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BACKGROUND: Thymomas can benefit of cytoreductive surgery even if a complete resection is not feasible. The pleural cavity is the most common site of progression and the resection of pleural metastases can be performed in selected patients. We evaluated the results of stereotactic body radiation therapy for the treatment of pleural metastases in patients not eligible for surgery. METHODS: We retrospectively selected 22 patients treated with stereotactic body radiation therapy for pleural metastases between 2013 and 2019. According to RECIST criteria 1.1 modified for thymic epithelial tumors, time to local failure and progression free survival were calculated using Kaplan-Meier method. RESULTS: The median age was 40 years (range, 29–73 years). There were 1 A, 3 AB, 3 B1, 3 B2, 3 B2/B3 and 9 B3 thymomas. Pleural metastases and primary tumor were synchronous in 8 patients. Five patients had a single pleural metastatic site and 17 presented multiple localizations. Sixteen patients received stereotactic body radiation therapy on multiple sites of pleural metastases. The median dose of radiation was 30 Gy (range, 24–40 Gy). With a median follow-up of 33.2 months (95% CI: 13.1–53.3 months), ten patients experienced disease progression with a median progression free survival was 20.4 months (95% CI: 10.7–30.0 months). The disease control rate was 79% and 41% after 1 and 2 years, respectively. Local disease control rate was 92% and 78% after 1 and 2 years, respectively. There were not significant differences in progression free survival between patients diagnosed with synchronous and metachronous metastases (P=0.477), across those treated or not with chemotherapy (P=0.189) and between those who received or not a previous surgical resection of the pleural metastases (P=0.871). There were not grade 3–4 toxicities related to the treatment. CONCLUSIONS: Stereotactic body radiation therapy of pleural metastases is feasible and offers a promising local control of diseases. The impact of this treatment on patients’ survival is hardly predictable because of the heterogeneous clinical behavior of thymomas.

Purpose An analysis is performed of the setup errors measured by a kV cone beam computed tomography (CBCT) for intracranial stereotactic radiotherapy (SRT) patients immobilized by a thermoplastic mask and a bite-block and positioned using stereotactic coordinates. We evaluated the overall positioning precision and accuracy of the immobilizing and localizing systems. The potential of image-guided radiotherapy to replace stereotactic methods is discussed. Methods and Materials Fifty-seven patients received brain SRT. After a frame-guided setup, before each fraction (131 fractions), a CBCT was acquired and the detected displacements corrected online. Translational and rotational errors were analyzed calculating overall mean and standard deviation. A separate analysis was performed for bite-block (in conjunction with mask) and for simple thermoplastic mask. Interobserver variability for CBCT three-dimensional registration was assessed. The residual error after correction and intrafractional motion were calculated. Results The mean module of the three-dimensional displacement vector was 3.0 ± 1.4 mm. Setup errors for bite block and mask were smaller (2.9 ± 1.3 mm) than those for thermoplastic mask alone (3.2 ± 1.5 mm), but statistical significance was not reached ( p = 0.15). Interobserver variability was negligible. The maximum margin calculated for residual errors and intra fraction motion was small but not negligible (1.57 mm). Conclusions Considering the detected setup errors, daily image guidance is essential for the efficacy of SRT treatments when mask immobilization is used, and even when a bite-block is used in conjunction. The frame setup is still used as a starting point for the opportunity of rotational corrections. Residual margins after on-line corrections must be evaluated.

Purpose Different biologically equivalent dose (BED) values associated with stereotactic radiotherapy (SRT) of patients with primary and metastatic pulmonary nodules were studied. The BED values were calculated for tumoral tissue and low α/β ratio, assuming that better local response could be obtained by using stereotactic high-BED treatment. Methods and Materials Fifty-eight patients with T1–T3 N0 non–small-cell lung cancer and 46 patients with metastatic lung nodules were treated with SRT. The BED was calculated for α/β ratios of 3 and 10. Overall survival (OS) was assessed according to Kaplan-Meier and appraised as a function of three BED levels: low (30–50 Gy), medium (50–70 Gy), and high (70–98 Gy; α/β = 10). Results The OS rates for all 104 patients at 12, 24, and 36 months were 73%, 48.3%, and 35.8%, respectively. Local response greater than 50% for low, medium, and high BED values was observed in 54%, 47%, and 73%, respectively. In the high-BED treated group, OS rates at 12, 24, and 36 months (80.9%, 70%, and 53.6%, respectively) were significantly improved compared with low- (69%, 46.1%, and 30.7%, respectively) and medium-BED (67%, 28%, and 21%, respectively) treated patients. Results are also discussed in terms of BED calculated on α/β 3 Gy characteristic of the microcapillary bed. No acute toxicity higher than Grade 1 was observed. Conclusions Radioablation of pulmonary neoplastic nodules may be achieved with SRT delivered by using a high-dose fraction with high BED value.

