Stereotactic radiotherapy (SRT) for differentiated thyroid cancer (DTC) oligometastases: an AIRO (Italian association of radiotherapy and clinical oncology) systematic review.

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

How radical prostatectomy procedures have changed over the last 10 years in Italy: a comparative analysis based on more than 1500 patients participating in the MIRROR-SIU/LUNA and the Pros-IT CNR study.

PURPOSE: Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy. METHODS: The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients' characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND). RESULTS: The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%, p < 0.001) and NS prostatectomy (58.4% vs. 52.9%, p = 0.04), but received LND less frequently (47.7% vs. 76.7%, p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS ≥ (4 + 3) and positive cancer cores ≥ 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies. CONCLUSIONS: PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium-high risk diagnosed PCa.

Short fractionation radiotherapy for early prostate cancer in the time of COVID-19: long-term excellent outcomes from a multicenter Italian trial suggest a larger adoption in clinical practice.

INTRODUCTION: To evaluate stereotactic body radiotherapy (SBRT) in low-risk Prostate Cancer patients as preferred treatment option in emergency health conditions. MATERIALS AND METHODS: From April 2013 to September 2015, 28 patients with low-risk prostate cancer were prospectively enrolled. The SBRT prescribed dose was 36.25 Gy in 5 fractions, twice a week. Primary endpoints were acute and late toxicity. Secondary endpoints were biochemical recurrence free survival (bRFS) and overall survival. RESULTS: Median follow-up was 65.5 months (range 52-81). No acute G3 or G4 toxicity was recorded. Acute G1 or G2 genitourinary (GU) toxicity occurred in 43% and acute G1-G2 gastrointestinal (GI) toxicity in 14%. Late G1 and G3 GU toxicity in 18% and 3.5%, respectively. The G3 toxicity was not directly attributable to radiotherapy. Late G1 GI toxicity occurred in 18%. 5yy bRFS was 96.5% (95% CI 82.3-99.4%). CONCLUSIONS: Stereotactic body radiotherapy for early prostate cancer reported safe toxicity profile and a good clinical outcome at the median follow-up of 5 years. It may be an useful option if radiotherapy is required in emergency medical conditions.

Palliative radiotherapy indications during the COVID-19 pandemic and in future complex logistic settings: the NORMALITY model.

INTRODUCTION: The COVID-19 pandemic has challenged healthcare systems worldwide over the last few months, and it continues to do so. Although some restrictions are being removed, it is not certain when the pandemic is going to be definitively over. Pandemics can be seen as a highly complex logistic scenario. From this perspective, some of the indications provided for palliative radiotherapy (PRT) during the COVID-19 pandemic could be maintained in the future in settings that limit the possibility of patients achieving symptom relief by radiotherapy. This paper has two aims: (1) to provide a summary of the indications for PRT during the COVID-19 pandemic; since some indications can differ slightly, and to avoid any possible contradictions, an expert panel composed of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) and the Palliative Care and Supportive Therapies Working Group (AIRO-palliative) voted by consensus on the summary; (2) to introduce a clinical care model for PRT [endorsed by AIRO and by a spontaneous Italian collaborative network for PRT named "La Rete del Sollievo" ("The Net of Relief")]. The proposed model, denoted "No cOmpRoMise on quality of life by pALliative radiotherapy" (NORMALITY), is based on an AIRO-palliative consensus-based list of clinical indications for PRT and on practical suggestions regarding the management of patients potentially suitable for PRT but dealing with highly complex logistics scenarios (similar to the ongoing logistics limits due to COVID-19). MATERIAL AND METHODS: First, a summary of the available literature guidelines for PRT published during the COVID-19 pandemic was prepared. A systematic literature search based on the PRISMA approach was performed to retrieve the available literature reporting guideline indications fully or partially focused on PRT. Tables reporting each addressed clinical presentation and respective literature indications were prepared and distributed into two main groups: palliative emergencies and palliative non-emergencies. These summaries were voted in by consensus by selected members of the AIRO and AIRO-palliative panels. Second, based on the summary for palliative indications during the COVID-19 pandemic, a clinical care model to facilitate recruitment and delivery of PRT to patients in complex logistic scenarios was proposed. The summary tables were critically integrated and shuffled according to clinical presentations and then voted on in a second consensus round. Along with the adapted guideline indications, some methods of performing the first triage of patients and facilitating a teleconsultation preliminary to the first in-person visit were developed. RESULTS: After the revision of 161 documents, 13 papers were selected for analysis. From the papers, 19 clinical presentation items were collected; in total, 61 question items were extracted and voted on (i.e., for each presentation, more than one indication was provided from the literature). Two tables summarizing the PRT indications during the COVID-19 pandemic available from the literature (PRT COVID-19 summary tables) were developed: palliative emergencies and palliative non-emergencies. The consensus of the vote by the AIRO panel for the PRT COVID-19 summary was reached. The PRT COVID-19 summary tables for palliative emergencies and palliative non-emergencies were adapted for clinical presentations possibly associated with patients in complex clinical scenarios other than the COVID-19 pandemic. The two new indication tables (i.e., "Normality model of PRT indications") for both palliative emergencies and palliative non-emergencies were voted on in a second consensus round. The consensus rate was reached and strong. Written forms facilitating two levels of teleconsultation (triage and remote visits) were also developed, both in English and in Italian, to evaluate the patients for possible indications for PRT before scheduling clinical visits. CONCLUSION: We provide a comprehensive summary of the literature guideline indications for PRT during COVID-19 pandemic. We also propose a clinical care model including clinical indications and written forms facilitating two levels of teleconsultation (triage and remote visits) to evaluate the patients for indications of PRT before scheduling clinical visits. The normality model could facilitate the provision of PRT to patients in future complex logistic scenarios.

