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Survival rates of prostate cancer (PCa) patients have improved considerably as a result of earlier diagnosis and therapies, including radiotherapy (RT) and androgen deprivation therapy (ADT). Patients on ADT develop cancer treatment-induced bone loss (CTIBL) and a high risk of fragility fractures. Bone health (BH) assessment is strongly recommended, together with timely initiation of treatments, to counteract CTIBL and preserve bone strength. Therefore, we decided to develop an interdisciplinary pathway of care (IPC) dedicated to non-metastatic PCa patients on long-term ADT and RT.An interdisciplinary team allocated resources to support an IPC to manage patients' CTIBL and prevent fragility fractures. The team provided a diagnostic and therapeutic workflow according to patients' and professional perspectives, consistent with recommendations and healthcare policies. The hospital's quality department certified the IPC, the Ethical Committee approved procedures over the workflow. The Fracture Liaison Service (FLS) standards inspired services and professionals' activities and interactions.Preliminary data support the feasibility of the IPC from professionals' and patients' perspectives. Median age of the enrolled patients was 75 years, more than a half (58.9%) had low grade osteopenia or normal BMD (T-score ≥-1.5 standard deviation, SD), while 23.5% and 17.6% had osteoporosis and osteopenia, respectively. The IPC meets the requirements of a FLS concerning crucial indicators.Our IPC was a suitable approach to assure timely identification, assessment, initiation, and monitoring of adherence to anti-fracture treatments among non-metastatic PCa patients on long-term ADT and RT. Further data are required to show its effectiveness on fragility fracture prevention.

This paper focuses on stereotactic radiotherapy (SRT ) interactions with targeted therapies and immune system modulating agents because SRT inevitably interacts with them in the treatment of oligometastatic patients. Radiation oncologists need to be aware of the advantages and risks of these interactions which can, on one hand, enhance the effect of therapy or, on the other, potentiate reciprocal toxicities. To date, few prospective studies have evaluated the interactions of SRT with new-generation drugs and data are mainly based on retrospective experiences, which are often related to small sample sizes.

To quantify the dosimetric impact of contouring variability of axillary lymph nodes (L2, L3, L4) in breast cancer (BC) locoregional radiotherapy (RT).18 RT centres were asked to plan a locoregional treatment on their own planning target volume (single centre, SC-PTV) which was created by applying their institutional margins to the clinical target volume of the axillary nodes of three BC patients (P1, P2, P3) previously delineated (SC-CTV). The gold standard CTVs (GS-CTVs) of P1, P2 and P3 were developed by BC experts' consensus and validated with STAPLE algorithm. For each participating centre, the GS-PTV of each patient was created by applying the same margins as those used for the SC-CTV to SC-PTV expansion and replaced the SC-PTV in the treatment plan. Datasets were imported into MIM v6.1.7 [MIM Software Inc.], where dose-volume histograms (DVHs) were extracted and differences were analysed.17/18 centres used intensity-modulated RT (IMRT). The CTV to PTV margins ranged from 0 to 10 mm (median 5 mm). No correlation was observed between GS-CTV coverage by 95% isodose and GS-PTV margins width. Doses delivered to 98% (D98) and 95% (D95) of GS-CTVs were significantly lower than those delivered to the SC-CTVs. No significant difference between SC-CTV and GS-CTV was observed in maximum dose (D2), always under 110%. Mean dose ≥99% of the SC-CTVs and GS-CTVs was satisfied in 84% and 50%, respectively. In less than one half of plans, GS-CTV V95% was above 90%. Breaking down the GS-CTV into the three nodal levels (L2, L3 and L4), L4 had the lowest probability to be covered by the 95% isodose.Overall, GS-CTV resulted worse coverage, especially for L4. IMRT was largely used and CTV-to-PTV margins did not compensate for contouring issues. The results highlighted the need for delineation training and standardization.

Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice.This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations.An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders.Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

Recent advances in non-metastatic breast cancer radiation therapy significantly reshaped our views on modern dose and fractionation schedules. Especially the advent of hypofractionation and partial breast irradiation defined a new concept of treatment optimization, that should strongly include both patient and tumour characteristics in the physician’s decision-making process. Unfortunately, hypofractionation for breast cancer radiation therapy needed long time to enter the routine practice during the last decades despite the level-1 evidence published over time. Hereby we present the Italian Association for Radiotherapy and Clinical Oncology (AIRO) Breast Cancer Group position statements for postoperative breast cancer radiation therapy volume, dose, and fractionation to harmonically boost routine clinical practice implementation following evidence-based data.

