Advanced non-melanoma skin cancer in elderly patients: When surgery says NO, interventional radiotherapy (brachytherapy) says YES.

Purpose: The prevalence of non-melanoma skin cancer (NMSC) increases, especially in older adults with comorbidities, narrowing radical treatment options. About 5% of skin cancer patients are diagnosed with an advanced stage, which impairs daily functioning. The study was to present a retrospective summary of elderly patients unfit for surgery and treated with various brachytherapy (BT) techniques tailored individually for locally advanced NMSCs in a reference BT department. Clinical case presentations supported the findings. Material and methods: Inoperable patients older than 75 years presenting with advanced pathologically confirmed NMSCs were retrospectively identified. All cases were individually assessed, and the best suiting radical treatment option was chosen, including contact, interstitial, or hybrid high-dose-rate (HDR) or pulsed-dose-rate (PDR) BT. Doses ranging from 45 to 60 Gy were administered to clinical target volume (CTV) in different time schedules. All patients were closely followed-up until complete remission. Results: Ten elderly patients (mean age, 84 years) with differently located locally advanced NMSCs (all staged T3) were treated between 2007 and 2022. Six basal and four squamous cell carcinoma cases showed most painful symptoms as well as bleeding and exudation. Six patients underwent HDR-BT and four PDR-BT. Six patients had superficial, and four interstitial or hybrid applications. All patients completed the intended protocols. Median follow-up was 8.5 months (range, 3-35 months). Six out of ten patients died from other reasons before analysis. All case data were presented in the text and respective figures. Conclusions: Advanced NMSCs in elderly patients are challenging in terms of cure. Inoperable cases may be referred for feasible and locally effective interventional radiotherapy (BT). Individually tailored BT leads to an excellent disease control, function sparing, symptoms release, and quality of life improvement. Large treated volumes are related to prolonged healing. BT should be discussed in a multidisciplinary tumor board regarding older patients with symptomatic functions affecting advanced NMSCs.

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.

Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients.

BACKGROUND: Primary glioblastoma is characterized by an extremely poor prognosis. The promoter methylation of GATA4 leads to the loss of its expression in many cancer types. The formation of high-grade astrocytomas can be promoted by the concurrent loss of TP53 and GATA4 in normal human astrocytes. Nevertheless, the impact of GATA4 alterations with linkage to TP53 changes in gliomagenesis is poorly understood. This study aimed to evaluate GATA4 protein expression, GATA4 promoter methylation, p53 expression, TP53 promoter methylation, and mutation status in patients with primary glioblastoma and to assess the possible prognostic impact of these alterations on overall survival. MATERIALS AND METHODS: Thirty-one patients with primary glioblastoma were included. GATA4 and p53 expressions were determined immunohistochemically, and GATA4 and TP53 promoter methylations were analyzed via methylation-specific PCR. TP53 mutations were investigated via Sanger sequencing. RESULTS: The prognostic value of GATA4 depends on p53 expression. Patients without GATA4 protein expression were more frequently negative for TP53 mutations and had better prognoses than the GATA4 positive patients. In patients positive for GATA4 protein expression, p53 expression was associated with the worst outcome. However, in patients positive for p53 expression, the loss of GATA4 protein expression seemed to be associated with improved prognosis. GATA4 promoter methylation was not associated with a lack of GATA4 protein expression. CONCLUSIONS: Our data indicate that there is a possibility that GATA4 could function as a prognostic factor in glioblastoma patients, but in connection with p53 expression. A lack of GATA4 expression is not dependent on GATA4 promoter methylation. GATA4 alone has no influence on survival time in glioblastoma patients.

Prospective analysis of the impact of adjuvant treatment with external beam radiation therapy and vaginal brachytherapy on health-related quality of life in patients with early-stage endometrioid endometrial carcinoma.