Purpose: Both anti-CD20 antibodies (ibritumomab; ZEVALIN® and tositumomab; BEXXAR®) currently used for radioimmunotherapy of B cell non-Hodgkin’s lymphoma are murine immunoglobulins. The aim of this feasibility study was to evaluate the safety and efficacy of radioimmunotherapy with a human chimeric anti-CD20 antibody labelled with Yttrium-90 (90Y-rituximab) in patients with B cell lymphoma. Methods: Patients with CD20+ B-cell lymphoma in partial remission or with progressive disease after at least one line of therapy were included. 90Y-rituximab was administered according to a similar schedule as currently approved by the European Medicines Agency for the treatment with 90Y-ibritumomab tiuxetan (ZEVALIN®): a first infusion of rituximab 250 mg/m² is repeated one week later and directly followed by the injection of 90Y-rituximab (14,8 MBq/kg). 18FDG-PET/CT was performed before treatment and repeated 3 months after for response assessment. Results: Twenty-six patients were treated with 90Y-rituximab. Disease histologies included mainly follicular lymphomas (53%). Toxicity was primarily haematological. The incidence of grade 3-4 neutropenia, thrombocytopenia and anemia were 34%, 38%, and 8% respectively, with spontaneous recovery in all but one patient that needed autologous stem cell transplant for refractory thrombocytopenia. Among the relevant long-term side effects, one patient developed secondary myelodysplasia 2 years after the treatment. The overall response rate was 88% (95% CI: 70%-98%), including 65% complete metabolic responses and 23% partial metabolic responses. After a median follow-up of 29.6 months, the Kaplan-Meier estimated median progression-free survival was 9, 1 months (95% CI 6,1-17,9). Median time to next treatment was 24 months (95% CI: 12, 2-28). Conclusion: Radioimmunotherapy with 90Y-rituximab in patients with relapsed CD20+ B-cell lymphomas is safe, well tolerated and effective when the ZEVALIN® treatment schedule is used.

Purpose To evaluate a retrospective single-institution outcome after hypofractionated stereotactic body radiotherapy (SBRT) for adrenal metastases. Methods and Materials Between February 2002 and December 2009, we treated 48 patients with SBRT for adrenal metastases. The median age of the patient population was 62.7 years (range, 43–77 years). In the majority of patients, the prescription dose was 36 Gy in 3 fractions (70% isodose, 17.14 Gy per fraction at the isocenter). Eight patients were treated with single-fraction stereotactic radiosurgery and forty patients with multi-fraction stereotactic radiotherapy. Results Overall, the series of patients was followed up for a median of 16.2 months (range, 3–63 months). At the time of analysis, 20 patients were alive and 28 patients were dead. The 1- and 2-year actuarial overall survival rates were 39.7% and 14.5%, respectively. We recorded 48 distant failures and 2 local failures, with a median interval to local failure of 4.9 months. The actuarial 1-year disease control rate was 9%; the actuarial 1- and 2-year local control rate was 90%. Conclusion Our retrospective study indicated that SBRT for the treatment of adrenal metastases represents a safe and effective option with a control rate of 90% at 2 years.

