AUTONOMOUS SYSTEMS & SAFETY ISSUES: THE ROADMAP TO ENABLE NEW ADVANCES IN INDUSTRIAL APPLICATIONS

The paper addresses the safety issues related to the development of new solutions based on autonomous systems for industrial applications and the necessity to develop experimental environments for investigating these cases; a set of examples is proposed in order to provide cases and challenges as well as to suggest approaches to address these problems

Three weekly versus weekly concurrent cisplatin: safety propensity score analysis on 166 head and neck cancer patients

Background Radio-chemotherapy with CDDP is the standard for H&N squamous cell cancer. CDDP 100 mg/m(2)/q3 is the standard; alternative schedules are used to reduce toxicity, mostly 40 mg/m(2)/q1. Methods Patients were treated from 1/2010 to 1/2017 in two Radiation Oncology Centres. Propensity score analysis (PS) was retrospectively used to compare these two schedules. Results Patients analyzed were 166. Most (114/166) had 1w-CDDP while 52 had 3w-CDDP. In the 3w-CDDP group, patients were younger, with better performance status, smaller disease extent and a more common nodal involvement than in the 1w-CDDP. Acute toxicity was similar in the groups. Treatment compliance was lower in the w-CCDP. Overall survival before PS was better for female, for oropharyngeal disease and for 3w-CDDP group. After PS, survival was not related to the CDDP schedule. Conclusions 3w-CDDP remains the standard for fit patients, weekly schedule could be safely used in selected patients

Adenoid Cystic Carcinoma/Basal Cell Carcinoma of the Prostate: Overview and Update on Rare Prostate Cancer Subtypes

Adenoid cystic carcinoma/basaloid cell carcinoma of the prostate (ACC/BCC) is a very rare variant of prostate cancer with uncertain behavior. Few cases are reported in the literature. Data on treatment options are scarce. The aim of our work was to retrospectively review the published reports. Thirty-three case reports or case series were analyzed (106 patients in total). Pathological features, management, and follow-up information were evaluated. Despite the relatively low level of evidence given the unavoidable lack of prospective trials for such a rare prostate tumor, the following considerations were made: prostate ACC/BCC is an aggressive tumor often presenting with locally advanced disease and incidental diagnosis occurs during transurethral resection of the prostate for urinary obstructive symptoms. Prostate-specific antigen was not a reliable marker for diagnosis nor follow-up. Adequate staging with Computed Tomography (CT) scan and Magnetic Resonance Imaging (MRI) should be performed before treatment and during follow-up, while there is no evidence for the use of Positron Emission Tomography (PET). Radical surgery with negative margins and possibly adjuvant radiotherapy appear to be the treatments of choice. The response to androgen deprivation therapy was poor. Currently, there is no evidence of the use of truly effective systemic therapies

Stereotactic Body Radiation Therapy (SBRT) for Oligorecurrent/Oligoprogressive Mediastinal and Hilar Lymph Node Metastasis: A Systematic Review

