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.

Combination of Local Ablative Techniques with Radiotherapy for Primary and Recurrent Lung Cancer: A Systematic Review.

In patients with early-stage or recurrent NSCLC who are unable to tolerate surgery, a benefit could derive only from a systemic therapy or another few forms of local therapy. A systematic review was performed to evaluate the feasibility and the effectiveness of radiotherapy combined with local ablative therapies in the treatment of primary and recurrent lung cancer in terms of toxicity profile and local control rate. Six studies featuring a total of 115 patients who met eligibility criteria and 119 lesions were included. Three studies evaluated lung cancer patients with a medically inoperable condition treated with image-guided local ablative therapies followed by radiotherapy: their local control rate (LC) ranged from 75% to 91.7% with only 15 patients (19.4%) reporting local recurrence after combined modality treatment. The other three studies provided a salvage option for patients with locally recurrent NSCLC after RT: the median follow-up period varied from 8.3 to 69.3 months with an LC rate ranging from 50% to 100%. The most common complications were radiation pneumonitis (9.5%) and pneumothorax (29.8%). The proposed intervention appears to be promising in terms of toxicity profile and local control rate. Further prospective studies are need to better delineate combining LTA-RT treatment benefits in this setting.

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.

Salvage High-Dose-Rate Interventional Radiotherapy (Brachytherapy) Combined with Surgery for Regionally Relapsed Head and Neck Cancers.

(1) Background: to report on the use of high-dose-rate (HDR) interventional radiotherapy (brachytherapy, IRT) as a salvage treatment for patients with regionally relapsed head and neck cancers. (2) Methods: A retrospective study of 60 patients treated with HDR-IRT for loco-regionally relapsed head and neck cancers at our institution (2016-2020). Treatment procedure, results, and related toxicities were collected. Local and overall survival outcomes were analyzed. (3) Results: The median follow-up was 22.4 months. Twenty-nine (48.3%) patients had locoregional recurrences with a median time of 28.9 months. The local-recurrence free-survival was 88.1% and 37.3% at 3 years and 5 years. At the last follow-up, 21 patients were alive and the median time to death was 24 months. The overall survival was 39.2% and 16.6% at 3 years and 5 years. Collectively, there were 28 events of grade ≥ 3 late toxicities recorded in 21 patients (35%). (4) Conclusions: Salvage HDR-IRT combined with surgery offers a second-line curative treatment option for regionally relapsed head and neck cancers with acceptable outcomes and toxicities.

Salvage high-dose-rate interventional radiotherapy (brachytherapy) for locally relapsed prostate cancer after radical prostatectomy and subsequent external irradiation.

Purpose: To report the use of high-dose-rate (HDR) interventional radiotherapy (brachytherapy, IRT) as a salvage treatment for macroscopic histologically confirmed local relapse of prostatic cancer after prostatectomy and subsequent external irradiation. Material and methods: A retrospective study of patients with prostate adenocarcinoma, treated with HDR-IRT for an isolated local relapse after prostatectomy and external irradiation at our institution (2010-2020). Treatment results and treatment related-toxicity were recorded. Clinical outcomes were analyzed. Results: Ten patients were identified. The median age was 63 years (range, 59-74 years), and the median follow-up time was 34 months (range, 10-68 months). Four patients had a biochemical relapse, and the mean time to prostate specific antigen (PSA) increase was 13 months. One-year biochemical failure-free survival (bFFS), 3-year bFFS, and 4-year bFFS were 80%, 60%, and 60%, respectively. Most of the treatment-related toxicities were grade 1-2. Two patients experienced grade 3 late genitourinary toxicity. Conclusions: HDR-IRT seems to be an effective treatment option showing acceptable toxicity for prostate cancer patients with isolated macroscopic histologically confirmed local relapse after prostatectomy and subsequent external irradiation.

Salvage Perioperative Interstitial High-Dose-Rate Interventional Radiotherapy (Brachytherapy) for Local Recurrences of the Chest Wall Following Mastectomy and Previous External Irradiation.

