Renal cell cancer (RCC) has traditionally been considered radioresistant. Because of this, conventional radiotherapy (RT) has been predominantly relegated to the palliation of symptomatic metastatic disease. The implementation of stereotactic ablative radiotherapy (SABR) has made it possible to deliver higher ablative doses safely, shifting the renal radioresistance paradigm. SABR has increasingly been adopted into the multidisciplinary framework for the treatment of locally recurrent, oligoprogressive, and oligometastatic disease. Furthermore, there is growing evidence of SABR as a non-invasive definitive therapy in patients with primary RCC who are medically inoperable or who decline surgery, unsuited to invasive ablation (surgery or percutaneous techniques), or at high-risk of requiring post-operative dialysis. Encouraging outcomes have even been reported in cases of solitary kidney or pre-existing chronic disease (poor eGFR), with a high likelihood of preserving renal function. A review of clinical evidence supporting the use of ablative radiotherapy (SABR) in primary, recurrent, and metastatic RCC has been conducted. Given the potential immunogenic effect of the high RT doses, we also explore emerging opportunities to combine SABR with systemic treatments. In addition, we explore future directions and ongoing clinical trials in the evolving landscape of this disease.

BACKGROUND: Brain metastases (BMs) frequently occur in cancer patients, and stereotactic radiation therapy (SRT) is a preferred treatment option. In this retrospective study, we analyzed patients treated by SRT for a single BM during their first SRT session and we compared two subgroups: \"Cohort 1\" with patients did not undergo cerebral re-irradiation and \"Cohort 2\" with patients received at least one subsequent SRT session for cerebral recurrence.
METHODS: We included patients who received SRT for a single BM between January 2010 and June 2020. Cohort 1 comprised 152 patients, and Cohort 2 had 46 patients.
RESULTS: Cohort 2 exhibited younger patients with higher Karnofsky performance status (KPS). Median overall survival was considerably longer in Cohort 2 (21.8 months) compared to Cohort 1 (6.1 months). Local and cerebral recurrence rates were significantly higher in Cohort 2 (p < 0.001), attributed to patient selection and longer survival. The combined score of age and KPS proved to be a predictive factor for survival, with patients under 65 years of age and KPS > 80 showing the best survival rates in the overall population.
CONCLUSIONS: This retrospective study highlights that the combined score of age and KPS can predict better survival, especially for patients under 65 years with a KPS score above 80. Further research involving larger and more diverse populations is essential to validate and expand upon these findings.

UNASSIGNED: A significant number of individuals diagnosed with non-small cell lung cancer (NSCLC) have distant metastases, and the concept of oligometastatic NSCLC has shown promise in achieving a cure. Stereotactic body radiation therapy (SBRT) is currently considered a viable treatment option for a limited number of tumor metastases. It has also been demonstrated that third-generation tyrosine kinase inhibitors (TKIs) are effective in extending the survival of patients with epidermal growth factor receptor (EGFR)-mutated NSCLC. Hence, the combination of SBRT with third-generation TKIs holds the potential to enhance treatment efficacy in patients with oligometastatic EGFR-mutated NSCLC. This review aimed to assess the possibility of combining SBRT with TKIs as an optimum treatment option for patients with oligometastatic EGFR-mutated NSCLC.
UNASSIGNED: We performed a narrative review by searching the PubMed, Web of Science, Elsevier and ClinicalTrials.gov databases for articles published in the English language from January 2009 to February 2024 and by reviewing the bibliographies of key references to identify important literature related to combining SBRT with third-generation TKIs in oligometastatic EGFR-mutated NSCLC.
UNASSIGNED: This review aimed to assess the viability of combining SBRT and EGFR-TKIs in oligometastatic EGFR-mutated NSCLC. Current clinical trials suggest that the combined therapies have better progression free survival (PFS) when using SBRT as either concurrent with EGFR-TKIs or consolidated with EGFR-TKIs. Furthermore, research with third-generation EGFR-TKIs and SBRT combinations has demonstrated tolerable toxicity levels without significant additional adverse effects as compared to prior therapies. However, further clinical trials are required to establish its effectiveness.
UNASSIGNED: The combined approach of SBRT and TKIs can effectively impede the progression of oligometastatic NSCLC in patients harboring EGFR mutations and, most notably, can prolong progression-free survival rates. However, the feasibility of combining SBRT with third-generation TKIs in clinical trials remains unclear.

