Squamous cell carcinoma of the nasal vestibule: a diagnostic and therapeutic challenge.

Nasal vestibule squamous cell carcinoma (NVSCC) is an exceedingly rare malignancy, often misclassified due to its anatomical location and lack of a standardized definition. This review aims to consolidate current evidence on NVSCC, focusing on epidemiology, risk factors, classification, clinical presentation, treatment modalities, and prognostic factors. The NV anatomy is delineated, emphasizing the need for a clear definition to avoid misclassification. Risk factors include smoking, sunlight exposure, and debated associations with chalk exposure or viral factors. Clinical presentation includes symptoms like nasal obstruction, pain, burning, and bleeding, often misdiagnosed as inflammatory conditions. NVSCC exhibits distinct local spread patterns along cartilaginous surfaces, with the facial and submandibular lymph nodes at higher metastatic risk. Current classifications lack consensus, hindering comparison of outcomes. Treatment varies, with surgery or radiotherapy for early-stage tumors and multimodality approaches for advanced cases. The choice between surgery and radiotherapy is debated, with potential advantages and drawbacks for each. Radiotherapy, especially with Interventional RadioTherapy (IRT, previously known as brachytherapy), is gaining prominence, showing promising outcomes in terms of local control and cosmetic results. Prophylactic neck treatment remains controversial, with indications based on tumor characteristics. Prognostic factors include T classification, tumor size, surgical margins, nodal involvement, and histological features. Long-term survival rates range widely, emphasizing the need for further studies to refine management strategies for this rare malignancy. In conclusion, NVSCC poses diagnostic and therapeutic challenges, warranting multidisciplinary approaches and continued research efforts to optimize patient outcomes.

Interventional Radiotherapy (Brachytherapy) in Eyelid and Ocular Surface Tumors: A Review for Treatment of Naïve and Recurrent Malignancies.

The goal of radiotherapy in the treatment of eyelid and ocular surface tumors is to eradicate tumor burden in a manner that maintains visual function and preserve surrounding sensitive ocular tissue. Interventional radiotherapy (IRT-brachytherapy) is a radiotherapy technique associated with a highly focal dose distribution, with the advantage of boosting limited size target volumes to very high dose while sparing normal tissue. The reduction in the ocular and adnexal complications that result from this form of therapy, has led in recent years, to an increase in the use of IRT for the treatment of eyelid and ocular surface tumors. For eyelid malignancies, IRT is used as an independent treatment in small eyelids tumors, in postoperative treatment of high-risk patients and as well as salvage therapy in local recurrences. In the treatment of conjunctival malignancies, due to the high risk of local recurrence, the use of adjuvant therapies as IRT has shown to improve outcomes. In this review, we focus on eyelid and ocular surface IRT techniques and provide an overview of indication, outcomes and toxicity of IRT for the treatment of naïve and recurrent eyelid and conjunctival tumors.

Contact skin radiotherapy (brachytherapy) for the treatment of non-melanoma skin cancers during COVID-19 pandemic.

In the context of the SARS-CoV-2 pandemic, it is important to ensure the quality of cancer treatment as well as patients and health professionals' safety. Individual-based treatment options should be considered in patients with advanced epithelial skin cancer, who are typically elderly and frail. Aim of this study was to assess feasibility and safety of Contact Skin Radiation Therapy (CSRT) to treat basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) during SARS-CoV-2 pandemic. Patients with advanced and difficult-to-treat BCC or SCC were discussed at skin multidisciplinary tumor board (S-MDTB) from February the 21st to May the 4th (phase 1 Italian Pandemic) and retrospectively analyzed. Patient's triage following internal recommendations was daily performed. CSRT was delivered in 8 fractions of 5 Gy each, twice a day. Beyond the clinical outcomes, treatment success indicators, such as the completion of CSRT without SARS-CoV-2 occurrence, were identified to evaluate the feasibility of CSRT during pandemic. A post-treatment psychological assessment regarding patient's safety perception was performed. Six male patients (median age 80 years; range 62-92) with histologically confirmed BCC or SCC were treated with CSRT. Complete clinical remission was achieved in 5/6 patients (83.4%). No high-grade acute toxicities occurred during treatment. No patients or healthcare personnel developed SARS-CoV-2 infection. All the treatment success indicators were achieved. CSRT represents a safe, and feasible treatment option even during the pandemic emergency period. Hypofractionation could be an option to reduce total number of fractions and, consequently, infective risk exposition.

