Role of elective brain irradiation during combined chemoradiotherapy for limited disease non-small cell lung cancer

Abstract

We have studied the clinical impact of elective brain irradiation (EBI) in patients with locally advanced, non-small cell lung cancer (LA-NSC). All patients received combination chemotherapy (cyclophosphamide + doxorubicin (Adriamycin) + cisplatin = CAP) or CAP plus radiotherapy as the initial treatment for their active tumor or as an adjuvant therapy. Of 97 evaluable patients, 46 were randomized to receive EBI (3 000 rad in 10 fractions given over two weeks). The characteristics of both groups were comparable by sex, age, performance status, pretherapy weight loss, histologic cell type, clinical staging, and type of prior therapy. EBI significantly decreased the incidence of central nervous system (CNS) metastasis in the treated group compared to the control group (4% vs 27%, p = .002). CNS involvement occurred in the treated group after failure at other sites whereas 12 of 14 control patients had CNS metastases as the first site of relapse. EBI decreased the incidence of CNS metastasis in all prognostic categories. Using multivariate analysis, the beneficial effect was shown to be significant in females, patients with good performance status, weight loss less than 6%, squamous cell histology, state III disease or no prior therapy. EBI significantly increased CNS metastasis-free interval with a beneficial effect that was significant in males, patients with weight loss less than 6%, squamous cell histology or responders. Although no survival benefit was observed for the treated group because of the adverse effect from other relapses, EBI will become more important as better treatment programs are developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors associated with the development of brain metastases

“…55 The incidence of brain metastases was markedly decreased with PCI (4% vs 27%; P < .01), although there was no difference in survival secondary to extracranial progression. In this study, PCI significantly reduced the incidence of brain metastases only in those with squamous-cell histology.…”

Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall‐cell lung cancer

“…Although randomized studies have failed to establish a survival benefit for PCI, subset analysis was not performed and it remains possible that selected patients, particularly those without evidence of disease at the primary or other extracranial sites, may significantly benefit from the prevention of brain metastasis. [10][11][12][13] Likewise, some studies have suggested that early detection of brain metastasis from NSCLC and prompt treatment with SRS can significantly improve survival, particularly among those without evidence of extracranial disease. 14,15 Whereas the optimal local-regional treatment approach for locally advanced NSCLC is uncertain, the integration of surgery as a component of multimodality therapy may enable the identification of a subset of patients, those with a pathological complete response (pCR) to neoadjuvant chemotherapy or chemoradiotherapy, who may be at high risk for the subsequent development of brain metastases.…”

“…[10][11][12] However, these results have been criticized because of patient heterogeneity and for possible imbalances in stratification according to established prognostic variables. It is unknown to what extent the development of local-regional failure or extracranial disease progression may have obscured any potential benefits that PCI may have conferred.…”

Patient preferences regarding prophylactic cranial irradiation: A discrete choice experiment

“…[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.…”