Salvage re-irradiation in non-melanoma skin cancers: A multicenter analysis.

BACKGROUND AND PURPOSE: We conducted a multicentre real-world study to assess the outcomes of radical salvage re-irradiation for non-melanoma skin cancer (nMSC) recurrences following definitive or postoperative radiotherapy. MATERIALS AND METHODS: Data on patients treated between 2006 and 2022 with re-irradiation for nMSCs were retrospectively collected from five high-volume brachytherapy centers. The primary endpoint was local control (LC). Secondary endpoints included overall survival, progression-free survival, and adverse events (AEs). The Kaplan-Meier estimator and Cox Proportional-Hazards Model were utilised in the analysis. RESULTS: A total of 58 patients with a median age of 78.4 years with recurrences of previously irradiated nMSC in the head and neck region were included in the analysis. The majority had cutaneous basal cell carcinoma (BCC; 91.4%), and were irradiated with high-dose-rate brachytherapy (HDR-BT; 91.4%). The most common locations included the nasal region (36.2%) and external ear (18.9%). The 1-year LC was 73.1% and decreased to 41.7% at three years. The size of the re-irradiated lesion was the single independent prognostic factor in Cox analysis (per mm; HR 1.07; 95% CI 1.04-1.11; p < 0.001). Grade 3 or worse AEs were reported in 7 cases (12.1%). CONCLUSION: Re-irradiation for nMSCs, predominantly administered with brachytherapy for radiorecurrent BCC, is associated with high recurrence rates, and the risk of failure significantly increases with the size of the treated lesion. Re-irradiation could be an option for selected elderly patients with small, localised, inoperable recurrences after RT to achieve local control or defer systemic treatment; however, prospective trials are necessary to confirm its safety and efficacy.

Stages I-III Inoperable Endometrial Carcinoma: A Retrospective Analysis by the Gynaecological Cancer GEC-ESTRO Working Group of Patients Treated with External Beam Irradiation and 3D-Image Guided Brachytherapy.

BACKGROUND/PURPOSE: Analyse the outcomes of stages I-III inoperable endometrial cancer (IEC) patients treated with external-beam-irradiation (EBRT) and 3D-image-guided-brachytherapy (IGBT). MATERIAL AND METHODS: Medical records of IEC patients receiving EBRT + IGBT in eight European and one Canadian centres (2004-2019) were examined, including: pelvic ± para-aortic EBRT and lymph node boost; anaesthetic procedure, applicators, BT-planning imaging, clinical target volume (CTV), brachytherapy schedule, and EQD2 to the CTV(α/ß=4.5Gy) and D2 cm3(α/ß=3Gy) for organs at risk. Complications are evaluated using CTCAEv4 scores. The 2- and 5-year survival probability according to stages was estimated (cancer-specific survival (CSS), disease-free survival (DFS), local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS)). STATISTICS: descriptive analysis and the Kaplan-Meier method. RESULTS: 103 patients (stages: I-44, II-14, III-44) were included. Median follow-up: 28 months (7-170). All patients received pelvic ± para-aortic EBRT. Median D90-EQD2(α/ß=4.5) to the CTV:73.3 Gy (44.6-132.7), 69.9 Gy (44.7-87.9 and 75.2 Gy (55.1-97) in stages I, II, and III, respectively. Thirty patients presented relapse (stages: 10-I, 3-II, 17-III): 24 uterine (stages: 7-I, 3-II, 14-III), 15 nodal (stages: 4-I, 1-II, 10-III), and 23 distant (stages: 6-I, 2-II, 15-III). Five year CSS was 71.2% (stages: 82%-I-II and 56%-III) and DFS, LRFS, LRRFS, and DMFS were 55.5%, 59%, 72%, and 67.2%, respectively. Late G3-G4 complications (crude): 1.3% small bowel, 2.5% rectum, and 5% bladder. CONCLUSION: In stages I-III of the IEC, EBRT + IGBT offer good 2- and 5-year CSS of 88.7% and 71.2%, respectively, with the best outcomes in stages I-II. Prospective studies are needed to determine how better outcomes can be achieved.

