Can interventional radiotherapy (brachytherapy) be an alternative to surgery in early-stage oral cavity cancer? A systematic review.

PURPOSE: Brachytherapy (BT), also known as interventional radiotherapy (IRT), has proven its utility in the treatment of localized tumors. The aim of this review was to examine the efficacy of modern BT in early-stage oral cavity cancer (OCC) in terms of local control (LC), overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and safety. METHODS: The SPIDER framework was used, with sample (S), phenomena of interest (PI), design (D), evaluation (E), and research type (R) corresponding to early-stage oral cavity cancer (S); BT (PI); named types of qualitative data collection and analysis (D); LC, OS, DFS, CSS, and toxicity (E); qualitative method (R). Systematic research using PubMed and Scopus was performed to identify full articles evaluating the efficacy of BT in patients with early-stage OCC. The studies were identified using medical subject headings (MeSH). We also performed a PubMed search with the keywords "brachytherapy oral cavity cancer, surgery." The search was restricted to the English language. The timeframe 2002-2022 as year of publication was considered. We analyzed clinical studies of patients with OCC treated with BT alone only as full text; conference papers, surveys, letters, editorials, book chapters, and reviews were excluded. RESULTS: The literature search resulted in 517 articles. After the selection process, 7 studies fulfilled the inclusion criteria and were included in this review, totaling 456 patients with early-stage node-negative OCC who were treated with BT alone (304 patients). Five-year LC, DFS, and OS for the BT group were 60-100%, 82-91%, and 50-84%, respectively. CONCLUSION: In conclusion, our review suggests that BT is effective in the treatment of early-stage OCC, particularly for T1N0 of the lip, mobile tongue, and buccal mucosa cancers, with good functional and toxicity profiles.

Sodium-hyaluronate mouthwash on radiotherapy-induced xerostomia: a randomised clinical trial.

INTRODUCTION: Radiotherapy-induced xerostomia (RIX) is one of the most common adverse effects of radiotherapy (RT) in head and neck cancer patients (HNC) and a major determinant of survivors' quality of life. The primary objective was to evaluate the reduction of patients' xerostomia symptoms after the utilisation of a sodium-hyaluronate mouthwash compared to a placebo solution. The secondary objectives were to evaluate the improvement of quality of life and to evaluate the patients' satisfaction. METHODS: The protocol was approved by the ethical committee (Ref. 50,053/19) and registered at ClinicalTrials.gov (ID: NCT05103124). The study was a double-blind randomised clinical trial (RCT) with a crossover design and was conducted at the Fondazione Policlinico Universitario A. Gemelli, Rome. RESULTS: Thirty-two patients completed the study protocol. Lower values of the modified Xerostomia Questionnaire (XQ) were retrieved when comparing the baseline scores to the ones after the treatment, when compared with placebo (Mann-Whitney U test = 0.01); higher values of patients' satisfaction (Likert scale) and modified XQ were retrieved for the sodium-hyaluronate mouthwash (Mann-Whitney U test = 0.001). CONCLUSIONS: This RCT highlights the advantages of treating RIX with the sodium-hyaluronate mouthwash since it seems to be clinically effective in reducing its symptoms, without any reported adverse events. CLINICALTRIALS: gov: NCT05103124 in 17/10/2021.

Magnetic resonance-guided stereotactic body radiation therapy (MRgSBRT) for oligometastatic patients: a single-center experience.

PURPOSE: Stereotactic body radiotherapy is increasingly used for the treatment of oligometastatic disease. Magnetic resonance-guided stereotactic radiotherapy (MRgSBRT) offers the opportunity to perform dose escalation protocols while reducing the unnecessary irradiation of the surrounding organs at risk. The aim of this retrospective, monoinstitutional study is to evaluate the feasibility and clinical benefit (CB) of MRgSBRT in the setting of oligometastatic patients. MATERIALS AND METHODS: Data from oligometastatic patients treated with MRgSBRT were collected. The primary objectives were to define the 12-month progression-free survival (PFS) and local progression-free survival (LPFS) and 24-month overall survival (OS) rate. The objective response rate (ORR) included complete response (CR) and partial response (PR). CB was defined as the achievement of ORR and stable disease (SD). Toxicities were also assessed according to the CTCAE version 5.0 scale. RESULTS: From February 2017 to March 2021, 59 consecutive patients with a total of 80 lesions were treated by MRgSBRT on a 0.35 T hybrid unit. CR and PR as well as SD were observed in 30 (37.5%), 7 (8.75%), and 17 (21.25%) lesions, respectively. Furthermore, CB was evaluated at a rate of 67.5% with an ORR of 46.25%. Median follow-up time was 14 months (range: 3-46 months). The 12-month LPFS and PFS rates were 70% and 23%, while 24-month OS rate was 93%. No acute toxicity was reported, whereas late pulmonary fibrosis G1 was observed in 9 patients (15.25%). CONCLUSION: MRgSBRT was well tolerated by patients with reported low toxicity levels and a satisfying CB.

