Adjuvant radiotherapy treatment for soft tissue sarcoma of extremities and trunk. A retrospective mono-institutional analysis.

Soft tissue sarcomas (STS) are uncommon, heterogeneous malignant tumors of mesodermal origin. Other than conservative surgery (CS), neoadjuvant or adjuvant radiotherapy (RT) is recommended when the risk of local recurrence is high. The aim of this study is to present our Institutional experience in adjuvant RT for treatment of STS of extremities and trunk (with either brachytherapy (BRT), external beam RT (EBRT), or both) and to provide an insight of toxicity and oncological outcomes for each RT modality. According to the RT treatment approach, patients were divided into three categories: 1) BRT alone; 2) EBRT alone; 3) combined BRT+EBRT. Differences among the three groups were assessed by the Chi-squared test. Patients' follow-up was performed every 6 months for the first two years after the end of RT and then once a year. Data from 90 patients were analyzed. The overall 3-year distant relapse-free survival (DRFS), progression-free survival (PFS), and overall survival (OS) were 84%, 80%, and 97%, respectively. Acute erythema was the most frequent side effect, although severe grade 3 toxicity was present in 5 patients. Chronic toxicity of any grade was reported in 14 patients. The incidence of chronic toxicity did not show any association with treatment modality. Multivariate analysis suggested a significant correlation between acute toxicity and tumor size, RT modality, and RT dose. In conclusion, good local control and toxicity profile were observed, despite negative patients' selection at baseline. Further investigation on wider series is warranted in order to define the optimal combination with systemic therapy.

Lung optimized treatment with CyberKnife® in inoperable lung cancer patients: feasibility analysis of a mono-institutional 115 patient series.

CyberKnife® Lung Optimized Treatment (LOT) allows the treatment of lung cancer without invasive fiducial implantation. The aim of this retrospective analysis was to evaluate the feasibility, toxicity and clinical outcome. One hundred fifteen patients (124 lesions) were treated with CyberKnife® using LOT. The median age was 72.6 years (range 31.8-90.3). From 124 treated lesions, 52 were with histopathological confirmation (41 primitive pulmonary cancers, 8 pulmonary metastases) and 72 as untyped tumors. For 5 patients (6 lesions) treatment was an in-field re-irradiation. Concomitant therapy was administered in 7 patients. Zero-View tracking was applied in 69 patients, 1-View in 33 patients, 2-View in 22 patients. The median total dose was 45 Gy (range 18-54), median dose/fraction was 15 Gy (range 4-18) with a median prescription isodose of 80% (range 68-85). The median planning target volume (PTV) was 25 cm3 (range 3-195). The median follow-up was 20 months (range 7-47). Thirty-seven patients (32%) were alive with no evidence of disease, 39 patients (34%) were alive with clinically evident disease, and 38 patients (33%) died of the disease. The 1- and 2-year overall survival (OS) rate was 83% and 61%. The median time to progression was 19 months (95% confidence interval: 11-19 months), 1- and 2-year progression-free survival (PFS) rates were 62% and 41%, respectively. Smaller PTV was significantly associated with better OS, PFS and in-field PFS in univariate and multivariate analyses. Acute toxicity was observed in 36 patients (41%). Late toxicity was registered in 25 patients (29%). G3 late toxicity was observed in one patient (1.1%). Our data suggest that fiducial less-stereotactic body radiation therapy (SBRT) is a feasible, well-tolerated and potentially effective treatment with high compliance in the setting of inoperable patients due to concomitant disease or previous treatments.

Patients' needs in proton therapy: A survey among ten European facilities.