Free-breathing stereotactic radiotherapy for lung malignancies requires reliable prediction of respiratory motion and accurate target localization. A protocol was adopted for reproducibility and reduction of respiratory motion and for target localization by CBCT image guidance. Tumor respiratory displacements and tumor positioning errors relative to bony anatomy alignment are analyzed.Image guided SRT was performed for 99 lung malignancies. Two groups of patients were considered: group A did not perform any breathing control; group B controlled visually their respiratory cycle and volumes on an Active Breathing Coordinator (ABC) monitor during the acquisition of simulation CT and CBCT, and treatment delivery. GTV on end inhale and exhale CT data sets were fused in an ITV and the extent of tumor motion evaluated between these 2 phases. A pre-treatment CBCT was acquired and aligned to the reference CT using bony anatomy; for tumor positioning the ITV contour on the reference CT was matched to the visible tumor on CBCT. Interobserver variability of tumor positioning was evaluated. ITV and CBCT tumor dimensions were compared.3D tumor breathing displacement (mean+/-SD) was significantly higher for group A (14.7+/-9.9 mm) than for group B (4.7+/-3.1 mm). The detected differences between tumor and bony structure alignment below 3 mm were 68% for group B and 45% for group A, reaching statistical significance. Interobserver variability was 1.7+/-1.1 mm (mean+/-SD). Dimensions of tumor image on CBCT were consistent with ITV dimensions for group B (max difference 14%).The adopted protocol seems effective in reducing respiratory internal movements and margin. Tumor positioning errors relative to bony anatomy are also reduced. However bony anatomy as a surrogate of the target may still lead to some relevant positioning errors. Target visualization on CBCT is essential for an accurate localization in lung SRT.

Purpose/Objective(s): The patients biologically relapsed after radical prostatectomy or radiotherapy usually are referred to hormonal and/or chemotherapeutic palliative treatments. Selected groups of these Patients have limited nodal relapse that are amenable to an eradicative radiotherapy using high precision and high conformal techniques. Otherwise for biologically relapsed patients is not easy to recognize the site of recurrence and select those in which eradicative radiotherapy can be performed. To this purpose and for radiotherapy planning we have used choline C11 or F18 positron emission tomography and, at the same time, we evaluate the possibility of a correlation, not yet clear, between PSA values and result of PET scan. Materials/Methods: 61 patients showing biological relapse (according to ASTRO definition), were examinated. Out of these, 23 relapsed after surgery, 12 after radical radiotherapy and 26 after both. Radiotherapy was planned on pathological lymphatic areas according to disease extension showed by PET scan. Dose was prescribed to 90% isodose: 12 patients received 70 Gy in 35 fractions, 8 patients received hypofractionated treatment (32.50 Gy in 5 fractions).Treatment was delivered by 6 MV Linac trough multiple arcs using dynamic micromultileaf and IMAT optimization. Target position was controlled by Cone-Beam CT (Elekta Sinergy) before each fraction using enlarged nodes, well visible on CBCT, for matching. Results: PET scan was positive in 34 patients (55%), median value of PSA for positive scan was 7.39 (range 0.5-125) and 1.12 (range 0.1-77.6) in patients with negative scan. Relapses was limited to the lymphonodes in 20 Pats. (54%) (14 pelvic, 3 para-aortic and 3 mediastinal nodes) without distant metastases. PSA value after radiotherapy was evaluable in 12 patients: out these, 11 showed PSA values fallen to prerecurrence values, and one patient unchanged value. Choline PET scanning repeated in 5 of these patients revealed a disappearance of uptake in the lymphatic irradiated area. PSA nadir, without any other specific therapies, was maintained with a median of 4.72 months (range 1.2-15.33 ). Six patients are still without any signs of disease, 4 recurred in others lymphatic areas and 2 showed distant metastases (bone). No acute treatment related toxicity occurred. Conclusions: In our experience the PET Choline scan appear as a useful tool to detect the site of recurrence post prostatectomy and or radiotherapy in about 50% of patients. Half of these patients showed recurrence only on lymphonodes that are amenable to eradicative treatment. High doses of radiotherapy, delivered with high conformal technique allows to high rate of local control without any toxicity, leaving the hormonal therapy for future relapses. In our experience doesn’t exist a threshold value of PSA to predict a positive scan (range 0.5-125 for positive and 0.1-77.6 for negative scan). Highest values of PSA are rather an indication of trend of positiveness of PET scans.