OBJECTIVES: Our study evaluates the impact of adjuvant treatment with external beam radiotherapy (EBRT) combined with vaginal high dose rate brachytherapy (HDR BT) on health related quality of life (HRQL) in patients with early stage endometrioid endometrial carcinoma. MATERIAL AND METHODS: From March 2019 to February 2021, 60 patients were enrolled with early stage endometrioid endometrial carcinoma, and qualified to adjuvant treatment after hysterectomy. HRQL was assessed using the EORTC QLQ-C30 questionnaire, with the endometrial cancer-specific HRQL module EORTC QLQ-EN24. Questionnaires were completed in four timepoints during adjuvant radiotherapy. RESULTS: A significant decrease in mean global health status / quality of life (p < 0.001) and role functioning (p = 0.028) was noted, as assessed in EORTC QLQ-C30 scale. Among the EORTC QLQ-C30 symptoms scales, significant differences were noted in the fatigue scale (p = 0.003), pain scale (p = 0.001), constipation scale (p < 0.001) and diarrhea scale (p < 0.001) over time. The EORTC QRQ-EN24 analysis showed significant deterioration in the urological symptoms scale (p < 0.001), gastrointestinal symptoms scale (p < 0.001) and in the mean pain in back and pelvis scale (p = 0.003). CONCLUSIONS: Adjuvant radiotherapy in patients with early-stage endometrioid endometrial cancer after hysterectomy is associated with worse quality of life, especially due to the toxicity of the treatment in relation to the gastrointestinal tract and urinary system.

Thermally boosted interstitial high-dose-rate brachytherapy in high-risk early-stage breast cancer conserving therapy - large cohort long-term results.

Background: Early-stage high-risk breast cancer (BC) is standardly treated with breast-conserving therapy (BCT), combined with systemic therapy and radiotherapy (RT) ± tumor bed boost, e.g., with interstitial high-dose-rate brachytherapy (HDR-BT). To improve local recurrence rate (LRR), BT radiosensitization (thermal boost, TB) with interstitial microwave hyperthermia (MWHT) may be an option. The paper aims to report a retrospective single-institutional study on 5- and 10-year local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), overall survival (OS), cosmetic outcome (CO), and late toxicity (fibrosis, fat necrosis) after thermally enhanced HDR-BT boost to the BC tumor bed. Materials and methods: In 2006-2018, 557 early-stage (I-IIIA) high-risk BC patients were treated with BCT. If indicated, they were administered systemic therapy, then referred for 40.0-50.0 Gy whole breast irradiation (WBI) and 10 Gy interstitial HDR-BT boost (group A). Eligible patients had a single MWHT session preceding BT (group B). Based on present risk factors (RF), medium-risk (1-2 RF) and high-risk subgroups (≥ 3 RF) were formed. Patients were standardly checked, and control mammography (MMG) was performed yearly. Breast cosmesis (Harvard scale) and fibrosis were recorded. LC, DMFS, DFS, and OS were statistically analyzed. Results: Out of 557 patients aged 57 years (26-84), 364 (63.4%) had interstitial HDR-BT boost (group A), and 193 (34.6%) were preheated with MWHT (group B). Patients in group B had a higher clinical stage and had more RFs. The median follow-up was 65.9. Estimated 5-year and 10-year LC resulted in 98.5% and 97.5%, respectively. There was no difference in LC, DMFS, DFS, and OS between groups A and B and between extracted high-risk subgroups A and B. Five- and ten-year OS probability was 95.4% and 88.0%, respectively, with no difference between groups A and B. Harvard criteria-based CO assessment revealed good/excellent cosmesis in 74.9-79.1%. Tumor bed hardening was present in 40.1-42.2%. Asymptomatic fat necrosis-related macrocalcifications were detected in 15.6%, more frequently in group B (p = 0.016). Conclusions: Thermally boosted or not, HDR-BT was locally highly effective as part of combined treatment. Five- and ten-year LC, DMFS, DFS, and OS were high and equally distributed between the groups, although TB was prescribed in more advanced one with more RFs. TB did not influence CO and fibrosis. TB added to late toxicity regarding asymptomatic fat necrosis detected on MMG.

