of disease after salvage) for uT3 lesions and uT2 lesions that were not freely mobile., Conclusions: Patients with small mobile tumors that are either uT1 or have only a scar after debulking achieve excellent local control with endocavitary RT. About 15% of mobile uT2 tumors fail RT; therefore, careful follow-up is critical. Small uT3 tumors are appropriate for this treatment only if substantial contraindications to proctectomy are present.

The approach to the implementation of a Quality Assurance Program applied from 1 October 2000 at the Radiotherapy Service of the "Università Cattolica del S. Cuore, Policlinico "A. Gemelli" of Rome, is described. Some major aspects of this program are analyzed.

The Quality Handbook includes the description of the activities carried out in Radiotherapy and the methodology used to ensure the Quality Assurance according to the principles indicated in national and international documents of reference and the recommendations of accreditation agencies. The structure of the Quality Handbook, the main aspects of single chapters, the selected quality indicators undergoing inspections are analysed and procedures to be followed for changes and updating of the Quality Handbook are described. The Quality Assurance program is illustrated in another article of this issue.

Brachytherapy is a conventional method of radiation therapy characterized by peculiar technical, clinical, operational and radioprotection problems. Therefore, the management of a service or department of brachytherapy requires a specific organization aimed at Quality Assurance. In this report, the personal experience with the drawing up of a Quality Handbook of brachytherapy with reference to the method used and the structure of the document, is described.

Sixty per cent of oncologic patients need radiation therapy for cure or palliation. In fact, in most neoplastic diseases, a better local control positively impacts on disease-free survival and overall survival. The efficacy of radiotherapy depends on several factors: while some are tumor-related, others are host-related. Radiobiological phenomena are also important: ionizing radiation is responsible for cell damage (double rupture of DNA chains), mostly an indirect mechanism with the formation of free radicals. Their toxic action is enhanced by the oxygen partial pressure at the cellular level. A number of studies have confirmed that good tissue oxygenation is a function of a high hemoglobin level in the peripheral blood (Hb > or = 13 g/dL). Unfortunately, these values are rarely present in oncologic patients due to the disease-related toxicosis as well as to the therapy induced hematologic toxicity. The treatment of anemia is free of risk for the recent developments in technology which with gene cloning and the technique of recombinant DNA has allowed the production of human recombinant erythropoietin. Erythropoietin is produced by the interstitial cells of renal tubules in response to hypoxia. It prevents apoptosis and promotes erythroid proliferation and differentiation with consequent reticulocyte release and hemoglobin synthesis. It is not completely understood whether the efficacy of radiotherapy depends on hemoglobin values present at the start of irradiation (often less than 12-13 g/dL) or on the higher ones observed during and at the end of radiotherapy. Therefore, preventive systemic erythropoietin therapy in non anemic patients in terms of costs/benefits is at present non sustainable. To the contrary, in patients undergoing radiotherapy to extended fields or aggressive multimodal treatments, for the higher risk of anemia, the early use of this treatment can be hypothesized in case of initial anemia to improve therapy compliance and prevent negative conditioning of results. Keeping in mind that grade 1 minimum toxicity for red cells, according to the Radiation Therapy Oncology Group (RTOG) is equal to 11 gHb/dL we think that this value can be considered as cutoff to start erythropoietin therapy.