Introduction: Mediastinal or hilar lymph node metastases are a challenging condition in patients affected by solid tumors. Stereotactic body radiation therapy (SBRT) could play a crucial role in the therapeutic management and in the so-called “no-fly zone”, delivering high doses of radiation in relatively few treatment fractions with excellent sparing of healthy surrounding tissues and low toxicity. The aim of this systematic review is to evaluate the feasibility and tolerability of SBRT in the treatment of mediastinal and hilar lesions with particular regard to the radiotherapy doses, dose constraints for organs at risk, and clinical outcomes. Materials and methods: Two blinded investigators performed a critical review of the Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA), starting from a specific question: What is the clinical impact of SBRT for the treatment of oligorecurrent/oligoprogressive mediastinal and hilar metastasis? All retrospective and prospective clinical trials published in English up to February 2022 were analyzed. Results: A total of 552 articles were identified and 12 of them were selected with a total number of 478 patients treated with SBRT for mediastinal or hilar node recurrence. All the studies are retrospective, published between 2015 and 2021 with a median follow-up ranging from 12 to 42.2 months. Studies following SBRT for lung lesions or retreatments after thorax radiotherapy for stage III lung cancer were also included. The studies showed extensive heterogeneity in terms of patient and treatment characteristics. Non-small cell lung cancer was the most frequently reported histology. Different dose schemes were used, with a higher prevalence of 4–8 Gy in 5 or 6 fractions, but dose escalation was also used up to 52 Gy in 4 fractions with dose constraints mainly derived from RTOG 0813 trial. The radiotherapy technique most frequently used was volumetric modulated arc therapy (VMAT) with a median PTV volume ranging from 7 to 25.7 cc. The clinical outcome seems to be very encouraging with 1-year local control (LC), overall survival (OS) and progression-free survival (PFS) rates ranging from 84 to 94%, 53 to 88% and 23 to 53.9%, respectively. Half of the studies did not report toxicity greater than G3 and only five cases of fatal toxicity were reported. CONCLUSIONS: From the present review, it is not possible to draw definitive conclusions because of the heterogeneity of the studies analyzed. However, SBRT appears to be a safe and effective option in the treatment of mediastinal and hilar lymph node recurrence, with a good toxicity profile. Its use in clinical practice is still limited, and there is extensive heterogeneity in patient selection and fractionation schedules. Good performance status, small PTV volume, absence of previous thoracic irradiation, and administration of a high biologically effective dose (BED) seem to be factors that correlate with greater local control and better survival rates. In the presence of symptoms related to the thoracic lymph nodes, SBRT determines a rapid control that lasts over time. We look forward to the prospective studies that are underway for definitive conclusions

Dosimetric Evaluation of the Inter-Fraction Motion of Organs at Risk in SBRT for Nodal Oligometastatic Prostate Cancer

In this paper, we aim to evaluate the entity of inter-fraction organ motion and deformation in stereotactic body radiotherapy (SBRT) treatments for nodal oligometastatic prostate cancer (PCa). Thirty-three patients with lymph nodes showing oligometastatic PCa treated with SBRT were included. Organs at risk (OARs) were delineated using both simulation computer tomography (s-CT) and daily cone beam CTs (CBCTs) using the Raystation planning system. For each OAR, the union volume (UV) between all the CBCTs and s-CT was computed. An expanded volume (EV) of the s-CT OARs was applied using six different margins (3, 5, 8, 10, 15, and 20 mm). A percentage volume (V%) was computed to assess the intersection between each EV and UV. The OAR deformation and motion were further evaluated using the dice similarity coefficient (DSC) and mean distance to agreement (Mean_DA). The percentage maximum dose variations for all the OARs were estimated. A recalculation with higher dose prescriptions was performed by prescribing 36 Gy/3 fx, as well as 45 Gy/3 fx. The cauda showed the highest matching (DSC = 0.72; Mean_DA = 0.14 cm), and the colon showed the lowest one (DSC = 0.37; Mean_DA = 0.44 cm). The minimum margin, which ensured a V% > 95%, was 3 mm (97.5%) for the cauda and 15 mm (96.6%) for the colon. All the OARs reached the compliance of the constraints in each session. Regarding 36 Gy-plans, the ileum punctual compliance Dmax failed in 58.8% of patients, and it failed in 70.6% of the patients for the ileum, 7.14% for the colon, and 12.5% for the bladder in the case of 45 Gy-plans. This study is an ancillary study of the RADIOSA clinical trial (AIRC IG-22159) and can be used as a benchmark for dose escalation

Dosimetric Evaluation of the Inter-Fraction Motion of Organs at Risk in SBRT for Nodal Oligometastatic Prostate Cancer