Aims: The number of Proton Therapy (PT) facilities is still limited worldwide, and the access to treatment could be characterized by patients' logistic and economic challenges. Aim of the present survey is to assess the support provided to patients undergoing PT across Europe. Methods: Through a personnel contact, an online questionnaire (62 multiple-choice and open-ended questions) via Microsoft Forms was administered to 10 European PT centers. The questionnaire consisted of 62 questions divided into 6 sections: i) personal data; ii) general information on clinical activity; iii) fractionation, concurrent systemic treatments and technical aspects of PT facility; iv) indication to PT and reimbursement policies; v) economic and/ or logistic support to patients vi) participants agreement on statements related to the possible limitation of access to PT. A qualitative analysis was performed and reported. Results: From March to May 2022 all ten involved centers filled the survey. Nine centers treat from 100 to 500 patients per year. Paediatric patients accounted for 10-30%, 30-50% and 50-70% of the entire cohort for 7, 2 and 1 center, respectively. The most frequent tumours treated in adult population were brain tumours, sarcomas and head and neck carcinomas; in all centers, the mean duration of PT is longer than 3 weeks. In 80% of cases, the treatment reimbursement for PT is supplied by the respective country's Health National System (HNS). HNS also provides economic support to patients in 70% of centers, while logistic and meal support is provided in 20% and 40% of centers, respectively. PT facilities offer economic and/or logistic support in 90% of the cases. Logistic support for parents of pediatric patients is provided by HNS only in one-third of centers. Overall, 70% of respondents agree that geographic challenges could limit a patient's access to proton facilities and 60% believe that additional support should be given to patients referred for PT care. Conclusions: Relevant differences exist among European countries in supporting patients referred to PT in their logistic and economic challenges. Further efforts should be made by HNSs and PT facilities to reduce the risk of inequities in access to cancer care with protons.

Phantom study of stereotactic radioablation for ventricular tachycardia (STRA-MI-VT) using Cyberknife Synchrony Respiratory Tracking System with a single fiducial marker.

PURPOSE: Within the STRA-MI-VT phase Ib/II trial (NCT04066517), the aim of this phantom study was to explore the feasibility of Cyberknife treatments on cardiac lesions by tracking as a single marker the lead tip of an implantable cardioverter defibrillator. The residual displacement of the lesion during the tracking was studied, planning margins were found and the dosimetric accuracy of the treatment was checked. MATERIALS AND METHODS: A lead was inserted into a phantom (EasyCube phantom, Sun Nuclear Co, USA) and then placed on the translating ExacTrac Gating System (BrainLAB AG, Germany). The phantom was rotated, a virtual lesion was identified and its displacement during the tracking was studied. Two plans were compared, calculated on the unrotated volume and on the envelope of the unrotated and the rotated volumes. The plans were delivered using the Cyberknife System (Accuray Inc, USA) and their dosimetric accuracy verified by gamma analysis with gafchromic films. RESULTS: The residual margin increases enhancing the distance between the lead and the lesion. It is 4 mm for distance 0 cm and 5 mm for distance 5 cm. The coverage is reduced by 3.8% (interquartile range 2.5%-4.7%) when the dose is prescribed on the unrotated volume. All treatment plans are accurate and 3% 3 mm gamma analysis results are greater than 94%. CONCLUSIONS: Results showed that tracking with a single marker is feasible considering adequate residual planning margins. The volumes could be further reduced by using additional markers, for example by placing them on the patient's skin.

STRA-MI-VT (STereotactic RadioAblation by Multimodal Imaging for Ventricular Tachycardia): rationale and design of an Italian experimental prospective study.

BACKGROUND: Ventricular tachycardia (VT) is a life-threatening condition, which usually implies the need of an implantable cardioverter defibrillator in combination with antiarrhythmic drugs and catheter ablation. Stereotactic body radiotherapy (SBRT) represents a common form of therapy in oncology, which has emerged as a well-tolerated and promising alternative option for the treatment of refractory VT in patients with structural heart disease. OBJECTIVE: In the STRA-MI-VT trial, we will investigate as primary endpoints safety and efficacy of SBRT for the treatment of recurrent VT in patients not eligible for catheter ablation. Secondary aim will be to evaluate SBRT effects on global mortality, changes in heart function, and in the quality of life during follow-up. METHODS: This is a spontaneous, prospective, experimental (phase Ib/II), open-label study (NCT04066517); 15 patients with structural heart disease and intractable VT will be enrolled within a 2-year period. Advanced multimodal cardiac imaging preceding chest CT-simulation will serve to elaborate the treatment plan on different linear accelerators with target and organs-at-risk definition. SBRT will consist in a single radioablation session of 25 Gy. Follow-up will last up to 12 months. CONCLUSIONS: We test the hypothesis that SBRT reduces the VT burden in a safe and effective way, leading to an improvement in quality of life and survival. If the results will be favorable, radioablation will turn into a potential alternative option for selected patients with an indication to VT ablation, based on the opportunity to treat ventricular arrhythmogenic substrates in a convenient and less-invasive manner.

