Interventional Radiotherapy (Brachytherapy) for Nasal Vestibule: Novel Strategies to Prevent Side Effects.

Interventional radiotherapy (brachytherapy) has become the new therapeutic standard in the management of early stages nasal vestibule tumors; in fact it allows for high local control rates and low toxicity profiles. However, since more and more patients will receive interventional radiotherapy (brachytherapy) as primary treatment, it is desirable to implement novel strategies to reduce the dose to organs at risk with the future aim to result in further lowering long-term side effects. MATERIALS AND METHODS: We were able to identify two different strategies to reduce dose to the treatment volume, including the implantation technique (the implant can be interstitial, endocavitary or mixed and the catheters may be placed either using the Paris system rules or the anatomical approach) and the dose distribution within the implant (the most commonly used parameter to consider is the dose non-uniformity ratio). We subsequently propose two novel strategies to reduce dose to organs at risk, including the use of metal shields for fixed organs as in the case of the eyes and the use of a mouth swab to push away mobile organs, such in the case of the mandible. We used two different algorithms to verify the values namely the TG-43 and the TG-186. RESULTS: We provided an accurate literature review regarding strategies to reduce toxicity to the treatment volume, underlining the pros and cons of all implantation techniques and about the use dose non-uniformity ratio. Regarding the innovative strategies to reduce the dose to organs at risk, we investigated the use of eye shielding and the use of swabs to push away the mandible by performing an innovative calculation using two different algorithms in a series of three consecutive patients. Our results show that the dose reduction, both in the case of the mandible and in the case of eye shielding, was statistically significant. CONCLUSION: Proper knowledge of the best implantation technique and dose non-uniformity ratio as highlighted by existing literature is mandatory in order to reduce toxicity within the treatment volume. With regard to the dose reduction to the organs at risk we have demonstrated that the use of eye shielding and mouth swab could play a pivotal role in clinical practice; in fact, they are effective at lowering the doses to the surrounding organs and do not require any change to the current clinical workflow.

Multilayer intensity modulated contact interventional radiotherapy (brachytherapy): Stretching the therapeutic window in skin cancer.

Interventional radiotherapy (IRT, brachytherapy) is a highly effective treatment method for non-melanoma skin cancer (NMSC). Traditionally, the maximum depth of NMSC lesions considered eligible for contact IRT was 5 mm; however, following several national surveys and recent recommendations, such cut-off, lesions thicker than 5 mm may be treated by contact IRT. The use of image guidance in defining the actual depth in treating NMSC to correctly identify clinical target volume (CTV) and prevent unnecessary toxicity is of paramount importance. The aim of the paper was to describe a multilayer arrangement of catheters to treat NMSC lesions thicker than 5 mm, thus proposing an example of dynamic intensity modulated IRT, using different catheter-to-skin distance of sources to reach the best CTV coverage and maximally reduce the excess of dose to the skin.

Killing Two Birds with One Stone: Is the COVID-19 Vaccination Campaign an Opportunity to Improve Adherence to Cancer Screening Programmes? The Challenge of a Pilot Project in a Large Local Health Authority in Rome.

The COVID-19 pandemic has affected health services worldwide. The suspension of cancer screening programs during the lockdown period, coupled with the other measures taken to limit the SARS-CoV-2 spread, contributed to the idea that cancer preventive interventions are deferrable. In this opinion paper, we present some data on cancer screening coverage in one of the largest Local Health Authorities in Italy in recent years. Within this context, we introduce the benefits of a pilot project in which we took advantage of the great attention on the COVID-19 vaccination campaign to improve screening uptake. In this project, we offered men and women eligible for cancer screening the opportunity to book appointments while waiting to be vaccinated. In addition, trained healthcare personnel were available on-site to discuss any barriers to participation with the attendees. Despite the project having only just started, preliminary results are encouraging, with positive feedback from the attendees. In conclusion, we advocate for the need to adopt a comprehensive approach when it comes to population health, and we use this project as an example to discuss how it is possible to contribute to minimizing the long-term impact of the COVID-19 pandemic with resources already in place.

Dosimetric impact of applying a model-based dose calculation algorithm for skin cancer brachytherapy (interventional radiotherapy).

