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Electrochemotherapy (ECT) is an emerging therapeutic approach gaining growing interest for its potential immunomodulatory effects in cancer treatment. This narrative review systematically examines the current state of knowledge regarding the interplay between ECT and the immune system. Through an analysis of preclinical and clinical studies, the review highlights ECT capacity to induce immunogenic cell death, activate dendritic cells, release tumor antigens, trigger inflammatory responses, and occasionally manifest systemic effects—the abscopal phenomenon. These mechanisms collectively suggest the ECT potential to influence both local tumor control and immune responses. While implications for clinical practice appear promising, warranting the consideration of ECT as a complementary treatment to immunotherapy, the evidence remains preliminary. Consequently, further research is needed to elucidate the underlying mechanisms, optimize treatment protocols, explore potential synergies, and decipher the parameters influencing the abscopal effect. As the field advances, the integration of ECT’s potential immunomodulatory aspects into clinical practice will need careful evaluation and collaboration among clinical practitioners, researchers, and policymakers.

Historically, several classification systems have been used for brachytherapy, and they were based on the type of clinical purpose, type of implant and timing of the implant, dose-rate, and type of loading for treatment delivery. However, over the last decades, there have been some major technological advancements, including the introduction of image-guidance and possibility to modulate the dose delivered, which have led several authors (in order to highlight the differences between old technique and new approach) to label it in a different way by replacing “brachytherapy” with “interventional radiotherapy”. Modern interventional procedures involve several key aspects, which contribute to the complexity of implant phase, such as implant type, imaging used during the procedure, and role of multi-disciplinary team in operating room. By assigning scores to these procedural elements, it is possible to classify the procedure’s complexity using a COMIRI classification (COMplexity Index of interventional Radiotherapy Implants). The aim of the COMIRI classification system is to appropriately highlight the need for suitable resources based on the complexity level of different procedures in terms of personnel expertise, equipment availability, and multi-disciplinary teamwork.

This review explores the integration of artificial intelligence (AI) in interventional radiotherapy (IRT), emphasizing its potential to streamline workflows and enhance patient care. Through a systematic analysis of 78 relevant papers spanning from 2002 to 2024, we identified significant advancements in contouring, treatment planning, outcome prediction, and quality assurance. AI-driven approaches offer promise in reducing procedural times, personalizing treatments, and improving treatment outcomes for oncological patients. However, challenges such as clinical validation and quality assurance protocols persist. Nonetheless, AI presents a transformative opportunity to optimize IRT and meet evolving patient needs.

Purpose: To evaluate the clinicopathological characteristics and the effectiveness of post-operative high-dose-rate (HDR) interventional radiotherapy (IRT - brachytherapy) in managing advanced ocular surface squamous neoplasia (OSSN) and eyelid tumors. Methods: Nineteen patients with advanced malignancies affecting the ocular surface (stage ≥ T2) and eyelids (staging ≥ T3) were enrolled. Post-operative HDR-IRT treatment followed surgery after multidisciplinary discussion. In our series a total dose of 49 Gy was administered in 14 fractions of 3.5 Gy each, 2 doses per day. Local disease control is the study's main outcome. Death rate, total survival, disease-free survival, and toxicity are secondary outcomes. Results: Local recurrence was observed in 4 cases, 2 were conjunctival melanomas and 2 were conjunctival squamous cell carcinoma. The median OS was 56.3 months. The 12, 24 and 36 months survival rate was respectively 100.00% (IQR: 100.00% - 100.00%), 100.00% (IQR: 100.00% - 100.00%), 100.00% (IQR: 100.00% - 100.00%) respectively . The median DFS was 56.3 months. The 12, 24 and 36 months disease survival rate was respectively 85.71% (IQR: 69.21% - 100.00%), 68.57% (IQR: 42.11% - 100.00%), 68.57% (IQR: 42.11% - 100.00%) respectively. In eyelid tumors, madarosis and eyelid abnormalities are the main side effects, while in OSSNs, dry eye symptoms are frequently reported. Conclusion: Postoperative HDR-IRT has been effective in advanced eyelid cancers control. More challenging appears instead an effective treatment of advanced OSSNs, particularly conjunctival melanomas. Multicenter studies are needed to get a larger patient sample and to evaluate different radiotherapy dosages by different histologic and T types of tumors.