EROS 2.0 study: evaluation of two interventional radiotherapy (brachytherapy) schedules for endometrial cancer: a comparison of late vaginal toxicity rates.

BACKGROUND: To compare the late toxicity rates after two different high dose rate (HDR) adjuvant intravaginal interventional radiotherapy (IRT-brachytherapy) dose schedules in stage I-II endometrial cancer. METHODS: Stage I-II patients with endometrial cancer treated with surgery (with or without lymphadenectomy) and adjuvant HDR-IRT between 2014 and 2020 were included in this analysis. Patients were treated with two schedules. In the first cohort (C1), 21 Gy were delivered in three weekly fractions (7 Gy) prescribed 0.5 cm from the applicator surface. In the second cohort (C2), 24 Gy were delivered in four weekly fractions (6 Gy). The clinical target volume was the upper third of the vagina for C1 and the upper 3 cm for C2. HDR-IRT technique and point prescription (5 mm depth from the applicator surface) were the same for all patients. Vaginal toxicity was scored according to the CTCAE 5.0 scale in terms of the presence versus absence of any toxicity grade. The correlation among toxicity and clinical covariates (age, lymphadenectomy, fractionation, stage) was tested by Pearson correlation test (univariate) and by logistic regression (multivariable). RESULTS: 114 stage I and three stage II patients, median age 62 (range: 32-85) years, were included in this analysis. The mean follow-up was 56.3 months in C1 (40-76) and 20 months in C2 (8-42). Vaginal late toxicity was recorded in 40 and 15 patients in C1 and 2, respectively. Age, lymphadenectomy, and fractionation were significantly correlated with toxicity at univariate analysis (p value = 0.029, 0.006, and 0.002, respectively), while stepwise logistic regression confirmed only age and fractionation as significantly correlated parameters (p value = 0.02 and 0.001, respectively). Three-year local relapse-free, distant metastasis-free and cause-specific survival rates were 96.6%, 94.8%, and 99.1%, respectively. CONCLUSIONS: This analysis showed lower vaginal late toxicity rate in C2 compared to C1.

Assessment of Sexual Dysfunction in Cervical Cancer Patients after Different Treatment Modality: A Systematic Review.

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.

Interventional radiotherapy (brachytherapy) achieves very good long-term quality of life in children and adolescents with soft-tissue sarcoma.

BACKGROUND: Effective local therapy (surgery, radiation) and systemic multidrug chemotherapy are mandatory for curing childhood sarcoma. The standard radiation therapy for pediatric patients with soft-tissue sarcoma (STS) is external beam radiotherapy (EBRT). Because EBRT may cause long-term side effects with adverse effects on the patients' health and quality of life (QoL), alternative strategies are required. Interventional radiotherapy (IRT; brachytherapy) is established as a standard treatment for several tumors in adulthood. Single-center series have reported low levels of late effects and improved QoL in survivors treated with IRT in childhood. However, IRT is still applied infrequently in pediatric patients. METHODS: Thirty patients with STS were treated with IRT between 1992 and 2012 at the University Hospital Schleswig Holstein, Germany. Five patients were lost to follow-up, and 25 patients (mean age at time of data collection 24.8 years [range, 10.7-36.1]) could be analyzed focusing on overall survival and QoL (EORTC-C30 questionnaire). For more detailed information regarding general and health-specific questions, a separate questionnaire was developed. RESULTS: Nineteen of 25 patients were alive 13.4 [1.6-25.2] years after first cancer disease, and the three-year overall survival was 76% (SE, 0.09). The score of QoL/global health status (76.2 [16.6-100]) in our patients outvalues the European (66.1) and equals the German (75.9) reference value. CONCLUSION: IRT is an effective treatment option for pediatric patients with localized STS. Its role among other radiation dose-sparing techniques such as proton beam therapy has to be defined in prospective studies.

