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Purpose The aim of this paper was to evaluate treatment outcomes following interventional radiotherapy (brachytherapy - BT) for nasal vestibule cancer. Material and methods Considering histological diagnosis and staging, a multidisciplinary tumor board indicated an exclusive interventional radiotherapy for all patients. Plastic tubes were placed mainly with interstitial approach. The total dose was 44 Gy in 14 fractions, 3 Gy/fraction (except for the first and last fractions, 4 Gy), 2 fractions per day (b.i.d.), 5 days a week. Inclusion criteria for this analysis were: patients affected by squamous cell carcinoma with follow-up more than 6 months. Results 20 patients with primary nasal vestibule cancer were treated with IRT from May 2012 to June 2019. We excluded 4 patients due to follow-up less than 6 months and 2 patients affected by basal cell carcinoma. In total, 14 consecutive previously untreated patients were considered for definitive analysis, median age was 67.5 (range, 51-83) years, median follow-up was 53 (range, 6-84) months. All patients followed the protocol except one, who received a total dose of 42 Gy in 12 fractions, 3 Gy per 6 fractions, and 4 Gy per 6 fractions. Local control at 12, 24, and 36 months was 85.7%. Overall survival at 12 months was 92.3%, at 24 months was 76.9%, and at 36 months was 69.2%. Staging system proposed by Wang was statistically significant on local control (LC), disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). Excellent cosmetic results were observed. Conclusions This study confirms that interventional radiotherapy could be considered as a definitive treatment in nasal vestibule cancer with excellent oncological and cosmetic outcomes.

Purpose Aim of this study was to develop a generalised radiomics model for predicting pathological complete response after neoadjuvant chemo-radiotherapy in locally advanced rectal cancer patients using pre-CRT T2-weighted images acquired at a 1.5 T and a 3 T scanner. Methods In two institutions, 195 patients were scanned: 136 patients were scanned on a 1.5 T MR scanner, 59 patients on a 3 T MR scanner. Gross tumour volumes were delineated on the MR images and 496 radiomic features were extracted, applying the intensity-based (IB) filter. Features were standardised with Z-score normalisation and an initial feature selection was carried out using Wilcoxon–Mann–Whitney test: The most significant features at 1.5 T and 3 T were selected as main features. Several logistic regression models combining the main features with a third one selected by those resulting significant were elaborated and evaluated in terms of area under curve (AUC). A tenfold cross-validation was repeated 300 times to evaluate the model robustness. Results Three features were selected: maximum fractal dimension with IB = 0–50, energy and grey-level non-uniformity calculated on the run-length matrix with IB = 0–50. The AUC of the model applied to the whole dataset after cross-validation was 0.72, while values of 0.70 and 0.83 were obtained when 1.5 T and 3 T patients were considered, respectively. Conclusions The model elaborated showed good performance, even when data from patients scanned on 1.5 T and 3 T were merged. This shows that magnetic field intensity variability can be overcome by means of selecting appropriate image features.

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.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.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.This contrast-enhanced CT-based model can be helpful to early identify poor responder's hepatocellular carcinoma patients and personalize treatments.

Introduction/Background* Vulvar cancer (VC) is a rare gynaecologic cancer with poor outcomes in locally advanced disease. This study aims to evaluate in a retrospective, multicentred, real-world dataset of patients affected by VC efficacy and safety of exclusive (chemo)radiotherapy (eRT), focusing especially to the treatment prescription among participant centers joining the Observational itaLian stuDy on vuLvar cAncer radical raDiotherapY (OLDLADY) project endorsed by the GYN study group of the AIRO (Italian Association of Radiotherapy and Clinical Oncology). Methodology Patients affected by VC and treated by eRT from January 2010 to December 2018 in Seven Italian radiotherapy centers were retrospectively included and clinical data were collected, analysing tumour staging, treatment prescription, clinical and toxicity outcomes. Result(s)* The multicentred retrospective cohort was composed by 90 patients (patient populations shown in table 1), with a median age of 76 years (range 32-92). A considerable heterogeneity was found in the treatment prescription, radiotherapy doses and concomitant chemotherapy schedules. The most relevant acute toxicity revealed for the patient cohort was skin toxicity (26%); instead, the rate of severe skin fibrosis was 4.4%. After a median follow-up of 10 months (range 1-199), the 2-year actuarial local control rate (LC), the 2-year disease free survival rate (DFS) and the overall survival rate (OS) were 42.2%, 40%, and 36.7%, respectively. Kaplan-Meier curves were computed and reported in figure 1. Conclusion* A diverse spectrum of radiotherapy options to exclusively treat patients affected by VC was reported. Clinical outcomes are still confirmed to be poor. The results suggest the clinical evaluation of the impact of treatment standardisation, in terms of doses and volumes, in a further perspective study.