Purpose: Brachytherapy (BT, interventional radiotherapy) is a well-established radiotherapy technique capable of delivering high doses to tumors while sparing organs at risk (OARs). Currently, the clinically accepted dose calculation algorithm used is TG-43. In the TG-186 report, new model-based dose calculation algorithms (MBDCA), such as Elekta's advanced collapsed cone engine (ACE), have been introduced, although their clinical application is yet to be fully realized. This study aimed to investigate two aspects of TG-186: firstly, a comparison of dose distributions calculated with TG-43 and TG-186 for skin tumors; and secondly, an exploration of the impact of using a water bolus on the coverage of clinical target volume (CTV) and OARs. Material and methods: Ten treatment plans for high-dose-rate IRT were developed. All plans were initially calculated using the TG-43 algorithm, and were subsequently re-calculated with TG-186. In addition, one of the treatment plans was assessed with both TG-43 and TG-186, using 10 different water bolus thicknesses ranging from 0 to 5 cm. To assess dose variations, the following dose-volume histogram (DVH) parameters were compared: D2cc and D0.01cc for OARs, and V150, V100, V95 and V90 for CTV coverage. Results and conclusions: The average dosimetric results for CTV and OARs, as calculated by both algorithms, revealed statistically significant lower values for TG-186 when compared with TG-43. The presence of a bolus was observed to enhance CTV coverage for the TG-186 algorithm, with a bolus thickness of 2 cm being the point at which ACE calculations matched those of TG-43. This study identified significant differences in dosimetric parameters for skin tumors when comparing the TG-43 and TG-186 algorithms. Moreover, it was demonstrated that the inclusion of a water bolus increased CTV coverage in TG-186 calculations.

Advanced usage of Ti3C2Tx MXenes for photothermal therapy on different 3D breast cancer models.

Globally, breast cancer is the most diagnosed invasive cancer among women. Current therapies (e.g., chemotherapy) show numerous limitations due to the lack of selectivity and involved side effects, which urgently asks for novel approaches with enhanced tumor-killing efficacy. We previously demonstrated that MXenes, new bioactive nanomaterials with promising photophysical properties, are capable to increase the efficiency of the targeted breast cancer photothermal therapy (PTT). In this work, we investigated the effect of few- and multi-layer Ti3C2Tx MXenes mediated-PTT on two different 3D reliable breast cancer models such as conventional and bio-printed spheroids. We performed PTT on both cancer models using a non-toxic MXene concentration of 50 µg/mL. After PTT, a significant reduction in the cell viability along with a notable increase in reactive oxygen species (ROS) was observed. Moreover, we studied the effect of PTT on the migration of macrophages and endothelial cells toward cancer regions in both 3D models. Our results indicate that PTT mediated by both few- and multi-layer MXenes significantly modulates the tumor progression through cells' death by increasing the temperature, which holds particularly true for the bio-printed model.

INSIDIA 2.0 High-Throughput Analysis of 3D Cancer Models: Multiparametric Quantification of Graphene Quantum Dots Photothermal Therapy for Glioblastoma and Pancreatic Cancer.

Cancer spheroids are in vitro 3D models that became crucial in nanomaterials science thanks to the possibility of performing high throughput screening of nanoparticles and combined nanoparticle-drug therapies on in vitro models. However, most of the current spheroid analysis methods involve manual steps. This is a time-consuming process and is extremely liable to the variability of individual operators. For this reason, rapid, user-friendly, ready-to-use, high-throughput image analysis software is necessary. In this work, we report the INSIDIA 2.0 macro, which offers researchers high-throughput and high content quantitative analysis of in vitro 3D cancer cell spheroids and allows advanced parametrization of the expanding and invading cancer cellular mass. INSIDIA has been implemented to provide in-depth morphologic analysis and has been used for the analysis of the effect of graphene quantum dots photothermal therapy on glioblastoma (U87) and pancreatic cancer (PANC-1) spheroids. Thanks to INSIDIA 2.0 analysis, two types of effects have been observed: In U87 spheroids, death is accompanied by a decrease in area of the entire spheroid, with a decrease in entropy due to the generation of a high uniform density spheroid core. On the other hand, PANC-1 spheroids' death caused by nanoparticle photothermal disruption is accompanied with an overall increase in area and entropy due to the progressive loss of integrity and increase in variability of spheroid texture. We have summarized these effects in a quantitative parameter of spheroid disruption demonstrating that INSIDIA 2.0 multiparametric analysis can be used to quantify cell death in a non-invasive, fast, and high-throughput fashion.

Urban Health and Social Marginality: Perceived Health Status and Interaction with Healthcare Professionals of a Hard-to-Reach Community Living in a Suburban Area of Rome (Italy).