Brachyterapy: The radiation oncologist opinion.

The role of the radiation oncologist in the management of patients affected by prostate cancer is increasingly considered thanks to important technological innovations that have marked the radiotherapeutic approach in its three main fields: external beam radiotherapy (EB-RT), brachytherapy (interventional radiotherapy, I-RT), and metabolic radiotherapy (M-RT) through the use of new radiopharmaceuticals. Regarding the modern brachytherapy, the introduction of intensity-modulated techniques (IM-IRT), thanks to the implementation of HDR remote-after loading machines, and image-guided techniques (IG-IRT), has led to advantages in optimizing dose distribution after implantation with the possibility of modulating the dose according to the intraprostatic dominant lesions, limiting the dose to the surrounding tissues with improvement in local control and a significant reduction in side effects. I-RT today represents a safe, scientifically established, effective and well-tolerated treatment for patients affected by prostate cancer. Like most special techniques, in order to obtain the best results, it must be performed in centers with a high volume of activity and consolidated experience with an interdisciplinary approach.

Artificial intelligence in interventional radiotherapy (brachytherapy): Enhancing patient-centered care and addressing patients' needs.

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.

GEC-ESTRO recommendations for head & neck cancer brachytherapy (interventional radiotherapy): 2nd update with focus on HDR and PDR.

Modern brachytherapy (BT) is playing an important role in the multidisciplinary treatment of Head and Neck (H&N) cancer, as an organ- and function-preserving therapy. Low-dose-rate (LDR) technology has been replaced by modern remote afterloading and stepping source equipment using pulsed dose rate (PDR) or high dose rate (HDR) sources, improved image guidance and 3D treatment planning systems. This is an update of the previous GEC-ESTRO recommendations for H&N tumors, mainly applied to squamous carcinomas. Indications, results and recommended doses for different tumor sites are presented according to the published studies.

High-tailored Anal Canal Radiotherapy (HIT-ART): Outcomes of a 10-Year Single Center Clinical Experience.

BACKGROUND/AIM: The current standard for anal cancer treatment is essentially a 'one size fits all' approach where the dose of radiotherapy is similar whether the tumor is very small or very large. Trials are ongoing to evaluate dose de-escalation or escalation in localized disease depending on tumor size. The aim of the study was to assess results of a personalized approach involving dose stratification by stage and boost dose adjusted according to tumor early response. PATIENTS AND METHODS: We retrospectively reviewed squamous cell anal cancer (SCAC) patients treated between 2011 and 2021 by long-course intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy (CT); a sequential boost could be administered by IMRT or interventional radiotherapy (IRT) to obtain a total equivalent dose in 2 Gy (EQD2) of 54-60 Gy. RESULTS: We analyzed 110 patients (61% T3-4 stage, 71% node-positive). A total of 68.2% of patients received a sequential boost, mainly by IRT; median total EQD2 to primary site was 59.3 Gy. Acute ≥G3 toxicity rate was 36.4%. Median follow-up (FUP) was 35.4 months. A total of 83% of patients achieved clinical complete response (cCR); locoregional recurrence (LRR) occurred in 20.9% and distant metastases in 6.4% of cases. A total of 12.7% patients underwent salvage surgery. A total of 25.5% of patients reported ≥G2 and 4.5% ≥G3 late toxicity. The estimated 3-year overall survival, disease-free survival and colostomy-free survival were 92%, 72% and 84% respectively; 3-year-LRR was 22%. Nodal stage was associated with poorer cCR probability and higher LRR (p<0.05). CONCLUSION: Our results on a large cohort of patients with locally advanced SCAC and long FUP time confirmed the efficacy of IMRT; high local control and manageable toxicity also suggest IRT as a promising method in treatment personalization.