Basal Cell Carcinoma After High Dose Rate Brachytherapy: Medium-term Dermoscopic Evaluation of Cancer's Response.

INTRODUCTION: Basal cell carcinoma of the facial region remains a challenge for contemporary oncology due to the presence of aesthetic regions and critical organs. Surgery is not always the optimal solution, and high dose rate (HDR) brachytherapy has emerged as an organ-sparing treatment method whose effectiveness has been proven by a growing number of publications. Dermoscopy is a diagnostic tool that bridges clinical and pathological examination of skin lesions. It is routinely used for diagnosis, monitoring of treatment, and post-treatment evaluation; however, the literature lacks data concerning changes in dermoscopic patterns of skin cancers during and after irradiation. METHODS: Our team conducted a prospective non-randomized trial of 39 patients with high-risk basal cell carcinomas (BCCs), mostly localized within the high-risk zone (H-zone) of the facial region, and who qualified for HDR brachytherapy. HDR contact brachytherapy with custom-made surface molds was introduced, delivering a dose of 45 Gy in 9 fractions prescribed to the tumor. Every patient was observed clinically and dermoscopically at three observational points: before treatment, at the end of treatment (3rd week), and 24 weeks after the end of therapy. The evolution of clinical and dermoscopic patterns was observed by two independent dermoscopists using current diagnostic criteria. A database of 12,088 photographic observations was evaluated. RESULTS: Univariate logistic regression proved that brachytherapy decreases the number of clinical and dermoscopic patterns typical for basal cell carcinoma, as well as dermoscopic features not related to BCC, presumably due to the formation of scar tissue. In addition, univariate logistic regression with random effects proved a positive correlation between tumor size and presence of various dermoscopic patterns typical for BCC. CONCLUSION: Dermoscopy is proven to be easy to perform and an adequate monitoring tool for patients with BCCs undergoing HDR brachytherapy.

Salvage prostate brachytherapy in radiorecurrent prostate cancer: An international Delphi consensus study.

BACKGROUND AND PURPOSE: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. MATERIALS AND METHODS: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. RESULTS: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2-3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. CONCLUSION: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study.

Brachytherapy boost improves survival and decreases risk of developing distant metastases compared to external beam radiotherapy alone in intermediate and high risk group prostate cancer patients.

BACKGROUND AND PURPOSE: Despite several prospective trials showing a clinical benefit of combining external beam radiotherapy (EBRT) with brachytherapy boost (BTB) for the treatment of intermediate- and high-risk prostate cancer (PCa) patients, none of these trials was designed to test for a survival difference. In this study, we aimed to collect a large multi-institutional database to determine whether BT boost was associated with a statistically significant improvement in survival and a reduction of distant metastases based on real-world data. MATERIAL AND METHODS: We collected the data of patients treated for intermediate- or high-risk PCa with definitive EBRT or BTB, with or without androgen deprivation therapy (ADT), between January 2003 and December 2014 at two tertiary institutions. The statistical endpoints included overall survival (OS), freedom from distant metastases (FFDM), and metastases-free survival (MFS). The impact of treatment modality was assessed using Cox regression models and log-rank testing after one-to-one propensity score matching. RESULTS: A total of 1641 patients treated with EBRT (n = 1148) or high-dose-rate BTB (n = 493) were analyzed. The median survival and clinical follow-up were 117.8 (IQR 78-143.3) and 60.7 months, respectively. The radiotherapy modality (BTB) remained an independent prognostic factor for OS (HR 0.75; 95% CI 0.63-0.88; p < 0.001), FFDM (HR 0.54; 95% CI 0.4-0.73; p < 0.001), and MFS (HR 0.72; 95% CI 0.61-0.85; p < 0.001). After propensity score matching, the remaining 986 patients were well-balanced in terms of age, maximum PSA, ISUP grade group, and TNM T stage. OS (p < 0.001), FFDM (p = 0.001) and MFS (p < 0.001) were significantly higher in the BTB group. CONCLUSIONS: There is a strong positive association between BTB and OS, FFDM, and MFS in PCa patients treated with definitive RT for intermediate- or high-risk PCa.