(1) Background: To investigate the technical feasibility, safety, and efficacy of interstitial perioperative high-dose-rate interventional radiotherapy (HDR-IRT, brachytherapy) as a local salvage treatment combined with surgery for local chest wall recurrences following mastectomy and subsequent external beam radiation treatment (EBRT). (2) Methods: A retrospective analysis of 56 patients treated with interstitial HDR-IRT in combination with local surgery of a chest wall recurrence of breast cancer after previous treatment with mastectomy and EBRT from 2008 to 2020. (3) Results: Local recurrence following HDR-IRT was encountered in seven (12.5%) patients. The 1-year local recurrence-free survival (RFS), 3-year RFS, and 5-year RFS were 91%, 82%, and 82%, respectively. The 1-year overall survival (OS), 3-year OS, and 5-year OS was 85.5%, 58%, and 30%, respectively. Acute grade 1-2 radiation dermatitis was observed in 22 (39.3%) patients. Late ≥grade 3 toxicities were encountered in five (8.9%) patients. (4) Conclusions: Salvage perioperative interstitial high-dose-rate interventional radiotherapy (brachytherapy) combined with surgery seems to be an effective interdisciplinary management with acceptable treatment-related toxicity for local recurrences of the chest wall following mastectomy and previous external irradiation.

Multimodal locoregional procedures for cancer pain management: a literature review.

Pain is the most common and fearsome symptom in cancer patients, particularly in the advanced stage of disease. In cancer pain management, the first option is represented by analgesic drugs, whereas surgery is rarely used. Prior to considering surgical intervention, less invasive locoregional procedures are available from the wide pain management arsenal. In this review article, comprehensive information about the most commonly used locoregional options available for treating cancer pain focusing on interventional radiology (neurolysis, augmentation techniques, and embolization) and interventional radiotherapy were provided, also highlighting the potential ways to increase the effectiveness of treatments.

Liquid Biopsy-Guided Interventional Oncology: A Proof of Concept with a Special Focus on Radiotherapy and Radiology.

Although the role of liquid biopsy (LB) to measure minimal residual disease (MRD) in the treatment of epithelial cancer is well known, the biology of the change in the availability of circulating biomarkers arising throughout treatments such as radiotherapy and interventional radio-oncology is less explained. Deep knowledge of how therapeutic effects can influence the biology of the release mechanism at the base of the biomarkers available in the bloodstream is needed for selecting the appropriate treatment-induced tumor circulating biomarker. Combining existing progress in the LB and interventional oncology (IO) fields, a proof of concept is provided, discussing the advantages of the traditional risk assessment of relapsing lesions, limitations, and the timing of detection of the circulating biomarker. The current review aims to help both interventional radiologists and interventional radiation oncologists evaluate the possibility of drawing a tailor-made board of blood-based surveillance markers to reveal subclinical diseases and avoid overtreatment.

Why is a very easy, useful, old technique underused? An overview of esophageal brachytherapy - interventional radiotherapy.

Endoesophageal brachytherapy (EBT) or endoesofageal interventional radiotherapy (EIRT) is an effective technique that has been used with varying frequency for many years. It is a very good technique in T1-T2 inoperable esophageal cancer and in the palliation of dysphagia. However, only some centers have access to this technique, and consequently, it is underused. Here, we discussed the indications and several technical aspects as well as the literature available. Also, why this technique is underused and how this can be overcome. We consider that EBT is a very effective technique that should be used whenever indicated.

H&N and Skin (HNS) GEC-ESTRO Working Group critical review of recommendations regarding prescription depth, bolus thickness and maximum dose in skin superficial brachytherapy with flaps and customized moulds.

The aim of this publication is the assessment of the existing guidelines for non-melanoma skin cancer (NMSC) superficial brachytherapy (BT) and make a critical review based on the existing literature about the maximum dose prescription depth, bolus thickness and maximum skin surface dose (Dmax) of the published clinical practice. A systematic review of NMSC superficial BT published articles was carried out by the GEC-ESTRO Head & Neck and Skin (HNS) Working Group (WG). 10 members and 2 external reviewers compared the published clinical procedures with the recommendations in the current guidelines and examined the grade of evidence. Our review verified that there is a large variation among centres with regards to clinical practice in superficial BT and identified studies where published parameters such as maximum dose prescription depth, bolus thickness and Dmax exceed the constraints recommended in the guidelines, while showing excellent results in terms of local control, toxicity and cosmesis. This review confirmed that current recommendations on skin superficial BT do not include published experience on tumours treated with superficial BT that require dose prescription depth beyond the recommended 5 mm under the skin surface and that the existing literature does not provide sufficient evidence to relate dosimetry of superficial BT to patient reported outcome measures. The GEC-ESTRO HNS WG considers acceptable to prescribe superficial BT dose at a depth above 5 mm beyond the skin surface, and modify the bolus thickness to optimize the treatment plan and adjust the acceptable maximum dose on the skin surface, all pending clinical situation.

Immunosuppressive treatment and radiotherapy in kidney transplant patients: A systematic review.

