Safety and Efficacy of Irradiation Boost Based on 18F-FET-PET in Patients with Newly Diagnosed Glioblastoma.

PURPOSE: Dual timepoint fluoro-ethyl-tyrosine (FET)-PET acquisition (10 and 60 minutes after FET injection) improves the definition of glioblastoma (GBM) location and shape. Here we evaluated the safety and efficacy of simultaneous integrated boost (SIB) planned using dual FET-PET for postoperative GBM treatment. PATIENTS AND METHODS: In this prospective pilot study (March 2017-December 2020), 17 patients qualified for FET-PET-based SIB intensity-modulated radiotherapy after resection. The prescribed dose was 78 and 60 Gy (2.6 and 2.0 Gy per fraction, respectively) for the FET-PET- and magnetic resonance (MR)-based target volumes. Eleven patients had FET-PET within 9 months to precisely define biological responses. Progression-free survival (PFS), overall survival (OS), toxicities, and radiation necrosis were evaluated. Six patients (35%) had tumors with MGMT promoter methylation. RESULTS: The 1- and 2-year OS and PFS rates were 73% and 43% and 53% and 13%, respectively. The median OS and PFS were 24 [95% confidence interval (CI), 9-26] and 12 (95% CI, 6-18) months, respectively. Two patients developed uncontrolled seizures during radiotherapy and could not receive treatment per protocol. In patients treated per protocol, 7 of 15 presented with new or increased neurologic deficits in the first month after irradiation. Radiation necrosis was diagnosed by MRI 3 months after SIB in 5 patients and later in another 2 patients. In 2 patients, the tumor was larger in FET-PET images after 6 months. CONCLUSIONS: Survival outcomes using our novel dose-escalation concept (total 78 Gy) were promising, even within the MGMT unmethylated subgroup. Excessive neurotoxicity was not observed, but radionecrosis was common and must be considered in future trials.

Stereotactic Radiosurgery of Brain Metastasis in Patients with a Poor Prognosis: Effective or Overtreatment?

PURPOSE: Stereotactic radiosurgery (SRS) of brain metastasis in patients with a poor prognosis remains controversial. Here, we compared results of SRS alone to whole brain radiotherapy (WBRT) in poor-prognosis patients and defined the most important unfavorable prognostic factors related to early death after SRS alone. PATIENTS AND METHODS: In this retrospective analysis of prospective SRS data, 180 patients with brain metastases not previously treated with WBRT were analyzed. Results of SRS were compared to WBRT by propensity score matching in patients with a poor prognosis defined by graded prognostic assessment (GPA) <2. Further, SRS patients were divided into training (n=82) and validation (n=48) cohorts. Overall survival (OS) and the risk of early death were defined by univariable and multivariable analyses. RESULTS: Median survival of the WBRT and SRS cohorts was 86 days (IQR: 38-172 days) and 201 days (IQR: 86-not reached), respectively (p<0.0001). OS in patients with GPA<2 was significantly longer in the SRS vs WBRT group (123 vs 58 days; p=0.008). Survival was longer in the SRS group in a propensity score matched analysis. In multivariable analysis, GPA (OR: 0.44, 95%CI: 0.21-0.95; p=0.001), extensive extracranial disease (OR: 0.13, 95%CI: 0.02-0.66; p=0.013), and serious neurological deficits (OR: 0.13, 95%CI: 0.04-0.45; p=0.001) were associated with early death. If one factor was favorable, 73% (training) and 92% (validation) of patients survived three months. Patients with GPA <2 presenting with serious neurological deficits and extensive extracranial disease had a low expected benefit due to the highest risk of death within three months (AUC: 0.822 training; 0.932 validation). CONCLUSION: SRS is a viable treatment option for patients with a poor prognosis defined as GPA <2. Good neurological status, extracranial oligometastatic disease, or GPA ≥2 should be present to justify SRS in patients with brain metastases.

The impact of adjuvant radiotherapy on molecular prognostic markers in gliomas.

PURPOSE: Changes in MGMT promoter methylation, IDH1 and IDH2 mutation, and 1p/19q co-deletion status in gliomas between first and subsequent resections and their associated clinical factors are poorly described. In this study, we assayed these biomarkers in the clinical setting. PATIENTS AND METHODS: We used multiplex ligation-dependent probe amplification to measure MGMT promoter methylation, IDH mutation status, and 1p/19q co-deletion in 45 paired tumor samples from patients undergoing resection and subsequent re-resections for gliomas. RESULTS: Molecular changes were present in 20 patients (44%). At least one molecular characteristic changed over time in 89% of patients with primary grade III tumors. Gliomas with IDH wild-type and/or non-co-deleted were stable, but IDH1/2 mutation and/or co-deletion were sometimes lost at the time of recurrence. In a multivariate analysis, adjuvant radiotherapy alone was independently associated (P=0.02) with changes in molecular profile. CONCLUSION: Molecular biomarkers change in gliomas during the course of the disease, most often MGMT methylation status. These changes in genetic profiles are related to adjuvant treatment with radiotherapy alone, which might be important for individualized treatment planning over the disease course.

Prospective evaluation of anxiety, depression and quality of life in medically inoperable early stage non-small cell lung cancer patients treated with stereotactic ablative radiotherapy.

AIM: The aim of this prospective study was to evaluate the level of anxiety, depression, and quality of life (QoL) in medically inoperable patients with early stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR). BACKGROUND: Prolonged survival is equally important as maintaining high QoL and good psychological functioning during the treatment of lung cancer. Nowadays available SABR has markedly changed clinical care and outcomes in the group of medically inoperable patients. To our knowledge, analysis of QoL and psychological state has not been performed in Polish patients with early NSCLC treated with SABR. MATERIALS AND METHODS: Research group consisted of medically inoperable, early NSCLC (T1-2aN0M0) patients qualified to SABR. Patients were asked to complete Polish versions of the European Organization for Research and Treatment of Cancer Quality of Life - Core Questionnaire (EORTC QLQ-C30) with the Lung Cancer Questionnaire (LC13) and Hospital Anxiety and Depression Scale (HAD). These questionnaires were repeated 2 weeks and then 3 months after treatment completion. RESULTS: We enrolled 51 patients who met the inclusion criteria. SABR did not deteriorate QoL and psychological functioning. On the contrary, clinically meaningful improvement was observed in emotional functioning, level of insomnia, anxiety and depression. Significantly worse improvement was shown in patients with chronic obstructive pulmonary disease (COPD). CONCLUSIONS: Our results confirm that SABR is well tolerated and does not have a deleterious effect on QoL and psychological state. Results of our study indicate the importance of additional psychological care in the group of patients with COPD.