Glioblastoma is the most common histologic type of all gliomas and contributes to 57.3% of all cases. Despite the standard management based on surgical resection and radiotherapy, it is related to poor outcome, with a 5-year relative survival rate below 6.9%. In order to improve the overall outcome for patients, the new therapeutic strategies are needed. Herein, we describe the current state of knowledge on novel targeted therapies in glioblastoma. Based on recent studies, we compared treatment efficacy measured by overall survival and progression-free survival in patients treated with selected potential antitumor drugs. The results of the application of the analyzed inhibitors are highly variable despite the encouraging conclusions of previous preclinical studies. This paper focused on drugs that target major glioblastoma kinases. As far, the results of some BRAF inhibitors are favorable. Vemurafenib demonstrated a long-term efficacy in clinical trials while the combination of dabrafenib and trametinib improves PFS compared with both vemurafenib and dabrafenib alone. There is no evidence that any MEK inhibitor is effective in monotherapy. According to the current state of knowledge, BRAF and MEK inhibition are more advantageous than BRAF inhibitor monotherapy. Moreover, mTOR inhibitors (especially paxalisib) may be considered a particularly important group. Everolimus demonstrated a partial response in a significant proportion of patients when combined with bevacizumab, however its actual role in the treatment is unclear. Neither nintedanib nor pemigatinib were efficient in treatment of GBM. Among the anti-VEGF drugs, bevacizumab monotherapy was a well-tolerated option, significantly associated with anti-GBM activity in patients with recurrent GBM. The efficacy of aflibercept and pazopanib in monotherapy has not been demonstrated. Apatinib has been proven to be effective and tolerable by a single clinical trial, but more research is needed. Lenvatinib is under trial. Finally, promising results from a study with regorafenib may be confirmed by the ongoing randomized AGILE trial. The studies conducted so far have provided a relatively wide range of drugs, which are at least well tolerated and demonstrated some efficacy in the randomized clinical trials. The comprehensive understanding of the molecular biology of gliomas promises to further improve the treatment outcomes of patients.

Background: Eyelid tumors are rare skin cancers, the most common of which is basal cell carcinoma characterized primarily by local growth. In addition to surgery, radiotherapy is among the basic methods of treatment. External beam radiotherapy is associated with the risk of complications within ocular structures, especially the lens. In the case of interstitial brachytherapy, it is possible to administer a high dose to the clinical target volume (CTV), while reducing it in the most sensitive structures. Methods: This paper presents the results of an analysis of 28 patients treated with interstitial high dose rate (HDR) brachytherapy for skin cancers of the upper and lower eyelid; medial and lateral canthus; and the cheek, nose and temples with the infiltration of ocular structures. The patients were treated according to two irradiation schedules: 49 Gy in 14 fractions of 3.5 Gy twice a day for 7 days of treatment, and 45 Gy in 5 Gy fractions twice a day for 5 days. The mean follow-up was 22 months (3–49 months). Results: two patients (6%) had a relapse: a local recurrence within the irradiated area in one of them, and metastases to lymph nodes in the other. The most common early complication was conjunctivitis (74%), and the most common late complication was dry eye syndrome (59%). Conclusions: Interstitial HDR brachytherapy for skin cancers of the upper and lower eyelid; medial and lateral cants; and the cheek, nose and temples with infiltration of ocular structures is a highly effective, short and relatively low burden type of treatment.