Aim. Breast IRRADIATA (Italian Repository of RADIotherapy dATA) is a collaborative nationwide project supported by the Italian Society of Radiotherapy and Clinical Oncology (AIRO) and the Italian League Against Cancer (LILT). It focuses on breast cancer (BC) patients treated with radiotherapy (RT) and was developed to create a national registry and define the patterns of care in Italy. A dedicated tool for data collection was created and pilot tested. The results of this feasibility study are reported here. Methods. To validate the applicability of a user-friendly data collection tool, a feasibility study involving 17 Italian Radiation Oncology Centers was conducted from July to October 2021, generating a data repository of 335 BC patients treated between January and March 2020, with a minimum follow-up time of 6 months. A snapshot of the clinical presentation, treatment modalities and radiotherapy toxicity in these patients was obtained. A Data Entry Survey and a Satisfaction Questionnaire were also sent to all participants. Results. All institutions completed the pilot study. Regarding the Data Entry survey, all questions achieved 100% of responses and no participant reported spending more than 10 min time for either the first data entry or for the updating of follow-up. Results from the Satisfaction Questionnaire revealed that the project was described as excellent by 14 centers (82.3%) and good by 3 (17.7%). Conclusion. Current knowledge for the treatment of high-prevalence diseases, such as BC, has evolved toward patient-centered medicine, evidence-based care and real-world evidence (RWE), which means evidence obtained from real-world data (RWD). To this aim, Breast IRRADIATA was developed as a simple tool to probe the current pattern of RT care in Italy. The pilot feasibility of IRRADIATA encourages a larger application of this tool nationwide and opens the way to the assessment of the pattern of care radiotherapy directed to other cancers.

Despite the advances in surgery and radio-chemotherapy, the prognosis of glioblastoma (GBM) remains poor with about 13% of patients alive at 24 months.A total of 75 long-term survivors (LTS), defined as alive at least 24 months from diagnosis, were retrospectively analyzed. Overall survival (OS) and recurrence-free-survival (RFS) were calculated and related to patient characteristics and treatment received.Median age and Karnofsky performance status (KPS) were 56 years and 100%, respectively. After surgery (gross tumor resection-GTR in 62, 83% patients), all LTS received concomitant temozolomide (TMZ) with radiotherapy and 70 (93%) adjuvant TMZ. Of these, 10 (13%) discontinued TMZ prior the completion of 6 cycles, 37 (49%) received 6 cycles and 23 (31%) 6 cycles. Sixty-nine (92%) patients experienced a first tumor recurrence at a median time of 21 months. Of these, 32 (46%) were submitted to a second surgery, 34 (49%) to other no-surgical treatments and 3 (5%) only supportive care. At multivariate analysis, OS was significantly improved by second surgery after first recurrence (P = 0.0032) and by cycles of adjuvant TMZ 6 versus ≤6 (P = 0.05). More than six cycles of TMZ significantly conditioned also first RFS (P = 0.011) and second RFS (P = 0.033).The large majority of LTS had 65 years, had a high KPS and received GTR. OS and RFS resulted significantly related to an extended administration of adjuvant TMZ (6 cycles) and a second surgery in case of recurrence.

Metastasis-directed therapy (MDT) is an investigational treatment option in patients with oligorecurrent prostate cancer (PCa). The aim of this retrospective study is to report oncologic outcome and toxicity of elective nodal radiotherapy (ENRT) in PCa patients affected by pelvic nodal oligorecurrence. 41 consecutive patients were treated with salvage radiotherapy. At biochemical recurrence after primary treatment, oligorecurrent disease was detected by positron emission tomography (PET) in 94% of the patients. Image-guided intensity modulated radiation therapy (IMRT) was delivered using tomotherapy. 83% of the patients received androgen deprivation therapy (ADT) in combination with ENRT. Survival analysis was performed with Kaplan–Meier method, log-rank test was used to analyze associations between survival end-points and clinical parameters. Multivariate analysis was performed using Cox proportional hazards regression models. Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The median at follow-up was 33.6 months. At 3 years, overall survival (OS), cancer-specific survival (CSS), and biochemical progression-free survival (b-PFS) were 89%, 92%, and 53%, respectively. At univariate analysis, all survival end-points were correlated with the number of positive pelvic lymph nodes at oligorecurrence (≤ 3 vs > 3). Biochemical-PFS was correlated with PSA (p = 0.034) and PSA doubling time (p = 0.004) at oligorecurrence. At multivariate analysis, no independent variable was statistically significant. No patient experienced grade ≥ 2 late toxicity after radiotherapy. The number of metastatic lymph nodes and PSA doubling time seems to be important prognostic factors in the pelvic oligorecurrent setting. Salvage radiotherapy combined with short-course ADT might be a valid treatment strategy.

Background Salvage re-irradiation in patients affected by radiorecurrent prostate cancer might be a valid as well as challenging treatment option. The aim of this study was to evaluate feasibility and toxicity of salvage external beam radiotherapy (EBRT) re-treatment in patients affected by radiorecurrent prostate cancer within the prostate gland or the prostate bed. Materials and Methods 15 patients underwent EBRT re-treatment using helical tomotherapy (HT), with daily Megavolt computed tomography image-guidance. We registered toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Biochemical relapse was defined as a PSA increase > 20% compared with the pre-EBRT re-treatment value. Survival curves were calculated using the Kaplan-Meier method. Results All patients received a total dose of 50 Gy (25 × 2 Gy), and 7 (46.6%) had concomitant androgen deprivation therapy (median duration of 12 months). With a median follow-up of 40.9 months, the 2-year and 4-year biochemical relapse-free survival were 55% and 35%, respectively. Acute and late genito-urinary (GU) toxicity ≥2 were recorded in 4 (26.6%) and 5 (33.3%) patients, respectively, and the 4-year late GU toxicity was 30%. Acute gastrointestinal toxicity ≥2 was recorded in 2 (13.3%) cases, whereas no patient experienced late toxicity. Conclusions Despite the inherent bias of a retrospective analysis, our long-term results showed a low toxicity profile with a relatively low rate of biochemical control for HT re-treatment in patients affected by local radiorecurrent prostate cancer. Prospective trials are needed to investigate the role of EBRT in this setting.