Long-Term Outcomes of Stereotactic Body Radiotherapy (SBRT) for Intraprostatic Relapse after Definitive Radiotherapy for Prostate Cancer: Patterns of Failure and Association between Volume of Irradiation and Late Toxicity.

The aim of this retrospective study was to assess the adverse effects and outcomes of salvage re-irradiation with stereotactic body radiotherapy (sSBRT) for local recurrence of prostate cancer (PCa) after definitive radiotherapy (RT). The study was focused on the adverse effects and prognostic factors for treatment toxicity, followed by an analysis of patterns of failure and survival. Patients treated with sSBRT between 2012 and 2020 at a tertiary institution were included. The exclusion criteria were a primary or salvage radical prostatectomy or a palliative sSBRT dose. Patients with oligorecurrence were eligible if all metastatic lesions were treated locally with curative intent. The Kaplan-Meier method was used to estimate time to grade ≥ 3 toxicity, local control (LC), freedom from distant metastases (FFDM), progression-free survival (PFS), biochemical control (BC) and overall survival (OS). The differences between groups (focal vs. whole-gland sSBRT) were compared using the log-rank test. The Cox proportional hazards model was used to assess prognostic factors for the listed endpoints. A total of 56 patients with a median age of 70.9 years and a median follow-up of 38.6 months were included in the analysis. The majority of them received local sSBRT only (45; 80.4%), while the rest were simultaneously treated for oligometastases (11; 19.6%). Overall, 18 (32.1%) patients experienced any grade ≥ 3 toxicity, including 1 (6.7%) patient who received focal sSBRT, and 17 (41.5%) patients treated with whole-gland sSBRT. The Planning Target Volume (per cc; HR 1.01; 95% CI 1-1.02; p = 0.025) and use of ADT (yes vs. no; HR 0.35; 95%CI 0.13-0.93; p = 0.035) were independent prognostic factors for the risk of grade ≥ 3 toxicity. The estimated rate of grade ≥ 3 adverse events was significantly higher (43.8% vs. 7.1% at 2 years; p = 0.006), and there was no improvement in the LC (92.9% vs. 85.3% at 2 years; p = 0.759) in patients treated with whole-gland sSBRT compared to focal sSBRT. The 2- and 5-year LC were 87.6% and 47.9%, respectively; the 2- and 5-year FFDM were 72.7% and 42.8%, respectively; and the 2- and 5-year PFS were 67.9% and 28.7%, respectively. The primary pattern of failure was distant metastasis. The sSBRT for local recurrence of PCa after definitive RT was associated with a high risk of severe grade ≥ 3 toxicity, which significantly increased with the volume and extent of re-irradiation.

Pre-Treatment Hemoglobin Concentration and Absolute Monocyte Count as Independent Prognostic Factors for Survival in Localized or Locally Advanced Prostate Cancer Patients Undergoing Radiotherapy.

