The efficacy and roles of combining temozolomide with whole brain radiotherapy in protection neurocognitive function and improvement quality of life of non-small-cell lung cancer patients with brain metastases

Abstract

BackgroundBrain metastasis (BM) is a poor prognostic factor for non-small-cell lung cancer (NSCLC). The efficacy and roles of combining temozolomide (TMZ) with whole brain radiotherapy (WBRT) in protection neurocognitive function (NCF) and improvement quality of life (QOL) were investigated and compared with WBRT alone in the treatment of NSCLC patients with BM.MethodsA total of 238 NSCLC patients with BM were reviewed and categorized into WBRT plus TMZ (RCT) arm and WBRT alone (RT), respectively. The efficacy was evaluated with Pearson chi-square or Fisher’s exact tests, Log-rank test and Cox proportional hazards model. NCF was assessed by using revised Hopkins Verbal Learning Test (HVLT-R), Controlled Oral Word Association (COWA) test and Trail-making Test (TMT). QOL was assessed by the Functional Assessment of Cancer Treatment-Lung (FACT-L) Chinese version 4.0 questionnaire.ResultsThe average intracranial objective response (ORR) and disease control rate (DCR) for all the patients were 26.9 and 95.8%, respectively. The intracranial ORR and DCR for RCT and RT arm were 34.9% vs. 20.2% (p = 0.01) and 98.4% vs. 92.7% (p = 0.03), respectively. The median intracranial progression-free survival (PFS) and overall survival (OS) of NSCLC patients with BM were 5.2 and 7.3 months, respectively. The median PFS of RCT arm was significantly longer than that of RT arm (5.9 vs. 4.9 months, p = 0.002). The median OS of the RCT arm was also slightly longer than that of the RT arm (8.5 vs. 5.9 months), but without statistical significance (p = 0.11). Multivariate analysis indicated that TMZ was a significant factor for PFS. Statistically significant differences on NCF and QOL were observed between CRT and RT arms at 5 months. RCT showed a trend of toxicities increase compared with RT, however, the toxicities were tolerable and manageable.ConclusionsAdding TMZ to WBRT in the treatment of NSCLC patients with BM could improve the intracranial ORR, DCR, and median PFS compared with WBRT alone. Although no remarkable difference on median OS was found, adding TMZ could prevent NCF and QOL from worsening. The side effects increased by adding TMZ, but the difference was not statistical significance and toxicities were well tolerated.

Non-small cell lung cancer leptomeningeal metastases treated with intrathecal therapy plus osimertinib and temozolomide and whole-brain radiation therapy: a case report

“…Neurocognitive dysfunction has been identified after whole-brain radiation and chemotherapy. 8 , 9 However, our patient only experienced a slight decrease in recent memory, comprehension, and occasionally a slight decrease in hearing ability, which did not affect his normal daily life.…”

“… 7 A subgroup analysis showed that the treatment of NSCLC patients with whole-brain radiation therapy (WBRT) combined with TMZ had a significantly superior objective response rate (ORR; RR =1.38) to that of WBRT alone (RR =1.34, P <0.00001). 8 WBRT is one of the therapeutic options for LM. Although it may damage neurocognitive functions, 9 it is the preferred option, especially for patients with symptomatic multiple brain metastases.…”

Quality of life and efficacy of temozolomide combined with whole-brain radiotherapy in patients with brain metastases from non-small-cell lung cancer

“…In another trial, the addition of TMZ to RT conferred an advantage in terms of PFS and OR (P<0.05), but there was no significant improvement in OS compared with RT alone. There was little difference in QoL between the two groups (20). A trial reported that the OR rate of concomitant WBRT with TMZ was 45%.…”

Comparative Study Between Whole Brain Radiotherapy And Concurrent Temozolomide Versus Whole Brain Radiotherapy Alone For Patients Of Brain Metastasis

“…They documented that RT plus TMZ arm was associated with signi cantly more grade 3 to 4 nausea and thrombocytopenia. [17] Yong et al [20] and Deng et al [21] concluded that though TMZ in combination with WBRT is associated with higher incidence of adverse events particularly nausea and thrombocytopenia but patients can tolerate these effects and can be managed using medications.…”