Introduction/Background* Vulvar cancer (VC) is a rare gynaecologic malignancy. The study aims to evaluate in a retrospective, multicentred, real-world dataset of patients affected by VC efficacy and safety of adjuvant (chemo)radiotherapy (aRT), focusing especially to the treatment prescription among participant centers joining the Observational itaLian stuDy on vuLvar cAncer adjuvant raDiotherapY (OLDLADY) project endorsed by the GYN study group of the AIRO (Italian Association of Radiotherapy and Clinical Oncology). Methodology Patients affected by VC and treated by eRT from January 2010 to December 2018 in Nine Italian radiotherapy centers were retrospectively included and clinical data were collected, analysing tumour staging, treatment prescription, clinical and toxicity outcomes. Result(s)* The multicentred retrospective cohort was composed by 181 patients (patient populations shown in table 1), with a median age of 71.5 years (range 17-90). A considerable heterogeneity was found in the treatment prescription, radiotherapy doses and concomitant chemotherapy schedules. The most relevant acute toxicity revealed for the patient cohort was skin toxicity (22.1%); instead, the rate of severe chronic lymphoedema was 1.1%. After a median follow-up of 30 months (range 1-185), the 2-year actuarial local control rate (LC), the 2-year disease free survival rate (DFS) and the overall survival rate (OS) were 57.2%, 49.4%, and 55.1%, respectively. Kaplan-Meier curves were computed and reported in figure 1. Conclusion* A diverse spectrum of radiotherapy options to exclusively treat patients affected by VC was reported. To achieve higher treatment standardisation, in terms of prescribed doses and volumes, this study suggest further cooperative prospective studies.

Radiotherapy is highly involved in the management of prostate cancer. Its features and potential applications experienced a radical evolution over last decades, as they are associated to the continuous evolution of available technology and current oncological innovations. Some application of radiotherapy like brachytherapy have been recently enriched by innovative features and multidisciplinary dedications. In this report we aim to put some questions regarding the following issues regarding multiple aspects of modern application of radiation oncology: the current application of radiation oncology; the modern role of stereotactic body radiotherapy (SBRT) for both the management of primary lesions and for lymph-nodal recurrence; the management of the oligometastatic presentations; the role of brachytherapy; the aid played by the application of the organ at risk spacer (spacer OAR), fiducial markers, electromagnetic tracking systems and on-line Magnetic Resonance guided radiotherapy (MRgRT), and the role of the new opportunity represented by radiomic analysis.

The Objective Breast Cosmesis Scale (OBCS) is an objective method that documents the aesthetic changes in breast cancer patients. This work evaluates the kOBCS© software (http://www.kobcs.info) which simplifies the estimation of the OBCS values. Five schematic drawings were photographed and imported into the kOBCS©. Thirty photos of breast cancer patients were imported into kOBCS©; 20 users (experts and non-experts) evaluated the photographs on two different settings. Subjective evaluation was performed using the Harvard breast cosmesis scale. There was a highly significant correlation between the OBCS values based on hand measurements and the values estimated by kOBCS© (r = 0.997, P

Following the personaliied medicine paradigm, there is a growing interest in medical agents capable of predicting the effect of therapies on patients, by exploiting the amount of data that is now available for each patient. In disciplines like oncology, where images and scans are available, the exploitation of medical images can provide an additional source of potentially useful information. The study and analysis of features extracted by medical images, exploited for predictive purposes, is termed radiomics. A number of tools are available for supporting some of the steps of the radiomics process, but there is a lack of approaches which are able to deal with all the steps of the process.In this paper, we introduce a medical agent-based decision support system capable of handling the whole radiomics process. The proposed system is tested on two independent data sets of patients treated for rectal cancer. Experimental results indicate that the system is able to generate highly performant centre-specific predictive model, and show the issues related to differences in data sets collected by different centres, and how such issues can affect the performance of the generated predictive models.