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice. Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group. We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology ( www.sign.ac.uk ). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations. Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered. Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation). Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders. Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

Over the past century, technologic advances have promoted the evolution of radiation therapy into a precise treatment modality allowing for the maximal administration of dose to tumors while sparing normal tissues. In parallel with this technological maturation, the rapid expansion in understanding the basic biology and heterogeneity of cancer has led to the development of several compounds that target specific pathways. Many of them are in advanced steps of clinical development for combination treatments with radiotherapy, and can be incorporated into radiation oncology practice for a personalized approach to maximize the therapeutic gain. This review describes the rationale for combining novel agents with radiation, and provides an overview of the current landscape focused on treatment efficacy.

Computer-assisted analysis of three-dimensional imaging data (radiomics) has received a lot of research attention as a possible means to improve the management of patients with lung cancer. Building robust predictive models for clinical decision making requires the imaging features to be stable enough to changes in the acquisition and extraction settings. Experimenting on 517 lung lesions from a cohort of 207 patients, we assessed the stability of 88 texture features from the following classes: first-order (13 features), Grey-level Co-Occurrence Matrix (24), Grey-level Difference Matrix (14), Grey-level Run-length Matrix (16), Grey-level Size Zone Matrix (16) and Neighbouring Grey-tone Difference Matrix (five). The analysis was based on a public dataset of lung nodules and open-access routines for feature extraction, which makes the study fully reproducible. Our results identified 30 features that had good or excellent stability relative to lesion delineation, 28 to intensity quantisation and 18 to both. We conclude that selecting the right set of imaging features is critical for building clinical predictive models, particularly when changes in lesion delineation and/or intensity quantisation are involved.

Objectives: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). Methods: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. Results: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by −29.25% and −27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. Conclusions: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. Advances in knowledge The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.

This review is aimed at evaluating whether radiation therapy (RT) can be omitted in older adult early-stage low-risk breast cancer (BC) patients. The published data are particularly relevant at present, during the COVID-19 pandemic emergency, to define a treatment strategy and to prioritize essential therapy. Cochrane Database of Systematic Reviews and PubMED were systematically researched from outset through April 2020 using Mesh terms. Only randomized controlled trials (RCT), with one arm without adjuvant whole-breast irradiation (WBI), were included in the analysis. Recent literature regarding the COVID pandemic and BC RT was assessed. The reported RCTs identified a group of BC patients (pT1-2N0M0 R0, grade 1–2, estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative tumours) in which the absolute risk of local recurrence (LR) was considered low enough to omit RT. The most common risk factors were tumor diameter, nodal and receptor status. Adjuvant RT had a significant impact on LR but not on distant metastasis (DM) or death. During the COVID 19 pandemic, results from RTCs were re-considered to define treatment recommendations for BC patients. International scientific societies and radiation oncology experts suggested RT omission, whenever possible, in older adult early-stage BC patients. Adjuvant RT might be omitted in a highly selected group of older adult early-stage BC patients with favourable prognostic factors. Hypofractionated regimens should be the standard. RT omission, partial breast irradiation (PBI), and ultra- hypofractionated regimens could be considered in selected cases due to the pandemic.

Background Accurate segmentation of pulmonary nodules on computed tomography (CT) scans plays a crucial role in the evaluation and management of patients with suspicion of lung cancer (LC). When performed manually, not only the process requires highly skilled operators, but is also tiresome and time-consuming. To assist the physician in this task several automated and semi-automated methods have been proposed in the literature. In recent years, in particular, the appearance of deep learning has brought about major advances in the field. Methods Twenty-four (12 conventional and 12 based on deep learning) semi-automated-'one-click'-methods for segmenting pulmonary nodules on CT were evaluated in this study. The experiments were carried out on two datasets: a proprietary one (383 images from a cohort of 111 patients) and a public one (259 images from a cohort of 100). All the patients had a positive transcript for suspect pulmonary nodules. Results The methods based on deep learning clearly outperformed the conventional ones. The best performance [Sorensen-Dice coefficient (DSC)] in the two datasets was, respectively, 0.853 and 0.763 for the deep learning methods, and 0.761 and 0.704 for the traditional ones. Conclusions Deep learning is a viable approach for semi-automated segmentation of pulmonary nodules on CT scans.

In this paper, we investigate the role of shape and texture features from 18F-FDG PET/CT to discriminate between benign and malignant solitary pulmonary nodules. To this end, we retrospectively evaluated cross-sectional data from 111 patients (64 males, 47 females, age = 67.5 &plusmn, 11.0) all with histologically confirmed benign (n=39) or malignant (n=72) solitary pulmonary nodules. Eighteen three-dimensional imaging features, including conventional, texture, and shape features from PET and CT were tested for significant differences (Wilcoxon-Mann-Withney) between the benign and malignant groups. Prediction models based on different feature sets and three classification strategies (Classification Tree, k-Nearest Neighbours, and Na&iuml, ve Bayes) were also evaluated to assess the potential benefit of shape and texture features compared with conventional imaging features alone. Eight features from CT and 15 from PET were significantly different between the benign and malignant groups. Adding shape and texture features increased the performance of both the CT-based and PET-based prediction models with overall accuracy gain being 3.4&ndash, 11.2 pp and 2.2&ndash, 10.2 pp, respectively. In conclusion, we found that shape and texture features from 18F-FDG PET/CT can lead to a better discrimination between benign and malignant lung nodules by increasing the accuracy of the prediction models by an appreciable margin.