Brachytherapy (BRT) plays a pivotal role in the treatment of tumors, offering precise radiation therapy directly to the affected area. However, this technique demands extensive training and skills development, posing challenges for widespread adoption and ensuring patient safety. This narrative review explored the utilization of augmented reality (AR) in BRT, seeking to summarize existing evidence, discuss key findings, limitations, and quality of research as well as outline future research directions. The review revealed promising findings regarding the integration of AR in BRT. Studies have suggested the feasibility and potential benefits of AR in education, training, intra-operative guidance, and treatment planning. However, the evidence remains limited and heterogeneous, with most studies in preliminary phases. Standardization, prospective clinical trials, patient-centered outcomes assessment, and cost-effectiveness analysis emerge as critical areas for future research. Augmented reality holds transformative potential for BRT by enhancing precision, safety, and training efficiency. To fully implement these benefits, the field requires standardized protocols, rigorous clinical trials, and in-depth patient-centered investigations. Policy-makers and healthcare providers should closely monitor developments in AR and consider its implementation in clinical practice, contingent and robust evidence, and cost-effectiveness analysis. The pro-active pursuit of evidence-based practices will contribute to optimizing patient care in BRT.

Radiotherapy (RT) and electrochemotherapy (ECT) are established local treatments for cancer. While effective, both therapies have limitations, especially in treating bulky and poorly oxygenated tumors. ECT has emerged as a promising palliative treatment, raising interest in exploring its combination with RT to enhance tumor response. However, the potential benefits and challenges of combining these treatments remain unclear. A systematic review was conducted following PRISMA guidelines. PubMed, Scopus, and Cochrane libraries were searched. Studies were screened and selected based on predefined inclusion and exclusion criteria. Ten studies were included, comprising in vitro and in vivo experiments. Different tumor types were treated with ECT alone or in combination with RT. ECT plus RT demonstrated superior tumor response compared to that under single therapies or other combinations, regardless of the cytotoxic agent and RT dose. However, no study demonstrated a clear superadditive effect in cell survival curves, suggesting inconclusive evidence of specific ECT-induced radiosensitization. Toxicity data were limited. In conclusion, the combination of ECT and RT consistently improved tumor response compared to that with individual therapies, supporting the potential benefit of their combination. However, evidence for a specific ECT-induced radiosensitization effect is currently lacking. Additional investigations are necessary to elucidate the potential benefits of this combination therapy.

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.

Abstract Purpose The complexity of multimodal approaches in cancer management has lately led to the establishment of multidisciplinary tumor boards (MDTBs) to define targeted, patient-centered treatment strategies. However, few data are available regarding the application of this approach in Ocular Oncology. Hereby, the Authors analyze the implementation and outcomes of a trained MDTB in a tertiary ocular oncology referral center. Methods A retrospective descriptive analysis of MDTB meetings discussing patients with ocular and periocular cancers, over a 12-months period, was carried out. Data were grouped by main site involved, topics discussed and final clinical decisions therefore taken. Meetings were held by a constant ‘Core team’ or – when required – by a broader ‘Extended team’. Results During the observational period 86 cases were discussed. In 27 patients ocular surface tissues were involved (31%), in 25 patients orbital tissues (29%), in 22 patients eyelids (26%), and in 12 patients intraocular tissues (14%). In 13 cases (15%) naïve or referred new patients, in 34 cases (40%) imaging or histopathologic reports and in 39 cases (45%) treatment plans were discussed. Regarding final decisions, a treatment plan was scheduled in 47 cases (55%) and a diagnostic ascertainment was required in 27 patients (31%); locally advanced and/or systemic diseases were referred or teamed up with other specialists in 12 cases (14%). Conclusions Ocular Oncology multidisciplinary team, by sharing expertise of different specialists, ensures a comprehensive evaluation of patients improving the accuracy of diagnosis and staging upon which planning a proper treatment. Further studies are needed to assess if this approach may also improve the outcomes and prognosis of patients.