The aim of our study was to compare dosimetric aspects of three radioablation modalities – direct high-dose-rate brachytherapy (HDR-BT) and virtually planned stereotactic body radiation therapy performed on CyberKnife (SBRTck) and Elekta Versa HD LINAC (SBRTe) applied in patients with liver metastases. We selected 30 patients with liver metastases, who received liver interstitial HDR-BT and virtually prepared plans for SBRTck and SBRTe. In all the cases, the prescribed dose was a single fraction of 25 Gy. Treatment delivery time, doses delivered to PTV and organs at risk, as well as conformity indices, were calculated and compared. The longest median treatment delivery time was observed in SBRTck in contrast to HDR-BT and SBRTe which were significantly shorter and comparable. HDR-BT plans achieved better coverage of PTV (except for D98%) in contrast to SBRT modalities. Between both SBRT modalities, SBRTck plans resulted in better dose coverage in Dmean, D50%, and D90% values compared to SBRTe without difference in D98%. The SBRTe was the most advantageous considering the PCI and R100%. SBRTck plans achieved the best HI, while R50% value was comparable between SBRTe and SBRTck. The lowest median doses delivered to uninvolved liver volume (V5Gy, V9.1Gy) were achieved with HDR-BT, while the difference between SBRT modalities was insignificant. SBRT plans were better regarding more favourable dose distribution in the duodenum and right kidney, while HDR-BT achieved lower doses in the stomach, heart, great vessels, ribs, skin and spinal cord. There were no significant differences in bowel and biliary tract dose distribution between all selected modalities. HDR-BT resulted in more favourable dose distribution within PTVs and lower doses in organs at risk, which suggests that this treatment modality could be regarded as an alternative to other local ablative therapies in carefully selected patients’ with liver malignancies. Future studies should further address the issue of comparing treatment modalities in different liver locations and clinical scenarios.

The current standard of care (SoC) for patients with extensive-disease small-cell lung cancer (ED-SCLC) is chemo-immunotherapy. The efficacy of radiotherapy (RT) for chest consolidation has been established for patients with ED-SCLC who have responded to chemotherapy. There is a lack of data on incorporating RT as chest consolidation and metastasis-directed therapy for ED-SCLC. The RISE (Radiotherapy for Extensive-Stage Small-Cell Lung Cancer) study aims to evaluate the effectiveness of different RT strategies for residual lesions for patients with ED-SCLC who receive chemo-immunotherapy. A total of 165 patients with ED-SCLC will be recruited, with 55 patients assigned to each of the three study arms. Patients with stabilization or partial regression, according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, during chemo-immunotherapy will be included. • Arm I will serve as the control group, comprising patients who continue SoC of programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) immunotherapy (durvalumab or atezolizumab) following platinum-based chemo-immunotherapy. • Arm II will receive the SoC with consolidative RT to the chest area and potentially, according to palliative indications to metastatic lesions, delivered in 30 Gy in 3-Gy fractions. • Arm III will receive SoC with RT of 45 Gy in 3-Gy fractions to the chest area and stereotactic body radiotherapy (SBRT) with 24 Gy in 8-Gy fractions to the metastatic lesions. Blood samples for circulating tumor DNA (ctDNA) will be collected before RT, during each week of treatment, and at the time of disease progression. The primary endpoint is progression-free survival (PFS) based on RECIST 1.1 or patient death. 1. Secondary endpoints are OS, treatment toxicity (frequency of G3 toxicity according to CTCAE v.5.0), area of progression (primary tumor localization/new lesions), Overall response rate (ORR), and the response rate in non-irradiated lesions. The study population of patients with ED-SCLC has a poor prognosis. Dose-escalated chest RT and SBRT (for up to 10 metastases) administered with modern techniques offer the possibility to improve OS and PFS. Clinicaltrials.gov NCT06529081 (Registered 26th Jul 2024).

Context: Surgery is the gold standard for the local treatment of primary renal cell carcinoma (RCC), but alternatives are emerging. We conducted a systematic review and meta-analysis to assess the results of prospective studies using definitive stereotactic body radiotherapy (SBRT) to treat primary localised RCC. Evidence acquisition: This review was prospectively registered in PROSPERO (CRD42023447274). We searched PubMed, Embase, Scopus, and Google Scholar for reports of prospective studies published since 2003, describing the outcomes of SBRT for localised RCC. Meta-analyses were performed for local control (LC), overall survival (OS), and rates of adverse events (AEs) using generalised linear mixed models (GLMMs). Outcomes were presented as rates with corresponding 95% confidence intervals (95% CIs). Risk-of-bias was assessed using the ROBINS-I tool. Evidence synthesis: Of the 2983 records, 13 prospective studies (n = 308) were included in the meta-analysis. The median diameter of the irradiated tumours ranged between 1.9 and 5.5 cm in individual studies. Grade ≥ 3 AEs were reported in 15 patients, and their estimated rate was 0.03 (95%CI: 0.01–0.11; n = 291). One- and two-year LC rates were 0.98 (95%CI: 0.95–0.99; n = 293) and 0.97 (95%CI: 0.93–0.99; n = 253), while one- and two-year OS rates were 0.95 (95%CI: 0.88–0.98; n = 294) and 0.86 (95%CI: 0.77–0.91; n = 224). There was no statistically significant heterogeneity, and the estimations were consistent after excluding studies at a high risk of bias in a sensitivity analysis. Major limitations include a relatively short follow-up, inhomogeneous reporting of renal function deterioration, and a lack of prospective comparative evidence. Conclusions: The short-term results suggest that SBRT is a valuable treatment method for selected inoperable patients (or those who refuse surgery) with localised RCC associated with low rates of high-grade AEs and excellent LC. However, until the long-term data from randomised controlled trials are available, surgical management remains a standard of care in operable patients.

