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Purpose: To assess the performance of a new optimization system, VOLO, for CyberKnife MLC-based SBRT plans in comparison with the existing Sequential optimizer., Methods: MLC-plans were created for 25 SBRT cases (liver, prostate, pancreas and spine) using both VOLO and Sequential. Monitor units (MU), delivery time (DT), PTV coverage, conformity (nCI), dose gradient (R50%) and OAR doses were used for comparison and combined to obtain a mathematical score (MS) of plan quality for each solution. MS strength was validated by changing parameter weights and by a blinded clinical plan evaluation. The optimization times (OT) and the average segment areas (SA) were also compared., Results: VOLO solutions offered significantly lower mean DT (-19%) and MU (-13%). OT were below 15 min for VOLO, whereas for Sequential, values spanned from 8 to 160 min. SAs were significantly larger for VOLO: on average 10 cm 2 versus 7 cm 2 . VOLO optimized plans achieved a higher MS than Sequential for all tested parameter combinations. PTV coverage and OAR sparing were comparable for both groups of solutions. Although slight differences in R50% and nCI were found, the parameters most affecting MS were MU and DT. VOLO solutions were selected in 80% of cases by both physicians with 88% inter-observer agreement., Conclusions: The good performance of the VOLO optimization system, together with the large reduction in OT, make it a useful tool to improve the efficiency of CK SBRT planning and delivery. The proposed methodology for comparing different planning solutions can be applied in other contexts., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study evaluated the plan quality of CyberKnife MLC-based treatment planning in comparison to the Iris collimator for abdominal and pelvic SBRT. Multiple dosimetric parameters were considered together with a global scoring index validated by clinical scoring., Methods and Materials: Iris and MLC plans were created for 28 liver, 15 pancreas and 13 prostate cases including a wide range of PTV sizes (24-643 cm 3 ). Plans were compared in terms of coverage, conformity (nCI), dose gradient (R50%), homogeneity (HI), OAR doses, PTV gEUD, MU, treatment time both estimated by TPS (t TPS ) and measured. A global plan quality score index was calculated for IRIS and MLC solutions and validated by a clinical score given independently by two observers., Results: Compared to Iris, MLC achieved equivalent coverage and conformity without compromising OAR sparing and improving R50% (p < 0.001). MLC gEUD was slightly lower than Iris (p < 0.05) for abdominal cases. MLC reduced significantly MU (-15%) and t TPS (-22%). Time reduction was partially lost when measured. The global score index was significantly higher for MLC solutions which were selected in 73% and 64% of cases respectively by the first and second observer., Conclusion: Iris and MLC comparison was not straightforward when based on multiple dosimetric parameters. The use of a mathematical overall score index integrated with a clinical scoring was essential to confirm MLC plans advantages over Iris solutions., (Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Aims and Background: Radiobiological and technical considerations have traditionally limited the role of radiation therapy in the context of primary and secondary cardiac malignancies. Stereotactic body radiotherapy (SBRT) is a promising modality for the delivery of focused high-dose radiation with ablative potential to complex targets such as small, deep-seated, moving lesions, allowing also for re-irradiation., Methods: Between January 2013 and October 2013, 3 patients underwent SBRT for cardiac lesions: 2 patients had recurrent, previously irradiated cardiac angiosarcomas (PCA) and 1 patient had a cardiac metastasis from melanoma. They were treated with fiducial-guided robotic radiotherapy with CyberKnife. As for dose prescription, 24 Gy in 3 fractions (80% isodose) and 30 Gy in 5 fractions (80% isodose) were administered to the recurrent PCAs and cardiac metastasis, respectively., Results: At 2 months after SBRT, cardiac MRI showed a partial response in the patients treated for recurrent PCA while the cardiac metastasis remained stable. In all cases, absence of local progression was subsequently confirmed by contrast-enhanced cardiac MRI after 6 months, without any evidence of treatment-related side effects., Conclusions: Fiducial-guided SBRT proved to be feasible and effective in preventing local disease progression in selected patients with cardiac malignancies.

Purpose: The aim of our study was to retrospectively evaluate the feasibility and clinical benefit of cyberknife stereotactic radiosurgery (CSRS) in patients treated at Florence University for recurrent, pre-irradiated brain lesions., Materials and Methods: Thirteen patients were retreated with cyberknife. Mean age was 47.1 years (range 33-77 years). Karnofsky performance status ranged from 60 to 100 (median 80). Eleven (84.6%) out of 13 patients had metastatic lesions: four (36.4%) had primary lung, three (27.2%) had primary breast cancer and four (36.4%) other types of solid malignancies. Two (15.4%) out of 13 patients had recurrent of glioblastoma., Results: In terms of compliance with CSRS, the majority of patients did not develop any acute side effects. However, two (15.4%) out of 13 patients developed acute grade 2 toxicity requiring an increase of steroid medication. At the time of the last follow-up, response rates were as follows: complete response in one case (16.6%), partial response in three (50%) and stable disease in two (33.4%)., Conclusions: Re-irradiation with CSRS is a feasible and effective option for pre-irradiated, recurrent brain lesions to obtain clinical benefit without excessive acute toxicity.