Background: Periocular malignancies may be clinically different from the examples arising at other sites, with possible delayed diagnosis and greater challenges for treatment and repair. Line-field confocal optical coherence tomography (LC-OCT) is a recently developed technique characterized by an unprecedented capacity to acquire high-definition images in vertical and horizontal modes. In this study, we aimed to investigate the LC-OCT morphological features of a series of eyelid skin lesions, correlating them to histopathological findings. Methods: Patients with biopsy-proven equivocal skin lesion in the eyelid area, previously investigated by means of LC-OCT, were included in the study. Percentage overall agreement was estimated for LC-OCT and histopathological diagnosis for study cases. Results: A total of 51 patients (28 women, 23 men; mean age 66.4 years old), for a total of 51 skin lesions, were assessed. The histopathological diagnosis consisted of 30 malignant and 21 benign tumors. Different entities were characterized by peculiar findings in LC-OCT, alike to histopathological features, allowing for an accurate “in vivo” classification in almost all cases, with a diagnostic concordance with histopathology of 92.1% (47/51). Conclusions: By integrating this new imaging technique into the assessment of suspicious tumors in this area, diagnostic accuracy may increase, improving strategies adopted in multidisciplinary meetings and patient-centered care.

The standard treatment for locally advanced cervical cancer (LACC) is platinum-based chemotherapy in association with external beam radiotherapy (EBRT) and brachytherapy (BT), often also called ‘interventional radiotherapy’ (IRT). Magnetic resonance imaging (MRI) is the most accurate imaging modality for both staging and response evaluation; therefore MRI-guided IRT has become the method of choice for planning a radiation boost after EBRT. The aim of this paper was to describe the MRI radiological workflow currently ongoing at our Institution. In addition, we provided a detailed pictorial essay of our experience, especially for radiologists, to implement MRI-based IRT spread in clinical practice.

Uveal melanoma (UM) is the most common intra-ocular tumor in Caucasian adults and may derive from melanocytes. Historically, the first therapeutic approach to treat UM has been surgical removal of the eye, with obvious consequences in terms of function, cosmesis, and psychological impact on patients. Collaborative Ocular Melanoma Study (COMS) introduced the first uniform approach to perform interventional radiotherapy (IRT – brachytherapy) procedure in a standardized way that allowed to demonstrate equivalence of IRT with enucleation in terms of overall survival. Since this milestone, several international guidelines have been issued with regard to several technical aspects of this procedure, which has become the mainstream therapy worldwide. However, nowadays, there is still a lack of consensus about the criteria to definitively assess UM response after IRT. We present a collection of paradigmatic cases treated in our institution, and then discuss in detail the latest available evidence on the topic.

Background and Objectives: Clinical management of vagal schwannoma is a real diagnostic and therapeutic challenge because the medical history and clinical examination are often non-specific and vagal nerve injury following surgical resection still represents an unsolved problem. The aim of this paper is to provide a case series along with a diagnostic and therapeutic algorithm for vagal schwannoma of the head and neck, combining our experience with clinical evidence available in the literature. Materials and Methods: We retrospectively analyzed a series of patients affected by vagal schwannoma who were treated between 2000 and 2020. In addition, a review of the literature on vagal schwannoma management was conducted. Based on the cases described and the literature review, we made a diagnostic and therapeutic algorithm for the management of vagal schwannoma. Results: We were able to identify 10 patients affected by vagal schwannoma and treated between 2000 and 2020. All patients presented with a painless, mobile, slow-growing lateral neck mass with onset varying from a few months to years. The preoperative diagnostic workup included ultrasound (US) in nine cases, computed tomography (CT) with contrast in six patients and magnetic resonance imaging (MRI) of the neck in seven cases. All patients included in this study were surgically treated. Conclusions: Vagal schwannoma management represents a true challenge for clinicians and surgery is currently the most effective therapeutic strategy. A multidisciplinary approach through the collaboration of otolaryngologist with other specialists is desirable to develop a tailored treatment plan for the patient.