Background/aim Non-melanoma skin cancers (NMSC) are the most common neoplasms worldwide and their incidence has been proven to increase in recent years and their treatment should aim at cancer cure as well as cosmetic and functional results. The aim of the study was to report the results of our mono-institutional series of high-dose-rate radiotherapy (cHDR-RT) in NMSC, based on a homogenous technique and two different treatment schedules. Patients and methods All patients affected by NMSC who were consecutively evaluated and treated at our Interventional Oncology Center from October 2018 to August 2020, were included. Patients underwent cHDR-RT using flap applicators and remotely afterloaded Ir-192 sources. Results Overall, 51 patients were treated for a total of 67 lesions. Local control (LC) and disease-specific survival (DSS) were 94.0% and 100%, respectively. Grade 1, grade 2, grade 3 and grade 4 acute toxicity rates were 24.6%, 3.5%, 3.5%, and 0.0%, respectively. The cosmetic results were graded as excellent/good, fair, and poor in 73.7%, 19.3%, and 7.0%. Conclusion cHDR-RT of NMSC is an effective alternative to surgery due to excellent outcomes both in terms of local control and aesthetic results especially in the face.

Melanoma is an extremely aggressive tumor and is considered to be an extremely immunogenic tumor because compared to other cancers it usually presents a well-expressed lymphoid infiltration. The aim of this paper is to perform a multidisciplinary comprehensive review of the evidence available about the combination of radiotherapy and immunotherapy for melanoma. Radiation, in fact, can increase tumor antigens visibility and promote priming of T cells but can also exert immunosuppressive action on tumor microenvironment. Combining radiotherapy with immunotherapy provides an opportunity to increase immunostimulatory potential of radiation. We therefore provide the latest clinical evidence about radiobiological rationale, radiotherapy techniques, timing, and role both in advanced and systemic disease (with a special focus on ocular melanoma and brain, liver, and bone metastases) with a particular attention also in geriatric patients. The combination of immunotherapy and radiotherapy seems to be a safe therapeutic option, supported by a clear biological rationale, even though the available data confirm that radiotherapy is employed more for metastatic than for non-metastatic disease. Such a combination shows promising results in terms of survival outcomes; however, further studies, hopefully prospective, are needed to confirm such evidence.

Purpose: Orbital pseudotumor (or pseudotumor orbitae) is a benign entity, also known as idiopathic orbital inflammatory syndrome (IOIS), which encompasses a wide range of non-tumoral, space occupying lesions of the orbit. In selected cases of refractory disease or presence of side effects or even comorbidities that limit systemic therapies, radiotherapy could play a role in the management because it has been demonstrated that irradiation is effective in suppressing the inflammatory process. Methods: A systematic review of the literature about the main scientific databases was launched and the time interval included all published articles present in the databases from their inception until September 2020. Results: We were able to identify 19 studies eligible for inclusion in this review from 1978 to 2018. Overall the data of 241 patients were collected and are presented in this systematic review. The response rate varied between 74% and 100% with a median recurrence rate of 10%. The median total dose was 20 Gy whereas the mean total dose was 21 Gy with a range from 4 to 36 Gy. Regarding the fractionation, 2 Gy/fraction daily was the most widely used. Conclusions: Radiotherapy seemed to achieve good response rates however, in most of the studies, inclusion criteria and outcome parameters are not uniform and therefore the results are difficult to compare. Often important parameters such as chronic pain and permanent functional deficits are not assessed in the outcome. Therefore, prospective studies, with good cohort characteristics and a clear definition of the outcome, are required.

The aim of this study is to investigate the role of Delta Radiomics analysis in the prediction of one-year local control (1yLC) in patients affected by locally advanced pancreatic cancer (LAPC) and treated using Magnetic Resonance guided Radiotherapy (MRgRT). A total of 35 patients from two institutions were enrolled: A 0.35 Tesla T2*/T1 MR image was acquired for each case during simulation and on each treatment fraction. Physical dose was converted in biologically effective dose (BED) to compensate for different radiotherapy schemes. Delta Radiomics analysis was performed considering the gross tumour volume (GTV) delineated on MR images acquired at BED of 20, 40, and 60 Gy. The performance of the delta features in predicting 1yLC was investigated in terms of Wilcoxon Mann&ndash, Whitney test and area under receiver operating characteristic (ROC) curve (AUC). The most significant feature in predicting 1yLC was the variation of cluster shade calculated at BED = 40 Gy, with a p-value of 0.005 and an AUC of 0.78 (0.61&ndash, 0.94). Delta Radiomics analysis on low-field MR images might play a promising role in 1yLC prediction for LAPC patients: further studies including an external validation dataset and a larger cohort of patients are recommended to confirm the validity of this preliminary experience.