The prognostic value of inflammatory indices, such as the absolute monocyte count (AMC), has been a subject of interest in recent prostate cancer (PCa) studies, while hemoglobin concentration (HGB) has been recognized as a survival factor in castration-resistant metastatic prostate cancer, but its value remains unclear in localized diseases. The aim of this study was to test the prognostic value of these two simple and inexpensive biomarkers for survival and was based on a cohort of 1016 patients treated with primary radiotherapy and androgen deprivation therapy for localized or locally advanced intermediate- or high-risk PCa. Complete survival data were available for all cases and were based on the National Cancer Registry, with a median observation time of 120 months (Interquartile Range (IQR) 80.9-144.7). Missing blood test data were supplemented using the Nearest Neighbor Imputation, and the Cox Proportional Hazards Regression model was used for analysis. The median age was 68.8 years (IQR 63.3-73.5). The five-year overall survival was 82.8%, and 508 patients were alive at the time of analysis. The median time between blood tests and the first day of radiotherapy was 6 days (IQR 0-19). HGB (p = 0.009) and AMC (p = 0.003) were independent prognostic factors for survival, along with age, Gleason Grade Group, clinical T stage and maximum prostate-specific antigen concentration. This study demonstrates that HGB and AMC can be useful biomarkers for overall survival in patients treated with radiotherapy for localized intermediate- or high-risk PCa.

Magnetic resonance imaging in cervical cancer interventional radiotherapy (brachytherapy): a pictorial essay focused on radiologist management.

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

In-bore MR prostate biopsy - initial experience.

INTRODUCTION: The introduction of multiparametric MRI (mpMRI) has been a breakthrough in the diagnosis of noninvasive clinically significant prostate cancer. Currently, MR-guided prostate biopsy (in-bore biopsy) is the only biopsy method that uses real-time MRI in patients with suspected prostate cancer. The aim of the study was a retrospective analysis of the correlation between MRI results and histological findings of prostate samples suspected of malignancy, which were taken during MRI-guided biopsy. MATERIAL AND METHODS: Thirty-nine patients with 57 lesion biopsies were enrolled in the study. Patients were aged 48-84 years (mean age 67.2 ± 9.4 years). RESULTS: Cancer was histologically confirmed in 24 lesions, including primary cancer in 14 lesions and local recurrence in 10 lesions. Cancer was not detected in the remaining lesions (n = 33). Malignancy was confirmed in 90% of lesions previously reported as PI-RADS 5. Only one Prostate Imaging and Reporting and Data System (PI-RADS 5) lesion was histologically negative (prostatitis). Cancer was detected in 50% of lesions defined as PI-RADS 4. Cancer cells were not found in any of 23 lesions defined as PI-RADS 3 (53.5%). Most of the lesions assessed as PI-RADS 3 were located in the transitional zone (n = 19). Only four PI-RADS 3 lesions were found in the peripheral zone. Large lesions or lesions feasible for cognitive TRUS biopsy were not referred for MRI biopsy, which resulted in a higher proportion of lesions assessed as PI-RADS 3. Fourteen lesions suspected of local recurrence were assessed in our study. Cancer was found in approximately 72% of the lesions. CONCLUSIONS: Performing prostate biopsy under the guidance of real-time MRI allows precise collection of material for histological examination (even from a very small lesion). As a result, both primary cancer and local recurrence after previous radiotherapy of prostate cancer can be confirmed.

High dose rate brachytherapy in nonmelanoma skin cancer-Systematic review.

Nonmelanoma skin cancers (NMSCs) are the most common malignancies worldwide. Millions of new cases every year present challenge to healthcare systems. Recent years brought numerous new data concerning high dose rate (HDR) brachytherapy (BT) as treatment option for NMSCs. International guidelines do not recognize BT as a method of choice given lack of randomized trials, however many prospective and retrospective studies show promising results. Aim of the study was to present the efficacy of HDR BT, with analysis of its safety and adverse effects based on review of the English published medical full-text papers. Literature review of 13 articles published between 1999 and 2021 was performed. Pubmed and Google Scholar databases were searched on October 2021 using keywords: ([Basal cell carcinoma] OR [squamous cell carcinoma] OR [non-melanoma skin cancer]) AND (HDR brachytherapy). Fourteen full-text English articles with follow up over 1 year and study group over 50 patients were included into analysis. In analyzed material, 2403 patients received HDR BT. Local control varied between 71% and 99%.Dominant reported cosmetic effect was good or very good. Results were cross-referenced with recent meta-analyses comparing BT to surgical excision, Mohs microsurgery and external beam radiotherapy. Radiodermitis is the main adverse effect of radiation treatment during and after radiotherapy. HDR BT emerges as potentially noninferior treatment method providing very good reported cosmetic outcomes.

