Prophylactic Cranial Irradiation in Operable Stage IIIA Non–Small-Cell Lung Cancer Treated With Neoadjuvant Chemoradiotherapy: Results From a German Multicenter Randomized Trial

BACKGROUND The risk of developing brain metastases after definitive treatment of locally advanced nonsmall cell lung cancer (NSCLC) is approximately 30%-50%. The risk for patients with early stage disease is less defined. The authors sought to investigate this further and to study potential risk factors. METHODS The records of all patients who underwent surgery for T1-T2 N0-N1 NSCLC at Duke University between the years 1995 and 2005 were reviewed. The cumulative incidence of brain metastases and distant metastases was estimated by using the Kaplan-Meier method. A multivariate analysis assessed factors associated with the development of brain metastases. RESULTS Of 975 consecutive patients, 85% were stage I, and 15% were stage II. Adjuvant chemotherapy was given to 7%. The 5-year actuarial risk of developing brain metastases and distant metastases was 10%(95% confidence interval [CI], 8-13) and 34%(95% CI, 30-39), respectively. Of patients developing brain metastases, the brain was the sole site of failure in 43%. On multivariate analysis, younger age (hazard ratio [HR], 1.03 per year), larger tumor size (HR, 1.26 per cm), lymphovascular space invasion (HR, 1.87), and hilar lymph node involvement (HR, 1.18) were associated with an increased risk of developing brain metastases. CONCLUSIONS In this large series of patients treated surgically for early stage NSCLC, the 5-year actuarial risk of developing brain metastases was 10%. A better understanding of predictive factors and biological susceptibility is needed to identify the subset of patients with early stage NSCLC who are at particularly high risk. Cancer 2010;116:5038-46.

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“…57 Patients in Arm B were scheduled to receive PCI (2 Gy Â15), but patients in Arm A were not. Thus, PCI was not a randomized variable.…”

Section: Biological Predictorsmentioning

confidence: 99%

Factors associated with the development of brain metastases

Hubbs

Boyd

Hollis

et al. 2010

Cancer

115

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“…The literature search identified six RCTs (14-18, 21, 22) and six retrospective or non-randomised prospective trials investigating survival benefits and the incidence of BM of PCI in patients with NSCLC (7,8,11,16,19,23) (Table I). Five articles assessed the effects of PCI on NF and QOL (11,12,16,18,20) (Table II). Gore et al (14) and Sun et al (20) both reported on analysis from the RTOG 0214 trial.…”

Section: Resultsmentioning

confidence: 99%

“…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.…”

Section: Abstract Background: the Use Of Prophylactic Cranial Irradimentioning

confidence: 99%

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

Precival

Landy

Poole

et al. 2018

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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,

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“…[18] Six randomised controlled trials have evaluated the role of PCI in LA-NSCLC, with five studies demonstrating a statistically significant reduction in the incidence of BM with PCI, but no survival advantage. [10,[19][20][21][22][23] The most recent of these studies was underpowered for a survival endpoint. [10] It is not clear whether patient refusal was the reason why target accrual was not met.…”

Section: Discussionmentioning

confidence: 99%