Innovative therapeutic strategies to overcome radioresistance in breast cancer.

Despite a comparatively favorable prognosis relative to other malignancies, breast cancer continues to significantly impact women's health globally, partly due to its high incidence rate. A critical factor in treatment failure is radiation resistance - the capacity of tumor cells to withstand high doses of ionizing radiation. Advancements in understanding the cellular and molecular mechanisms underlying radioresistance, coupled with enhanced characterization of radioresistant cell clones, are paving the way for the development of novel treatment modalities that hold potential for future clinical application. In the context of combating radioresistance in breast cancer, potential targets of interest include long non-coding RNAs (lncRNAs), micro RNAs (miRNAs), and their associated signaling pathways, along with other signal transduction routes amenable to pharmacological intervention. Furthermore, technical, and methodological innovations, such as the integration of hyperthermia or nanoparticles with radiotherapy, have the potential to enhance treatment responses in patients with radioresistant breast cancer. This review endeavors to provide a comprehensive survey of the current scientific landscape, focusing on novel therapeutic advancements specifically addressing radioresistant breast cancer.

Prognosis versus Actual Outcomes in Stereotactic Radiosurgery of Brain Metastases: Reliability of Common Prognostic Parameters and Indices.

This study aims to evaluate the clinical outcome of stereotactic radiosurgery as the sole treatment for brain metastases and to assess prognostic factors influencing survival. A total of 108 consecutive patients with 213 metastases were retrospectively analyzed. Treatment was determined with close-meshed MRI follow-up. Various prognostic factors were assessed, and several prognostic indices were compared regarding their reliability to estimate overall survival. Median overall survival was 15 months; one-year overall survival was 50.5%. Both one- and two-year local controls were 90.9%. The rate of new metastases after SRS was 49.1%. Multivariate analysis of prognostic factors revealed that the presence of extracranial metastases, male sex, lower KPI, and progressive extracranial disease were significant risk factors for decreased survival. Of all evaluated prognostic indices, the Basic Score for Brain Metastases (BSBMs) showed the best correlation with overall survival. A substantial survival advantage was found for female patients after SRS when compared to male patients (18 versus 9 months, p = 0.003). SRS of brain metastasis is a safe and effective treatment option when frequent monitoring for new metastases with MRI is performed. Common prognostic scores lack reliable estimation of survival times. Female sex should be considered as an additional independent positive prognostic factor influencing survival.

Impact of COVID-19 on Radiation Oncology, an Austrian Experience.

The COVID-19 pandemic has an unprecedented impact on cancer treatment worldwide. We aimed to evaluate the effects of the pandemic on the radiation treatment of patients in order to provide data for future management of such crises. We compared the number of performed radiotherapy sessions of the pandemic period from February 2020 until May 2021 with those of 2018 and 2019 for reference. At our department, no referred patients had to be rejected or postponed, nor any significant changes in fractionation schedules implemented. Nevertheless, there was a substantial drop in overall radiotherapy sessions in 2020 following the first incidence wave of up to -25% (in June) in comparison to previous years. For breast cancer, a maximum decline of sessions of -45% (July) was recorded. Only a short drop of prostate cancer sessions (max -35%, May) followed by a rebound (+42%, July) was observed. Over the investigated period, a loss of 4.4% of expected patients never recovered. The severe impact of COVID-19 on cancer treatment, likely caused by retarded diagnosis and delayed interdisciplinary co-treatment, is reflected in a lower count of radiotherapy sessions. Radiation oncology is a crucial cornerstone in upholding both curative treatment options and treatment capacity during a pandemic.

The Role of Cancer Stem Cells in Radiation Resistance.

Cancer stem cells (CSC) are a distinct subpopulation within a tumor. They are able to self-renew and differentiate and possess a high capability to repair DNA damage, exhibit low levels of reactive oxygen species (ROS), and proliferate slowly. These features render CSC resistant to various therapies, including radiation therapy (RT). Eradication of all CSC is a requirement for an effective antineoplastic treatment and is therefore of utmost importance for the patient. This makes CSC the prime targets for any therapeutic approach. Albeit clinical data is still scarce, experimental data and first clinical trials give hope that CSC-targeted treatment has the potential to improve antineoplastic therapies, especially for tumors that are known to be treatment resistant, such as glioblastoma. In this review, we will discuss CSC in the context of RT, describe known mechanisms of resistance, examine the possibilities of CSC as biomarkers, and discuss possible new treatment approaches.

Intrafractional 6D head movement increases with time of mask fixation during stereotactic intracranial RT-sessions.

BACKGROUND: The present study investigates the intrafractional accuracy of a frameless thermoplastic mask used for head immobilization during stereotactic radiotherapy. Non-invasive masks cannot completely prohibit head movements. Previous studies attempted to estimate the magnitude of intrafractional inaccuracy by means of pre- and postfractional measurements only. However, this might not be sufficient to accurately map also intrafractional head movements. MATERIALS AND METHODS: Intrafractional deviation of mask-fixed head positions was measured in five patients during a total of 94 fractions by means of close-meshed repeated ExacTrac measurements (every 1.4 min) conducted during the entire treatment session. A median of six (range: 4 to 11) measurements were recorded per fraction, delivering a dataset of 453 measurements. RESULTS: Random errors (SD) for the x, y and z axes were 0.27 mm, 0.29 mm and 0.29 mm, respectively. Median 3D deviation was 0.29 mm. Of all 3D intrafractional motions, 5.5 and 0.4% exceeded 1 mm and 2 mm, respectively. A moderate correlation between treatment duration and mean 3D displacement was determined (rs = 0.45). Mean 3D deviation increased from 0.21 mm (SD = 0.26 mm) in the first 2 min to a maximum of 0.53 mm (SD = 0.31 mm) after 10 min of treatment time. CONCLUSION: Pre- and post-treatment measurement is not sufficient to adequately determine the range of intrafractional head motion. Thermoplastic masks provide both reliable interfractional and intrafractional immobilization for image-guided stereotactic hypofractionated radiotherapy. Greater positioning accuracy may be obtained by reducing treatment duration (< 6 min) and applying intrafractional correction. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03896555, Registered 01 April 2019 - retrospectively registered.