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.

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.

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.

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.

Grade migration and important prognostic factors in a pathology specimen for radical radiotherapy in prostate cancer patients.

The study aimed to evaluate grade migration and prognosis depending on pathologic features in patients with prostate cancer treated with radical external beam radiotherapy. The study included 139 patients with an initial Gleason score of 7 (3+4 or 4+3) i.e., Grade Group 2-3 (GG2-GG3) treated between 2008 and 2013. The clinical outcome was assessed with respect to biochemical control (BC) and biochemical disease-free survival (bDFS). After re-evaluation, the majority of patients (96 patients - 69%) were up-graded from GG2-3. Finally, there were 4 patients (3%) with grade GG1, 12 patients (9%) - GG2, 27 patients (19%) - GG3, 51 patients (37%) - GG4 and 45 patients (32%) - GG5. In 42 patients (30%) a cribriform pattern was observed. Among the analyzed factors only the GGs were important for BC (p = 0.011) and the cribriform pattern was of borderline significance (p = 0.06). The 5-year biochemical control was 100% in GG1-3 and 84% in GG4-5. The 5-year biochemical control was 81% and 93%, if cribriform or no cribriform pattern was detected, respectively. In conclusion, re-evaluation and verification of pathology specimens in accordance with contemporary rules upgraded the Gleason score in the majority of patients. The aggressive behavior of prostate cancer starts to occur from GG 4. Cribriform pattern almost tripled the biochemical failure rate.

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.

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.

Individual multi-catheter mould technique in high-dose-rate brachytherapy - personalized approach in treating multifocal angiosarcoma of the face.

PURPOSE: The aim of this study was to report individual surface mould multi-catheter high-dose-rate (IMM HDR) application as a salvage treatment for a head and neck angiosarcoma patient, previously treated with surgery followed by external beam radiotherapy. MATERIAL AND METHODS: A 74-year-old male reported to our center with an uncommon malignant neoplasm of blood vessels. The patient was qualified for a wide local excision (WLE) of tumor with simultaneous reconstruction using a free-flap collected from the patient's thigh. After surgery, the patient was qualified for adjuvant external-beam radiotherapy (EBRT). Volumetric arc therapy (VMAT; RapidArc®, Varian Medical Systems) was used to deliver 52.8 Gy/1.6 Gy in 33 fractions. Overall treatment time was 51 days. Six months after radiotherapy, an incisional biopsy of non-healing ulcer of the nasal bridge revealed angiosarcoma. Wide local excision with skin graft reconstruction was planned. Due to multifocal disease and lack of possibility for further margin, the resection surgery was completed after skin graft reconstruction from the right thigh. Surface IMM HDR was considered as an alternative option for further treatment. Total dose of 48 Gy (12 fractions) was planned. RESULTS: One month after surface IMM HDR, healing process of the skin was observed in the treated regions and six months later, the irradiated areas recovered. General condition of the patient deteriorated two years after diagnosis and one year after HDR. He was hospitalized to receive palliative care. CONCLUSIONS: HDR brachytherapy may be a valuable option for angiosarcoma treatment. Difficult lesion location may yield non-radical surgery. Surface IMM HDR provides highly conformal plan and allow adjusting the dose to individual clinical situation.

Nineteen-year single-center experience in 76 patients with penile cancer treated with high-dose-rate brachytherapy.

PURPOSE: To report the outcomes for 76 patients with penile cancer treated with high-dose-rate brachytherapy (HDR-BT) at a single institution. METHODS: Seventy-six patients with penile cancer treated with HDR-BT in our department between October 1998 and September 2018 were analyzed. Seventy underwent interstitial HDR-BT (fractionation dose range of 3-3.5 Gy given twice a day with an interval of at least six hours between the fractions), and six underwent superficial treatment with mold applicators (fractionation dose range of 4-7 Gy given once or twice a week). RESULTS: Median follow-up was 76 months (7-204 months). In the whole group, 22/76 local failures (28.9%) were observed: 14/76 (18.4%) local recurrences and 8/76 (10.5%) cases of persistent disease. Median time to recurrence was 24 months (9-54 months). Inguinal lymph node metastases were observed in 18/76 cases (23.7%). Distant metastases occurred in 12/76 (15.8%) cases. Patients with local recurrence and persistent disease underwent salvage penectomies, except four who refused surgery and underwent a second course of interstitial HDR-BT. Five- and 10-year cause-specific survival were 85.0% and 77.8%, respectively. Local control at 5 and 10 years was 65.6%. Five- and 10-year penile preservation were 69.5% and 66.9%, respectively. There was no G3 or G4 acute toxicity. One urethral stenosis (1.3%) occurred in a patient with a T3 tumor and was treated successfully with dilatation. CONCLUSIONS: HDR-BT provides good local control of penile cancer and is a good option for penis preservation therapy and in our experience achieves a penile preservation rate at 10 years of 66.9%.