Psychopathology in children: The transdiagnostic contribution of affiliative capacity and inhibitory control.

Recent initiatives have focused on integrating transdiagnostic biobehavioral processes or dispositions with dimensional models of psychopathology. Toward this goal, biobehavioral traits of affiliative capacity (AFF) and inhibitory control (INH) hold particular promise as they demonstrate transdiagnostic stability and predictive validity across developmental stages and differing measurement modalities. The current study employed data from different modes of measurement in a sample of 1830 children aged 5-10 years to test for associations of AFF and INH, individually and interactively, with broad dimensions of psychopathology. Low AFF, assessed via parent-report, evidenced predictive relations with distress- and externalizing-related problems. INH as assessed by cognitive-task performance did not relate itself to either psychopathology dimension, but it moderated the effects observed for low AFF, such that high INH protected against distress symptoms in low-AFF participants, whereas low INH amplified distress and externalizing symptoms in low-AFF participants. Results are discussed in the context of the interface of general trait transdiagnostic risk factors with quantitatively derived dimensional models of psychopathology.

Effect of internal port on dose distribution in post-mastectomy radiotherapy for breast cancer patients after expander breast reconstruction.

Background: In patients with expander-based reconstruction a few dosimetric analyses detected radiation therapy dose perturbation due to the internal port of an expander, potentially leading to toxicity or loss of local control. This study aimed at adding data on this field. Materials and methods: A dosimetric analysis was conducted in 30 chest wall treatment planning without and with correction for port artifact. In plans with artifact correction density was overwritten as 1 g/cm3. Medium, minimum and maximum chest wall doses were compared in the two plans. Both plans, with and without correction, were compared on an anthropomorphic phantom with a tissue expander on the chest covered by a bolus simulating the skin. Ex vivo dosimetry was carried out on the phantom and in vivo dosimetry in three patients by using film strips during one treatment fraction. Estimated doses and measured film doses were compared. Results: No significant differences emerged in the minimum, medium and maximum doses in the two plans, without and with correction for port artifacts. Ex vivo and in vivo analyses showed a good correspondence between detected and calculated doses without and with correction. Conclusions: The port did not significantly affect dose distribution in patients who will receive post-mastectomy radiation therapy.

Form Factors as Potential Imaging Biomarkers to Differentiate Benign vs. Malignant Lung Lesions on CT Scans.

Indeterminate lung nodules detected on CT scans are common findings in clinical practice. Their correct assessment is critical, as early diagnosis of malignancy is crucial to maximise the treatment outcome. In this work, we evaluated the role of form factors as imaging biomarkers to differentiate benign vs. malignant lung lesions on CT scans. We tested a total of three conventional imaging features, six form factors, and two shape features for significant differences between benign and malignant lung lesions on CT scans. The study population consisted of 192 lung nodules from two independent datasets, containing 109 (38 benign, 71 malignant) and 83 (42 benign, 41 malignant) lung lesions, respectively. The standard of reference was either histological evaluation or stability on radiological followup. The statistical significance was determined via the Mann-Whitney U nonparametric test, and the ability of the form factors to discriminate a benign vs. a malignant lesion was assessed through multivariate prediction models based on Support Vector Machines. The univariate analysis returned four form factors (Angelidakis compactness and flatness, Kong flatness, and maximum projection sphericity) that were significantly different between the benign and malignant group in both datasets. In particular, we found that the benign lesions were on average flatter than the malignant ones; conversely, the malignant ones were on average more compact (isotropic) than the benign ones. The multivariate prediction models showed that adding form factors to conventional imaging features improved the prediction accuracy by up to 14.5 pp. We conclude that form factors evaluated on lung nodules on CT scans can improve the differential diagnosis between benign and malignant lesions.

The Italian Association for Radiotherapy and Clinical Oncology (AIRO) position statements for postoperative breast cancer radiation therapy volume, dose, and fractionation.

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.

Exploring the Effects of Parental Involvement on Broad and Specific Dimensions of Behavioral Problems in Adolescence.