Phase III Randomized Study of Induction Chemotherapy Followed by Definitive Radiotherapy + Cetuximab Versus Chemoradiotherapy in Squamous Cell Carcinoma of Head and Neck: The INTERCEPTOR-GONO Study (NCT00999700).

OBJECTIVES: Induction chemotherapy followed by cetuximab and RT (IBRT) (Arm A) was compared to cisplatin/RT (CRT) (Arm B) in a randomized phase III study. PATIENTS AND METHODS: Naïve patients with stage III-IVa, histologically proven locally advanced head and neck cancer (LASCCHN) were eligible. Arm A (IBRT): 3 TPF induction followed by cetuximab-RT (equivalent daily dose 2 Gy up to 70 Gy); Arm B: 3 cisplatin concurrent with the same RT scheduling. Due to slow accrual and incomplete data collection a futility analysis was performed. RESULTS: 236/282 patients were evaluable. Therefore, no formal analyses can be made between the two arms. OS was 45.2/53.6 months in Arm A/B. Complete responses were achieved in 64% of patients in both arms. Neutropenia and skin toxicity were significantly worse in Arm A and body weight loss was significantly worse in Arm B. Compliance with the planned drug administration was higher in Arm B (p = 0.0008). CONCLUSION: The study suggests that IBRT and CRT have similar efficacy, activity and toxicity.

How Can Imaging Help the Radiation Oncologist in Multiple Myeloma Treatment.

Multiple myeloma is an incurable malignant tumor of plasma cells of the bone marrow; most patients present a disseminated disease with important bone involvement. Even though a chemotherapy-based approach is the major treatment, radiotherapy often has a supportive role for symptom relief but also a radical role for patients with indolent disease or localized forms. In both cases imaging is the basis for treatment planning and for correct patient classification. This paper aims to describe and summarize how radiation oncologists could use imaging information to personalize the treatment for each patient.

Impact of Surgical Approach on Patient-Reported Outcomes after Radical Prostatectomy: A Propensity Score-Weighted Analysis from a Multicenter, Prospective, Observational Study (The Pros-IT CNR Study).