Aim To retrospectively assess toxicity and survival in 15 selected Glioblastoma patients treated with a sequential fractionated stereotactic radiotherapy (FSRT) boost after chemo-radiotherapy (CHT-RT) and compare their survival outcomes with a control group. Patients and methods Toxicity was assessed with the CTCAE 3.0 scale. The Kaplan-Meier method was used to design survival curves, log-rank test for bivariate analysis and Cox proportional hazard regression model for multivariate analysis. Results The median follow-up was 16 months (range=5-60). One case of headache and one of radionecrosis (RN) occurred. Median overall survival (OS) was 25 months in the boost group vs. 14 in the no-boost group (p=0.004). Median progression-free survival (PFS) was 15 months in the boost group versus 8 in the no-boost group (p=0.046). At multivariate analysis FSRT boost resulted significantly associated with OS and PFS. Conclusion In our series a sequential FSRT boost resulted in safe outcomes and significantly associated with survival.

Quantitative extraction of imaging features from medical scans (‘radiomics’) has attracted a lot of research attention in the last few years. The literature has consistently emphasized the potential use of radiomics for computer-assisted diagnosis, as well as for predicting survival and response to treatment. Radiomics is appealing in that it enables full-field analysis of the lesion, provides nearly real-time results, and is non-invasive. Still, a lot of studies suffer from a series of drawbacks such as lack of standardization and repeatability. Such limitations, along with the unmet demand for large enough image datasets for training the algorithms, are major hurdles that still limit the application of radiomics on a large scale. In this paper, we review the current developments, potential applications, limitations, and perspectives of PET/CT radiomics with specific focus on the management of patients with lung cancer.

To explore the radiosensitizing effect of AZD8931, a novel equipotent and reversible inhibitor of signaling by EGFR (HER1), HER2 and HER3 receptors, focusing on cell cycle progression, apoptosis and clonogenic capacity in the human LoVo colorectal cancer (CRC) cell line, also in comparison with the EGFR-blocking monoclonal antibody Cetuximab or the EGFR tyrosine kinase selective small molecular inhibitor Gefitinib.Cells were pretreated with EGFR inhibitors for 5 consecutive days and then exposed or not to ionizing radiation (IR) (2 Gy daily for 3 consecutive days). Cell proliferation, cell cycle progression and apoptosis were evaluated by flow cytometry and enzyme-linked immunosorbent assay (ELISA), clonogenic potential and radiosensitivity were studied by colony formation assay.AZD8931 induced cell cycle arrest and apoptosis more effectively than Gefitinib and Cetuximab and, more importantly, it was significantly more potent than Gefitinib and Cetuximab in radiosensitizing cells. This radiosensitizing action by AZD8931 mainly occurred by markedly reducing cell cycle progression into S phase, the most radioresistant phase of cell cycle, secondly by inducing apoptosis and reducing clonogenic survival.Our results show that AZD8931 increases IR efficacy in LoVo cells, suggesting that it works as a potent radiosensitizer, even more efficient than Gefitinib and Cetuximab, opening new pathways of investigation for further in vitro and in vivo studies aimed at confirming its potential to improve local radiotherapy in CRC.

To evaluate the incidence of toxicity in breast cancer with helical tomotherapy (HT).51 patients with breast cancer were assigned to postoperative radiotherapy by means of HT to the chest wall/breast plus draining nodes. During HT treatment, toxicity was monitored and were assessed using the Common Terminology Criteria for Adverse Events 4.0 scale.Acute skin G3 toxicity observed in 1.9% cases. No acute or late G4 toxicity was observed. At a median follow-up of 21 months 2 patients have late G1 toxicity.HT was associated with a low incidence of low-grade skin toxicity.

Background The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care.

Patient: Female, 60 Final Diagnosis: Complete remission Symptoms: None Medication: — Clinical Procedure: Radiotherapy Specialty: Oncology Objective: Rare disease Background: Synchronous bilateral breast cancer is rare. A case is presented where whole breast irradiation (WBI) was planned after breast conserving surgery in a patient with synchronous bilateral breast cancer. A comparison was made between the feasibility of helical tomotherapy and direct tomotherapy. Case Report: A 60-year-old woman was found to have bilateral breast nodules on routine mammographic screening, resulting in bilateral lumpectomy and sentinel lymph node biopsy. Histopathology showed a 6 mm diameter invasive ductal carcinoma in the right breast (Grade 1, hormone receptor positive, HER2 negative) and an 8mm diameter tubular carcinoma in the left breast (Grade 1, hormone receptor positive, HER2 negative). Lymph node biopsy and histology, chest X-ray, abdominal ultrasound scan, and bone scintigraphy were negative for metastases (both tumors were Stage 1). Adjuvant therapy with commenced with anastrozole, but no chemotherapy was given. Clinical target volumes (CTVs) were contoured on computed tomography (CT) images. For planning target volumes (PTVs), CTVs were expanded by 1 cm in all directions, except for the medial 5 mm. Since dose constraints to organs at risk (OARs) were beyond established limits, CTVs were expanded by 5 mm. For PTVs, OAR doses and homogeneity indices for helical tomotherapy and direct tomotherapy were compared. Helical tomotherapy provided better target volume coverage and OAR sparing than direct tomotherapy. Conclusions: In a case of bilateral synchronous Stage 1 and Grade 1 breast cancer, helical tomotherapy appeared more suitable than direct tomotherapy.