Few studies have differentiated the specificity from the generality of the associations between parental involvement and adolescent behavioral problems across levels of the psychopathology hierarchy. Among 537 adolescents aged 11-17 years, the current study considered the extent to which associations between mother- and father- involvement and behavioral problems (assessed via the parent-reported Child Behavior Checklist) were unique to a specific dimension or reflective of associations with higher-order factors. The hierarchical structure of behavioral problems fit well, with total problems at the top, internalizing and externalizing at the second level, and eight specific symptom dimensions at the third level. Mother and father involvement were protective factors for withdrawn/depressed symptoms and risk factors for anxious/depressed symptoms that were not accounted for by internalizing or total problems. Mother involvement was also a protective factor for rule-breaking behavior and a risk factor for social problems symptoms and aggressive behavior symptoms that were not accounted for by externalizing or total problems.

Integrating stereotactic radiotherapy and systemic therapies.

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.

Triarchic Neurobehavioral Correlates of Psychopathology in Young Children: Evidence from the Healthy Brain Network Initiative.

Recent initiatives emphasize the need to consider developmental and transdiagnostic contributions of temperamental variation to psychopathological expression. Triarchic neurobehavioral trait dimensions (boldness, meanness, disinhibition), which demonstrate compatibility with established temperament models and can be quantified using items from different existing inventories, are well-suited to pursuing these goals. We undertook to develop item-based scales for indexing these traits in 285 children (ages 5-10) tested in the Child Mind Institute's Healthy Brain Network (HBN) study, and evaluated their psychometric properties in two separate samples of similar-aged children: 519 others from the HBN study and 261 for whom parental-informant ratings were obtained through MTurk. Associations with psychopathology measures provided evidence for a) transdiagnostic utility of the triarchic scales, b) (reversed) boldness as the strongest predictor of internalizing problems, c) meanness as related to both internalizing and externalizing problems, d) disinhibition as the strongest predictor of externalizing problems, and e)a moderating effect of meanness level on disinhibition's relationship with externalizing problems. This research demonstrates that the triarchic traits can be effectively represented in young children and show expected relations with clinical outcome measures. As such, this work provides a foundation for developmental research clarifying the role that core neurobehavioral dispositions play in mental health.

Social Problems in Children: Exploring the Contribution of Triarchic Traits and Parenting.

Social problems are transdiagnostically relevant in the development of various forms of psychopathology. It is thus important to consider contributing factors both at the individual and contextual level. Among 110 children (Mage = 8.85 years), we examined the contribution of triarchic trait dimensions (boldness, meanness, disinhibition) and parenting to the explanation of social problems. Using existing parent-report scales, triarchic scale-level representations were developed and validated. Significant main effects emerged for all three trait dimensions; meanness and disinhibition positively, boldness negatively, associated with social problems. Higher levels of disinhibition and meanness were associated with increased social problems in the context of higher levels of negative, or decreased levels of positive parenting; boldness acted as a protective factor in these contexts. Results suggest that the triarchic trait dimensions (1) can be studied in children, (2) act as risk and protective factors, and (3) interact with parenting to contribute to social problems.

Helical tomotherapy re-irradiation for patients affected by local radiorecurrent prostate cancer.

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.

Biobehavioral threat sensitivity and amygdala volume: A twin neuroimaging study.

Current literature on the relationship between dispositional fear (or threat sensitivity) and amygdala gray matter volume (GMV) is heterogeneous, with findings including positive, negative, and null correlations. A clearer understanding of this relationship would help to determine the potential utility of amygdala volume as a biomarker of anxious/depressive (internalizing) disorders and contribute to understanding of neural mechanisms for variations in fearfulness. The study reported here used voxel-based morphometry to quantify amygdala GMV scores from structural neuroimaging data in a sample of 44 monozygotic twins (i.e., 22 pairs). Dispositional threat sensitivity (THT) was quantified using a biobehavioral cross-domain score that combined neurophysiological indicators with a psychological scale measure. Analyses revealed expected high concordance for amygdala GMV between co-twins. With respect to the major question of the study, a negative correlation was found between biobehavioral THT scores and amygdala volume - with individuals higher in THT showing smaller amygdala GMV scores. More modest associations of amygdala GMV with symptoms of social phobia, and fear disorder symptomology more broadly, were mediated by THT. These results provide insight into prior mixed findings and support the combined use of biological and behavioral measures to quantify characteristics relevant to mental health problems.

