Prophylactic Cranial Irradiation Versus Observation in Radically Treated Stage III Non–Small-Cell Lung Cancer: A Randomized Phase III NVALT-11/DLCRG-02 Study

Abstract

Purpose The purpose of the current study was to investigate whether prophylactic cranial irradiation (PCI) reduces the incidence of symptomatic brain metastases in patients with stage III non-small-cell lung cancer (NSCLC) treated with curative intention. Patients and Methods Patients with stage III NSCLC-staged with a contrast-enhanced brain computed tomography or magnetic resonance imaging-were randomly assigned to either observation or PCI after concurrent/sequential chemoradiotherapy with or without surgery. The primary end point-development of symptomatic brain metastases at 24 months-was defined as one or a combination of key symptoms that suggest brain metastases-signs of increased intracranial pressure, headache, nausea and vomiting, cognitive or affective disturbances, seizures, and focal neurologic symptoms-and magnetic resonance imaging or computed tomography demonstrating the existence of brain metastasis. Adverse effects, survival, quality of life, quality-adjusted survival, and health care costs were secondary end points. Results Between 2009 and 2015, 175 patients were randomly assigned: 87 received PCI and 88 underwent observation only. Median follow-up was 48.5 months (95% CI, 39 to 54 months). Six (7.0%) of 86 patients in the PCI group and 24 (27.2%) of 88 patients in the control group had symptomatic brain metastases ( P = .001). PCI significantly increased the time to develop symptomatic brain metastases (hazard ratio, 0.23; [95% CI, 0.09 to 0.56]; P = .0012). Median time to develop brain metastases was not reached in either arm. Overall survival was not significantly different between both arms. Grade 1 and 2 memory impairment (26 of 86 v seven of 88 patients) and cognitive disturbance (16 of 86 v three of 88 patients) were significantly increased in the PCI arm. Quality of life was only decreased 3 months post-PCI and was similar to the observation arm thereafter. Conclusion PCI significantly decreased the proportion of patients who developed symptomatic brain metastases with an increase of low-grade toxicity.

Risk factors for brain metastases in patients with non–small‐cell lung cancer

“…Previous studies have shown that PCI was able to reduce the occurrence rate of BM by approximately 50% . However, many studies have shown that PCI might have no beneficial effect on OS . In the RTOG‐0214 study, PCI failed to improve OS ( P = 0.86; 1‐year OS 75.6% vs 76.9% for PCI vs observation, respectively) .…”

“…Prophylactic cranial irradiation (PCI) is the most effective method for preventing the morbidity associated with BM in NSCLC patients. Previous studies have shown that PCI was able to reduce the occurrence rate of BM by approximately 50% . However, many studies have shown that PCI might have no beneficial effect on OS .…”

Interdisciplinary multimodality management of stage III nonsmall cell lung cancer

“…Whereas prophylactic cranial irradiation has been shown to improve survival in patients with small cell lung cancer and is a standard therapy, at least for patients with non-metastatic small cell lung cancer in complete remission [63], this is not clear for NSCLC [64][65][66]. Brain metastases are a common cause of relapse in patients with NSCLC, but although randomised trials consistently showed a reduction in the incidence of brain metastasis by using prophylactic cranial irradiation, this has not been translated into a gain in overall survival until now.…”

Strahlentherapie beim nicht metastasierten Lungenkarzinom

“…In einer kürzlich erschienenen randomisierten Phase-III-Studie wurde die prophylaktische Ganzhirnbestrahlung (PCI; 18 Fraktionen zu 2 Gy, 12 Fraktionen zu 2,5 Gy oder 10 Fraktionen zu 3 Gy) mit der Standard-Nachbeobachtung bei Patienten mit Stadium-III-NSCLC untersucht, die eine simultane oder sequenzielle Radiochemotherapie (ggf. mit anschließender Chirurgie) erhalten hatten [11]. Die Inzidenz der symptomatischen Hirnmetastasen und die Zeit bis zu deren Auftreten wurden durch die PCI statistisch signifikant reduziert (7,0 % vs. 27,2 %; p = 0,001 und p = 0,0012).…”