Prostate-specific antigen kinetics and metastasis-free survival in patients treated with external beam radiotherapy combined with high-dose-rate brachytherapy boost and androgen deprivation therapy for localized prostate cancer.

PURPOSE: Serum prostate-specific antigen (PSA) kinetics has been linked to prognosis in prostate cancer (PCa) patients. Our goal was to analyze the association between PSA kinetics and metastasis-free survival (MFS) in patients with localized PCa treated with high-dose-rate (HDR) brachytherapy (BT) boost combined with external beam radiotherapy (EBRT). MATERIAL AND METHODS: We retrospectively analyzed multiple PSA kinetics related to PSA nadir (nPSA), PSA bouncing, and biochemical recurrence (BCR) in 186 PCa patients treated with neoadjuvant androgen deprivation therapy (ADT), followed by EBRT combined with HDR-BT boost. Uni- and multivariate Cox regression models were calculated to assess the value of PSA-related parameters for the prediction of MFS. RESULTS: 5- and 10-year MFS were 95% and 84%, respectively. Median nPSA was 0.011 (IQR, 0.007-0.057) ng/ml and predicted MFS in multivariable analysis. Implementation of nPSA improved c-index of baseline model from 0.8 to 0.68. nPSA of 0.2 ng/ml offered the most optimal discriminatory ability for identifying patients with better prognoses. Time to nPSA (median, 11 months; IQR, 8-18 months) and PSA bounce, which occurred in 12.4% of patients, were not significantly associated with MFS. CONCLUSIONS: Lower values of nPSA are significantly associated with decreased risk of developing metastases in patients treated with EBRT combined with HDR-BT boost and ADT, and improve the accuracy of a clinical model for MFS.

Pre-operative high-dose-rate brachytherapy in early-stage cervical cancer: long-term single-center results.

PURPOSE: The aim of the study was to report the outcomes of pre-operative high-dose-rate brachytherapy (pHDR-BT), followed by hysterectomy in patients with early cervical cancer. MATERIAL AND METHODS: From January, 1998 to December, 2003, 113 women with IB1, IB2, and IIA1 cervical cancer (according to International Federation of Gynecology and Obstetrics [FIGO] 2018) were treated with pHDR-BT, and 6 to 8 weeks later followed by radical hysterectomy. Patients found to have positive lymph nodes, residual cervical cancer, involved parametria, or lymphovascular space invasion (LVSI) received post-operative adjuvant therapy. RESULTS: Post-operatively, 81.4% of patients had a complete response to pHDR-BT in the cervix, and 18.6% had residual cervical cancer. Failures occurred in 11/113 (9.7%) patients (all were stage IIA1), with pelvic recurrences in 5/113 (4.4%) and distant metastasis (DM) in 6/113 (5.3%). The 5- and 10-year disease-free survival (DFS) rates were 100% for IB1 and IB2, and 86.4% and 81.3% for IIA1, respectively. Lymph node involvement and/or residual cervical cancer correlated with worse DFS. Two vesicovaginal fistulas were observed (one in a patient treated only with pHDR-BT and one in a woman, who underwent adjuvant external-beam radiotherapy [EBRT]). Two rectovaginal fistulas and one case of proctitis were observed in patients treated with adjuvant EBRT. CONCLUSIONS: pHDR-BT in early cervical cancer is well-tolerated and effective in sterilizing tumor cells in the cervix. The growing number of publications in this area may help define an optimal therapeutic scheme, but randomized trials are required to determine the best candidates for this treatment modality.In our opinion, cervical cancer patients with FIGO stage IIA1 are not good candidates for pHDR-BT, and could be given this treatment only after rigorous selection, including assessment with state-of-the-art imaging, due to higher probability of treatment failure.