BACKGROUND: To report health-related quality of life outcomes as assessed by validated patient-reported outcome measures (PROMs) after radical prostatectomy (RP). -Methods: This study analyzed patients treated with RP within The PROState cancer monitoring in Italy, from the National Research Council (Pros-IT CNR). Italian versions of Short-Form Heath Survey and university of California los Angeles-prostate cancer index questionnaires were administered. PROMs were physical composite scores, mental composite scores and urinary, bowel, sexual functions and bothers (UF/B, BF/B, SF/B). Baseline unbalances were controlled with propensity scores and stabilized inverse weights; differences in PROMs between different RP approaches were estimated by mixed models. RESULTS: Of 541 patients treated with RP, 115 (21%) received open RP (ORP), 90 (17%) laparoscopic RP (LRP) and 336 (61%) robot-assisted RP (RARP). At head-to-head -comparisons, RARP showed higher 12-month UF vs. LRP (interaction treatment * time p = 0.03) and 6-month SF vs. ORP (p < 0.001). At 12-month from surgery, 67, 73 and 79% of patients used no pad for urinary loss in ORP, LRP and RARP respectively (no differences for each comparison). Conversely, 16, 27 and 40% of patients declared erections firm enough for sexual intercourse in ORP, LRP and RARP respectively (only significant difference for ORP vs. RARP, p = 0.0004). CONCLUSIONS: Different RP approaches lead to significant variations in urinary and sexual PROMs, with a general trend in favour of RARP. However, their clinical significance seems limited.

Applying radiation protection and safety in radiotherapy.

Radiotherapy is one of the primary treatment options in cancer management. Modern radiotherapy includes complex processes requiring many different kinds of expertise. Among them, knowledge and skills are needed in clinical oncology, radiobiology, radiotherapy planning and simulation, dose measurement and calculation, radiation safety and medical physics. Radiation oncologists should assume the full and final responsibility for treatment, follow-up and supportive care of the patient. For all these activities, radiation oncologist should coordinate and collaborate with a team including different professionals: nurses, radiographers (RTT), clinical engineers, information system experts, taking advantage in particular of the dosimetry expertise of the medical physicist. Radiation therapy is widely recognized to be one of the safest areas of modern medicine, and errors are very rare. However, radiation protection recommendations developed at national level should comply with the EURATOM Directive 2013/59. This paper describes several contemporary and emerging concerns related to radioprotection in radiation therapy including quality and safety in external beam radiotherapy and brachytherapy, foetal dose, secondary malignancies, and the safety issues related to the new techniques and treatment strategies.

Non-palliative radiotherapy in ab initio oligometastatic prostate cancer: an Italian national survey.

AIMS: The purpose of this survey was to investigate the current opinion among Italian radiation oncologists regarding the non-palliative radiotherapy in ab initio oligometastatic prostate cancer (OMPC) patients. METHODS: A link to complete the survey was sent via e-mail to Italian radiation oncologists on February 2018. It was requested that only one physician per facility completed the survey, and that he/she was dedicated to PC management in his/her daily clinical practice. The questionnaire consisted of 15 questions concerning the management of OMPC. RESULTS: One hundred and eleven radiation oncologists filled in the questionnaire. The majority of them see ≤ 10 patients affected by OMPC in a year. More than 80% of respondents would perform radiotherapy (RT) to both the prostate and all metastases sites, but mostly up to 2-3 metastases; furthermore, > 80% of physicians would perform RT on both nodal and bone secondary lesions. Most respondents deem a choline- or prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) mandatory before considering a patient affected by OMPC for non-palliative RT. The association of RT with androgen deprivation therapy for at least 12 months would be recommended by > 50% of respondents. In the follow-up phase, the majority would suggest a clinical examination and PSA every 3-6 months and a choline- or PSMA-PET only at biochemical progression. More than 90% of respondents confirmed to be interested in participating in a multicentre study regarding this subject. CONCLUSIONS: This survey investigated the current opinion of Italian radiation oncologists and confirmed their interest in OMPC management.

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: the Pros-IT CNR study.

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.

GUROPA survey: genito-urinary radiation oncology prescription attitudes.