BACKGROUND: Immunosuppression (IS) therapy may contribute to cancer development. Some authors have proposed to reduce immunosuppression drugs dose in case of viral infections, in immunosuppression-related diseases, and in patients undergoing radiotherapy. The present analysis reports the results of a systematic review on kidney transplant recipients undergoing immunosuppression and radiotherapy. AIM: To define if it is necessary reduce immunosuppression drugs during radiotherapy. METHODS: The literature search was based on three electronic databases (Pubmed, Scopus, and Web of Science) using selected keywords linked through the "AND" and "OR" Boolean operators to build specific strings for each electronic search engine. Two researchers independently screened the citations, and disagreement was resolved by discussion or through the intervention of a third author. The review was conducted and reported according to the PRISMA statement. Extracted data were narratively synthesized, and, where possible, frequencies, percentages, and ranges were calculated. RESULTS: The literature search resulted in 147 citations. After abstracts screening, 21 records were selected for full-text evaluation. Fifteen of these were excluded, leaving six papers considered suitable for analysis. There is still no clear evidence that withdrawing antimetabolites and/or calcineurin inhibitors and/or mammalian target of rapamycin-inhibitors, as opposed to continuing maintenance IS, improves patient survival in kidney transplant recipients with cancer undergoing radiotherapy. Only few retrospective studies on small cancer patient cohorts are available in this setting, but without comparison of different immunosuppression treatments. Even where immunosuppression therapy was described, patient survival seemed to be correlated only with cancer stage and type. CONCLUSION: The results of this systematic review do not support the reduction of immunosuppression dose in patients undergoing radiotherapy.

Long-Term Comparative Study on the Local Tumour Control of Different Ablation Technologies in Primary and Secondary Liver Malignancies.

Purpose: To evaluate local tumour control (LTC) by local ablation techniques (LAT) in liver malignancies. Materials and methods: In patients treated with LAT between January 2013 and October 2020 target lesions were characterised by histology, dimensions in three spatial axes, volume, vascularisation and challenging (CL) location. LAT used were: Radiofrequency Ablation (RFA), Microwave Ablation (MWA), Cryoablation (CRYO), Electrochemotherapy (ECT), and Interstitial Brachytherapy (IBT). Results: 211 LAT were performed in 155 patients. Mean follow-up including MRI for all patients was 11 months. Lesions treated with ECT and IBT were significantly larger and significantly more often located in CL in comparison to RFA, MWA and CRYO. Best LTC (all data for 12 months are given below) resulted after RFA (93%), followed by ECT (81%), CRYO (70%), IBT (68%) and MWA (61%), and further, entity-related for HCC (93%), followed by CRC (83%) and BrC (72%), without statistically significant differences. LTC in hypovascular lesions was worse (64%), followed by intermediate (82% p = 0.01) and hypervascular lesions (92% p = 0.07). Neither diameter (<3 cm: 81%/3−6 cm: 74%/>6 cm: 70%), nor volume (<10 cm3: 80%/10−20 cm3: 86%/>20 cm3: 67%), nor CL (75% in CL vs. 80% in non CL) had a significant impact on LTC. In CL, best LTC resulted after ECT (76%) and IBT (76%). Conclusion: With suitable LAT, similarly good local tumour control can be achieved regardless of lesion size and location of the target.

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.

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.

Biological Planning of Radiation Dose Based on In Vivo Dosimetry for Postoperative Vaginal-Cuff HDR Interventional Radiotherapy (Brachytherapy).

(1) Background: Postoperative vaginal-cuff HDR interventional radiotherapy (brachytherapy) is a standard treatment in early-stage endometrial cancer. This study reports the effect of in vivo dosimetry-based biological planning for two different fractionation schedules on the treatment-related toxicities. (2) Methods: 121 patients were treated. Group A (82) received 21 Gy in three fractions. Group B (39) received 20 Gy in four fractions. The dose was prescribed at a 5 mm depth or to the applicator surface according to the distance between the applicator and the rectum. In vivo dosimetry measured the dose of the rectum and/or urinary bladder. With a high measured dose, the dose prescription was changed from a 5 mm depth to the applicator surface. (3) Results: The median age was 66 years with 58.8 months mean follow-up. The dose prescription was changed in 20.7% of group A and in 41% of group B. Most toxicities were grade 1-2. Acute urinary toxicities were significantly higher in group A. The rates of acute and late urinary toxicities were significantly higher with a mean bladder dose/fraction of >2.5 Gy and a total bladder dose of >7.5 Gy. One patient had a vaginal recurrence. (4) Conclusions: Both schedules have excellent local control and acceptable rates of toxicities. Using in vivo dosimetry-based biological planning yielded an acceptable dose to the bladder and rectum.