Exclusive 3D-brachytherapy as a good option for stage-I inoperable endometrial cancer: a retrospective analysis in the gynaecological cancer GEC-ESTRO Working Group

PurposeAnalyse outcomes of stage-I inoperable endometrial cancer (EC) patients from seven European centres treated with 3D-image-guided brachytherapy (IGBT) alone.Materials and methodsFrom 2004 to 2018, 62 patients (41 stage-IA and 21 IB) were retrospectively studied, analysing anaesthetic procedure, applicator type, BT-planning imaging, clinical target volume (CTV), BT schedule, overall daily-dose equivalent to 2 Gy (EQD2(α/β=4.5 or 3)) to the CTV(α/β=4.5) and D2 cm3(α/β=3) for organs at risk. Complications were evaluated using CTCAEv4 scores. The 2 and 5 year survival was calculated [cancer-specific survival (CSS), disease-free survival (DFS), local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS)]. Descriptive analysis and the Kaplan–Meier method were used for survival analysis.ResultsMean follow-up: 32.8 months (SD 33.7). Spinal anaesthesia (38/62) followed by none (16/62) were the most common. Y-shaped Rotte applicators were used in 74% of patients. High-dose rate brachytherapy was administered in 89%. Median D90 to the CTV was 58.9 Gy (8.66–144 Gy). Eight patients presented relapse: four uterine, four nodal and four distant. The 2 and 5 year CSS was 93.3 and 80.5%, DFS 84.8 and 80.5%, LRFS was 93.1 and 88.7%, LRRFS was 91 and 91% and DMFS was 90.2 and 90.2%, respectively, CSS was better in stage-IA vs. IB (p = 0.043). Late vaginal and bladder G3-complication rates were 2.1%, respectively.ConclusionInoperable EC patients can be safely treated by BT with 2 and 5 year CSS of 93 and 80.5%, respectively, with even better results for IA cases. Prospective studies on 3D-IGBT are necessary to better analyse EC patient outcomes based on dose and treated volumes.

Physical parameters in thermal imaging of basal cell cancer patients treated with high-dose-rate brachytherapy - first study.

Background: The basal cell carcinoma (BCC) is often treated by surgery or radiotherapy using ionizing radiation. While there is an established diagnostic path before treatment and also for the follow-up there are no good noninvasive methods objectifying irradiated area evolution during treatment. The main goal of preliminary studies was to try to answer if there are any useful information that can be derived from temperature effects of high-dose-rate (HDR) brachytherapy in treatment of BCC. Moreover, the temperature gradient was introduced as a physical parameter characterizing the thermal map of the lesion, its surroundings and reference area, which provided information about cancer tissue thermal reaction to brachytherapy. Materials and methods: Thirty-three patients suffering from BCC were monitored with thermovision during the brachytherapy treatment. All lesions were diagnosed as superficial and were confirmed with histopathology examination. Results: Results of the study showed two groups of patients characterized with two thermal maps and temperature gradient describing the lesion and surrounding area of BCC. The first group was characterized by higher temperature of the lesion than the surrounding tissue temperature (mean dT = 0,41°) whereas the other one, with lower lesion temperature (mean dT = -0.42°). It seems that the temperature changes observed in designated areas before and after therapy may provide physicians with additional information which could be useful in planning the treatment process, especially when considering temperature gradient changes during therapy. Conclusions: Although the data obtained indicate the possibilities of temperature distribution in pre-irradiation cases, further research is required for estimation of clinical effects of treatment.

Exclusive 3D-brachytherapy as a good option for stage-I inoperable endometrial cancer: a retrospective analysis in the gynaecological cancer GEC-ESTRO Working Group.