AIMS: To investigate the role of Radiation Oncology in the management of genito-urinary (GU) cancer excluding prostate and penile cancer. METHODS: The questionnaire was focused on the evaluation of the degree of involvement of radiation oncologists in the work-up of bladder, renal cell carcinoma and testicular cancer (TC). RESULTS: Eighty-eight radiation oncologists completed the survey. The majority (85.4%) of participating radiation oncologists were senior consultants (> 5 years of experience). Sixty-four (73.6%) carried out a multidisciplinary tumor board discussion of GU cases, while 23 (26.4%) did not. Seventy-five percent of responders reported that, every year, visited < 50 GU patients (pts), 18.1% visited 50-100 pts and 6.9% visited > 100 pts. Bladder cancer, curative radiotherapy (RT) as part of trimodality approach was claimed to be adopted in less than 10 cases per year. Regarding renal cell carcinoma (RCC) patients, primary tumor directed RT was adopted only in 8 cases (9.4%) in at least 10 pts per year. Palliative RT was more frequent in RCC (48.2%) in over than 10 pts per year. In case of TC, the prescription of RT was limited (< 10 patients per year) due to the low incidence of disease and recent shift to surveillance as a first option in stage I seminoma. CONCLUSIONS: Our survey showed that radiation oncologists are rarely involved in the decision making strategy of GU cancer, despite many clinical trials support RT use. These patients probably deserve a more uniform approach based on updated, detailed and evidence-based recommendations.

Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis.

BACKGROUND: The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials. METHODS: For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival. FINDINGS: Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90-0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3-4·9) and at 10 years of 1·2% (-0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74-0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (-0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05-1·42; p=0·0098), with absolute differences at 5 years of -5·8% (-11·9 to 0·3) and at 10 years of -5·1% (-13·0 to 2·8). INTERPRETATION: This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested. FUNDING: Institut National du Cancer; and Ligue Nationale Contre le Cancer.

Pros-IT CNR: an Italian prostate cancer monitoring project.

AIMS: The Pros-IT CNR project aims to monitor a sample of Italian males ≥18 years of age who have been diagnosed in the participating centers with incident prostate cancer, by analyzing their clinical features, treatment protocols and outcome results in relation to quality of life. METHODS: Pros-IT CNR is an observational, prospective, multicenter study. The National Research Council (CNR), Neuroscience Institute, Aging Branch (Padua) is the promoting center. Ninety-seven Italian centers located throughout Italy were involved. The field study began in September 1, 2014. Subjects eligible were diagnosed with biopsy-verified prostate cancer, naïve. A sample size of 1500 patients was contemplated. A baseline assessment including anamnestic data, clinical history, risk factors, the initial diagnosis, cancer staging information and quality of life (Italian UCLA Prostate Cancer Index; SF-12 Scale) was completed. Six months after the initial diagnosis, a second assessment evaluating the patient's health status, the treatment carried out, and the quality of life will be made. A third assessment, evaluating the treatment follow-up and the quality of life, will be made 12 months after the initial diagnosis. The 4th, 5th, 6th and 7th assessments, similar to the third, will be completed 24, 36, 48 and 60 months after the initial diagnosis, respectively, and will include also a Food Frequency Questionnaire and the Physical Activity Scale for the Elderly. DISCUSSION: The study will provide information on patients' quality of life and its variations over time in relation to the treatments received for the prostate cancer.

Adjuvant intraoperative radiotherapy for selected breast cancers in previously irradiated women: Evidence for excellent feasibility and favorable outcomes.

BACKGROUND: The present report provides preliminary outcomes with intraoperative radiotherapy delivered to women with breast cancer included in a re-irradiation program. MATERIALS AND METHODS: From October 2010 to April 2014, thirty women were included in a re-irradiation protocol by exploiting IORT technique. The median time between the two irradiations was 10 years (range 3-50). All patients underwent conservative surgery, sentinel lymph node excision and IORT with electron beam delivered by a mobile linear accelerator. Primary endpoint was esthetic result and consequential/late toxicity; secondary endpoints were local control (LC), disease free survival (DFS) and overall survival (OS). RESULTS: With a median follow up of 47 months (range 10-78), we analyzed 29 patients (1 lost at follow up). Twenty-seven patients (90%) had presented breast cancer local relapse or a new primary cancer in the same breast after a previous conservative surgery plus radiation treatment; three patients (10%) had previously received irradiation with mantle field for Hodgkin Lymphoma. Esthetic result was excellent in 3 pts (10%), good in 12 pts (41%), fair in 8 pts (28%) and poor in 6 pts (21%). 12 (41%) patients showed subcutaneous fibrosis at the last follow-up. LC, DFS and OS at five years was 92.3%, 86.3% and 91.2%, respectively. CONCLUSION: Although we analyzed a small number of patients, our results are satisfactory and this approach is feasible even if it could not be considered the standard treatment. Further clinical trials exploring IORT are needed to identify possible subgroups of patients that might be suitable for this type of approach.