Role of Peripheral Blood Markers for Detecting Response and Predicting Prognosis in Patients with Non-small-cell Lung Cancer Undergoing Neoadjuvant Therapy and Surgery.

INTRODUCTION: To date, no validated predictors of response before neoadjuvant therapy (NAD) are currently available in locally advanced non-small-cell lung cancer (NSCLC). In this study, different peripheral blood markers were investigated before NAD (pre-NAD) and after NAD/before surgery (post-NAD) to evaluate their influence on the treatment outcomes. METHODS: Patients affected by locally advanced NSCLC (cT1-T4/N0-2/M0) who underwent NAD followed by surgery from January 1996 to December 2019 were considered for this retrospective analysis. The impact of peripheral blood markers on downstaging post-NAD and on overall survival (OS) was evaluated using multivariate logistic and Cox regression models. Time to event analysis was performed by means of Kaplan-Meier survival curves and Log Rank tests at 5 years from surgery. RESULTS: Two hundred and seventy-two consecutive patients were included. Most of the patients had Stage III NSCLC (83.5%). N2 disease was reported in 188 (69.1%) patients. Surgical resection was performed in patients with stable disease or downstaging post-NAD. Nodal downstaging was observed in 80% of clinical N2 (cN2) patients. The median follow-up of the total series was 74 months (range 6-302). Five-year OS in the overall population and in N2 population was 74.6% and 73.5%, respectively. The pre-surgery platelets level (PLT) (p = 0.019) and the variation (pre-NAD/post-NAD) of the neutrophil/lymphocyte ratio (p = 0.024) were identified as independent prognostic factors of OS. The preoperative PLT value (p value = 0.031) was confirmed as the only predictor of NAD response. CONCLUSIONS: The clinical role of peripheral blood markers in locally advanced NSCLC needs to be further investigated. Based on these preliminary results, these factors may be used as auxiliary markers for the prediction of response to neoadjuvant treatment and as prognostic factors for stratification in multimodal approaches.

Cumulative dose, toxicity, and outcomes of spinal metastases re-irradiation : Systematic review on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: The aim of this study was to identify patient-, tumor-, or treatment-related factors which may affect disease-related outcomes of re-irradiation (reRT) in patients with previously irradiated vertebral metastases. METHODS: A computerized search of the literature was performed by searching for terms related to reRT and spinal metastases in MEDLINE, EMBASE, OVID, and the Cochrane database from 1995 to 2019. Studies including at least 10 patients who had received reRT at the same site of initial radiotherapy for vertebral metastases with localized external beam radiotherapy were included. To determine the pooled ≥G3 acute and late toxicity rate, pain relief, local control, and overall survival, a meta-analysis technique of single-arm studies was performed. RESULTS: Nineteen studies including 1373 patients met the inclusion criteria for this systematic review. The pooled pain relief, neurological improvement, 1­year local control, and 1­year overall survival rates were 74.3%, 73.8%, 78.8%, and 54.6%, respectively, with moderate to high heterogeneity among studies. No difference in heterogeneity was evidenced for pain relief or local control after omitting studies not using stereotactic body radiotherapy (SBRT) or studies delivering biologically effective dose (BED) < 45 Gy10, whereas heterogeneity for 1­year OS was lower after omitting studies not using SBRT and delivering BED < 45 Gy10. The pooled results of grade ≥ 3 acute and late toxicity were 0.4% (95% confidence interval: 0.1-1.2%) and 2.2% (95% confidence interval: 1.2-37%), respectively, with low heterogeneity among studies. CONCLUSION: While this systematic review confirmed that reRT is both safe and effective for treating patients with recurrent spinal metastases, it could not identify factors which may affect outcomes of reRT in this patient population.