Aims and Background: We report the toxicity and preliminary clinical outcome in patients affected by locally recurrent head and neck cancer treated with stereotactic re-irradiation., Methods: Between February 2012 and August 2013, 17 patients were treated with CyberKnife as stereotactic re-irradiation for locally recurrent head and neck cancer. All patients had previously received a full dose radiation treatment with radical intent, with a median total dose of 66 Gy (range, 50-70) delivered with standard fractionation. The median interval between the primary radiotherapy and re-irradiation was 24 months (range, 10-168)., Results: All patients completed the prescribed treatment, which was delivered in 5 fractions. The median tumor dose administered was 30 Gy (range, 25-35) prescribed to the 80% isodose line. Treatment sites were as follows: neck lymph nodes in 5 patients, paranasal sinuses in 5, oropharynx in 2, nasopharynx, and larynx, oral cavity, nasal fossa and parotid gland each in 1 patient. The median target volume treated was 58.7 cm3 (range, 8.5-211.3). Sixteen patients (94%) were evaluated for response. At a median follow-up of 7.5 months (range, 2-17), 4 patients achieved complete response (25%), 5 had partial response (31%) and 7 showed stable disease (44%). No patient showed in-field progression after re-irradiation. Grade 3 acute toxicity was noted in one patient only; no late side effect was observed during the follow-up., Conclusions: Stereotactic re-irradiation with CyberKnife is an appealing non-surgical salvage treatment for selected patients with local-regionally recurrent head and neck cancer.

Meningiomas account for up to 20 % of all primary intracranial neoplasms; although the majority of these have a benign course, as many as 5-10 % can display more aggressive behavior and a higher incidence of disease progression. The benefit of immediate adjuvant radiotherapy is still being debated for atypical and malignant meningiomas. This study aimed to retrospectively assess prognostic factors and outcome in 68 patients with atypical and malignant meningiomas. Sixty-eight meningioma patients were treated with radiotherapy after initial resection or for recurrence, between January 1993 and December 2011. Surgery was macroscopically complete in 80 % of the patients; histology was atypical and malignant in 51 patients and 17 patients, respectively. Mean dose of radiotherapy was 54.6 Gy. Fifty-six percent of all patients received radiotherapy after surgical resection, 26 % at the first relapse, and 18 % at the second relapse. Median follow-up was 6.7 years, (range 1.5-19.9 years). The 5- and 10-year actuarial overall survival (OS) rates were 74.1 and 45.6 %, respectively. At univariate analysis age >60 years, radiotherapy dose >52 Gy showed statistical significance, (p = 0.04 and p = 0.03, respectively). At the multivariate analysis radiotherapy dose >52 Gy maintained the statistical significance, (p = 0.037). OS of patients treated with radiotherapy at diagnosis was longer than the survival of patients treated with salvage radiotherapy; however this difference did not reach statistical significance when tested for the entire series or for the subgroups of grade 2 and grade 3 patients. The 5- and 10-year disease-free survival (DFS) rates were 76.5 and 69.5 %, respectively, and were significantly influenced by size >5 cm (p = 0.04) and grading (p = 0.003) on univariate analysis. At multivariate analysis, size and grading both remained significant prognostic factors, p = 0.044 and p = 0.0006, respectively. Grade ≤ 2 acute side effects were seen during radiotherapy treatment in 16 % of the patients, with no ≥ grade 3 acute toxicity, based on the Common Terminology Criteria for Adverse Events. In this mono-institutional retrospective study, age and radiotherapy dose were associated with a longer OS, while preoperative size and grading of the tumor influenced DFS. Although there were some advantages in terms of OS for patients treated with postoperative radiotherapy, the benefit did not reach the significance. Multicenter prospective studies are necessary to clarify the management and the correct timing of radiotherapy in such a rare disease.