Patterns of prescription and adherence to European Association of Urology guidelines on androgen deprivation therapy in prostate cancer: an Italian multicentre cross-sectional analysis from the Choosing Treatment for Prostate Cancer (CHOICE) study.

OBJECTIVE: To evaluate both the patterns of prescription of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) and the adherence to European Association of Urology (EAU) guidelines for ADT prescription. METHODS: The Choosing Treatment for Prostate Cancer (CHOICE) study was an Italian multicentre cross-sectional study conducted between December 2010 and January 2012. A total of 1 386 patients, treated with ADT for PCa (first prescription or renewal of ADT), were selected. With regard to the EAU guidelines on ADT, the cohort was categorized into discordant ADT (Group A) and concordant ADT (Group B). RESULTS: The final cohort included 1 075 patients with a geographical distribution including North Italy (n = 627, 58.3%), Central Italy (n = 233, 21.7%) and South Italy (n = 215, 20.0%). In the category of patients treated with primary ADT, a total of 125 patients (56.3%) were classified as low risk according to D'Amico classification. With regard to the EAU guidelines, 285 (26.51%) and 790 patients (73.49%) were classified as discordant (Group A) and concordant (Group B), respectively. In Group A, patients were more likely to receive primary ADT (57.5%, 164/285 patients) than radical prostatectomy (RP; 30.9%, 88/285 patients), radiation therapy (RT; 6.7%, 19/285 patients) or RP + RT (17.7%, 14/285 patients; P < 0.01). Multivariate logistic regression analysis, adjusted for clinical and pathological variables, showed that patients from Central Italy (odds ratio [OR] 2.86; P < 0.05) and South Italy (OR 2.65; P < 0.05) were more likely to receive discordant ADT. CONCLUSION: EAU guideline adherence for ADT was low in Italy and was influenced by geographic area. Healthcare providers and urologists should consider these results in order to quantify the inadequate use of ADT and to set policy strategies to overcome this risk.

Image-guided radiation therapy (IGRT): practical recommendations of Italian Association of Radiation Oncology (AIRO).

The use of imaging to maximize precision and accuracy throughout the entire process of radiation therapy (RT) delivery has been called "Image-guided RT" (IGRT). RT has long been image guided: in fact, historically, the portal films and later electronic megavoltage images represented an early form of IGRT. A broad range of IGRT modalities is now available and adopted. The target location may be defined for each treatment fraction by several methods by localizing surrogates, including implanted fiducial markers, external surface markers or anatomical features (through planar imaging, fluoroscopy, KV or MV computed tomography, magnetic resonance imaging, ultrasound and X-ray imaging, electromagnetic localization, optical surface imaging, etc.). The aim of the present review is to define practical recommendations for IGRT.

Pharmacokinetics, pharmacodynamics and efficacy on pediatric tumors of the glioma radiosensitizer KU60019.