Melanoma is an extremely aggressive tumor and is considered to be an extremely immunogenic tumor because compared to other cancers it usually presents a well-expressed lymphoid infiltration. The aim of this paper is to perform a multidisciplinary comprehensive review of the evidence available about the combination of radiotherapy and immunotherapy for melanoma. Radiation, in fact, can increase tumor antigens visibility and promote priming of T cells but can also exert immunosuppressive action on tumor microenvironment. Combining radiotherapy with immunotherapy provides an opportunity to increase immunostimulatory potential of radiation. We therefore provide the latest clinical evidence about radiobiological rationale, radiotherapy techniques, timing, and role both in advanced and systemic disease (with a special focus on ocular melanoma and brain, liver, and bone metastases) with a particular attention also in geriatric patients. The combination of immunotherapy and radiotherapy seems to be a safe therapeutic option, supported by a clear biological rationale, even though the available data confirm that radiotherapy is employed more for metastatic than for non-metastatic disease. Such a combination shows promising results in terms of survival outcomes; however, further studies, hopefully prospective, are needed to confirm such evidence.

The clinical management of metastatic melanoma has been changed by BRAF (BRAFi) and MEK inhibitors (MEKi), which represent a standard treatment for BRAF-mutant melanoma. In oligoprogressive melanoma patients with BRAF mutations, target therapy can be combined with loco-regional radiotherapy (RT). However, the association of BRAF/MEK inhibitors and RT needs to be carefully monitored for potential increased toxicity. Despite the availability of some reports regarding the tolerability of RT + target therapy, data on simultaneous RT and BRAFi/MEKi are limited and mostly focused on the BRAFi vemurafenib. Here, we report a series of metastatic melanoma patients who received fractioned RT regimens for oligoprogressive disease in combination with the BRAFi dabrafenib and the MEKi trametinib, which have continued beyond progression. None of the cases developed relevant adverse events while receiving RT or interrupted dabrafenib and trametinib administration. These cases suggest that a long period of dabrafenib/trametinib interruption during radiotherapy for oligoprogressive disease can be avoided. Prospective trials are warranted to assess the efficacy and safety of the contemporary administration of BRAF/MEK inhibitors and radiotherapy for oligoprogressive disease.

INTROUDCTION Bullous pemphigoid (BP) is a common autoimmune bullous disease generally occurring in elderly patients. Itchy and tense blisters on normal skin or erythematous and edematous lesions on the trunk and extremities usually characterize BP. Trigger factors are still unclear while several case reports suggest a potential role of radiotherapy (RT) as BP trigger for disease onset or recrudescence. A review was performed in order to provide an update of literature. A case report of a patient affected by BP undergoing two radiotherapy courses for a primary breast cancer was also reported. MATERIALS AND METHODS A comprehensive review of the published literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. The review included studies describing BP and its relationships with RT treatments. RESULTS A total of 13 articles were reviewed. Studies characteristics analysis resulted in eleven case reports, one case series and one large-scale case–control study. CONCLUSIONS Literature update confirms the existence of a reasonable connection between RT and BP. Case report showed that a multidisciplinary management seems to assure the feasibility of RT in patients affected by BP, not depriving them of standard therapeutic opportunities.

Background and Objectives: Cervical cancer is a leading cause of mortality among women. Chemo-radiation followed by interventional radiotherapy (IRT) is the standard of care for stage IB–IVA FIGO. Several studies have shown that image-guided adaptive IRT resulted in excellent local and pelvic control, but it is associated with vaginal toxicity and intercourse problems. The purpose of this review is to evaluate the dysfunctions of the sexual sphere in patients with cervical cancer undergoing different cervix cancer treatments. Materials and Methods: We performed a comprehensive literature search using Pub med, Scopus and Cochrane to identify all the full articles evaluating the dysfunctions of the sexual sphere. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Results: One thousand three hundred fifty-six women included in five studies published from 2016 to 2022 were analyzed. The median age was 50 years (range 46–56 years). The median follow-up was 12 months (range 0–60). Cervical cancer diagnosis and treatment (radiotherapy, chemotherapy and surgery) negatively affected sexual intercourse. Sexual symptoms such as fibrosis, strictures, decreased elasticity and depth and mucosal atrophy promote sexual dysfunction by causing frigidity, lack of lubrication, arousal, orgasm and libido and dyspareunia. Conclusions: Physical, physiological and social factors all contribute to the modification of the sexual sphere. Cervical cancer survivors who were irradiated have lower sexual and vaginal function than the normal population. Although there are cures for reducing discomfort, effective communication about sexual dysfunctions following treatment is essential.