BACKGROUND: Up to 30% patients newly diagnosed with advanced non-small cell lung cancer (NSCLC) present with brain metastases. In the absence of oncogenic addiction, first-line immunotherapy, alone or in combination with chemotherapy, is the current standard of care. This review aims to synthesize the available data regarding the efficacy of immunotherapy in these patients, and to discuss the possibility of its being coordinated with local treatments such as radiotherapy.
BACKGROUND: NSCLC patients with brain metastases appear to have survival benefits with immunotherapy similar to those of NSCLC patients without brain metastases. However, this finding is based on mainly prospective studies having included highly selected patients with pre-treated and stable brain metastases. Several retrospective studies and two prospective single-arm studies have confirmed the intracranial efficacy of immunotherapy, either alone or in combination with chemotherapy.
CONCLUSIONS: The indications and optimal timing for cerebral radiotherapy remain subjects of debate. To date, there exists no randomized study assessing the addition of brain radiotherapy to first-line immunotherapy. That said, a recent meta-analysis showed increased intracerebral response when radiotherapy complemented immunotherapy.
CONCLUSIONS: For NSCLC patients with brain metastases, the available data suggest a clear benefit of first-line immunotherapy, whether alone or combined with chemotherapy. However, most of these data are drawn from retrospective, non-randomized studies with small sample sizes.

OBJECTIVE: To evaluate clinical outcomes after SABR in a cohort of early-stage non-small cell lung cancer (NSCLC) or pulmonary metastases in chronic obstructive pulmonary disease (COPD) patients with forced expiratory volume in the first second predicted (FEV1) ≤ 50%.
METHODS: Retrospective single-center study was performed to analyze clinical outcomes and toxicities in COPD patients with severe lung dysfunction treated with SABR from 1st June 2015 to 31st October 2022.
RESULTS: Thirty four patients (forty locations) were enrolled for analysis. Median follow-up was 2.9 years. Median age was 73.5 years (range, 65.6-80.1). FEV1 was 38% (range, 28.2-50.0) prior to radiotherapy. Median overall survival (OS) was 41.1 months (95% CI 38.9-not reached). OS rates at 2-, 3-, and 5- years were 79%, 71%, and 36%, respectively. Cancer-specific survival rates at 2-, 3-, and 5- years were 96%, 96%, and 68%, respectively. Local control rates at 2-, 3-, and 5- years were 88%, 83%, and 83%, respectively. No grade 4 or 5 toxicity was observed. The most common acute toxicity was pneumonitis (38.2%), of which only 1 patient (2.9%) reported grade 3 acute toxicity.
CONCLUSIONS: Lung SABR in patients with poor pulmonary function may be effective with acceptable toxicity.