Purpose We report the long-term results of phase II prospective study with accelerated partial breast irradiation (APBI) using interstitial multi-catheter high-dose-rate brachytherapy. Methods 240 patients received APBI (4 Gy, twice daily; total dose 32 Gy). Results Median follow-up was 96 months. Recurrences in the treated breast developed in 8 patients (3.3%) at a median of 73 months after APBI. The 5- and 10-year cumulative incidences were respectively, 1.8% (95%CI: 0.6–4.3) and 6.6% (95%CI: 2.7–12.9). Regional recurrences developed in 5 patients (2%) at a median of 28 months and distant metastases in 8 (3.3%) at a median of 32.5 months. Breast cancer specific mortality occurred in 6 patients (2.5%) at a median of 60 months. Acute toxicity developed in 71 (29.6%) patients (G1 in 60 and G2 in 11). Almost all were skin toxicity and hematomas. Late toxicity was observed in 90 patients (37.5%), G1 in 97 cases and G2 in 11. Some patients presented with more than one type of toxicity. Teleangectasia and fibrosis were the most common (48 and 44 cases respectively), followed by fat necrosis (in 18 patients) Tamoxifen emerged as the only risk factor for breast fibrosis ( p = 0.007). Cosmetic results were judged by the physicians as excellent in 174 (83.7%) patients, good in 25 (12%) fair in 8 (3.8%) and poor in 1 (0.5%); 174 patients (83.7%) judged outcomes as excellent, 26 (12.4%) as good, 7 (3.4%) as fair and 1 (0.5%) as poor. Physician/patient agreement was good (weighted k -value 0.72). Conclusions APBI with interstitial multi-catheter brachytherapy was associated with good outcomes, low relapse and toxicity rates. Few events during this long-term follow-up preclude identifying specific features of patients at risk of relapse and illustrate the need for a large data-base.

There is increasing evidence that shape and texture descriptors from imaging data could be used as image biomarkers for computer-assisted diagnosis and prognostication in a number of clinical conditions. It is believed that such quantitative features may help uncover patterns that would otherwise go unnoticed to the human eye, this way offering significant advantages against traditional visual interpretation. The objective of this paper is to provide an overview of the steps involved in the process – from image acquisition to feature extraction and classification. A significant part of the work deals with the description of the most common texture and shape features used in the literature; overall issues, perspectives and directions for future research are also discussed.

The study aims to investigate the correlations between positron emission tomography (PET) texture features, X-ray computed tomography (CT) texture features, and histological subtypes in non-small-cell lung cancer evaluated with 2-deoxy-2-[We retrospectively evaluated the baseline PET/CT scans of 81 patients with histologically proven non-small-cell lung cancer. Feature extraction and statistical analysis were carried out on the Matlab platform (MathWorks, Natick, USA).Intra-CT correlation analysis revealed a strong positive correlation between volume of the lesion (CTSignificant associations emerged between PET features, CT features, and histological type in NSCLC. Texture analysis on PET/CT shows potential to differentiate between histological types in patients with non-small-cell lung cancer.

Clinical development and use of novel systemic agents in combination with radiotherapy (RT) is at nowadays most advanced in the field of treatment of solid tumors. Although for many of these substances preclinical studies provide sufficient evidences on their principal capability to enhance radiation effects, the majority of them have not been investigated in even phase I clinical trials for safety in the context of RT. In clinical practice, unexpected acute and late side effects may emerge especially in combination with RT. As a matter of fact, despite combined modality treatment holds potential for enhancing the therapeutic ratio, some concerns are raised from the lack of high-quality clinical data to guide the care of patients who are treated with novel compounds in conjunction with RT. The aim of this review is to provide, from a radio-oncological point of view, an overview of the most advanced combined treatment concepts for solid tumors focusing on treatment toxicity.

Purpose Hypofractionated radiation therapy (RT) is controversial after radical prostatectomy (RP). In this interim analysis, our prospective observational study assessed acute genitourinary (GU) and gastrointestinal (GI) toxicity after hypofractionated adjuvant and salvage RT, as delivered by helical tomotherapy (HT), in patients with prostate cancer. Methods and Materials After undergoing RP with or without pelvic lymph node dissection, 112 patients were enrolled. Hypofractionated adjuvant RT (2.25 Gy daily for 29 fractions; total 65.25 Gy) was administered to 40 patients with high-risk features. Hypofractionated salvage RT (2.25 Gy daily for 32 or 33 fractions; total 72-74.25 Gy) was prescribed for 72 patients (24 with biochemical relapse, 48 with local relapse). Toxicity was graded according to the Common Terminology Criteria for Adverse Events version 4.02. The impact of RT on urinary flow was assessed by uroflowmetry. Results Acute GU toxicity occurred in 41 of 112 patients (36%) (G1 31, G2 10). Acute GI toxicity was observed in 55 (49%) patients (G1 44, G2 11). Uroflowmetry showed that only salvage RT reduced maximum flow significantly (maximum, 68 vs 50 mL/s; P = .003), perhaps because a higher RT dose had been administered. Conclusions After RP, moderate hypofractionated adjuvant and salvage RT were associated with acceptable incidences of slight-to-moderate acute GU and GI toxicity and had little impact on urinary flow. Prospective trials are warranted with longer follow-up in larger cohorts to confirm these findings.

