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Despite the recent advanced developments in radiation therapy planning, treatment planning for head-neck and pelvic cancers remains challenging due to large concave target volumes, multiple dose prescriptions and numerous organs at risk close to targets. Inter-institutional studies highlighted that plan quality strongly depends on planner experience and skills. Automated optimization of planning procedure may improve plan quality and best practice. We performed a comprehensive dosimetric and clinical evaluation of the Pinnacle 3 AutoPlanning engine, comparing automatically generated plans (AP) with the historically clinically accepted manually-generated ones (MP). Thirty-six patients (12 for each of the following anatomical sites: head-neck, high-risk prostate and endometrial cancer) were re-planned with the AutoPlanning engine. Planning and optimization workflow was developed to automatically generate “dual-arc” VMAT plans with simultaneously integrated boost. Various dose and dose-volume parameters were used to build three metrics able to supply a global Plan Quality Index evaluation in terms of dose conformity indexes, targets coverage and sparing of critical organs. All plans were scored in a blinded clinical evaluation by two senior radiation oncologists. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. Autoplanning was able to produce high-quality clinically acceptable plans in all cases. The main benefit of Autoplanning strategy was the improvement of overall treatment quality due to significant increased dose conformity and reduction of integral dose by 6–10%, keeping similar targets coverage. Overall planning time was reduced to 60–80 minutes, about a third of time needed for manual planning. In 94% of clinical evaluations, the AP plans scored equal or better to MP plans. Despite the increased fluence modulation, dose measurements reported an optimal agreement with dose calculations with a γ-pass-rate greater than 95% for 3%(global)-2 mm criteria. Autoplanning engine is an effective device enabling the generation of VMAT high quality treatment plans according to institutional specific planning protocols.

OBJECTIVEThe aim of this study was to investigate the impact of SUVmax fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) measured in the primary tumor, pelvic and para-aortic node with disease-free survival (DFS) and overall survival (OS) in patients with locally advanced cervical cancer. METHODS AND MATERIALSA total of 92 patients with histological diagnosis of locally advanced cervical cancer are treated with radiochemotherapy plus brachytherapy boost from January 2008 to April 2014 in our Institution. A pretreatment FDG-PET/CT for staging and radiotherapy planning was performed, and the value of SUVmax measured in primary tumor and positive nodes was related to DFS and OS. RESULTSUnivariate analysis showed that DFS is related to FDG-PET/CT positive para-aortic nodes (P = 0.01), International Federation of Gynecology and Obstetrics (FIGO) stage of disease (P = 0.01), and primary tumor SUVmax (P = 0.02), and OS is related to positive para-aortic nodes (P = 0.01) and primary tumor SUVmax (P = 0.02).In multivariate analysis, DFS is modified by FDG-PET/CT positive para-aortic lymph nodes, stage and high T SUVmax (P = 0.02; P = 0.003; P = 0.04), but the only worse prognostic factor of OS is the high SUVmax in the primary tumor (P = 0.01). CONCLUSIONSWe found that T SUVmax, stage, and para-aortic lymph node status assessed by FDG-PET were independent prognostic factors of DFS, whereas only T SUVmax correlated with OS.

The purpose of the present multicentric study was to review stereotactic body radiotherapy (SBRT) with or without chemotherapy (CHT) experience in locally advanced pancreatic cancer (LAPC). Endpoints were overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). Several parameters' impact on these outcomes was assessed. Fifty-six patients with LAPC undergoing SBRT+/-CHT were included. SBRT median BED was 48.0 Gy (range=28.0-78.7). Survival curves were calculated by Kaplan-Meier method. A Cox regression model was fitted. At a median follow-up of 15.0 months, 2-year OS, LC, DMFS were: 33.8% 55.4%, and 22.9%, respectively. Patients treated with BED ≥48 Gy showed improved OS (p=0.020) and LC (p=0.024). At multivariate analysis, BED ≥48 Gy was significantly associated to both higher OS (p=0.042) and LC (p=0.045), while post-SBRT CHT improved DMFS (p=0.003). SBRT proved to be tolerable and effective in LAPC. Moreover, BED ≥48 Gy was significantly correlated with improved OS and LC.