Palliative treatment with high-dose-rate endobronchial interventional radiotherapy (Brachytherapy) for lung cancer patients.

PURPOSE: to report on the use of high-dose-rate (HDR) endobronchial interventional radiotherapy (brachytherapy, EBIRT) for palliation of symptoms in patients with lung cancer. PATIENTS AND METHODS: retrospective review of lung cancer patients treated with HDR-EBIRT at our institution (1995-2017). Treatment results and treatment related toxicity were recorded. Clinical response was subjectively evaluated within 3 months after treatment. Overall survival (OS) was analyzed. RESULTS: 347 patients were identified. The median age was 69 years and the median follow-up time was 13.4 months. Most patients received external beam radiation therapy during the primary treatment. Within 3 months, 87.7% of the patients had complete or major response of their presenting symptoms. OS was 55.2% at 1 year, 18.3% at 2 years. Patients who had complete or major response had a longer median survival than other patients (13 versus 7 months, p = 0.03). Chronic bronchitis was found in 26.8%, while 7.8% of the patients died due to uncontrollable hemoptysis. CONCLUSION: HDR-EBIRT is a safe and effective treatment option for the palliative treatment of lung cancer patients. HDR-EBIRT is most suitable as a re-irradiation technique. Further clinical studies are needed to validate its role.

Non-melanoma Skin Cancer Treated by Contact High-dose-rate Radiotherapy (Brachytherapy): A Mono-institutional Series and Literature Review.

BACKGROUND/AIM: Non-melanoma skin cancers (NMSC) are the most common neoplasms worldwide and their incidence has been proven to increase in recent years and their treatment should aim at cancer cure as well as cosmetic and functional results. The aim of the study was to report the results of our mono-institutional series of high-dose-rate radiotherapy (cHDR-RT) in NMSC, based on a homogenous technique and two different treatment schedules. PATIENTS AND METHODS: All patients affected by NMSC who were consecutively evaluated and treated at our Interventional Oncology Center from October 2018 to August 2020, were included. Patients underwent cHDR-RT using flap applicators and remotely afterloaded Ir-192 sources. RESULTS: Overall, 51 patients were treated for a total of 67 lesions. Local control (LC) and disease-specific survival (DSS) were 94.0% and 100%, respectively. Grade 1, grade 2, grade 3 and grade 4 acute toxicity rates were 24.6%, 3.5%, 3.5%, and 0.0%, respectively. The cosmetic results were graded as excellent/good, fair, and poor in 73.7%, 19.3%, and 7.0%. CONCLUSION: cHDR-RT of NMSC is an effective alternative to surgery due to excellent outcomes both in terms of local control and aesthetic results especially in the face.

Personalized Image-Guided Therapies for Local Malignencies: Interdisciplinary Options for Interventional Radiology and Interventional Radiotherapy.

Minimal-invasive interventions considerably extend the therapeutic spectrum in oncology and open new dimensions in terms of survival, tolerability and patient-friendliness. Through the influence of image-guided interventions, many interdisciplinary therapy concepts have significantly evolved, and this process is by far not yet over. The rapid progression of minimal-invasive technologies offers hope for new therapeutic concepts in the short, medium and long term. Image-guided hybrid-technologies complement and even replace in selected cases classic surgery. In this newly begun era of immune-oncology, interdisciplinary collaboration and the focus on individualized and patient-friendly therapies are crucial.

Quality Assurance in Modern Gynecological HDR-Brachytherapy (Interventional Radiotherapy): Clinical Considerations and Comments.

The use of brachytherapy (interventional radiotherapy) in the treatment of gynecological cancers is a crucial element in both definitive and adjuvant settings. The recent developments in high-dose rate remote afterloaders, modern applicators, treatment-planning software, image guidance, and dose monitoring systems have led to improvement in the local control rates and in some cases improved the survival rates. The development of these highly advanced and complicated treatment modalities has been accompanied by challenges, which have made the existence of quality assurance protocols a must to ensure the integrity of the treatment process. Quality assurance aims at standardizing the technical and clinical procedures involved in the treatment of patients, which could eventually decrease the source of uncertainties whether technical (source/equipment related) or clinical. This commentary review sheds light (from a clinical point of view) on some potential sources of uncertainties associated with the use of modern brachytherapy in the treatment of gynecological cancers.