Interventional radiotherapy (brachytherapy) for re-irradiation of recurrent head and neck malignancies: oncologic outcomes and morbidity.

Objective: Management of recurrent head and neck cancer (HNC) is challenging. One option in previously irradiated patients is re-irradiation using interventional radiotherapy (IRT), the modern form of brachytherapy. Re-irradiation using IRT can be delivered as an exclusive strategy for salvage or through a postoperative or perioperative approach after salvage surgery. The aim of the present study is to analyse a bicentric Italian series focusing on the use of IRT as a re-irradiation modality and assess the resulting evidence concerning oncologic outcomes and morbidity. Methods: This is a retrospective study performed in two referral centres in Italy: Policlinico Universitario Agostino Gemelli in Rome and Azienda Ospedaliera Universitaria in Sassari. All patients who had previously received a full course of external beam RT and have been re-irradiated using high-dose-rate IRT between December 2010 and June 2023 were included. Patients were retreated either by a combination of surgery and perioperative (either endocavitary or interstitial) IRT or by exclusive interstitial IRT. Results: Thirty-four patients were included in the present series, 2 of whom underwent more than one IRT re-irradiation. Notably, no patient reported specific IRT-related toxicities. Median follow-up, excluding patients who died of HNC, was 24.5 months. Two-year local relapse-free survival was 26%, disease-specific survival 39.1%, and overall survival 36.6%. Conclusions: The present series is the largest reported experience of re-irradiation by IRT for HNC in Italy. The very low rate of toxicity confirms IRT as the safest re-irradiation modality. It is noteworthy to underline that IRT is a multidisciplinary strategy based on the close cooperation between surgeons and radiation oncologists during every phase, from the recommendation of treatment and implantation in the operating theatre, to its prescription and dose painting.

Local Control, Survival, and Toxicity Outcomes with High-Dose-Rate Peri-Operative Interventional Radiotherapy (Brachytherapy) in Head and Neck Cancers: A Systematic Review.

Background. Peri-operative interventional radiotherapy (POIRT) entails tumor resection, catheter implantation in the same surgery, and irradiation within the peri-operative period. It allows for maximal tumor burden reduction, better tumor bed identification, more flexible implant geometry, highly conformal irradiation, and treatment delay minimization. We reviewed the published local control, survival, toxicity, and quality of life (QOL) outcomes with POIRT for head and neck cancers (HNCs) in primary and re-irradiation settings. Materials and Methods. A systematic search of PubMed, Scopus, Science Direct, and other databases, supplemented by bibliography scanning and hand-searching, yielded 107 titles. Fifteen unique articles were eligible, five of which were merged with more updated studies. Of the ten remaining studies, four reported on primary POIRT, and seven reported on reirradiation POIRT. Given data heterogeneity, only qualitative synthesis was performed. Results. Primary POIRT in early tongue cancer results in 6-year recurrence-free (RFS) and overall survival (OS) of 92% for both; in advanced HNCs, the 9-year RFS and OS rates are 52% and 55%. Grade 1-2 toxicity is very common; grade 3-4 toxicity is rare, but grade 5 toxicity has been reported. POIRT re-irradiation for recurrent HNCs results in 5y RFS and OS rates of 37-55% and 17-50%; better outcomes are achieved with gross total resection (GTR). QOL data are lacking. Conclusions. Primary POIRT is safe and effective in early tongue cancers; its use in other HNC sites, especially in advanced disease, requires careful consideration. Re-irradiation POIRT is most effective and safe when combined with GTR; toxicity is significant and may be limited by careful case selection, implant planning and execution, use of smaller fraction sizes, and adherence to homogeneity constraints. Study Registration Number. PROSPERO Registry Number CRD42024548294.