The study aims to investigate the correlations between positron emission tomography (PET) texture features, X-ray computed tomography (CT) texture features, and histological subtypes in non-small-cell lung cancer evaluated with 2-deoxy-2-[18F]fluoro-D-glucose PET/CT. We retrospectively evaluated the baseline PET/CT scans of 81 patients with histologically proven non-small-cell lung cancer. Feature extraction and statistical analysis were carried out on the Matlab platform (MathWorks, Natick, USA). Intra-CT correlation analysis revealed a strong positive correlation between volume of the lesion (CTvol) and maximum density (CTmax), and between kurtosis (CTkrt) and maximum density (CTmax). A moderate positive correlation was found between volume (CTvol) and average density (CTmean), and between kurtosis (CTkrt) and average density (CTmean). Intra-PET analysis identified a strong positive correlation between the radiotracer uptake (SUVmax, SUVmean) and its degree of variability/disorder throughout the lesion (SUVstd, SUVent). Conversely, there was a strong negative correlation between the uptake (SUVmax, SUVmean) and its degree of uniformity (SUVuni). There was a positive moderate correlation between the metabolic tumor volume (MTV) and radiotracer uptake (SUVmax, SUVmean). Inter (PET-CT) correlation analysis identified a very strong positive correlation between the volume of the lesion at CT (CTvol) and the metabolic volume (MTV), a moderate positive correlation between average tissue density (CTmean) and radiotracer uptake (SUVmax, SUVmean), and between kurtosis at CT (CTkrt) and metabolic tumor volume (MTV). Squamous cell carcinomas had larger volume higher uptake, stronger PET variability and lower uniformity than the other subtypes. By contrast, adenocarcinomas exhibited significantly lower uptake, lower variability and higher uniformity than the other subtypes. Significant associations emerged between PET features, CT features, and histological type in NSCLC. Texture analysis on PET/CT shows potential to differentiate between histological types in patients with non-small-cell lung cancer.

BACKGROUND: This is an update of the original review published in 2007. Carcinoma of the rectum is a common malignancy, especially in high income countries. Local recurrence may occur after surgery alone. Preoperative radiotherapy (PRT) has the potential to reduce the risk of local recurrence and improve outcomes in rectal cancer. OBJECTIVES: To determine the effect of preoperative radiotherapy for people with localised resectable rectal cancer compared to surgery alone. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library; Issue 5, 2018) (4 June 2018), MEDLINE (Ovid) (1950 to 4 June 2018), and Embase (Ovid) (1974 to 4 June 2018). We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for relevant ongoing trials (4 June 2018). SELECTION CRITERIA: We included randomised controlled trials comparing PRT and surgery with surgery alone for people with localised advanced rectal cancer planned for radical surgery. We excluded trials that did not use contemporary radiotherapy techniques (with more than two fields to the pelvis). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the 'Risk of bias' domains for each included trial, and extracted data. For time‐to‐event data, we calculated the Peto odds ratio (Peto OR) and variances, and for dichotomous data we calculated risk ratios (RR) using the random‐effects method. Potential sources of heterogeneity hypothesised a priori included study quality, staging, and the use of total mesorectal excision (TME) surgery. MAIN RESULTS: We included four trials with a total of 4663 participants. All four trials reported short PRT courses, with three trials using 25 Gy in five fractions, and one trial using 20 Gy in four fractions. Only one study specifically required TME surgery for inclusion, whereas in another study 90% of participants received TME surgery. Preoperative radiotherapy probably reduces overall mortality at 4 to 12 years' follow‐up (4 trials, 4663 participants; Peto OR 0.90, 95% CI 0.83 to 0.98; moderate‐quality evidence). For every 1000 people who undergo surgery alone, 454 would die compared with 45 fewer (the true effect may lie between 77 fewer to 9 fewer) in the PRT group. There was some evidence from subgroup analyses that in trials using TME no or little effect of PRT on survival (P = 0.03 for the difference between subgroups). Preoperative radiotherapy may have little or no effect in reducing cause‐specific mortality for rectal cancer (2 trials, 2145 participants; Peto OR 0.89, 95% CI 0.77 to 1.03; low‐quality evidence). We found moderate‐quality evidence that PRT reduces local recurrence (4 trials, 4663 participants; Peto OR 0.48, 95% CI 0.40 to 0.57). In absolute terms, 161 out of 1000 patients receiving surgery alone would experience local recurrence compared with 83 fewer with PRT. The results were consistent in TME and non‐TME studies. There may be little or no difference in curative resection (4 trials, 4673 participants; RR 1.00, 95% CI 0.97 to 1.02; low‐quality evidence) or in the need for sphincter‐sparing surgery (3 trials, 4379 participants; RR 0.99, 95% CI 0.94 to 1.04; I(2) = 0%; low‐quality evidence) between PRT and surgery alone. Low‐quality evidence suggests that PRT may increase the risk of sepsis from 13% to 16% (2 trials, 2698 participants; RR 1.25, 95% CI 1.04 to 1.52) and surgical complications from 25% to 30% (2 trials, 2698 participants; RR 1.20, 95% CI 1.01 to 1.42) compared to surgery alone. Two trials evaluated quality of life using different scales. Both studies concluded that sexual dysfunction occurred more in the PRT group. Mixed results were found for faecal incontinence, and irradiated participants tended to resume work later than non‐irradiated participants between 6 and 12 months, but this effect had attenuated after 18 months (low‐quality evidence). AUTHORS' CONCLUSIONS: We found moderate‐quality evidence that PRT reduces overall mortality. Subgroup analysis did not confirm this effect in people undergoing TME surgery. We found consistent evidence that PRT reduces local recurrence. Risk of sepsis and postsurgical complications may be higher with PRT. The main limitation of the findings of the present review concerns their applicability. The included trials only assessed short‐course radiotherapy and did not use chemotherapy, which is widely used in the contemporary management of rectal cancer disease. The differences between the trials regarding the criteria used to define rectal cancer, staging, radiotherapy delivered, the time between radiotherapy and surgery, and the use of adjuvant or postoperative therapy did not appear to influence the size of effect across the studies. Future trials should focus on identifying participants that are most likely to benefit from PRT especially in terms of improving local control, sphincter preservation, and overall survival while reducing acute and late toxicities (especially rectal and sexual function), as well as determining the effect of radiotherapy when chemotherapy is used and the optimal timing of surgery following radiotherapy.