Skin toxicity after chest wall/breast plus level III-IV lymph nodes treatment with helical tomotherapy.

INTRODUCTION: To evaluate the incidence of toxicity in breast cancer with helical tomotherapy (HT). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: HT was associated with a low incidence of low-grade skin toxicity.

Preoperative radiotherapy and curative surgery for the management of localised rectal carcinoma.

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; I2 = 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.

Variability in axillary lymph node delineation for breast cancer radiotherapy in presence of guidelines on a multi-institutional platform.

AIM: To quantify the variability between radiation oncologists (ROs) when outlining axillary nodes in breast cancer. MATERIAL AND METHODS: For each participating center, three ROs with different levels of expertise, i.e., junior (J), senior (S) and expert (E), contoured axillary nodal levels (L1, L2, L3 and L4) on the CT images of three different patients (P) of an increasing degree of anatomical complexity (from P1 to P2 to P3), according to contouring guidelines. Consensus contours were generated using the simultaneous truth and performance level estimation (STAPLE) method. RESULTS: Fifteen centers and 42 ROs participated. Overall, the median Dice similarity coefficient was 0.66. Statistically significant differences were observed according to the level of expertise (better agreement for J and E, worse for S); the axillary level (better agreement for L1 and L4, worse for L3); the patient (better agreement for P1, worse for P3). Statistically significant differences in contouring were found in 18% of the inter-center comparison. Less than a half of the centers could claim to have a good agreement between the internal ROs. CONCLUSIONS: The overall intra-institute and inter-institute agreement was moderate. Central lymph-node levels were the most critical and variability increased as the complexity of the patient's anatomy increased. These findings might have an effect on the interpretation of results from multicenter and even mono-institute studies.

FDG PET and Split-Bolus Multi-Detector Row CT Fusion Imaging in Oncologic Patients: Preliminary Results.

PURPOSE: To assess the incremental value of split-bolus multidetector computed tomography (CT) combined with fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for follow-up of oncologic patients. MATERIALS AND METHODS: The institutional ethics committee approved the use of this protocol. Thirty-eight oncologic patients who underwent FDG PET/unenhanced multidetector CT and split-bolus multidetector CT for restaging were investigated retrospectively. The split-bolus CT protocol included imaging during the hepatic arterial and portal venous phases in one scan. Software was used for fusion of the independently acquired FDG PET and split-bolus CT data, and fused datasets were compared with FDG PET/unenhanced CT data. The standard of reference for diagnosis of lesions in all patients was a combination of histologic results (if available), clinical results (medical history, physical examination, and laboratory test results), and the results of follow-up imaging (conventional CT, magnetic resonance imaging, and/or ultrasonography) for at least 6 months. Descriptive statistics were used. RESULTS: Fifty-nine true-positive lesions were identified with fused FDG PET/split-bolus CT; 41 were concordant and detected with both split-bolus CT and PET/unenhanced CT, 16 with split-bolus CT only, and two with PET/unenhanced CT. Two different false-positive lesions were identified with PET/unenhanced CT and PET/split-bolus CT. Furthermore, in 20 of 38 (53%) patients, FDG PET/split-bolus CT allowed detection of important additional findings (n = 40) not detected at FDG PET/unenhanced CT. Both the tumor-related findings (n = 13, 32.5%) and the non-tumor-related findings (n = 27, 67.5%) were important to the clinical treatment of these patients. CONCLUSION: Fused FDG PET/split-bolus multidetector CT provides additional information compared with FDG PET/unenhanced multidetector CT in oncologic patients.

Influence of hormonal therapy in prostate cancer patients undergoing [18F]fluoromethyl choline PET/CT: a retrospective study.