The location of skin neoplasms in the area of the ears qualifies patients to the so-called high-risk group. The location of neoplasms within the auricle and around the ear often causes many problems in surgical treatment. This is due to the presence of cartilage, the difficulty of performing procedures with obtaining a visually satisfactory cosmetic effect, especially in the presence of extensive lesions and can lead to positive surgical margins which leads to a high risk of recurrence. In such cases, the use of brachytherapy, both as an independent method and as a complementary method after surgery, may be an effective method of local control with an acceptable risk of radiation complications. However, there are no large retrospective studies on the use of brachytherapy in this anatomical region. The aim of the study was to analyse the effectiveness, toxicity profile, and cosmetic effect of two different brachytherapy techniques (contact and interstitial brachytherapy). Methods: This paper presents the results of a retrospective analysis of 33 patients treated with contact or interstitial high-dose-rate (HDR) brachytherapy for skin cancers of the outer ear, involving the auricle and the skin of the adjacent area. Brachytherapy was used both as a definitive treatment (15 patients—43%) and adjuvant treatment after surgery (18 patients—57%). The basic criterion for adjuvant treatment was a positive or narrow (<1 mm) resection margin. Fraction doses from 3 to 7 Gy per fraction were used at intervals from six hours (interstitial brachytherapy) to a maximum of seven days (contact brachytherapy). The treatment time ranged from 1 to 42 days, and the total dose range was 7 to 49 Gy. The follow-up was 29.75 months (range 2–64). Results: In the group of patients treated with adjuvant therapy, in the patients with post-radiation reaction, the mean time from surgery to the start of brachytherapy was 7.72 ± 3.05 weeks, the median was 8 (6–12) weeks, and in the group without post-radiation reaction, the mean time was 11.13 ± 4.41 weeks, the median time was 11 weeks (8–14). The risk of a post-radiation reaction increased significantly more often in patients with more advanced disease. In the case of contact brachytherapy, the post-radiation reaction occurred significantly more often (14/21 patients—43%) than in the case of interstitial brachytherapy (3/11 patients—9.4%). In patients with post-radiation reactions, a significantly larger volume of the skin receiving a dose of 200% was found, and the volume receiving a dose of 150% was close to statistical significance. The mean volume of the skin receiving a 200% dose in the group with post-radiation reactions was 28.05 ± 16.56 cm³, the median was 24.86 (0.5–52.3) cm³, and the mean volume in the group without post-radiation reaction was 17.98 ± 10.96 cm³, median 14.95 (3.9–44.96) cm³. The result was statistically significant (Z = 2.035, p = 0.041). Conclusion: Interstitial HDR (high-dose-rate) brachytherapy for non-melanoma skin cancers around the ear is highly effective, short, and has a relatively low burden on the patient. The toxicity of the treatment was low. In the case of contact brachytherapy, the toxicity profile is slightly higher but acceptable for patients. This method is preferred in patients in whom interstitial brachytherapy is impossible to perform due to anatomical and logistical reasons. The unquestionable advantage of contact brachytherapy is its ability to be performed on an outpatient basis without the need to stay in the hospital. No severe and late CTCAE ≥III and late RTOG ≥III toxicity was observed. In patients after surgery, in order to minimise the risk of radiation reaction, it is optimal to start treatment at least eight weeks after surgery. In the presence of extensive lesions, the use of interstitial brachytherapy seems to be more advantageous, especially when the expected volume of healthy skin in the dose range of 200% and 150% is above 15 cm³ and 50 cm³, respectively.