We have recently reported that glioblastoma (GB)-initiating cells (GIC) with low expression and/or mutation of TP53 and high expression of PI3K ("responder" genetic profile) can be effectively and safely radiosensitized by the ATM inhibitor KU60019. We report here on drug's diffusion and elimination from the animal body and brain, its effects on orthotopic GB and efficacy toward pediatric GIC. Healthy mice were infused by convection enhanced delivery (CED) with KU60019 and the drug kinetics followed by high performance liquid chromatography-mass spectrometry. Already at the end of CED, KU60019 had diffused from the injection site to the ipsilateral and, to a lower extent, controlateral hemisphere. After 24 hr, no drug could be detected all over the brain or in other organs, indicating rapid draining and excretion. After intraperitoneal injection, traces only of KU60019 could be detected in the brain, indicating inability to cross the brain-blood barrier. Consistent with the induction of cell cycle progression previously observed in vitro, KU60019 stimulated proliferation of orthotopic GB cells with the highest effect observed 96 hr after drug delivery. Adult GIC with high expression of TP53 and low expression of PI3K could be radiosensitized by KU60019, although less promptly than GIC bearing the "responder" profile. Consistent with the kinetics of proliferation induction, the highest radiosensitizing effect was observed 96 hr after delivery of KU60019 to GIC. Pediatric GIC could be similarly radiosensitized after exposure to KU60019. The results indicate that ATM inhibition may allow to radiosensitize a wide range of adult and pediatric high-grade gliomas.

Identifying locally advanced basal cell carcinoma eligible for treatment with vismodegib: an expert panel consensus.

Basal cell carcinoma (BCC) is the most common skin cancer worldwide. Most occur on the head and neck, where cosmetic and functional outcomes are critical. BCC can be locally destructive if not diagnosed early and treated appropriately. Surgery is the treatment of choice for the majority of high-risk lesions. Aggressive, recurrent or unresectable tumors can be difficult to manage. Until recently, no approved systemic therapy was available for locally advanced or metastatic BCC inappropriate for surgery or radiotherapy. Vismodegib provides a systemic treatment option. However, a consensus definition of advanced BCC is lacking. A multidisciplinary panel with expertise in oncology, dermatology, dermatologic surgery and radiation oncology proposes a consensus definition based on published evidence and clinical experience.

[Synergy between radiotherapy and immunotherapy in the treatment of advanced malignancies: recent evidences of a new challenge in oncology]. / Sinergia tra radioterapia e immunoterapia nella cura dei tumori in stadio avanzato: recenti evidenze di una nuova sfida in oncologia.

Radiotherapy remains a cornerstone of oncological treatment modalities for many types of tumors. Recently, preliminary studies have evidenced that ionizing radiations delivered by High Tech Linear Accelerators may increase the effectiveness of patients' antitumor immunoresponse in the clinical setting even at distant sites. Radiations may awake the dormant antitumor T-cells by promoting also an "abscopal effect", i.e. the control of metastasis outside the irradiated tumor site. These emerging findings have stimulated the design of combinations of high tech radiotherapy with new immunotherapies in order to obtain a synergy against biologically aggressive cancers. In preclinical model and clinical trials radiotherapy has been widely associated with citokines, peptides, immunoagonists and mainly with immune checkpoint inhibitors to counteract the function of CTLA-4 or Programmed-Death-1 receptors or PD-L1/L2 ligands. In this review the complex biological processes induced by radiotherapy on immunosystem are briefly explained. Although several trials are still ongoing, the preliminary interesting results obtained by this innovative radio-immunotherapy synergy to control advanced malignancies are reported and discussed.

Predictability, efficacy and safety of radiosensitization of glioblastoma-initiating cells by the ATM inhibitor KU-60019.

We have previously shown that pharmacological inhibition of ataxia telangiectasia mutated (ATM) protein sensitizes glioblastoma-initiating cells (GICs) to ionizing radiation (IR). Herein, we report the experimental conditions to overcome GIC radioresistance in vitro using the specific ATM inhibitor KU-60019, two major determinants of the tumor response to this drug and the absence of toxicity of this treatment in vitro and in vivo. Repeated treatments with KU-60019 followed by IR substantially delayed GIC proliferation in vitro and even eradicated radioresistant cells, whereas GIC treated with vehicle plus radiation recovered early and expanded. The tumor response to the drug occurred under a cutoff level of expression of TP53 and over a cutoff level of expression of phosphatidylinositol 3-kinase (PI3K). No increased clastogenicity or point mutagenicity was induced by KU-60019 plus radiation when compared to vehicle plus radiation. No significant histological changes to the brain or other organs were observed after prolonged infusion into the brain of KU-60019 at millimolar concentrations. Taken together, these findings suggest that GIC-driven tumors with low expression of TP53 and high expression of PI3K might be effectively and safely radiosensitized by KU-60019.