PURPOSE: Analyse outcomes of stage-I inoperable endometrial cancer (EC) patients from seven European centres treated with 3D-image-guided brachytherapy (IGBT) alone. MATERIALS AND METHODS: From 2004 to 2018, 62 patients (41 stage-IA and 21 IB) were retrospectively studied, analysing anaesthetic procedure, applicator type, BT-planning imaging, clinical target volume (CTV), BT schedule, overall daily-dose equivalent to 2 Gy (EQD2(α/ß=4.5 or 3)) to the CTV(α/ß=4.5) and D2 cm3(α/ß=3) for organs at risk. Complications were evaluated using CTCAEv4 scores. The 2 and 5 year survival was calculated [cancer-specific survival (CSS), disease-free survival (DFS), local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS)]. Descriptive analysis and the Kaplan-Meier method were used for survival analysis. RESULTS: Mean follow-up: 32.8 months (SD 33.7). Spinal anaesthesia (38/62) followed by none (16/62) were the most common. Y-shaped Rotte applicators were used in 74% of patients. High-dose rate brachytherapy was administered in 89%. Median D90 to the CTV was 58.9 Gy (8.66-144 Gy). Eight patients presented relapse: four uterine, four nodal and four distant. The 2 and 5 year CSS was 93.3 and 80.5%, DFS 84.8 and 80.5%, LRFS was 93.1 and 88.7%, LRRFS was 91 and 91% and DMFS was 90.2 and 90.2%, respectively, CSS was better in stage-IA vs. IB (p = 0.043). Late vaginal and bladder G3-complication rates were 2.1%, respectively. CONCLUSION: Inoperable EC patients can be safely treated by BT with 2 and 5 year CSS of 93 and 80.5%, respectively, with even better results for IA cases. Prospective studies on 3D-IGBT are necessary to better analyse EC patient outcomes based on dose and treated volumes.

Basal Cell Carcinoma Treated with High Dose Rate (HDR) Brachytherapy-Early Evaluation of Clinical and Dermoscopic Patterns during Irradiation.

Basal cell carcinoma (BCC) is the most frequent malignancy of the Caucasian population. Dermoscopy is an established diagnostic method providing the bridge between clinical and pathological examination. Surface skin high dose rate (HDR) brachytherapy is an organ sparing treatment method used for non-surgical candidates. This prospective study aimed to observe clinical and dermoscopic features and their evolution in 23 patients with pathologically confirmed BCC that have been treated with HDR brachytherapy. In all cases, custom-made surface moulds were used. HDR brachytherapy was performed with 192Ir, dose 45Gy was delivered to the tumour in nine fractions of 5Gy, three times a week. The evolution of clinical and dermoscopic features was followed up at the beginning of treatment, and on the day of every fraction (t1-t9). Dermoscopic evaluation of neoplastic and non-neoplastic structures was based on current diagnostic criteria according to current literature. Univariate logistic regression showed a decreasing number of clinical and pathological features of basal cell carcinoma with every treatment fraction. The effect was more strongly pronounced for cancer-related dermoscopic structures compared with non-neoplastic features. We used multivariate ordinal logistic regression with random effects to prove that the patients' age corresponds with the tumour's response to radiation-which may implicate a better response to treatment among older patients. High dose rate brachytherapy decreases the number of clinical and dermoscopic features typical for basal cell carcinoma. The effect is more pronounced among older patients.

Advanced dose calculation algorithm in superficial brachytherapy - the impact of tissue inhomogeneity on treatment plan dosimetry.