Aims and background. To report the clinical outcome of linac-based or robotic, image-guided stereotactic body radiotherapy in patients affected by abdominal lymph node metastases from different primary cancers. Methods and methods. Twenty-six patients with 32 abdominal lymph node metastases were consecutively treated at the University of Florence between April 2011 and May 2012. The mean follow-up was 4.6 months (SD, 3.9; range, 0.3-13). The dose prescription ranged between 24 Gy and 36 Gy delivered in 1-5 fractions. Results. In terms of local control, complete response to stereotactic body radiotherapy was obtained in 18 cases (66.7%), partial response in 7 (25.9%), and stable disease in 2 (7.4%). At the Cox univariate regression analysis, an increased risk of partial response or absence of local response to radiotherapy was found for subjects of the female sex (P = 0.036), age less than 50 years (P = 0.022), primary tumor of the genital tract (P = 0.007), and previous chemotherapy (P = 0.057). An excellent local control rate (90.9%) was obtained in patients affected by abdominal lymph node metastases of prostatic origin. Conclusions. Stereotactic body radiotherapy for abdominal lymph node metastases is a safe and effective treatment in terms of high rates of local control, especially in a subset of patients affected by prostate cancer.

Purpose: To evaluate the effect of plan parameters on volumetric modulated arc therapy (VMAT) dosimetric accuracy, together with the possibility of scoring plan complexity., Methods: 142 clinical VMAT plans initially optimized using a 4° control point (CP) separation were evaluated. All plans were delivered by a 6 MV Linac to a biplanar diode array for patient-specific quality assurance (QA). Local Γ index analysis (3%, 3 mm and 2%, 2 mm) enabled the comparison between delivered and calculated dose. The following parameters were considered for each plan: average leaf travel (LT), modulation complexity score applied to VMAT (MCSv), MU value, and a multiplicative combination of LT and MCSv (LTMCS). Pearson's correlation analysis was performed between Γ passing rates and each parameter. The effects of CP angular separation on VMAT dosimetric accuracy were also analyzed by focusing on plans with high LT values. Forty out of 142 plans with LT above 350 mm were further optimized using a finer angle spacing (3° or 2°) and Γ analysis was performed. The average Γ passing rates obtained at 4° and at 3°∕2° sampling were compared. A further correlation analysis between all parameters and the Γ pass-rates was performed on 142 plans, but including the newly optimized 40 plans (CP every 3° or 2°) in place of the old ones (CP every 4°)., Results: A moderate significant (p < 0.05) correlation between each examined parameter and Γ passing rates was observed for the original 142 plans at 4° CP discretization. A negative correlation was found for LT with Pearson's r absolute values above 0.6, suggesting that a lower dosimetric accuracy may be expected for higher LT values when a 4° CP sampling is used. A positive correlation was observed for MCSv and LTMCS with r values above 0.5. In order to score plan complexity, threshold values of LTMCS were defined. The average Γ passing rates were significantly higher for the plans created using the finer CP spacing (3°∕2°) compared to the plans optimized using the standard 4° spacing (Student t-test p < 0.05). The correlation between LT and passing rates was strongly diminished when plans with finer angular separations were considered, yielding Pearson's r absolute values below 0.45., Conclusions: At 4° CP sampling, LT, MCSv, and LTMCS were found to be significantly correlated with VMAT dosimetric accuracy, expressed as Γ pass-rates. These parameters were found to be possible candidates for scoring plan complexity using threshold values. A finer CP separation (3°∕2°) led to a significant increase in dosimetric accuracy for plans with high leaf travel values, and to a decrease in correlation between LT and Γ passing rates. These results indicated that the influence of LT on VMAT dosimetric accuracy can be controlled by reducing CP separation. CP spacing for all plans requiring large leaf motion should not exceed 3°. The reported data were integrated to optimize our clinical workflow for plan creation, optimization, selection among rival plans, and patient-specific QA of VMAT treatments.

Aim: The purpose of this study was to evaluate the potential usefulness of [18F]-Choline PET/CT in the restaging of prostate cancer patients, who presented a rising PSA., Materials and Methods: We evaluated 170 prostate cancer patients, previously radically treated, that were referred for restaging with [18F]-Choline PET/CT., Results: A total of 129 patients (median PSA 4.29 ng/ml at relapse) showed one or more areas of high uptake on PET/CT scan, while 41 patients with a median PSA of 1.07 ng/ml at relapse showed negative PET/CT scans. No false negative was found, while 31 patients were identified as false positive. Specificity of Choline PET/CT in our series was 56.9 %, while sensibility was 100 %. At the time of restaging, a PSA value superior or equal to 1 ng/ml was found to be a statistically significant predictive factor of PET positivity, either at the univariate (p < 0.0001) and at the multivariate analysis (p < 0.0001)., Conclusions: Based on our findings, [18F]-Choline PET/CT is confirmed as a useful diagnostic tool to detect early recurrence, in patients with increasing PSA after primary treatment. However, in case of a mild increase in PSA, positive results must be validated with other techniques, as specificity and positive predictive value of [18F]-Choline PET/CT decrease with the lower values of PSA.