Local Failure After Accelerated Partial Breast Irradiation with Intraoperative Radiotherapy with Electrons: An Insight into Management and Outcome from an Italian Multicentric Study.

BACKGROUND: The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation. PATIENTS AND METHODS: Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated. RESULTS: A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6-6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT. CONCLUSIONS: Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.

Role of upper abdominal reirradiation for gastrointestinal malignancies: a systematic review of cumulative dose, toxicity, and outcomes on behalf of the Re-Irradiation Working Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: Abdominal recurrences of gastrointestinal malignancies are common. Evidence in clinical studies has shown that re-irradiation (Re-I) is tolerable and efficient in different tumor locations. In contrast, little clinical data are available on normal long-term Re­I tolerance doses. A systematic review of upper abdominal Re­I was performed with the aim of exploring the cumulative dose, toxicity, and outcomes. METHODS: A computerized search was undertaken in MEDLINE, EMBASE, OVID, and the Cochrane database. Only studies reporting toxicity and/or outcomes were taken into consideration. To improve the comparability of the different Re­I regimens and assess the relationship between Radiotherapy (RT) dose and toxicity, the equivalent dose in 2­Gy fractions was calculated according to the linear quadratic model. RESULTS: Sixteen studies met the inclusion criteria, with the total patients numbering 408. Median follow-up Re­I ranged from 5.9 to 45 months. The median time elapsed since previous RT treatment was 15 months (2-162 months). Re­I prescription doses were variable (22.5 Gy in 3 fractions to 126.5 Gy with 125I). Cumulative doses calculated for acute- and late-responding tissues ranged from 67.25 to 136 Gy and 30.3 to 188.38 Gy, respectively. Comprehensively, the pooled ≥G3 toxicity was 12% (95%CI: 7.6-19%). The overall 1­year survival and local recurrence-free survival rates were 53.7% (95%CI: 45.6-63.2%) and 66.5% (95% CI: 58.7-75.4%), respectively. Pain improvement was reported in 66.9% of patients. CONCLUSION: Due to limited evidence as a result of the retrospective design of the majority of the studies, our review suggests that upper abdominal Re­I is effective in terms of local control and palliation, with a moderate rate of severe toxicities.

A new frontier of image guidance: Organs at risk avoidance with MRI-guided respiratory-gated intensity modulated radiotherapy: Technical note and report of a case.

The case of a 50-year-old man affected by a rhabdomiosarcoma metastatic lesion in the left flank Is reported. The patient was addressed to 50.4 Gy radiotherapy with concomitant chemotherapy in order to locally control the lesion. A Tri-60-Co magnetic resonance hybrid radiotherapy unit was used for treatment delivery and a respiratory gating protocol was applied for the different breathing phases (Free Breathing, Deep Inspiration Breath Hold and Final Expiration Breath Hold). Three intensity modulated radiation therapy (IMRT) plans were calculated and Final Expiration Breath Hold plan was finally selected due to the absence of PTV coverage differences and better organs at risk sparing (i.e. kidneys). This case report suggests that organs at risk avoidance with MRI-guided respiratory-gated Radiotherapy is feasible and particularly advantageous whenever sparing the organs at risk is of utmost dosimetric or clinical importance.

Short-course radiotherapy in elderly patients with early stage non-melanoma skin cancer: a phase II study.

AIM: To evaluate outcome of an accelerated radiotherapy (RT) regimen in elderly patients with an early stage non-melanoma skin cancer (NMSC). METHODS: Total RT dose was 30 Gy in 5 Gy fractions in six consecutive days. RESULTS: Thirty-one patients were enrolled. Fourteen were aged ≥80 years. Acute skin and observed late toxicity were exclusively of grade 1. Thirty patients showed a complete response (median follow-up 30 months). Two-year actuarial local control was 93.2%. The cosmetic result was mostly judged as good or excellent. CONCLUSIONS: Short-course RT in elderly NMSC patients produces >90% local control of disease.

Can automation in radiotherapy reduce costs?