PURPOSE: Given tissue inhomogeneity and lack of backscatter media, superficial brachytherapy necessitates more accurate dosimetry than TG-43 formalism. However, the introduction of modern model-based dose calculation algorithms into clinical practice should be carefully evaluated. The aim of this work was to compare dose distributions calculated with TG-43 and advanced collapsed cone engine (ACE) algorithms for individual multi-catheter moulds, and investigate the impact of target size and the lack of bolus to differences between plans. MATERIAL AND METHODS: Eleven treatment plans for individual mould multi-catheter high-dose-rate brachytherapy (IMM HDR) were selected for retrospective analysis. All treatment plans were initially calculated with TG-43 formula and re-calculated using ACE algorithm. Plan re-calculation with ACE was repeated for each plan in order to assess the impact of bolus. To evaluate differences between TG-43 and ACE dose distributions, dose-volume histogram (DVH) parameters for each ROI were compared. Dmax (maximal point dose), D0.1cc, and D2cc were calculated for each risk's organ (OARs) and for external contour. For clinical target volume (CTV), D98, D90, D50, CTV coverage (CTV-V100), and dose delivered to reference point were compared between the plans. RESULTS: A significantly lower values (p < 0.05) of CTV parameters were observed for treatment plans calculated with ACE algorithm comparing to TG-43. Further analysis showed that differences between CTV-V100 for ACE and TG-43 plans depended on CTV volume. Dosimetric parameters for OARs were significantly lower in ACE plans than those of TG-43. Only D2cc for external and D0.1cc for both eye lenses in ACE plans were insignificantly different comparing to TG-43 plans. CONCLUSIONS: Results show that differences between dosimetric parameters are statistically significant. However, their clinical relevance is still undetermined. Careful re-evaluation of the clinical results based on long-term research on TG-43 is necessary to safely introduce modern algorithms to clinical practice.

The Proper Administration Sequence of Radiotherapy and Anti-Vascular Agent-DMXAA Is Essential to Inhibit the Growth of Melanoma Tumors.

Vascular disrupting agents (VDAs), such as DMXAA, effectively destroy tumor blood vessels and cause the formation of large areas of necrosis in the central parts of the tumors. However, the use of VDAs is associated with hypoxia activation and residues of rim cells on the edge of the tumor that are responsible for tumor regrowth. The aim of the study was to combine DMXAA with radiotherapy (brachytherapy) and find the appropriate administration sequence to obtain the maximum synergistic therapeutic effect. We show that the combination in which tumors were irradiated prior to VDAs administration is more effective in murine melanoma growth inhibition than in either of the agents individually or in reverse combination. For the first time, the significance of immune cells' activation in such a combination is demonstrated. The inhibition of tumor growth is linked to the reduction of tumor blood vessels, the increased infiltration of CD8+ cytotoxic T lymphocytes and NK cells and the polarization of macrophages to the cytotoxic M1 phenotype. The reverse combination of therapeutic agents showed no therapeutic effect and even abolished the effect of DMXAA. The combination of brachytherapy and vascular disrupting agent effectively inhibits the growth of melanoma tumors but requires careful planning of the sequence of administration of the agents.

Brachytherapy in a Single Dose of 10Gy as an "in situ" Vaccination.

Radiotherapy (RT) is one of the major methods of cancer treatment. RT destroys cancer cells, but also affects the tumor microenvironment (TME). The delicate balance between immunomodulation processes in TME is dependent, among other things, on a specific radiation dose. Despite many studies, the optimal dose has not been clearly determined. Here, we demonstrate that brachytherapy (contact radiotherapy) inhibits melanoma tumor growth in a dose-dependent manner. Doses of 10Gy and 15Gy cause the most effective tumor growth inhibition compared to the control group. Brachytherapy, at a single dose of ≥ 5Gy, resulted in reduced tumor blood vessel density. Only a dose of 10Gy had the greatest impact on changes in the levels of tumor-infiltrating immune cells. It most effectively reduced the accumulation of protumorogenic M2 tumor-associated macrophages and increased the infiltration of cytotoxic CD8+ T lymphocytes. To summarize, more knowledge about the effects of irradiation doses in anticancer therapy is needed. It may help in the optimization of RT treatment. Our results indicate that a single dose of 10Gy leads to the development of a robust immune response. It seems that it is able to convert a tumor microenvironment into an "in situ" vaccine and lead to a significant inhibition of tumor growth.