Abstract Background Pseudoprogression (psPD) represents false radiologic evidence of tumor progression and is observed in some glioblastoma (GBM) patients after postoperative chemoradiation (CRT) with temozolomide (TMZ). The ambiguity of the psPD diagnosis confounds identification of true progression and may lead to unnecessary interventions. The association between psPD and isocitrate dehydrogenase 1 (IDH1) mutational (mut) status is understudied, and its incidence may alter clinical decision making. Methods We retrospectively evaluated 120 patients with IDH1-mut (n = 60) and IDH1–wild-type (IDH-WT; [n = 60]) GBMs who received postoperative CRT with TMZ at 4 academic institutions. Response Assessment in Neuro-Oncology criteria were used to identify psPD rates in routine brain MRIs performed up to 90 days after CRT completion. Results Within 90 days of completing CRT, 9 GBM patients (1 [1.7%] IDH1-mut and 8 [13.3%] IDH1-WTs) demonstrated true progression, whereas 17 patients (3 [5%] IDH1-muts and 14 [23.3%] IDH1-WTs) demonstrated psPD (P = .004). IDH1-mut GBMs had a lower probability of psPD (hazard ratio: 0.173, 95% CI, 0.047-0.638, P = .008). Among the patients with radiologic signs suggestive of progression (n = 26), psPD was found to be the cause in 3 of 4 (75.0%) of the IDH1-mut GBMs and 14 of 22 (63.6%) of the IDH1-WT GBMs (P = .496). Median overall survival for IDH1-mut and IDH1-WT GBM patients was 40.3 and 23.0 months, respectively (P < .001). Conclusions IDH1-mut GBM patients demonstrate lower absolute rates of psPD expression. Irrespective of GBM subtype, psPD expression was more likely than true progression within 90 days of completing CRT. Continuing adjuvant treatment for IDH1-mut GBMs is suggested if radiologic progression is suspected during this time interval.
2025 Background: The rate of symptomatic radiation necrosis in patients treated with immune checkpoint inhibitor (ICI) therapy and concomitant single-fraction stereotactic radiosurgery (SRS) is as high as 20% (Martin et al., JAMA Oncology 2018). Here, we present the first results from the Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) trial, aimed to identify reduced-dose SRS that is safe and efficacious for this patient population. Methods: RADREMI is a prospective multicenter, single arm phase I pilot study. Patients age > 18 receiving ICI with SRS for 1-10 brain metastases on MRI from biopsy-confirmed primary malignancy with estimated median survival of at least 6 months (by disease-specific graded prognostic assessment) and no history of whole brain radiation therapy were eligible. The primary endpoint was six-month symptomatic radiation necrosis (defined as a six-month rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with imaging findings consistent with radiation necrosis), based on a historical six-month symptomatic radiation necrosis rate of 16% and an expected rate of 5%. Secondary endpoints included six-month local control and six-month radiographic radiation necrosis. Local control was defined according to Response Assessment in Neuro-Oncology (RANO) criteria, and was compared to historical controls of 87-91% six-month local control with RTOG 90-05 SRS dosing. The Fisher’s exact test was used for statistical analysis. This trial is registered at clinicaltrials.gov, NCT04047602. Results: Between December 18, 2019 and January 21, 2021, 39 lesions were treated in 17 patients receiving ICI delivered within 30 days before SRS from whom we recruited and obtained consent. All patients were treated with RADREMI dosing, which involved SRS doses of 18 Gy for lesions 0-2 cm, 14 Gy for lesions 2.1-3 cm, and 12 Gy for lesions 3.1-4 cm. The most common ICI used was single-agent pembrolizumab (49% of lesions, 59% of patients), followed by single-agent nivolumab (31% of lesions, 12% of patients). For the 11 lesions (six patients) meeting the primary endpoint (median follow-up = 259 days), the six-month symptomatic radiation necrosis rate was 0% per treated lesion, and 0% per treated patient, which was not significantly different from historical controls (p = 0.478). The six-month local control rate was 100% per treated lesion, and 100% per treated patient, comparable to historical controls (p = 0.476). Conclusions: In the first prospective trial to investigate dose-reduced SRS with concomitant ICI in treating metastatic brain disease, early results support the safety and efficacy of RADREMI dosing in this patient population. These findings warrant further multi-institutional collaborative trials of RADREMI dosing for this population. Clinical trial information: NCT04047602.
GammaTile® (GT Medical Technologies, Tempe, Arizona) is a surgically targeted radiation source, approved by FDA for brachytherapy in primary and secondary brain neoplasms. Each GammaTile is composed of a collagen sponge with four seeds of cesium 131 and is particularly useful in recurrent tumors. We report our early experience in seven patients with recurrent gliomas to assess this type of brachytherapy with particular attention to ease of use, complication, and surgical planning. This study represents a retrospective chart review of surgical use and early clinical outcomes of GammaTile in recurrent gliomas. The number of tiles was planned using pre-operative imaging and dosimetry was planned based on post-operative imaging. Patients were followed during their hospital stay and were followed up after discharge. Parameters such as case length, resection extent, complication, ICU length of stay (LOS), hospital LOS, pre-operative Glasgow Coma Scale (GCS), immediate post-operative GCS, post-operative imaging findings, recurrence at follow-up, length of follow-up, and dosimetry were collected in a retrospective manner. Seven patients were identified that met the inclusion criteria. Two patients were diagnosed with recurrent glioblastoma multiforme (GBM), one lower-grade glioma that recurred as a GBM, one GBM that recurred as a gliosarcoma, and two recurrent oligodendrogliomas. We found that operation time, ICU LOS, hospital LOS, pre- and post-operative GCS, and post-operative complications were within the expected ranges for tumor resection patients. Further, dosimetry data suggests that six out of seven patients received adequate radiation coverage, with the seventh having implantation limitations due to nearby organs at risk. We report no postoperative complications that can be attributed to the GammaTiles themselves. In our cohort, we report seven cases where GammaTiles were implanted in recurrent gliomas. No implant-related post-operative complications were identified. This early data suggests that GammaTile can be a safe form of brachytherapy in recurrent gliomas.
A 48-year-old man presented with 2 episodes of massive hemoptysis separated by 10 months. On the second occasion, bronchoscopy revealed an exophytic lesion at the takeoff of the left upper lobe bronchus that bled in a pulsatile fashion. The bleeding was emergently controlled by coagulation with a Nd:YAG laser. No vascular abnormality could be seen at this location by bronchial arteriography, therefore endovascular embolization was not an option. Surgical sleeve resection was not considered a reasonable option given the location of the lesion. Endobronchial brachytherapy (intraluminal radiation) was chosen as an alternative therapy because it is known to cause vasoconstriction and vascular sclerosis. The patient had complete bronchoscopic resolution of the lesion 10 weeks postradiation and has been free from hemoptysis for 26 months. The long-term efficacy and safety of endobronchial brachytherapy for vascular lesions of the airway has yet to be defined.