BACKGROUND: Computerized automation is likely to play an increasingly important role in radiotherapy. The objective of this study was to report the results of the first part of a program to implement a model for economical evaluation based on micro-costing method. To test the efficacy of the model, the financial impact of the introduction of an automation tool was estimated. A single- and multi-center validation of the model by a prospective collection of data is planned as the second step of the program. MATERIAL AND METHODS: The model was implemented by using an interactive spreadsheet (Microsoft Excel, 2010). The variables to be included were identified across three components: productivity, staff, and equipment. To calculate staff requirements, the workflow of Gemelli ART center was mapped out and relevant workload measures were defined. Profit and loss, productivity and staffing were identified as significant outcomes. Results were presented in terms of earnings before interest and taxes (EBIT). Three different scenarios were hypothesized: baseline situation at Gemelli ART (scenario 1); reduction by 2 minutes of the average duration of treatment fractions (scenario 2); and increased incidence of advanced treatment modalities (scenario 3). By using the model, predicted EBIT values for each scenario were calculated across a period of eight years (from 2015 to 2022). RESULTS: For both scenarios 2 and 3 costs are expected to slightly increase as compared to baseline situation that is particularly due to a little increase in clinical personnel costs. However, in both cases EBIT values are more favorable than baseline situation (EBIT values: scenario 1, 27%, scenario 2, 30%, scenario 3, 28% of revenues). CONCLUSION: A model based on a micro-costing method was able to estimate the financial consequences of the introduction of an automation tool in our radiotherapy department. A prospective collection of data at Gemelli ART and in a consortium of centers is currently under way to prospectively validate the model.

Radioprotective effect of calcium channel blockers against late rectal bleeding in prostate cancer.

OBJECTIVE: This study was done to assess the impact of clinical factors and in particular the use of drugs for concomitant illnesses on late radiation-induced rectal bleeding in patients with prostate cancer. MATERIALS AND METHODS: Patients with histologically proven prostate adenocarcinoma treated with radical radiotherapy and followed up for at least 6 months were selected. The correlation between late rectal bleeding and a number of factors was investigated by univariate and multivariate analysis. RESULTS: A total of 278 patients who underwent radiotherapy at our institution between October 2002 and May 2011 were selected. At univariate analysis, delivery of radiation doses higher than 70 Gy and use of angiotensin-converting enzyme inhibitors were associated with a higher incidence of rectal bleeding. Conversely, patients who used calcium channel blockers had a lower risk (3-year rectal bleeding-free survival 89.8 versus 66.5 %, p = 0.043). At multivariate analysis, use of calcium channel blockers was found to have a protective effect with a hazard ratio of 0.3 (95 % CI 0.12-0.96). Delivery of higher radiation doses was associated with an increased risk of rectal bleeding (hazard ratio 3.02, 95 % CI 1.23-7.38). CONCLUSIONS: Use of calcium channel blockers during and after radiotherapy treatment might have a protective effect against late rectal bleeding. If these results are reconfirmed by larger clinical series, calcium channel blockers may be tested as radioprotector agents in clinical trials.

Role of 18F-FDG PET/CT in Head and Neck Squamous Cell Carcinoma: Current Evidence and Innovative Applications.

This article provides an overview of the use of 18F-FDG PET/CT in various clinical scenarios of head-neck squamous cell carcinoma, ranging from initial staging to treatment-response assessment, and post-therapy follow-up, with a focus on the current evidence, debated issues, and innovative applications. Methodological aspects and the most frequent pitfalls in head-neck imaging interpretation are described. In the initial work-up, 18F-FDG PET/CT is recommended in patients with metastatic cervical lymphadenectomy and occult primary tumor; moreover, it is a well-established imaging tool for detecting cervical nodal involvement, distant metastases, and synchronous primary tumors. Various 18F-FDG pre-treatment parameters show prognostic value in terms of disease progression and overall survival. In this scenario, an emerging role is played by radiomics and machine learning. For radiation-treatment planning, 18F-FDG PET/CT provides an accurate delineation of target volumes and treatment adaptation. Due to its high negative predictive value, 18F-FDG PET/CT, performed at least 12 weeks after the completion of chemoradiotherapy, can prevent unnecessary neck dissections. In addition to radiomics and machine learning, emerging applications include PET/MRI, which combines the high soft-tissue contrast of MRI with the metabolic information of PET, and the use of PET radiopharmaceuticals other than 18F-FDG, which can answer specific clinical needs.