PRO-NOVELTY: Patient-Reported Outcomes in NOse VEstibule interventionaL radioTherapY (brachytherapy).

Background: The aim of this paper is to evaluate the impact on the quality of life of the treatment of nasal vestibule tumors by interventional radiotherapy (IRT-brachytherapy) through a patient reported outcome questionnaire. Methods: We prospectively collected data about patients undergoing IRT according to our institutional schedule of 44 Gy delivered in 14 fractions twice a day. We recorded both acute toxicity data, using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and quality of life data, using the 22-item Sino-Nasal Outcome Test (SNOT-22) at baseline (T0), at 1 month (T1), at 3 months (T3), and at 6 months (T6). Results: We enrolled 10 consecutive patients treated between February 2023 and October 2023. The decrease in terms of SNOT-22 mean value was statistically significant from T0 and T6 with a p-value < 0.001. A noteworthy clinical finding is that quality of life improved regardless of the occurrence of G1-G2 side effects. Conclusions: Using SNOT-22 on patients with nasal vestibule carcinoma treated with IRT has shown an improvement in quality of life that is not strictly dependent on the occurrence of expected G1-G2 side effects.

A Novel Positive-Contrast Magnetic Resonance Imaging Line Marker for High-Dose-Rate (HDR) MRI-Assisted Radiosurgery (MARS).

Magnetic resonance imaging (MRI) can facilitate accurate organ delineation and optimal dose distributions in high-dose-rate (HDR) MRI-Assisted Radiosurgery (MARS). Its use for this purpose has been limited by the lack of positive-contrast MRI markers that can clearly delineate the lumen of the HDR applicator and precisely show the path of the HDR source on T1- and T2-weighted MRI sequences. We investigated a novel MRI positive-contrast HDR brachytherapy or interventional radiotherapy line marker, C4:S, consisting of C4 (visible on T1-weighted images) complexed with saline. Longitudinal relaxation time (T1) and transverse relaxation time (T2) for C4:S were measured on a 1.5 T MRI scanner. High-density polyethylene (HDPE) tubing filled with C4:S as an HDR brachytherapy line marker was tested for visibility on T1- and T2-weighted MRI sequences in a tissue-equivalent female ultrasound training pelvis phantom. Relaxivity measurements indicated that C4:S solution had good T1-weighted contrast (relative to oil [fat] signal intensity) and good T2-weighted contrast (relative to water signal intensity) at both room temperature (relaxivity ratio > 1; r2/r1 = 1.43) and body temperature (relaxivity ratio > 1; r2/r1 = 1.38). These measurements were verified by the positive visualization of the C4:S (C4/saline 50:50) HDPE tube HDR brachytherapy line marker on both T1- and T2-weighted MRI sequences. Orientation did not affect the relaxivity of the C4:S contrast solution. C4:S encapsulated in HDPE tubing can be visualized as a positive line marker on both T1- and T2-weighted MRI sequences. MRI-guided HDR planning may be possible with these novel line markers for HDR MARS for several types of cancer.

Post-operative interventional radiotherapy (brachytherapy) in advanced ocular surface and eyelid tumors as an alternative to surgical retreatment.