Oligo metastatic renal cell carcinoma: stereotactic body radiation therapy, if, when and how?

BACKGROUND AND PURPOSE: Renal cell carcinoma (RCC) has traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach. Nevertheless, since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo metastatic RCC patients in terms of local control, delay of systemic treatment, overall survival and toxicity. PATIENTS AND METHODS: A Monocentric single institution retrospective data collection was performed. Inclusion criteria were: (1) oligo-recurrent or oligo-progressive disease (less than 5 metastases) in mRCC patients after radical/partial nephrectomy or during systemic therapy, (2) metastasectomy or other metastasis-directed, rather than SBRT not feasible, (3) any contraindication to receive systemic therapy (such as comorbidities), (4) all the histologies were included, (5) available signed informed consent form for treatment. Tumor response and toxicity were evaluated using the response evaluation criteria in solid tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. Progression-free survival in-field and out-field (in-field and out-field PFS) and overall survival (OS) were calculated via the Kaplan-Meier method. The drug treatment-free interval was calculated from the start of SBRT to the beginning of any systemic therapy. RESULTS: From 2010 to December 2018, 61 patients with extracranial and intracranial metastatic RCC underwent SBRT on 83 lesions. Intracranial and extracranial lesions were included. Forty-five (74%) patients were treated for a solitary metastatic lesion. Median RT dose was 25 Gy (range 10-52) in 5-10 fractions. With a median follow-up of 2.3 years (range 0-7.15), 1-year in-field PFS was 70%, 2-year in-field PFS was 55%. One year out-field PFS was 39% and 1-year OS was 78%. Concomitant systemic therapy was employed for only 11 (18%) patients, for the others 50 (82%) the drug treatment-free rate was 70% and 50% at 1 and 2 years, respectively. No > G1 acute and late toxicities were reported. CONCLUSION: The pattern of failure was pre-dominantly out-of-field, even if the population was negatively selected and the used RT dose could be considered palliative. Therefore, SBRT appears to be a well-tolerated, feasible and safe approach in oligo metastatic RCC patients with an excellent in-field PFS. SBRT might play a role in the management of selected RCC patients allowing for a delay systemic therapy begin (one out of two patients were free from new systemic therapy at 2 years after SBRT). Further research on SBRT dose escalation is warranted.

Dicrocoelium dendriticum induces autophagic vacuoles accumulation in human hepatocarcinoma cells.

The relationship between Dicrocoelium dendriticum and cancer has been poorly investigated so far, but a large amount of findings suggest that other trematodes can favour cancer in both animals and humans. In this study, the effects of D. dendriticum on cell proliferation, cell death mechanisms and oxidative stress induction were evaluated in hepatocellular carcinoma (HCC) cell lines (HepG2 and HuH7). Results showed that short time exposure to low concentrations of somatic antigens from D. dendriticum caused slight proliferation in both HepG2 and HuH7 cells while high concentrations and long exposure time to extracts from D. dendriticum caused a significant growth inhibition. This effect was, however, not paralleled by apoptosis but it occurred with an about 40% increase of the formation of autophagic vacuoles. In the same experimental conditions, a strong oxidative stress was recorded with an about 100% increase of the intracellular O(2-). These data suggest the occurrence of an escape anti-apoptotic mechanism in HCC cells. In conclusion, these results suggest a role for D. dendriticum in the chronic oxidative stress and in the regulation of transformation processes in HCC warranting additional investigations in this specific area of research.