In this paper, we aim to evaluate the entity of inter-fraction organ motion and deformation in stereotactic body radiotherapy (SBRT) treatments for nodal oligometastatic prostate cancer (PCa). Thirty-three patients with lymph nodes showing oligometastatic PCa treated with SBRT were included. Organs at risk (OARs) were delineated using both simulation computer tomography (s-CT) and daily cone beam CTs (CBCTs) using the Raystation planning system. For each OAR, the union volume (UV) between all the CBCTs and s-CT was computed. An expanded volume (EV) of the s-CT OARs was applied using six different margins (3, 5, 8, 10, 15, and 20 mm). A percentage volume (V%) was computed to assess the intersection between each EV and UV. The OAR deformation and motion were further evaluated using the dice similarity coefficient (DSC) and mean distance to agreement (Mean_DA). The percentage maximum dose variations for all the OARs were estimated. A recalculation with higher dose prescriptions was performed by prescribing 36 Gy/3 fx, as well as 45 Gy/3 fx. The cauda showed the highest matching (DSC = 0.72; Mean_DA = 0.14 cm), and the colon showed the lowest one (DSC = 0.37; Mean_DA = 0.44 cm). The minimum margin, which ensured a V% > 95%, was 3 mm (97.5%) for the cauda and 15 mm (96.6%) for the colon. All the OARs reached the compliance of the constraints in each session. Regarding 36 Gy-plans, the ileum punctual compliance Dmax failed in 58.8% of patients, and it failed in 70.6% of the patients for the ileum, 7.14% for the colon, and 12.5% for the bladder in the case of 45 Gy-plans. This study is an ancillary study of the RADIOSA clinical trial (AIRC IG-22159) and can be used as a benchmark for dose escalation

The Role of Interstitial Brachytherapy for Breast Cancer Treatment: An Overview of Indications, Applications, and Technical Notes

Breast cancer represents the second leading cause of cancer-related death in the female population, despite continuing advances in treatment options that have significantly accelerated in recent years. Conservative treatments have radically changed the concept of healing, also focusing on the psychological aspect of oncological treatments. In this scenario, radiotherapy plays a key role. Brachytherapy is an extremely versatile radiation technique that can be used in various settings for breast cancer treatment. Although it is invasive, technically complex, and requires a long learning curve, the dosimetric advantages and sparing of organs at risk are unequivocal. Literature data support muticatheter interstitial brachytherapy as the only method with strong scientific evidence to perform partial breast irradiation and reirradiation after previous conservative surgery and external beam radiotherapy, with longer follow-up than new, emerging radiation techniques, whose effectiveness is proven by over 20 years of experience. The aim of our work is to provide a comprehensive view of the use of interstitial brachytherapy to perform breast lumpectomy boost, breast-conserving accelerated partial breast irradiation, and salvage reirradiation for ipsilateral breast recurrence, with particular focus on the implant description, limits, and advantages of the technique

Exploring miRNA Signature and Other Potential Biomarkers for Oligometastatic Prostate Cancer Characterization: The Biological Challenge behind Clinical Practice. A Narrative Review

In recent years, a growing interest has been directed towards oligometastatic prostate cancer (OMPC), as patients with three to five metastatic lesions have shown a significantly better survival as compared with those harboring a higher number of lesions. The efficacy of local ablative treatments directed on metastatic lesions (metastases-directed treatments) was extensively investigated, with the aim of preventing further disease progression and delaying the start of systemic androgen deprivation therapies. Definitive diagnosis of prostate cancer is traditionally based on histopathological analysis. Nevertheless, a bioptic sample—static in nature—inevitably fails to reflect the dynamics of the tumor and its biological response due to the dynamic selective pressure of cancer therapies, which can profoundly influence spatio-temporal heterogeneity. Furthermore, even with new imaging technologies allowing an increasingly early detection, the diagnosis of oligometastasis is currently based exclusively on radiological investigations. Given these premises, the development of minimally-invasive liquid biopsies was recently promoted and implemented as predictive biomarkers both for clinical decision-making at pre-treatment (baseline assessment) and for monitoring treatment response during the clinical course of the disease. Through liquid biopsy, different biomarkers, commonly extracted from blood, urine or saliva, can be characterized and implemented in clinical routine to select targeted therapies and assess treatment response. Moreover, this approach has the potential to act as a tissue substitute and to accelerate the identification of novel and consistent predictive analytes cost-efficiently. However, the utility of tumor profiling is currently limited in OMPC due to the lack of clinically validated predictive biomarkers. In this scenario, different ongoing trials, such as the RADIOSA trial, might provide additional insights into the biology of the oligometastatic state and on the identification of novel biomarkers for the outlining of true oligometastatic patients, paving the way towards a wider ideal approach of personalized medicine. The aim of the present narrative review is to report the current state of the art on the solidity of liquid biopsy-related analytes such as CTCs, cfDNA, miRNA and epi-miRNA, and to provide a benchmark for their further clinical implementation. Arguably, this kind of molecular profiling could refine current developments in the era of precision oncology and lead to more refined therapeutic strategies in this subset of oligometastatic patients