The Role of Prophylactic Cranial Irradiation for Non-small Cell Lung Cancer

Abstract

Abstract. Background: The use of prophylactic cranial irradiation (PCI) to treat brain metastases (BM) in non-small cell lung cancer (NSCLC) is restricted due to the potential associated toxicity and lack of survival benefit. BM can have a negative impact on neurocognitive function (NF) and quality of life (QOLProphylactic cranial irradiation (PCI) is a technique that delivers radiation therapy (RT) to the whole brain to prevent the occurrence of brain metastases (BM) in aggressive cancer types that commonly metastasise to the brain (1). The rationale behind PCI is to eliminate undetectable micrometastases before they become clinically apparent (1).According to the American Cancer Society, about 85-95% of all lung cancer cases are non-small cell lung cancer (NSCLC) (2). The brain is the first site of metastases for up to 30% of these patients (3), with 60% of BM occurring in the first 6 months (4). With modern advances in the management of NSCLC, the risk of developing BM increases as survival is prolonged (5). The reported incidence of BM from NSCLC ranges from 17% to 54%, with younger patients, those with locally advanced-stage disease, adenocarcinoma and large cell types at the higher end of this range of incidence (4, 6-9). BM are associated with high morbidity, poor prognosis (10) and neurocognitive and quality of life (QOL) deficits (10-12).Patients with small cell lung cancer derive an overall (OS) and BM-free survival benefit from PCI (13). PCI for patients with NSCLC is not widely used due to the lack of established evidence for OS benefit and the potential for neurological toxicity post RT. PCI for NSCLC may not have an impact on OS or disease-free survival (DFS) but it has been shown to reduce the incidence of BM (11,(14)(15)(16)(17)(18)(19), therefore it is a matter of debate if these patients benefit from PCI.Late cognitive toxicities are suggested to be associated with PCI and these may be a factor in the prescribing of this treatment. The Radiation Therapy Oncology Group trial (RTOG)-0214 reported a significant decline in memory at 1 year with PCI use (20). Neurocognitive function (NF) decline may occur as a direct result of vascular injury, demyelination or radionecrosis (20).This review aimed to investigate published literature on the use of PCI in patients with NSCLC to assess the impact of PCI on disease-specific outcomes and report the effects of PCI on NF and QOL outcomes. Materials and MethodsTo ensure all appropriate studies were included in this review, a systematic approach was used for searching and selecting relevant publications. As the technique for treating PCI has remained relatively unchanged over the years,

Prevalence and Characteristics of Symptomatic Pneumonitis After Radiotherapy of Patients With Locally Advanced Lung Cancer

“…Radiotherapy alone or in combination with systemic therapies is commonly used for treating locally advanced lung cancers (2). As the prognosis of these patients is often limited, considerable research is carried out to improve their outcomes (9)(10)(11)(12)(13). If radiotherapy is administered, high doses are often required, particularly if the treatment approach is considered curative.…”

Phosphorylated-Akt overexpression is associated with a higher risk of brain metastasis in patients with non-small cell lung cancer

“…However, the results of previous studies evaluating PCI for NSCLC were less than satisfactory. Indeed, in most trials, PCI reduced the incidence of BM, but had no impact on overall survival [ 6 , 7 ]. This observation may reflect the fact that not all patients with NSCLC require PCI [ 2 ].…”

Brain metastases from non-small cell lung carcinoma: an overview of classical and novel treatment strategies

“…In respect of OS, because the studies had a very short follow-up, and for QoL, data were only collected in a few studies. The most recent systematic review published by Precival et al [41] shows identical results with a reduced incidence of metastases with PCI but no differences in OS. This lack of difference in OS may be due to methodological deficiencies in the studies, some of which were conducted on small series of patients or had incomplete recruitment.…”

“…27.4 months in the control group, with a p value of 0.13, although the study did not complete recruitment [ 40 ]. As an exception, the Southwest Oncology Group, SWOG [ 41 , 42 ], observed a significant reduction in OS in the PCI group, although this was probably due to the simultaneous administration of thoracic RT, and the high brain dose administered (37.5 Gy). Although the RTOG 84-03 study did not report a significant reduction in the incidence of brain metastases, 9% vs .…”