The study reports an urban health investigation conducted in Bastogi, an outskirt of Rome (Italy) characterised by social marginalization and deprivation. Our aim was to analyse the health perception, health-related behaviours, and interaction with healthcare professionals of the inhabitants of Bastogi compared to the population living in the area of the same local health unit (ASL). The Progresses of Health Authorities for Health in Italy questionnaire (PASSI) was administered to a sample of 210 inhabitants of Bastogi. Data were analysed and compared to those of the ASL collected in 2017-2018. The socio-economic indicators showed an overall worse condition for the inhabitants of Bastogi, with a significantly higher proportion of foreign and unemployed residents and a lower educational level compared to the ASL. Significant differences in the prevalence of non-communicable diseases, mental health complaints, and participation in prevention strategies, including cancer screening, were found. The questionnaire showed a lower help-seeking behaviour and a lack of reliance on health professionals in Bastogi inhabitants. Our findings highlight how social determinants produce health inequities and barriers to accessing healthcare. The difficulties of conducting quantitative research in complex and hard-to-reach contexts, characterized by high social vulnerability, are outlined.

The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives.

Protontherapy is a rapidly expanding radiotherapy modality where accelerated proton beams are used to precisely deliver the dose to the tumor target but is generally considered ineffective against radioresistant tumors. Proton-Boron Capture Therapy (PBCT) is a novel approach aimed at enhancing proton biological effectiveness. PBCT exploits a nuclear fusion reaction between low-energy protons and 11B atoms, i.e. p+11B→ 3α (p-B), which is supposed to produce highly-DNA damaging α-particles exclusively across the tumor-conformed Spread-Out Bragg Peak (SOBP), without harming healthy tissues in the beam entrance channel. To confirm previous work on PBCT, here we report new in-vitro data obtained at the 62-MeV ocular melanoma-dedicated proton beamline of the INFN-Laboratori Nazionali del Sud (LNS), Catania, Italy. For the first time, we also tested PBCT at the 250-MeV proton beamline used for deep-seated cancers at the Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy. We used Sodium Mercaptododecaborate (BSH) as 11B carrier, DU145 prostate cancer cells to assess cell killing and non-cancer epithelial breast MCF-10A cells for quantifying chromosome aberrations (CAs) by FISH painting and DNA repair pathway protein expression by western blotting. Cells were exposed at various depths along the two clinical SOBPs. Compared to exposure in the absence of boron, proton irradiation in the presence of BSH significantly reduced DU145 clonogenic survival and increased both frequency and complexity of CAs in MCF-10A cells at the mid- and distal SOBP positions, but not at the beam entrance. BSH-mediated enhancement of DNA damage response was also found at mid-SOBP. These results corroborate PBCT as a strategy to render protontherapy amenable towards radiotherapy-resilient tumor. If coupled with emerging proton FLASH radiotherapy modalities, PBCT could thus widen the protontherapy therapeutic index.

Impact of diverticular inflammation and complication assessment classification on the burden of medical therapies in preventing diverticular disease complications in Italy.

BACKGROUND: Several treatments are currently advised to manage diverticular disease (DD) patients, but their impact on the burden of the disease is unknown. Our aim was to assess the economic analysis of using the recent Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification on the burden of medical therapies prescribed in preventing DD complications occurrence in Italy. METHODS: We assessed retrospectively the cost/year of treatments in estimated DICA 1, DICA 2 and DICA 3 population. Analysis of diverticulosis prevalence was estimated according to data population provided by Italian Institute of Statistics (ISTAT). Cost of treatments calculated according to data on drugs' consumption collected during the DICA study. RESULTS: We estimated that >8 million of Italian people >60 years may have diverticulosis, and that about 75% of diverticular population are on DICA 1, about 30% on DICA 2, and about 13% on DICA 3. We estimated that >387 million of euros could be spent in DICA 1 population, >203 million of euros in DICA 2 population, and >88 million of euros in DICA 3 population. Since medical treatments did not show any significant advantage when treating DICA 1 and DICA 3 people in terms of prevention of acute diverticulitis occurrence/recurrence and surgery occurrence, we can estimated that >475 million of euros could be spent in Italy without any significant benefit in preventing DD complications occurrence. CONCLUSIONS: DICA endoscopic classification may have a significant impact on the burden of DD in Italy, because it helps to select DD people who effectively need treatments in terms of prevention of acute diverticulitis occurrence/recurrence and surgery occurrence.