Retrospective analysis of the effectiveness of volumetric modulated arc therapy half­body irradiation in palliation of pain in patients with multiple bone metastases.

Bone metastases are the most common cause of cancer-related pain. It has been reported that radiotherapy is efficient in the palliation of pain caused by bone metastases. Half-body irradiation (HBI) is a method of palliative treatment in patients with multiple metastases to bones. The present study aimed to evaluate the efficiency of upper and lower HBI in reducing pain in patients with multiple bone metastases treated with volumetric modulated arc therapy (VMAT) HBI. A total of 22 patients received HBI based on the VMAT technique between July 2018 and July 2020. Treatment plans were subject to a dosimetric analysis. The absorbed doses ranged from 6 to 8 Gy in a single fraction. The patients rated pain on the 11-point (0-10) verbal numeric pain score (VNPS) before irradiation and after 1 month of follow-up. To assess the analgesic effect of HBI radiotherapy, data from 19 patients who attended the follow-up visit were analyzed. Before the treatment, the median VNPS of pain was 5 (IQR, 3-8); after the follow-up period, it was 3 (IQR, 1-4) (P=0.003). The median VNPS of the maximum pain within the last month before treatment was 8 (IQR, 7-10) and after irradiation it was 5 (IQR, 4-7) (P<0.001). The median VNPS of the average pain within the last month before the treatment was 5 (IQR, 4-7); after the treatment, it was 3 (IQR, 2-5) (P=0.003). In conclusion, conformal VMAT-intensity-modulated radiation therapy HBI is an effective method for reducing pain in patients with painful multiple bone metastases. Conformal techniques of radiation allow for the reduction of doses to organs at risk thus potentially reducing the toxicity of treatment.

The impact of adjuvant treatment with external beam radiotherapy and vaginal brachytherapy on health-related quality of life in patients with early-stage endometrioid endometrial carcinoma - initial results of a prospective study.

OBJECTIVES: Our study evaluates the impact of adjuvant treatment with external beam radiotherapy (EBRT) combined with vaginal high-dose-rate brachytherapy (HDR BT) on health-related quality of life (HRQL) in patients with early-stage endometrioid endometrial carcinoma. MATERIAL AND METHODS: We assessed HRQL of patients based on the EORTC QLQ-C30 questionnaire, with endometrial cancer specific HRQL module - EORTC QLQ-EN24. From March 2019 to April 2020 we enrolled 20 patients with early-stage endometrioid endometrial carcinoma, qualified for adjuvant treatment after hysterectomy. We compared the scores measured with the questionnaires at the beginning and at the end of the treatment. RESULTS: There was a statistically significant decrease in the mean of global health status/quality of life assessed according to the EORTC QLQ-C30 scale, from 62.25 ± 13.12 at the beginning of the adjuvant radiotherapy to 55.85 ± 14.68 at the end of the treatment (p = 0.047). The mean appetite loss score was higher at the onset of the treatment as compared to its value after EBRT, 19.9 ± 27.33 vs 11.6 ± 19.52 (p = 0.043). Similarly to the mean constipation score, which was 29.85 ± 30.40 vs 11.6 ± 19.52 (p = 0.013). The mean diarrhoea symptom scale increased from 16.55 ± 20.16 to 56.75 ± 36.10 (p = 0.001). In the EORTC QLQ-EN24 scales, gastrointestinal symptoms scores were higher at the end of the treatment, (with the mean of 26.45 ± 22.76) as compared to 14.30 ± 16.52 at the beginning of EBRT (p = 0.003). CONCLUSIONS: Patients who receive adjuvant radiotherapy have decreased quality of life during the treatment reporting more serious gastrointestinal symptoms. The potential risk of treatment-related toxicity should be taken into account during the treatment planning process in order to minimize the deterioration of HRQL.