Pattern of practice of re-irradiation for ipsilateral breast tumor recurrence in Italy: a survey by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: The Re-irradiation and the Breast Cancer Working Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) conducted a survey to provide an overview of the policies for breast cancer (BC) re-irradiation (re-RT) among the Italian radiotherapy (RT) centers. METHODS: In October 2021, 183 RT centers were invited to answer a survey: after an initial section about general aspects, the questionnaire focused on radiation oncologists' (ROs) attitude toward re-RT in three different scenarios: ipsilateral breast tumor recurrence (IBTR) treated with second conservative surgery, IBTR treated with mastectomy and inoperable IBTR. Surveyed ROs were also asked to express their interest in being involved in a prospective trials. RESULTS: Seventy-seven/183 (42.0%) centers answered the Survey, only one RO per center was requested to answer. In particular, 86.5% ROs declared to have performed "curative" re-RT for IBTR during the previous two years (2019-2020): 76.7% respondents administered re-RT after second BCS, 50.9% after mastectomy, and 48.1% for inoperable IBTR. Re-RT practice varied widely among centers in terms of treatment volumes, dose and fractionation schedules, techniques and dose-volume constraints for organs at risks (OARs). Forty-six participants (59.7%) expressed their interest in participating in a prospective study investigating BC re-RT. CONCLUSIONS: About one out of three RT centers in Italy delivered re-RT for IBTR. Nevertheless, practice of re-RT varied widely among centers highlighting the needs for prospective studies to improve knowledge in this field.

REPeated mAgnetic resonance Image-guided stereotactic body Radiotherapy (MRIg-reSBRT) for oligometastatic patients: REPAIR, a mono-institutional retrospective study.

BACKGROUND: Oligo-progression or further recurrence is an open issue in the multi-integrated management of oligometastatic disease (OMD). Re-irradiation with stereotactic body radiotherapy (re-SBRT) technique could represent a valuable treatment option to improve OMD clinical outcomes. MRI-guided allows real-time visualization of the target volumes and online adaptive radiotherapy (oART). The aim of this retrospective study is to evaluate the efficacy and toxicity profile of MRI-guided repeated SBRT (MRIg-reSBRT) in the OMD setting and propose a re-SBRT classification. METHODS: We retrospectively analyzed patients (pts) with recurrent liver metastases or abdominal metastatic lesions between 1 and 5 centimeters from liver candidate to MRIg-reSBRT showing geometric overlap between the different SBRT courses and assessing whether they were in field (type 1) or not (type 2). RESULTS: Eighteen pts completed MRIg-reSBRT course for 25 metastatic hepatic/perihepatic lesions from July 2019 to January 2020. A total of 20 SBRT courses: 15 Type 1 re-SBRT (75%) and 5 Type 2 re-SBRT (25%) was delivered. Mean interval between the first SBRT and MRIg-reSBRT was 8,6 months. Mean prescribed dose for the first treatment was 43 Gy (range 24-50 Gy, mean BEDα/ß10=93), while 41 Gy (range 16-50 Gy, mean BEDα/ß10=92) for MRIg-reSBRT. Average liver dose was 3,9 Gy (range 1-10 Gy) and 3,7 Gy (range 1,6-8 Gy) for the first SBRT and MRIg-reSBRT, respectively. No acute or late toxicities were reported at a median follow-up of 10,7 months. The 1-year OS and PFS was 73,08% and 50%, respectively. Overall Clinical Benefit was 54%. CONCLUSIONS: MRIg-reSBRT could be considered an effective and safe option in the multi-integrated treatment of OMD.

A distributed feature selection pipeline for survival analysis using radiomics in non-small cell lung cancer patients.

Predictive modelling of cancer outcomes using radiomics faces dimensionality problems and data limitations, as radiomics features often number in the hundreds, and multi-institutional data sharing is ()often unfeasible. Federated learning (FL) and feature selection (FS) techniques combined can help overcome these issues, as one provides the means of training models without exchanging sensitive data, while the other identifies the most informative features, reduces overfitting, and improves model interpretability. Our proposed FS pipeline based on FL principles targets data-driven radiomics FS in a multivariate survival study of non-small cell lung cancer patients. The pipeline was run across datasets from three institutions without patient-level data exchange. It includes two FS techniques, Correlation-based Feature Selection and LASSO regularization, and Cox Proportional-Hazard regression with Overall Survival as endpoint. Trained and validated on 828 patients overall, our pipeline yielded a radiomic signature comprising "intensity-based energy" and "mean discretised intensity". Validation resulted in a mean Harrell C-index of 0.59, showcasing fair efficacy in risk stratification. In conclusion, we suggest a distributed radiomics approach that incorporates preliminary feature selection to systematically decrease the feature set based on data-driven considerations. This aims to address dimensionality challenges beyond those associated with data constraints and interpretability concerns.