The purpose of this chapter is to provide an overview, albeit brief, of the existing literature on personality, specifically antagonism, in nonhuman primates and to suggest directions for future research.

BACKGROUND: Despite decades of research, glioblastoma (GBM) remains the most malignant primary brain tumor. Different investigations have focused on the GBM’s heterogeneous features to develop an individualized patient management. A multi-institutional study, the GLI.F.A. (Glioblastoma: advanced Imaging Features Analysis) Project, was performed for a comprehensive analysis of GBM heterogeneity in order to create a multidimensional map for predictive models (PM) and decision support systems (DSS) in GBM. MATERIAL AND METHODS: Adult patient with newly diagnosed GBM, that undergo to surgery and chemo-radiotherapy according to EORTC 26981-22981-NCIC trial, were analyzed in this first phase of the study. Gross Tumor Volume (GTV) was contoured in the T1 post contrast and T2-FLAIR weighted images. A brain ontology and a platform for sharing and combining multiple datasets (SPIDER BOA System for Patient Individual Data Entry and Recording Beyond Ontology Awareness) were created in order to standardize data collection. Preoperative MRI features were extracted by the MODDICOM software. Wilcoxon Mann Whitney test, Log-rank test for Kaplan-Meier curves were utilized to evaluate the significance of the radiomic features on the T2-Flair and T1 images. The main outcomes we considered were overall survival, progression free survival and response to radio-chemotherapy (RTCT). The median value of the features was used to categorize the continue variables. RESULTS: Twenty-seven patients, treated from July 2014 to February 2018, were enrolled in this study. Median age was 61 years (range 45–75) and 20 patients are still alive. The MODDICOM software analyzed 94 image features. Significant features divided by MRI sequence and outcomes are reported in Tab1. The first order features, describing the statistical characteristics of images, resulted significant for OS on the T2-weighted MRI and for response to RTCT on the T1 weighted MRI; the second order features, describing the spatial correlation between images voxels, showed the most significant result for OS and PFS on contrast-enhanced T1. CONCLUSION: This preliminary univariate analysis suggests that the radiomic features relates to survival and clinical outcomes and that is possible to stratify patients according MR based quantitative imaging. A higher number of patients, multivariate analysis and external validation are next steps for getting reliable predictive models.

Our study evaluated skin and subcutaneous toxicity analyzing its correlation with patient- and treatment-related factors in a large mono-institutional series of women with early stage breast cancer treated with adjuvant hypofractionated whole breast radiotherapy (WBRT) with or without a sequential hypofractionated boost (HB). Two hundred and nineteen patients, median age 62 years, received adjuvant hypofractionated WBRT in 16 fractions to a total dose of 42.4 Gy. Patients with negative prognostic factors received a HB of 2.65 Gy for 4 or 5 (patients with focal positive surgical margins) fractions. Systemic adjuvant treatments were hormonal therapy (HT) and/or chemotherapy (CHT) and/or Trastuzumab. Toxicities were assessed using the Common Terminology Criteria for Adverse Events (CTCAE 4.03) scale at 5th, 10th, 16th, 20th day from the start of radiotherapy (RT) and 1, 6 and 12 months after the end of RT. Univariate and multivariate analysis estimated toxicity predictive factors. No case of treatment interruption and no acute or late G3 toxicities occurred. In the univariate analysis HB administration resulted a risk factor for acute toxicity, while CHT administration and number of excised lymph nodes ≥ 10 resulted a risk factor for late toxicity. In the multivariate analysis none of the evaluated factors emerged a risk factor for acute and/or late toxicity. Our results confirmed that hypofractionated WBRT even followed by a HB resulted safe and well tolerated. Longer follow-up is warranted to estimate late toxicity and treatment outcomes.