Background and Objectives: Lower extremity lymphedema (LEL) is one of the most relevant chronic and disabling sequelae after gynecological cancer therapy involving pelvic lymphadenectomy (PL). Supermicrosurgical lymphaticovenular anastomosis (LVA) is a safe and effective procedure to treat LEL, particularly indicated in early-stage cases when conservative therapies are insufficient to control the swelling. Usually, preoperative assessment of these patients shows patent and peristaltic lymphatic vessels that can be mapped throughout the limb to plan the sites of skin incision to perform LVA. The aim of this study is to report the efficacy of our approach based on planning LVA in three areas of the lower limb in improving early-stage gynecological cancer-related lymphedema (GCRL) secondary to PL. Materials and Methods: We retrospectively reviewed the data of patients who underwent LVA for the treatment of early-stage GCRL following PL. Patients who had undergone groin dissection were excluded. Our preoperative study based on indocyanine green lymphography (ICG-L) and color doppler ultrasound (CDU) planned three incision sites located in the groin, in the medial surface of the distal third of the thigh, and in the upper half of the leg, to perform LVA. The primary outcome measure was the variation of the mean circumference of the limb after surgery. The changes between preoperative and postoperative limbs’ measures were analyzed by Student’s t-test. p values < 0.05 were considered significant. Results: Thirty-three patients were included. In every patient, three incision sites were employed to perform LVA. A total of 119 LVA were established, with an average of 3.6 for each patient. The mean circumference of the operated limb showed a significant reduction after surgery, decreasing from 37 cm ± 4.1 cm to 36.1 cm ± 4.4 (p < 0.01). Conclusions: Our results suggest that in patients affected by early-stage GCRL secondary to PL, the placement of incision sites in all the anatomical subunits of the lower limb is one of the key factors in achieving good results after LVA.

Primary cutaneous B-cell lymphomas (PCBCL) are rare types of extranodal non-Hodgkin's lymphoma. The choice of treatment usually depends on the variant of PCBCL, number, size, and location of the lesions, involved body surface area as well as patient's age and health condition. The efficacy of radiotherapy (RT) in the treatment of PCBCL has been widely reported conversely, data about the acute and late skin toxicity, patient's treatment satisfaction and quality of life are scarce. A systematic search using PubMed, Scopus, and Cochrane library was performed to identify full original articles analyzing the safety of RT in patients with PCBCL with the primary outcome to assess the acute and late skin toxicity. Secondary outcomes were complete remission, disease free survival, and overall survival. The literature search resulted in 276 articles including eight studies assessing the safety of RT for the treatment of PCBCL. Most patients (median 73%, range 11.9–99.9%) were recorded as having acute skin toxicity of grade 1–2, while acute grade 3–4 toxicity occurred in a median of 8% (range 4–23%) of patients. A median of 20% (range 4–54%) of patients had late skin toxicity of grade 1–2. No late grade 3–4 toxicity was reported. Only one study evaluated patient's satisfaction showing that the 97% of patients were satisfied with radiation therapy. This systematic review confirms the safety of RT in the treatment of PCBCL. Patients with a PCBCL should be managed in highly specialized centers in the context of a multidisciplinary team including dermatologist, hematologist, pathologist, and radiation oncologist.

Background: Recent studies have highlighted the potentialities of a radiobiological parameter, the early regression index (ERITCP), in the treatment response prediction for rectal cancer patients treated with chemoradiotherapy followed by surgery. The aim of this study is to evaluate the performance of this parameter in predicting pathological complete response (pCR) in the context of low field MR guided radiotherapy (MRgRT) for cervical cancer (CC). Methods: A total of 16 patients affected by CC were enrolled. All patients underwent a MRgRT treatment, with prescription of 50.6 Gy in 22 fractions. A daily MR acquisition was performed at simulation and on each treatment fraction. Gross tumor volume (GTV) was delineated on the MR images acquired at the following biological effective dose (BED) levels: 14, 28, 42, 54 and 62 Gy. The ERITCP was calculated at the different BED levels and its predictive performance was quantified in terms of receiver operating characteristic (ROC) curve. Results: pCR was observed in 11/16 cases. The highest discriminative power of ERITCP was reported when a BED value of 28 Gy is reached, obtaining an area under curve (AUC) of 0.84. Conclusion: This study confirmed ERITCP as a promising response biomarker also for CC, although further studies with larger cohort of patients are recommended.