• Medical staff from oncology units are at high risk of burnout during COVID-19 pandemic. • The sense of belonging to the group and the contacting emotions play a central role in reducing these risks. • Gratitude is related to well-involving people who practice and receive it. • During lockdown, we adopted gratitude-focused “inter-group contact” tool.

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.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".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.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: 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.

Simple Summary Locally advanced vulvar cancer (LAVC) requires a multidisciplinary management. The aim of this paper is to conduct a review of all relevant studies regarding the role of radiotherapy in LAVC. Based on the available evidence, radiotherapy, with or without concurrent chemotherapy, has a relevant role in neoadjuvant, adjuvant or exclusive treatments. A multidisciplinary and multidimensional assessment can also be useful to identify the most suitable approach, in view of a better treatment personalization. Abstract Locally advanced vulvar cancer (LAVC) is a challenging disease, requiring multidisciplinary management. The aim of this review is to propose an integrated clinical approach including radiotherapy (RT) in the multidisciplinary management of LAVC to customize the treatment. A review of the literature was conducted on PubMed, Scopus, and Cochrane library to acquire all relevant studies on RT in LAVC. Based on the available evidence, RT, with or without concurrent chemotherapy, has a relevant role as adjuvant and exclusive treatment or in the neoadjuvant setting. However, multicentric prospective trials are needed to define the best treatment options based on tumor and patient characteristics. A multidisciplinary and multidimensional assessment can also be useful to identify the most suitable approach, considering patients’ age and comorbidities, in view of a better treatment personalization.

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.

PurposeDistant metastases are currently the main cause of treatment failure in locally advanced rectal cancer (LARC) patients. The aim of this research is to investigate a correlation between the variation of radiomics features using pre- and post-neoadjuvant chemoradiation (nCRT) magnetic resonance imaging (MRI) with 2 years distant metastasis (2yDM) rate in LARC patients.Methods and MaterialsDiagnostic pre- and post- nCRT MRI of LARC patients, treated in a single institution from May 2008 to June 2015 with an adequate follow-up time, were retrospectively collected. Gross tumor volumes (GTV) were contoured by an abdominal radiologist and blindly reviewed by a radiation oncologist expert in rectal cancer. The dataset was firstly randomly split into 90% training data, for features selection, and 10% testing data, for the validation. The final set of features after the selection was used to train 15 different classifiers using accuracy as target metric. The models’ performance was then assessed on the testing data and the best performing classifier was then selected, maximising the confusion matrix balanced accuracy (BA).ResultsData regarding 213 LARC patients (36% female, 64% male) were collected. Overall 2yDM was 17%. A total of 2,606 features extracted from the pre- and post- nCRT GTV were tested and 4 features were selected after features selection process. Among the 15 tested classifiers, logistic regression proved to be the best performing one with a testing set BA, sensitivity and specificity of 78.5%, 71.4% and 85.7%, respectively.ConclusionsThis study supports a possible role of delta radiomics in predicting following occurrence of distant metastasis. Further studies including a consistent external validation are needed to confirm these results and allows to translate radiomics model in clinical practice. Future integration with clinical and molecular data will be mandatory to fully personalized treatment and follow-up approaches.

Objectives The aim of this paper was to conduct a survey about the evolution of the information provided by Italian radiotherapy departments with a special focus on patients’ perspective. Methods A two-steps analysis was conducted in 2013 and 2020. Starting from analysis of data for the existing websites of Italian radiotherapy departments, main potential areas of interest for patients were discussed within a dedicated multidisciplinary team composed of radiation oncologists, a web designer, a blogger, a psyco-oncologist, a volunteer and a representative of patients’ association. Results Six patient-oriented features to evaluate the websites of Italian radiotherapy departments were identified and several other features not specifically patient-oriented were also reported in our survey. Conclusions A major effort is still needed to develop websites intended to be used by patients which should be both user-friendly and easily accessible. Social media are rapidly gaining a growing importance. Practice implications A pivotal role could be played by patients’ organization who should be empowered by connecting all the stakeholders involved in this field.