To retrospectively evaluate the outcome of patients with unresectable biliary cholangiocarcinoma (CC) treated with radiotherapy (RT) plus/minus chemotherapy (CHT). Data of patients with intrahepatic CC (ICC), Klatskin's tumor (KT), distal extrahepatic CC (ECC), and gallbladder cancer (GBC) diagnosed from 1991 to 2017 were retrospectively analyzed. The treatment was mainly based on RT plus concurrent CHT +/- brachytherapy (BRT) boost. The Kaplan-Meier method was used to calculate survival curves that were compared using the log-rank test. Seventy-six patients were included in this analysis (males: 59%; females: 41%; median age: 66.5 years). A minority of patients (7.9%) were treated for disease recurrence after surgery. According to TNM, 78.5% of patients had T stage >3 and 77.6% of patients were treated with concurrent CHT-RT while 22.3% received RT followed by sequential CHT. Median RT dose was 50 Gy (range: 16-75 Gy) delivered with conventional fractionation. CHT was based on Gemcitabine or 5-fluorouracil. BRT was prescribed to 51.3% of patient with a median dose of 14 Gy. Reported Grade ≥3 acute GI and hematological toxicity were 13.2% and 8.1%, respectively. No other severe acute toxicities were reported. One- and 2-year overall survival (OS) were 58.1% and 25.8%, respectively (median: 13.5 months), while 1- and 2-year progression-free survival (PFS) were 43.4% and 9.4%, respectively. None of the following variables had a significant impact on OS and PFS: BRT boost, tumor site, concurrent CHT, and the drugs used in concurrent CHT. In contrast, patients receiving RT with 2D technique showed a PFS significantly higher compared to patients treated with the 3D technique (median: 15.5 vs. 8.5 months; p=0.02). Combined modality treatment (RT+CHT±BRT) in unresectable biliary cancer was associated with acceptable toxicity and OS comparable to the actual standard treatment (CHT). The significantly improved PFS in patients undergoing 2D-RT raises doubts regarding the adequacy of target delineation in these neoplasms.

Preserving cognitive functions is a priority for most patients with brain metastases. Knowing the mechanisms of hyperglutamatergic neurotoxicity and the role of some hippocampal areas in cognitive decline (CD) led to testing both the antiglutamatergic pharmacological prophylaxis and hippocampal-sparing whole-brain radiotherapy (WBRT) techniques. These studies showed a relative reduction in CD four to six months after WBRT. However, the failure to achieve statistical significance in one study that tested memantine alone (RTOG 0614) led to widespread skepticism about this drug in the WBRT setting. Moreover, interest grew in the reasons for the strong patient dropout rates in the first few months after WBRT and for early CD onset. In fact, the latter can only partially be explained by subclinical tumor progression. An emerging interpretation of the (not only) cognitive impairment during and immediately after WBRT is the dysfunction of the limbic and hypothalamic system with its immune and hormonal consequences. This new understanding of WBRT-induced toxicity may represent the basis for further innovative trials. These studies should aim to: (i) evaluate in greater detail the cognitive effects and, more generally, the quality of life impairment during and immediately after WBRT; (ii) study the mechanisms producing these early effects; (iii) test in clinical studies, the modern and advanced WBRT techniques based on both hippocampal-sparing and hypothalamic-pituitary-sparing, currently evaluated only in planning studies; (iv) test new timings of antiglutamatergic drugs administration aimed at preventing not only late toxicity but also acute effects.

ObjectiveThis retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of patients with oligometastatic/persistent/recurrent cervical cancer.MethodsA standardized data collection from several radiotherapy centers that treated patients by stereotactic body radiotherapy between March 2006 and February 2021 was set up. Clinical and stereotactic body radiotherapy parameters were collected. Objective response rate was defined as a composite of complete and partial response, while clinical benefit included objective response rate plus stable disease. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Common Terminology Criteria for Adverse Events scales were used to grade toxicities. The primary endpoints were the rate of complete response to stereotactic body radiotherapy, and the 2 year actuarial local control rate on a ‘per lesion’ basis. The secondary end points were progression-free survival and overall survival, as well as toxicity.ResultsA total of 83 patients with oligometastatic/persistent/recurrent cervical cancer bearing 125 lesions treated by stereotactic body radiotherapy at 15 different centers were selected for analysis. Of the sites of metastatic disease, lymph node metastases were most common (55.2%), followed by parenchyma lesions (44.8%). Median total dose was 35 Gy (range 10–60), in five fractions (range 1–10), with a median dose/fraction of 7 Gy (range 4–26). Complete, partial, and stable response were found in 73 (58.4%), 29 (23.2%), and 16 (12.8%) lesions, respectively, reaching 94.4% of the clinical benefit rate. Forty-six (55.4%) patients had a complete response. Patients achieving complete response on a ‘per lesion’ basis experienced a 2 year actuarial local control rate of 89.0% versus 22.1% in lesions not achieving complete response (p<0.001). The 2 year actuarial progression-free survival rate was 42.5% in patients with complete response versus 7.8% in patients with partial response or stable or progressive disease (p=0.001). The 2 year actuarial overall survival rate was 68.9% in patients with complete response versus 44.3% in patients with partial response or stable or progressive disease (p=0.015). Fifteen patients (18.1%) had mild acute toxicity, totaling 29 side events. Late toxicity was documented in four patients (4.8%) totaling seven adverse events.ConclusionOur analysis confirmed the efficacy of stereotactic body radiotherapy in oligometastatic/persistent/recurrent cervical cancer patients. The low toxicity profile encourages the wider use of stereotactic body radiotherapy in this setting.