PURPOSE: The main purpose of treatment of advanced ocular surface and periocular malignant tumors is to eradicate the tumor while trying to preserve visual function and aesthetics. Our purpose is to describe the outcome of a retrospective case series of 10 patients with advanced ocular surface and periocular tumors treated surgically in first instance and then with postoperative interventional radiotherapy (IRT/Brachiterapy). MATERIALS AND METHODS: We describe the clinicopathological features, treatments and outcome, in a retrospective case series of 10 patients with advanced tumors involving ocular surface (staging ≥ T2) and eyelids (staging ≥ T3), with involvement of periocular and/or orbit tissues. Patients were first surgically treated, most of them with incomplete excision, and then underwent a post-operative interventional radiotherapy (IRT/Brachytherapy) as an alternative to more invasive and disfiguring surgical retreatment. Tumor location, risk factors, staging, histological features, and follow-up timing were analyzed. RESULTS: Three patients had advanced eyelid basal cell carcinomas, 2 patients were diagnosed with eyelid and conjunctival squamous cell carcinomas, 3 as sebaceous carcinomas, and 2 as primary conjunctival melanomas. The mean follow-up time from IRT to last clinical follow-up was 58.6 weeks, range 28.4-168 (median 43.65, IQR 28.9-72.9). Two patients - one with ocular surface SCC, the other with conjunctival melanoma - had a local recurrence 23.4 and 40,9 weeks after IRT, respectively. An overview of the current knowledge on adjuvant or post-operative IRT is also provided. CONCLUSIONS: IRT can be considered an effective therapeutic option to avoid more invasive surgical retreatment in advanced tumors involving eyelids and ocular surface.

Radiation Therapy in Non-Melanoma Skin Cancers: An Italian Survey on Behalf of the Italian Association of Radiotherapy and Clinical Oncology.

AIMS: The National Palliative Care and Interventional Radiotherapy Study Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) carried out a survey whose aim was to obtain a "snapshot" of the real-world practice of nonmelanoma skin cancer (NMSC) treatments in Italy. MATERIALS AND METHODS: The survey was conducted on SurveyMonkey's online interface and was sent via e-mail to our society Radiation Oncologists. RESULTS: Fifty-eight Italian radiation oncologists (ROs), representing 54 centers, answered the survey. Thirteen percent of the ROs declared they treat fewer than 10 NMSC lesions annually, 36% treat between 11 and 20, and 51% treat more than 20 lesions annually. Interventional radiotherapy (IRT) was offered by 25% of the ROs, and every case was reportedly discussed by a multidisciplinary team (71%). Electrons (74%), volumetric modulated arc therapy (V-MAT) (57%), three-dimensional conformal radiotherapy (3D-CRT) (43%), and IRT (26%) were the main treatment options. With external beam radiotherapy (EBRT), 46 and 53 different RT schedules were treated for curative and palliative intent, respectively; whereas for IRT, there were 21 and 7 for curative and palliative intent, respectively. The most popular EBRT curative options were 50-70.95/22-35 fractions (fx) and 50-70 Gy/16-20fx and for EBRT palliative settings, 30Gy/10fx, and 20-35Gy/5fx. For IRT, the most popular curative options were 32-50Gy/8-10fx and 30-54Gy/3-5fx, whereas 30Gy/6fz was the palliative option. Less than 10 re-RT cases were reported in one year in 42.5%, 11-20 cases in 42.5%, and >20 cases annually in 15%. Electrons (61%), VMAT (49%), and BRT (25%) were the most widely used approaches: 20-40Gy in 10fx and 20-25Gy in 5fx were the recommended fractionations. CONCLUSION: The survey shows a variegated reality. A national registry with more detailed data could help in undercover its causes.

Ocular Brachytherapy (Interventional Radiotherapy): Preserving the Vision.

Uveal melanoma represents the most common intraocular neoplasia among adults. Brachytherapy (interventional radiotherapy; IRT) has a great advantage, when compared with enucleation, both in terms of organ and function sparing. The Collaborative Ocular Melanoma Study introduced into clinical practice a standardised procedure that allowed the equivalence of IRT with enucleation in terms of overall survival to be demonstrated. IRT is carried out by placing a plaque in direct contact with the sclera under the uveal melanoma. Several radioactive sources may be used, including 106-ruthenium, 125-iodine, 103-palladium and 90-strontium. It is a multidisciplinary procedure requiring the collaboration of interventional radiation oncologists and ophthalmologists in the operating theatre and medical physicists for an accurate treatment time calculation. It also relies on ultrasound imaging to identify the lesion and verifiy the correct plaque placement. An emerging tool of paramount importance could be the use of artificial intelligence and predictive models to identify those patients at higher risk of developing late side-effects and therefore who may deserve preventive and supportive therapies.