The aim of this study was to evaluate the variation of radiomics features, defined as “delta radiomics”, in patients undergoing neoadjuvant radiochemotherapy (RCT) for rectal cancer treated with hybrid magnetic resonance (MR)-guided radiotherapy (MRgRT). The delta radiomics features were then correlated with clinical complete response (cCR) outcome, to investigate their predictive power. A total of 16 patients were enrolled, and 5 patients (31%) showed cCR at restaging examinations. T2*/T1 MR images acquired with a hybrid 0.35 T MRgRT unit were considered for this analysis. An imaging acquisition protocol of 6 MR scans per patient was performed: the first MR was acquired at first simulation (t0) and the remaining ones at fractions 5, 10, 15, 20 and 25. Radiomics features were extracted from the gross tumour volume (GTV), and each feature was correlated with the corresponding delivered dose. The variations of each feature during treatment were quantified, and the ratio between the values calculated at different dose levels and the one extracted at t0 was calculated too. The Wilcoxon–Mann–Whitney test was performed to identify the features whose variation can be predictive of cCR, assessed with a MR acquired 6 weeks after RCT and digital examination. The most predictive feature ratios in cCR prediction were the L_least and glnu ones, calculated at the second week of treatment (22 Gy) with a p value = 0.001. Delta radiomics approach showed promising results and the quantitative analysis of images throughout MRgRT treatment can successfully predict cCR offering an innovative personalized medicine approach to rectal cancer treatment.

IntroductionMultidisciplinary treatment strategy involving adjuvant radiotherapy for advanced vulvar cancer could be useful in offering the best personalized clinical approach. In 2013, the VULvar CANcer Multi-Disciplinary Team (Vul.Can MDT) was set up in our institution, in order to share knowledge and expertise, high-quality diagnosis, and evidence-based decision making in the context of personalized medicine. The aim of this observational study was to report on our series of vulvar cancer patients managed postoperatively with radiotherapy within the framework of a formal multidisciplinary tumor board.MethodsCoupling surgical and oncological international guidelines with “case-by-case” discussions, a multi-specialist consensus was progressively reached and internal recommendations were developed and introduced in the daily routine. Data from vulvar cancer patients who underwent primary surgery and adjuvant radiotherapy throughout a 5-year period were retrospectively collected. Actuarial local control was the primary endpoint, while secondary end-points were acute and late toxicities, disease-free survival, and overall survival. Toxicity was evaluated according to the Common Toxicity Criteria Adverse Event v 4.0 scale.ResultsThe analysis included 35 patients with squamous vulvar cancer treated with adjuvant radiotherapy±chemotherapy, from April 2013 to September 2017. Median age was 70 years (range 18–87), all patients underwent surgery followed by concomitant chemoradiation (45.7%) or radiotherapy alone (54.3%). The median prophylactic dose on lymphatic drainage was 45 Gy, while positive nodes and perineal area received 51.2 Gy and 52.6 Gy, respectively. Chemotherapy involved the cisplatin-based regimen (45.7%)±5-fluorouracil (37.1%). Median follow-up was 32 months (range 6–72): the 24-months local control, disease-free survival, and actuarial overall survival rates were 88.6%, 82.0%, and 91.0%, respectively. Low rates of severe acute (12%) and late (3%) toxicities occurred.DiscussionThe outcomes of this series support the benefit of a multidisciplinary personalized approach in the management of vulvar cancer.

Process Mining is of growing importance in the healthcare domain, where the quality of delivered services depends on the suitable and efficient execution of processes encoding the vast amount of clinical knowledge gained via the evidence-based medicine paradigm. In particular, to assess and measure the quality of delivered treatments, there is a strong interest in tools able to perform conformance checking. In process mining for the healthcare domain, a number of major challenges are posed by: (i) the complexity of involved data, that refers to patients' aspects such as disease, behaviour, clinical history, psychology, etc; (ii) the availability of data, that come from the heterogeneous, fragmented and scant connected healthcare system; and (iii) the wide range of available standards for communication (DICOM, IHE, etc.) or data representation (ICD9, SNOMED, etc.) purposes. To effectively perform process mining in the healthcare domain, it is crucial to build event logs capturing all the steps of running processes, which have to be derived by the knowledge stored in the Electronic Health Records. It is therefore crucial to cope with aforementioned data-related challenges. In this paper, we aim at supporting the exploitation of process mining in the healthcare domain, particularly with regards to conformance checking. We therefore introduce a set of specifically-designed techniques, provided as a suite of software packages written in R. In particular, the suite provides a flexible and agile way to automatically and reliably build Event Log from clinical data sources, and to effectively perform conformance checking.

