The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival.

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.

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.

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.

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.

Postsurgical radiotherapy (RT) has been early proven to prevent local tumor recurrence, initially performed with whole brain RT (WBRT). Subsequent to disadvantageous cognitive sequalae for the patient and the broad distribution of modern linear accelerators, focal irradiation of the tumor has omitted WBRT in most cases. In many studies, the effectiveness of local RT of the resection cavity, either as single-fraction stereotactic radiosurgery (SRS) or hypo-fractionated stereotactic RT (hFSRT), has been demonstrated to be effective and safe. However, whereas prospective high-level incidence is still lacking on which dose and fractionation scheme is the best choice for the patient, further ablative techniques have come into play. Neoadjuvant SRS (N-SRS) prior to resection combines straightforward target delineation with an accelerated post-surgical phase, allowing an earlier start of systemic treatment or rehabilitation as indicated. In addition, low-energy intraoperative RT (IORT) on the surgical bed has been introduced as another alternative to external beam RT, offering sterilization of the cavity surface with steep dose gradients towards the healthy brain. This consensus paper summarizes current local treatment strategies for resectable brain metastases regarding available data and patient-centered decision-making.

UNASSIGNED: Trigeminal neuralgia (TN) is characterised by recurrent paroxysmal brief episodes of electric shock-like pain along the trigeminal nerve distribution. Based on the underlying cause, the current classification systems have classified TN into idiopathic, classical and secondary TN. This manuscript presents a case report of a patient seen in the clinic with features of TN secondary to an intracranial lesion.
UNASSIGNED: A 39-year-old female presented to the clinic with a 15-month history of severe, intermittent, short-lasting episodes of pain affecting the left lower teeth, jaw, nose and temporal region. The patient reported familiar shock-like pain during the physical examination when the skin of the left ala of the nose was lightly touched. The rest of the clinical examination was non-significant. The magnetic resonance imaging (MRI) of the brain showed an approximately 20 mm wide lesion at the level of the left cerebellopontine angle. After subsequent tests, the lesion was diagnosed as meningioma, and the patient was treated with stereotactic radiation therapy.
UNASSIGNED: In up to 10% of TN cases, the underlying cause can be due to a brain tumour. Although persistent pain, sensory or motor nerve dysfunction, gait disturbances and other neurological signs may concurrently exist, raising a red flag for intracranial pathology, patients often present with pain alone as the heralding symptom of a brain tumour. Due to this, it is imperative that all patients suspected of having TN undergo an MRI of the brain as part of the diagnostic work-up.

Focal radiation necrosis of the brain (fRNB) is a late adverse event that can occur following the treatment of benign or malignant brain lesions with stereotactic radiation therapy (SRT) or stereotactic radiosurgery (SRS). Recent studies have shown that the incidence of fRNB is higher in cancer patients who received immune checkpoint inhibitors. The use of bevacizumab (BEV), a monoclonal antibody that targets the vascular endothelial growth factor (VEGF), is an effective treatment for fRNB when given at a dose of 5-7.5 mg/kg every two weeks. In this single-center retrospective case series, we investigated the effectiveness of a low-dose regimen of BEV (400 mg loading dose followed by 100 mg every 4 weeks) in patients diagnosed with fRNB. A total of 13 patients were included in the study; twelve of them experienced improvement in their existing clinical symptoms, and all patients had a decrease in the volume of edema on MRI scans. No clinically significant treatment-related adverse effects were observed. Our preliminary findings suggest that this fixed low-dose regimen of BEV can be a well-tolerated and cost-effective alternative treatment option for patients diagnosed with fRNB, and it is deserving of further investigation.