Aim: In men with adverse pathology after radical prostatectomy, the most appropriate timing to administer radiotherapy (RT) remains a topic of debate. We analyzed in terms of efficacy, prognostic factors and toxicity the two therapeutic strategies: immediate postoperative radiotherapy (PORT) and salvage radiotherapy (SART)., Materials and Methods: Between January 1995 and November 2010, 307 patients underwent adjuvant or salvage radiotherapy, after prostatectomy., Results: In the PORT group, 42 patients (20.7 %) had biochemical failure, with a median time to biochemical failure of 1.8 years; two parameters (age at diagnosis and PSA pre-RT) resulted to be significant at the survival analysis for overall survival (p = 0.003 and p = 0.046, respectively). In the SART group, 33 patients (31.7 %) had biochemical relapse; sixteen patients died of prostate cancer; postoperative hormones therapy, conformal radiotherapy and level of PSA pre-RT >1.0 ng/ml resulted to be significant at the survival analysis, p = 0.009, p = 0.039 and p = 0.002, respectively., Conclusion: Our study is limited by its retrospective and nonrandomized design. As such, decisions to treat with adjuvant or salvage radiotherapy and the time to initiate therapy were based on patient preference and physician counseling. Our recommendation is to suggest adjuvant radiotherapy for all patients with adverse prognostic factors and to reserve salvage radiotherapy for low-risk patients, when the biochemical recurrence occurs.

Aims and Background: Waiting time for radiotherapy is a major problem in clinical practice. We developed a model to create a priority list of patients waiting for radiotherapy according to clinical criteria, where booking of patients is not on a "first-come, first-served" basis and where prioritization has not been left up to individual discretion., Methods: The system is based on an algorithm that assigns to each patient a personal code (priority code, PC) that can be used as a continuous variable to have a priority list. PCpatient = D0patient + PWTsubgroup of treatment. Palliative treatments were categorized according to the clinical urgency. Radical treatments were stratified by primary tumors, by the setting of treatment (preoperative, curative, postoperative) and by the main prognostic factors. Each subgroup of patients has a "priority waiting time" (PWT subgroup of treatment). Calculation of the PC starts from a differentiated date according to clinical scenario [Reference date (D0)], which is taken from the clinical history of the patient., Results: Patients are differentiated according to clinical criteria and according to time elapsed from diagnosis. The priority list can be automatically updated day by day. Delays in patient referral or imaging availability are minimized., Conclusions: The model represents a tool for an objective and automatic prioritization of the patients who are waiting for radiotherapy.

This review aims to summarize what is currently known about neurocognitive outcome and quality of life in patients with brain tumors treated with radiotherapy. Whether potential tumor-controlling benefits of radiotherapy outweigh its potential toxicity in the natural history of brain tumors is a matter of debate. This review focuses on some of the adult main brain tumors, for which the issue of neurocognitive decline has been thoroughly studied: low-grade gliomas, brain metastases, and primary central nervous system lymphomas. The aims of this review are: (1) the analysis of existing data regarding the relationship between radiotherapy and neurocognitive outcome; (2) the identification of strategies to minimize radiotherapy-related neurotoxicity by reducing the dose or the volume; (3) the evidence-based data concerning radiotherapy withdrawal; and (4) the definition of patients subgroups that could benefit from immediate radiotherapy. For high grade gliomas, the main findings from literature are summarized and some strategies to reduce the neurotoxicity of the treatment are presented. Although further prospective studies with adequate neuropsychological follow-up are needed, this article suggests that cognitive deficits in patients with brain tumor have a multifactorial genesis: radiotherapy may contribute to the neurocognitive deterioration, but the causes of this decline include the tumor itself, disease progression, other treatment modalities and comorbidities. Treatment variables, such as total and fractional dose, target volume, and irradiation technique can dramatically affect the safety of radiotherapy: optimizing radiation parameters could be an excellent approach to improve outcome and to reduce neurotoxicity. At the same time, delayed radiotherapy could be a valid option for highly selected patients.