UNASSIGNED: Stereotactic radiation therapy (SRT) is commonly used to treat brain metastases (BMs). This retrospective study compared two SRT techniques, dynamic conformal arc therapy (DCAT) and volumetric modulated arc therapy (VMAT), for single BM treatments.
UNASSIGNED: Data of patients treated between January 2010 and June 2020 were considered. Patients with multiple BMs, resected BMs, reirradiation, whole-brain radiation therapy and brainstem metastases were excluded. We focused our analysis on 97 patients who received 23.1 Gy in three fractions. Acute toxicities and follow-up outcomes were recorded. Dosimetric data were analyzed in two subgroups (PTV ≤ 10 cc and PTV > 10 cc).
UNASSIGNED: DCAT and VMAT were used in 70 (72.2 %) and 27 (27.8 %) patients, respectively. Acute toxicities were not significantly different between groups (p = 0.259), and no difference was detected in the incidence rate of radionecrosis, local recurrence and cerebral recurrence (p > 0.999, p > 0.999 and p = 0.682, respectively). PTV coverage was better with DCAT for small volumes (PTV ≤ 10 cc). Mean conformity index (CI) was significantly higher with VMAT and mean gradient index (GI) was significantly lower with DCAT whatever volume subgroups (p < 0.001). DCAT had more heterogeneous plans and VMAT required more monitor units. DCAT resulted in reduced low and intermediate doses, whereas VMAT led to decreased high doses.
UNASSIGNED: DCAT and VMAT are two effective and safe SRT techniques for BMs treatment. In the era of re-irradiation, it is important to reduce the doses delivered to healthy tissues. Further prospective studies are needed to validate these findings.

BACKGROUND: Radiotherapy plays a vital role in the management of high-grade gliomas. However, the radio resistance of glioma cells limits the effect of radiation and drives recurrence inside the irradiated tumor volume leading to poor outcomes for patients.
METHODS: High-grade glioma cell radioresistance significantly contributes to radiotherapy failure, highlighting the importance of identifying predictive biomarkers for radioresistance. An increasing body of evidence complies with the Yes Associated Protein 1 (Yap-1) and heat shock protein 90 (Hsp90) as biomarkers for radioresistance in glioma cells. A number of studies suggest the potential of radioresistance-associated factors as biomarkers and/ or novel therapeutic targets in glioma cells. Thus, it is essential for glioblastoma patients to identify robust druggable targets involved in radioresistance, optimizing irradiation protocol, and understanding their underlying molecular mechanisms.
RESULTS: Therefore, in the present study, we hypothesized that hypofractionated Gamma Knife radiation therapy (HF-GKRT) could target Yap-1 and Hsp90 and downregulate the mechanism of radioresistance in high-grade glioma cells.
CONCLUSIONS: For this purpose, expression levels of radioresistance markers Yap-1 and Hsp90 were evaluated after treatment with HF-GKRT, and this was compared with single fraction Gamma Knife radiation therapy (SF-GKRT) in U87MG primary human glioblastoma cell line model. This would help design a novel radiation therapy regimen for glioblastoma patients by reducing the risk of radioresistance.

UNASSIGNED: Due to superior image quality and daily adaptive planning, MR-guided stereotactic body radiation therapy (MRgSBRT) has the potential to further widen the therapeutic window in radiotherapy of localized prostate cancer. This study reports on acute toxicity rates and patient-reported outcomes after MR-guided adaptive ultrahypofractionated radiotherapy for localized prostate cancer within the prospective, multicenter phase II SMILE trial.
UNASSIGNED: A total of 69 patients with localized prostate cancer underwent MRgSBRT with daily online plan adaptation. Inclusion criteria comprised a tumor stage ≤ T3a, serum PSA value ≤ 20 ng/ml, ISUP Grade group ≤ 4. A dose of 37.5 Gy was prescribed to the PTV in five fractions on alternating days with an optional simultaneous boost of 40 Gy to the dominant intraprostatic lesion defined by multiparametric MRI. Acute genitourinary (GU-) and gastrointestinal (GI-) toxicity, as defined by CTCAE v. 5.0 and RTOG as well as patient-reported outcomes according to EORTC QLQ-C30 and -PR25 scores were analyzed at completion of radiotherapy, 6 and 12 weeks after radiotherapy and compared to baseline symptoms.
UNASSIGNED: There were no toxicity-related treatment discontinuations. At the 12-week follow-up visit, no grade 3 + toxicities were reported according to CTCAE. Up until the 12-week visit, in total 16 patients (23 %) experienced a grade 2 GU or GI toxicity. Toxicity rates peaked at the end of radiation therapy and subsided within the 12-week follow-up period. At the 12-week follow-up visit, no residual grade 2 GU toxicities were reported and 1 patient (1 %) had residual grade 2 enteritic symptoms. With exception to a significant improvement in the emotional functioning score following MRgSBRT, no clinically meaningful changes in the global health status nor in relevant subscores were reported.
UNASSIGNED: Daily online-adaptive MRgSBRT for localized prostate cancer resulted in an excellent overall toxicity profile without any major negative impact on quality of life.