Aims To demonstrate that radiotherapy (RT) is a valid alternative to surgery in men ≤70 years old with localized prostate cancer. Methods From 1988 to 2009, 214 patients with T1-2 N0 M0 prostate cancer were treated with RT. The effects of patient- and treatment-related risk factors on toxicity were investigated. Results Median follow-up was 105 months (range 14.2-180). The 5-, 10-, and 15-year biochemical relapse-free survival for all 214 patients was 80%, 61.9%, and 57.5%, respectively. In bivariate analysis, age (≤65 vs 65-70 years) was not a significant factor for biochemical relapse, while radiation dose was (p = 0.05) in multivariate analysis. Cancer-specific survival rates at 5, 10, and 15 years were 98.4%, 93.2%, and 69.7%, respectively. Median overall survival (OS) was 167 months (95% confidence interval 147.3-186.7). The OS rates at 5, 10, and 15 years were 91.8%, 75.8%, and 42.5%, respectively. Acute genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 105 (49%) and 98 patients (45.8%), respectively, with only 2 cases of grade III GI toxicity. Late GU and GI toxicities occurred in 17 (7.9%) and 20 (9.3%) patients, respectively, with 1 grade III GI toxicity and 2 grade III GU toxicities. Risk factors for late toxicity were age and RT dose and technique, which were unrelated to acute toxicity. Conclusions Age ≤70 years does not consistently confer a negative prognosis for localized prostate cancer. Radiotherapy appears to be a viable alternative to surgery, offering excellent long-term cancer control.

Aim and Background Conservative surgery and radiotherapy for early breast cancer offers a better quality of life than mastectomy. As 80–85% of breast relapses develop close to the tumour bed, partial breast irradiation was developed to overcome drawbacks with standard radiotherapy. This study compares quality of life and cosmesis after partial breast multi-catheter high-dose rate interstitial brachytherapy or standard radiotherapy. Methods A questionnaire, exploring body image, fear of recurrence, satisfaction with treatment and cosmesis, was administered to 39 partial and 78 whole breast patients at a median of 20 and 80 months after radiotherapy. Patients' and physicians' cosmetic assessments were compared. Results Groups were well-matched, except for: a higher percentage of chemotherapy-treated patients in the whole breast group and a older median age and a higher percentage of infiltrating ductal carcinoma G1 in partial breast group. At first and second analysis no significant inter-group difference emerged on body image and fear of recurrence, while partial breast patients were more satisfied with cosmetic outcome and at first analysis with treatment. Comparing results from first and second analysis into each treatment group, body image was significantly better at the first analysis in both groups. Fear of recurrence was unchanged. No differences were found in cosmesis as assessed by patients. At first and second analyses physicians' assessment of cosmesis was significantly better in the partial breast group. Conclusions Even at longer follow-up, quality of life is similar after partial or whole breast irradiation. Cosmesis is better after partial breast irradiation.

Purpose : Encrusted cystitis is a rare chronic inflammatory disease characterized by calcified plaques of the bladder, previously altered by varies conditions as urological procedures, caused by urea-splitting bacteria. Only one case has been reported on encrusted cystitis occurring after surgery and radiation therapy for a pelvic neoplasm. We report on encrusted cystitis occurred after definitive radiotherapy for bulky uterine cervix cancer, and examine the doses to the bladder wall and the procedure of radiation treatment performed as a possible cause of the onset of the disease. Case presentation : A 52-year-old female developed encrusted cystitis, caused by Corynebacterium spp., after 14 months from definitive chemo-radiotherapy and 2/D brachytherapy treatment for FIGO stage IB2 uterine cervix cancer. For pelvic radiotherapy, the mean bladder dose was 48.47 Gy (range 31.20–51.91); maximal bladder point doses at each brachytherapy insertions were 7.62 Gy, 4.94 Gy and 6.27 Gy at first, second, and third fraction, respectively. Total biological effective dose (BED) at bladder point was 140.05 Gy3. The patient was administered antibiotic therapy with linezolid and urine acidification with vitamin C; dietary norms were also suggested. After therapy, complete remission of symptoms and radiological findings were achieved, and the planned surgery for removing the calcified plaques was not completed. After 5 years from the cervical cancer diagnosis, the patient was disease-free without urinary symptoms. Conclusions : The high doses administered to the bladder wall and the repeated catheterizations performed at each brachytherapy insertions may have favored the infection and promoted the occurrence of the encrusted cystitis.

AIM To analyze risk factors for acute rectal toxicity during hypofractionated intensity-modulated radiotherapy (IMRT) for prostate cancer. PATIENTS AND METHODS A total of 195 patients received 74.25 Gy in 33 fractions to the prostate and, if involved, to the seminal vescicles (SV). When the risk of SV involvement was >15% according to the Roach's formula, they received 62 Gy in 33 fractions. Overall, 107/195 patients (54.87%) received hormonal therapy (luteinizing hormone-releasing hormone analogue, anti-androgen, or both). Common Terminology Criteria for Adverse Events version 3.0 was used to classify rectal toxicity. RESULTS Acute rectal toxicity occurred in 79 (40.51%) patients (grade 1 in 44). In univariate analysis, use of calcium channel blockers significantly reduced the acute rectal toxicity rate and 3-hydroxy-methylglutaryl CoA reductase inhibitors (statins) significantly reduced the rectal toxicity rate and grade. In multivariate analysis, only statin use was an independent protective factor. CONCLUSION In patients with prostate cancer treated with a moderate hypofractionated IMRT schedule, use of statins lowered the incidence and grade of acute rectal toxicity.