Gangliogliomas with anaplastic features are classified as grade III tumors by the World Health Organization. The clinical course and optimal treatment of anaplastic gangliogliomas have not been well understood to date. We report a case of a primary pure anaplastic ganglioglioma in a 14-year-old male treated with surgery and radiotherapy, who is disease-free 6 years after the diagnosis. A review of primary pure anaplastic gangliogliomas in children (between 3 and 21 years of age) is presented. Gross total removal and focal radiotherapy with a total dose of 54 Gy are recommended. The addition of chemotherapy should be evaluated. Prospective studies are needed to identify an appropriate chemotherapy schedule and to define biological factors in order to select those patients with a poor prognosis, who are to be treated with a more aggressive therapy., (Copyright © 2012 S. Karger AG, Basel.)

Background: The aim of this study was to review the treatment, toxicity, and outcomes in patients with stage I seminoma after orchidectomy., Patients and Methods: A retrospective chart review of all patients with stage I seminoma referred for initial treatment during the last 49 years was performed. Initial treatment approaches, toxicity, and outcomes were analyzed., Results: A total of 320 patients were seen between 1960 and 2009. Median age at diagnosis was 37 years (range: 20-72), with a median follow-up of 22.7 years (range: 1-48). All patients but 12 were treated with adjuvant radiotherapy. Acute toxicity was mainly gastrointestinal, with 7.6% classified as grade 2. The 10-year disease-specific survival and relapse-free survival were 97.7 and 97.6%, respectively. 8 patients (2.7%) developed a relapse and were managed with chemotherapy. 10 patients died, 6 of the disease and 4 from other causes (disease-free at time of death)., Conclusion: In the management of stage I seminoma, 3 treatment options are available; currently in the European Consensus, surveillance is the first choice, considering the overall comparable outcome and the low acute and late toxicity. Adjuvant radiotherapy and adjuvant chemotherapy should be considered as alternative options only if the patient declines the surveillance strategy., (2011 S. Karger AG, Basel.)

Objective: To investigate the pattern of care and outcomes for newly diagnosed glioblastoma in Italy and compare our results with the previous Italian Patterns of Care study to determine whether significant changes occurred in clinical practice during the past 10 years., Methods: Clinical, pathological, therapeutic, and survival data regarding 1059 patients treated in 18 radiotherapy centers between 2002 and 2007 were collected and retrospectively reviewed., Results: Most patients underwent both computed tomography and magnetic resonance imaging either preoperatively (62.7%) or postoperatively (35.5%). Only 123 patients (11.6%) underwent a biopsy. Radiochemotherapy with temozolomide was the most frequent adjuvant treatment (70.7%). Most patients (88.2%) received 3-dimensional conformal radiotherapy. Median survival was 9.5 months. Two- and 5-year survival rates were 24.8% and 3.9%, respectively. Multivariate analysis showed the statistical significance of age, postoperative Karnofsky Performance Status scale score, surgical extent, use of 3-dimensional conformal radiotherapy, and use of chemotherapy. Use of a more aggressive approach was associated with longer survival in elderly patients. Comparing our results with those of the subgroup of patients included in our previous study who were treated between 1997 and 2001, relevant differences were found: more frequent use of magnetic resonance imaging, surgical removal more common than biopsy, and widespread use of 3-dimensional conformal radiotherapy + temozolomide. Furthermore, a significant improvement in terms of survival was noted (P < .001)., Conclusion: Changes in the care of glioblastoma over the past few years are documented. Prognosis of glioblastoma patients has slightly but significantly improved with a small but noteworthy number of relatively long-term survivors.

Background and Purpose: Post-operative radiotherapy (PORT) in radically resected non-small cell lung cancer (NSCLC) has the aim to reduce loco regional recurrence and to improve overall survival. PORT has been evaluated in several trials but indication to post-operative treatment in N2 patients is still debated., Material and Methods: We retrospectively analyzed 175 patients treated at University of Florence between 1988 and 2004 with completely resected NSCLC stages IIIA-IIIB, N2 disease. Surgery consisted in a lobectomy in 58.9% and in a bi-lobectomy or in a pneumonectomy in 41.1% of patients. One hundred and nineteen patients underwent PORT and 56 patients did not receive PORT (no-PORT)., Results: At a median follow-up of 27.6 months (range 4-233 months), we found a significant reduction in local recurrence (LR) in PORT group (log-rank test p=0.015; HR: 0.45; 95%CI: 0.24-0.87). No statistical difference were found in terms of overall survival (OS) (log-rank test p=0.92). Concerning other prognostic factors, male sex emerged as statistically significant (HR:4.33;1.04-18.02) on local progression free survival (LPFS) at univariate analysis. Acute and long-term toxicity was mild., Conclusion: Our retrospective analysis showed that PORT may improve local disease control in N2 NSCLC patients with an acceptable treatment-related toxicity., (Published by Elsevier Ireland Ltd.)