BACKGROUND: Patients with suspected recurrence of prostate cancer undergoing [18F]fluoromethyl choline ([18F]FCH) PET/CT were retrospectively evaluated to investigate the influence of hormonal therapy (HT) in [18F]FCH uptake. METHODS: [18F]FCH PET/CT was performed in 102 surgically treated patients with suspected recurrence (PSA increase >0.2 ng/mL) of prostate cancer, divided in two groups: under HT (N.=54) and without HT (N.=48) at the time of PET scanning. PET/CT was carried out by an integrated system (Biograph 6, CTI/Siemens, Knoxville, TN, USA) intravenously by administering 4.1 MBq/kg of [18F]FCH to each patient; images were acquired 60 minutes later. RESULTS: On the total number of patients, 66 were found to be true positives (TP), 9 false positives (FP), 5 false negatives (FN) and 22 true negatives (TN), sensitivity to [18F]FCH PET/CT was 93%, specificity 71%, accuracy 86%, positive predictive value (PPV) 88%, negative predictive value (NPV) 81%. In the 54 patients under HT, 38 were TP, 6 FP, 3 FN and 7 TN, sensitivity was 93%, specificity 54%, accuracy 83%, PPV 86% and NPV was 70%. In the 48 patients receiving no HT, 28 were TP, 3 FP, 2 FN and 15 TN, sensitivity was 93%, specificity 83%, accuracy 90%, PPV 90% and NPV 88%. A χ2 test showed that sensitivity, accuracy and PPV did not differ among patients with and without HT, while specificity and NPV were significantly lower (P<0.001) in HT treated patients. CONCLUSIONS: Sensitivity, accuracy and PPV were similar in patients with and without HT. Specificity and NPV were reduced in patients under HT, but further data are necessary to support if this reduction is casual or related to therapy and it could be confirmed in a larger series of patients.

Gefitinib enhances the effects of combined radiotherapy and 5-fluorouracil in a colorectal cancer cell line.

PURPOSE: In a phase I/II trial, patients with locally advanced rectal cancer received preoperative radiotherapy (RT) and concurrent with 5-fluorouracil (5-FU) and gefitinib. Results were promising. To elucidate the molecular and biological effects, we replicated the schedule in the LoVo human colorectal adenocarcinoma cell line. METHODS: RT (2 Gy daily for 3 days), 5-FU (0.3, 0.6, 1.25, 2.5, 5, 10 µM) and gefitinib (0.2, 0.4, 0.8 µM) were administered alone, in double combinations and all together. We assessed viable cells, cell cycle, cyclin, p53 and p21 expression, signalling pathways by means of phosphorylated epidermal growth factor receptor (p-EGFR), p-AKT and p-ERK 1-2 and clonogenic capacity. RESULTS: RT and 5-FU were cytotoxic. Gefitinib was cytostatic. RT reduced clonogenic capacity more than 5-FU. 5-FU induced more cell death than RT, but surviving cells were proliferative (cyclins and p-EGFR increased). 5-FU + RT had a synergistic effect. Gefitinib, enhancing G1 accumulation, reduced proliferation of cells surviving 5-FU and 5-FU + RT. It slightly increased the cytotoxicity of RT and 5-FU. CONCLUSIONS: As gefitinib limited the proliferation rate of cells surviving 5-FU and 5-FU + RT in the LoVo cell line, it may be a useful addition to chemotherapy and RT in rectal cancer patients.

SPECT and PET serve as molecular imaging techniques and in vivo biomarkers for brain metastases.

Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET) represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI) is discussed.

Sequential Moderate Hypofractionated Boost in Breast Cancer Patients: A Monoinstitutional Analysis of Late Side Effects.