The myQA SRS (IBA) is a new to market 2D complementary metal oxide semiconductor detector array with an active area 140 × 120 mm2 and 0.4 mm resolution, making it a potential real-time dosimetry alternative to radiochromic film for stereotactic plan verification. Characterisation of the device was completed to assess performance. The dosimetric properties of the device were assessed for 6FF and 6FFF beams from a Varian TrueBeam STx with high definition multileaf collimator. Clinical suitability of the device for Patient Specific Quality Assurance was verified using ten SRS/SBRT plans, compared against other detectors, as well as multi leaf collimator (MLC) tests including picket fence and chair. Gamma analysis was performed using myQA software with criteria of 4%/1 mm. The device demonstrated compliance with recommended specifications for basic tests. After the required warm-up period, the maximum deviation in detector signal from initial readings was 0.2%. Short-term and long-term reproducibility was 0.1% (6FF) and 1.0% (6FFF), respectively. Dose linearity was within 0.3% (6FF) and 0.7% (6FFF) and dose-rate dependence within 1.7% (6FF) and 2.9% (6FFF) and were verified with a Farmer type ionization chamber (PTW 30013). Angular dependence was quantified for coplanar and non-coplanar situations. Output factors and beam profiles measured on the device showed agreement within 1% of baseline RAZOR diode (IBA) and CC04 ionisation chamber (IBA) measurements for field sizes 1 × 1 to 10 × 10 cm2. The minimum gamma (4%/1 mm) pass rates for MLC-pattern tests were 96.5% and 98.1% for the myQA SRS and film, respectively. The average gamma (4%/1 mm) pass rates for SBRT and SRS plans were 98.8% and 99.8% respectively. This work represents one of the first studies performed on the commissioning and performance characterisation of this novel device, demonstrating its accuracy and reliability, making it highly useful as a film alternative in stereotactic treatment plan verification.

Magnetic resonance imaging (MRI) provides excellent visualization of central nervous system (CNS) tumors due to its superior soft tissue contrast. Magnetic resonance-guided radiotherapy (MRgRT) has historically been limited to use in the initial treatment planning stage due to cost and feasibility. MRI-guided linear accelerators (MRLs) allow clinicians to visualize tumors and organs at risk (OARs) directly before and during treatment, a process known as online MRgRT. This novel system permits adaptive treatment planning based on anatomical changes to ensure accurate dose delivery to the tumor while minimizing unnecessary toxicity to healthy tissue. These advancements are critical to treatment adaptation in the brain and spinal cord, where both preliminary MRI and daily CT guidance have typically had limited benefit. In this narrative review, we investigate the application of online MRgRT in the treatment of various CNS malignancies and any relevant ongoing clinical trials. Imaging of glioblastoma patients has shown significant changes in the gross tumor volume over a standard course of chemoradiotherapy. The use of adaptive online MRgRT in these patients demonstrated reduced target volumes with cavity shrinkage and a resulting reduction in radiation dose to uninvolved tissue. Dosimetric feasibility studies have shown MRL-guided stereotactic radiotherapy (SRT) for intracranial and spine tumors to have potential dosimetric advantages and reduced morbidity compared with conventional linear accelerators. Similarly, dosimetric feasibility studies have shown promise in hippocampal avoidance whole brain radiotherapy (HA-WBRT). Next, we explore the potential of MRL-based multiparametric MRI (mpMRI) and genomically informed radiotherapy to treat CNS disease with cutting-edge precision. Lastly, we explore the challenges of treating CNS malignancies and special limitations MRL systems face.