Objective/PurposeExtramammary 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 MethodsA 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.ResultsAccording 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.ConclusionsTo date, literature highlights the role of RT in the management of EMPD, but with low level of evidences.

Purpose The purpose of this paper is to describe a methodology to deal with conformance checking through the implementation of computer-interpretable-clinical guidelines (CIGs), and present an application of the methodology to real-world data and a clinical pathway for radiotherapy-related oncological treatment. Design/methodology/approach This methodology is implemented by a software able to use the hospital electronic health record data to assess the adherence of the actual executed clinical processes to a clinical pathway, monitoring at the same time management-related efficiency and performance parameters, and ideally, suggesting ways to improve them. Findings Three use cases are presented, in which the results of conformance checking are used to compare different branches of the executed guidelines with respect to the adherence to ideal process, temporal distribution of state-to-state transitions, and overall treatment efficacy, in order to extract data-driven evidence that could be of interest for the hospital management. Originality/value This approach has the result of applying management-oriented data mining technique on sequential data, typical of process mining, to the result of a conformity check between the preliminary knowledge defined by clinicians and the real-world data, typical of CIGs.

Purpose: The objective of this study is finding an intensity based histogram (IBH) signature to predict pathologic complete response (pCR) probability using only pre-treatment magnetic resonance (MR) and validate it externally in order to create a workflow for the external validation of an MR IBH signature and to apply the model out of the environment where it has been tuned. The impact of pCR and the final predictors on the survival outcome were also evaluated. Methods and Materials: Three centers using different MR scanners were involved in this retrospective study. The first center recruited 162 patients for model training, and the second and third centers provided 34 plus 25 patients for external validation. Patients provided written consent. Accrual period was from May 2008 to December 2014. After surgery pathologic response was defined. T2-weighted MR scans acquired before chemoradiation therapy (CRT) were used for analysis addressed on primary lesions. Images were pre-processed using Laplacian of Gaussian (LoG) filter with multiple σ, and first order intensity histogram-based features (kurtosis, skewness, and entropy) were extracted. Features selection was performed using Mann-Whitney test. Tumor staging (cT, cN) was added to build a logistic regression model and predict pCR. Model performance was evaluated with internal and external validation using area under the curve (AUC) of the receiver operator characteristic (ROC) and calibration with Hosmer-Lemeshow test. The linear cross-correlation matrix (Pearson's coefficient) and the variance inflation factor (VIF) were used to check the correlation and the co-linearity among the final predictors. The amount of the information added through the radiomics features was estimated by using the DeLong's test, and the impact of pCR and the final predictors on survival outcomes were evaluated through the Kaplan-Meier curves by using the log-rank test and the multivariate Cox model. Results: Candidate-to-analysis features were skewness (σ = 0.485, P value =.01) and entropy (σ = 0.344, P value

The aim of this study was to propose a methodology to investigate the tumour heterogeneity and evaluate its ability to predict pathologically complete response (pCR) after chemo-radiotherapy (CRT) in locally advanced rectal cancer (LARC). This approach consisted in normalising the pixel intensities of the tumour and identifying the different sub-regions using an intensity-based thresholding. The spatial organisation of these subpopulations was quantified using the fractal dimension (FD). This approach was implemented in a radiomic workflow and applied to 198 T2-weighted pre-treatment magnetic resonance (MR) images of LARC patients. Three types of features were extracted from the gross tumour volume (GTV): morphological, statistical and fractal features. Feature selection was performed using the Wilcoxon test and a logistic regression model was calculated to predict the pCR probability after CRT. The model was elaborated considering the patients treated in two institutions: Fondazione Policlinico Universitario "Agostino Gemelli" of Rome (173 cases, training set) and University Medical Centre of Maastricht (25 cases, validation set). The results obtained showed that the fractal parameters of the subpopulations have the highest performance in predicting pCR. The predictive model elaborated had an area under the curve (AUC) equal to 0.77 +/- 0.07. The model reliability was confirmed by the validation set (AUC = 0.79 +/- 0.09). This study suggests that the fractal analysis can play an important role in radiomics, providing valuable information not only about the GTV structure, but also about its inner subpopulations.