The Impact of HAPPY (Humanity Assurance Protocol in Interventional Radiotherapy) on the Psychological Well-being of Gynecological Cancer Patients.

BACKGROUND: HAPPY (Humanity Assurance Protocol in interventional radiotherapy) reports the necessity for gynecological cancer patients to undergo interventional radiotherapy (IRT, also called brachytherapy). The present paper has evaluated how some precautions may improve the psychological well-being of the patients during IRT. METHODS: Patients with gynecological cancer undergoing IRT-HDR were analyzed. Patients answered three questionnaires before the IRT procedure (T0) and at the end of IRT (T1): Distress Thermometer (DT), Numerical Rating Scale for IRT procedure distress (NRS), and Hospital Anxiety and Depression Scale (HADS). Correlations have been calculated pairwise through pandas. corrwith with a Pearson algorithm, and the p-values have been calculated through scipy.stats.pearsonr. Plots have been generated through seaborn and matplotlib. A Wilcoxon test was used. RESULTS: 55 patients were selected for this study. The median age of the patients was 64 (range, 39-84) years. 52 patients were with stage I endometrial cancer, whereas 3/3 patients with cervical cancer had locally advanced stages (IIB-IVA). 26 patients had a high education level (47.3%), and 38 were married or with a partner (69.1%). Only 14/55 (25.45%) patients were working. The HADS, DT, and NRS averages before the IRT procedure (T0) were 10.2, 3.8, and 4.3, respectively. After applying the HAPPY protocol, the HADS, DT, and NRS averages after IRT (T1) were 9.4, 3.4, and 2.6, respectively. The Wilcoxon signed rank test analysis showed a significant improvement in NRS (p < 0.00001) and HADS (p = 0.034). Living with a partner, parents or relatives was the only parameter statistically significantly associated with better DT pre-IRT (p = 0.04), HADS pre-IRT (p = 0.01), DT post-IRT (p = 0.01), and HADS post-IRT (p = 0.04). CONCLUSION: In our study, the HAPPY protocol was associated with a significant reduction in patients' distress, anxiety, and discomfort.

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.

The role of interventional radiotherapy (brachytherapy) in nasopharynx tumors: A systematic review.

Purpose: Nasopharyngeal cancers (NPC) are very aggressive, and the recurrence rate after radical therapy is high. This study aimed to evaluate the efficacy of brachytherapy (BT) also called interventional radiotherapy (IRT) in primary NPC in comparison with external beam radiotherapy (EBRT) alone. Material and methods: A systematic search was performed in Scopus, Cochrane, and PubMed databases. Clinical query based on PICO framework was as follows: In patients with NPC (P), is EBRT plus IRT (I) superior to EBRT alone (C) in terms of local control (LC) and toxicity (O)? Full articles evaluating the efficacy of IRT as a boost after EBRT in patients with NPC were considered. Results: Eight papers, including 1,320 patients fulfilled the inclusion criteria. The median 5-year LC for IRT group and no-IRT group was 98% (range, 95.8-100%) and 86% (range, 80.2-91%), respectively; the median 5-year overall survival (OS) for IRT group and no-IRT group was 93.3% (range, 89.2-97.5%) and 82.9% (range, 74.8-91.1%), respectively; the median 5-year DFS for IRT group and no-IRT group was 94.2% (range, 92.5-96%) and 83.9% (range, 73.3-94.6%), respectively; the median 5-year cancer-specific survival (CSS) for IRT group and no-IRT group was 96% (range, 94.5-97.5%) and 88.2% (range, 83.4-93.1%), respectively. G1-2 and G3-4 toxicities were similar in some articles, or significantly lower in patients treated with IRT in other papers. Conclusions: Data suggest that IRT may improve results of external beam radiotherapy in primary NPCs, especially when using new technologies.