The primary endpoint of this phase I study was the maximum tolerated dose (MTD) of middle half body (MHB) accelerated radiotherapy (RT) in multiple bone metastatic (BM) prostate cancer (PCa) patients. Three step dose escalation [13 Gy (3.25 Gy/fraction), 14 Gy (3.5 Gy/fraction), and 15 Gy (3.75 Gy/fraction)] in three consecutive patient cohorts were planned. RT was delivered in two consecutive days and two daily fractions. Six patients were enrolled in the first two cohorts and 12 in the third cohort. Grade ≥3 toxicity was considered as a dose-limiting toxicity (DLT). Twenty-five patients (median age=71 years, median follow-up=7.4 months) were enrolled. Defined MTD dose was 15 Gy. Overall pain response rate was 76%: 9 patients (36%) showed complete and 10 patients (40%) reported partial response of pain. MHB accelerated RT (total dose: 15 Gy) delivered in two consecutive days and two daily fractions is well tolerated.

We aimed to perform an anatomical evaluation of the carotid bulb using CT-angiography, implement a new reliable index for carotid stenosis quantification and to assess the accuracy of relationship between NASCET and ECST methods in a large adult population. The cross-sectional areas of the healthy carotid at five levels were measured by two experienced radiologists. A regression analysis was performed in order to quantify the relationship between the areas of the carotid bulb at different carotid bulbar level. A new index (Regression indeX, RegX) for carotid stenosis quantification was proposed. Five different stenoses with different grade in three bulbar locations were simulated for all patients for a total of 1365 stenoses and were used for a direct comparison of the RegX, NASCET, and ECST methods. The results of this study demonstrated that the RegX index provided a consistent and accurate measure of carotid stenosis through the application of the ECST method, avoiding the limitations of NASCET method. Furthermore, our results strongly depart from the consolidated relationships between NASCET and ECST values used in clinical practice and reported in extensive medical literature. In particular, we highlighted that a major misdiagnosis in patient selection for CEA could be introduced because of the large underestimation of real stenosis degree provided by the NASCET method. A reappraisal of carotid stenosis patients’ work-up is evoked by the effectiveness of state-of-the-art noninvasive contemporary carotid imaging.

Skin metastases occur in 5–30% of breast cancer (BC) patients. Standard treatments include systemic therapies (chemotherapy, endocrine therapy, and immunotherapy) and local treatments (surgery and radiotherapy). Electrochemotherapy (ECT) could be another option in this setting based on preclinical and clinical studies. Aim of this review was to analyze the available evidence on ECT in skin metastases from BC. Studies reporting on ECT in skin metastases from BC were included in this review. Studies not reporting toxicity or tumor response or not reporting results separately from other primary cancers were excluded. The search was based on Medline, Scopus, and The Cochrane Library databases. Eleven studies including 464 patients were analyzed. ECT was performed using intravenous/intratumoral bleomycin (10 studies) or intratumoral cisplatin (one study). Complete and overall pooled response rates were 46.2% (95%CI 33.2–59.4 and 74.6% (95%CI 60.6–86.4) in studies reporting results on a per patient basis and 61.9% (95%CI 53.8–69.6) and 86.9% (95%CI 80.0–92.6) in studies reporting results on a per lesion basis, respectively. Worse response rates in larger lesions were observed in three studies. The incidence of toxicity was heterogeneous but adverse events were mild and manageable in all studies. One- and 3-year local progression-free survival was 86.2% and 81.0% in two studies, respectively. ECT is tolerable and effective in terms of response in BC skin metastases especially in less advanced lesions. Further studies are justified to compare ECT with other treatments in this setting.

Heterotopic ossification (HO) is a common complication following total hip arthroplasty. Various prophylactic treatments have been proposed, including radiotherapy (RT). This review summarizes the evidence from meta-analyses on the efficacy of RT in preventing hip HO. A literature search was conducted on PubMed. The quality of the meta-analyses was assessed using the AMSTAR-2 tool. Seven meta-analyses were included. One meta-analysis reported a significant reduction in HO occurrence after RT compared to the control group. Comparing RT and non-steroidal anti-inflammatory drugs, one and two meta-analyses showed significantly greater efficacy of RT in preventing severe HO and better outcomes in patients receiving drugs, respectively. Regarding RT settings, the postoperative and preoperative RT were each supported by one meta-analysis. Furthermore, two meta-analyses showed an advantage of multi-fractionated RT over single fraction RT. The overall confidence rate of the meta-analyses was moderate, low, and critically low in one, three, and three meta-analyses, respectively. RT is a confirmed prophylactic intervention for HO. However, the precise optimization of timing, dosage, and fractionation requires elucidation. Future research should focus on the development of predictive models through large-scale data collection and advanced analytics to refine individualized treatment strategies and assess RT comparative effectiveness with drugs.