BACKGROUND/AIM: In breast cancer (BC) patients who have received breast-conserving surgery, moderate hypofractionation is standard of care for whole-breast irradiation (HF-WBI). On the other hand, the fractionation schedule for the boost is less well defined. A previous prospective study of our group aimed at evaluating acute and late cutaneous and subcutaneous side effects related to a sequential hypofractionated boost (HB) in patients who had received HF-WBI. The present study aimed at evaluating late side effects at a longer follow-up. PATIENTS AND METHODS: From 2014 to 2015, 219 BC patients received moderate HF-WBI (42.4 Gy in 16 fractions) at the Radiation Oncology Section of the University of Perugia. Patients with negative prognostic factors received a HB (2.65 Gy for 4 or 5 fractions). Late side effects were assessed using the Common Terminology Criteria for Adverse Events v5.0. Univariate and multivariate analyses estimated predictive factors for late toxicity. RESULTS: Median follow-up was 8.6 years (range=6.7-9.6). One hundred and sixty-five patients were evaluable in the present analysis; HB was administered to 47.3% of them. Late cutaneous and subcutaneous side effects occurred in 26/165 patients (15.8%); and all were G1. In univariate analysis ≥10 excised lymph nodes and HB administration emerged as risk factors for late side effects (p=0.003 and p=0.041, respectively). In multivariate analysis only ≥10 excised lymph nodes were confirmed as a risk factor for side effects (OR=3.431; 95%CI=1.209-9.737). CONCLUSION: HB after HF-WBI was safe and well-tolerated, even at a long-term follow-up; consequently, it can be used in routine practice.

Pattern of practice of re-irradiation for ipsilateral breast tumor recurrence in Italy: a survey by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: The Re-irradiation and the Breast Cancer Working Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) conducted a survey to provide an overview of the policies for breast cancer (BC) re-irradiation (re-RT) among the Italian radiotherapy (RT) centers. METHODS: In October 2021, 183 RT centers were invited to answer a survey: after an initial section about general aspects, the questionnaire focused on radiation oncologists' (ROs) attitude toward re-RT in three different scenarios: ipsilateral breast tumor recurrence (IBTR) treated with second conservative surgery, IBTR treated with mastectomy and inoperable IBTR. Surveyed ROs were also asked to express their interest in being involved in a prospective trials. RESULTS: Seventy-seven/183 (42.0%) centers answered the Survey, only one RO per center was requested to answer. In particular, 86.5% ROs declared to have performed "curative" re-RT for IBTR during the previous two years (2019-2020): 76.7% respondents administered re-RT after second BCS, 50.9% after mastectomy, and 48.1% for inoperable IBTR. Re-RT practice varied widely among centers in terms of treatment volumes, dose and fractionation schedules, techniques and dose-volume constraints for organs at risks (OARs). Forty-six participants (59.7%) expressed their interest in participating in a prospective study investigating BC re-RT. CONCLUSIONS: About one out of three RT centers in Italy delivered re-RT for IBTR. Nevertheless, practice of re-RT varied widely among centers highlighting the needs for prospective studies to improve knowledge in this field.

Parp-inhibitors in the therapeutic landscape of breast cancer patients with BRCA1 and BRCA2 pathogenic germline variants: An Italian consensus paper and critical review.

The introduction of PARP inhibitors has revolutionized the management and treatment of patients with pathogenic germline variants of BRCA1/2 who have developed breast cancer. The implementation of PARP inhibitors in clinical settings can be challenging due to their overlapping indications with other drugs, including both recently approved medications and those with proven efficacy. This study utilized the Delphi method to present the first Italian consensus regarding genetic testing, the use of PARP inhibitors in both early and metastatic settings, and strategies for managing the potential toxicity of these novel drugs. The Panel unanimously agreed on various issues, including the timing, techniques, and patient characteristics for BRCA1/2 genetic testing, andthe appropriate placement of PARP inhibitors in the treatment algorithm for both early and advanced breast cancer. Nevertheless, some areas of divergence became evident, particularly regarding the use of axillary surgery for therapeutic purposes and the application of hormone replacement therapy in cases of bilateral mastectomy and risk-reducing salpingo-oophorectomy for patients treated for triple negative breast cancer. Additional research is needed in these particular domains to improve the care of patients with breast cancer who bear an increased genetic risk.