Accelerated intensity-modulated radiotherapy plus temozolomide in patients with glioblastoma: a phase I dose-escalation study (ISIDE-BT-1).

BACKGROUND: We performed a dose-escalation trial to determine the maximum tolerated dose (MTD) of intensity-modulated radiotherapy (IMRT) with standard concurrent and sequential-dose temozolomide (TMZ) in patients with glioblastoma multiforme. METHODS: Histologically proven glioblastoma patients underwent IMRT dose escalation. IMRT was delivered over 5 weeks with the simultaneous integrated boost (SIB) technique to the two planning target volumes (PTVs) defined by adding 5-mm margin to the respective clinical target volumes (CTVs). CTV1 was the tumor bed plus the enhancing lesion with 10-mm margin; CTV2 was the area of perifocal edema with 20-mm margin. Only the PTV1 dose was escalated (planned dose escalation: 60, 62.5, 65, 67.5, 70 Gy) while the PTV2 dose remained the same (45 Gy). RESULTS: Forty consecutive glioblastoma patients were treated. While no dose-limiting toxicity (DLT) was recorded during the dose escalation up to 67.5/2.7 Gy, two out of the first six consecutively enrolled patients on the highest dose level (70/2.8 Gy) experienced a DLT, and therefore a cohort expansion was required. 3/14 patients experienced a DLT on the highest planned dose level, and therefore the MTD was not exceeded. After a median follow-up time of 25 months no grade >2 late neurological toxicity was recorded. CONCLUSIONS: By using a SIB IMRT technique, a radiation dose of 70 Gy in 25 fractions (biological effective dose--BED--of 92.8 Gy) can be delivered with concurrent and sequential standard dose TMZ, without unacceptable acute toxicity in patients with glioblastoma.

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.

Ventricular tachycardia ablation through radiation therapy (VT-ART) consortium: Concept description of an observational multicentric trial via matched pair analysis.

Introduction: Monomorphic ventricular tachycardia (VT) is a life-threatening condition often observed in patients with structural heart disease. Ventricular tachycardia ablation through radiation therapy (VT-ART) for sustained monomorphic ventricular tachycardia seems promising, effective, and safe. VT-ART delivers focused, high-dose radiation, usually in a single fraction of 25 Gy, allowing ablation of VT by inducing myocardial scars. The procedure is fully non-invasive; therefore, it can be easily performed in patients with contraindications to invasive ablation procedures. Definitive data are lacking, and no direct comparison with standard procedures is available. Discussion: The aim of this multicenter observational study is to evaluate the efficacy and safety of VT-ART, comparing the clinical outcome of patients undergone to VT-ART to patients not having received such a procedure. The two groups will not be collected by direct, prospective accrual to avoid randomization among the innovative and traditional arm: A retrospective selection through matched pair analysis will collect patients presenting features similar to the ones undergone VT-ART within the consortium (in each center independently). Our trial will enroll patients with optimized medical therapy in whom endocardial and/or epicardial radiofrequency ablation (RFA), the gold standard for VT ablation, is either unfeasible or fails to control VT recurrence. Our primary outcome is investigating the difference in overall cardiovascular survival among the group undergoing VT-ART and the one not exposed to the innovative procedure. The secondary outcome is evaluating the difference in ventricular event-free survival after the last procedure (i.e., last RFA vs. VT-ART) between the two groups. An additional secondary aim is to evaluate the reduction in the number of VT episodes comparing the 3 months before the procedure to the ones recorded at 6 months (from the 4th to 6th month) following VT-ART and RFA, respectively. Other secondary objectives include identifying the benefits of VT-ART on cardiac function, as evaluated through an electrocardiogram, echocardiographic, biochemical variables, and on patient quality of life. We calculated the sample size (in a 2:1 ratio) upon enrolling 149 patients: 100 in the non-exposed control group and 49 in the VT-ART group. Progressively, on a multicentric basis supervised by the promoting center in the VT-ART consortium, for each VT-ART patient enrollment, a matched pair patient profile according to the predefined features will be shared with the consortium to enroll a patient that has not undergone VT-ART. Conclusion: Our trial will provide insight into the efficacy and safety of VT-ART through a matched pair analysis, via an observational, multicentric study of two groups of patients with or without VT-ART in the multicentric consortium (with subgroup stratification into dynamic cohorts).