Small cell lung cancer intracranial metastases

Approximately 10% of patients present with small cell lung cancer intracranial metastases at the time of initial diagnosis.

Approximately 60% of patients with small cell lung cancer (SCLC) develop brain metastases.

The incidence of such metastases increases considerably during the course of disease, approaching 80% at 2 years.

2012

In 251 patients, the median age of them was 65 years, majority were male (67%), smokers or ex-smokers (98%), with performance status 0 to 1 (83%). At the time of diagnosis no metastases were found in 64 patients (25.5%) and metastases outside the brain were presented in 153 (61.0%). Brain metastases, confirmed by a CT scan, were present in 34 patients (13.5%), most of them had also metastases at other localisations. All patients received chemotherapy and all patients with confirmed brain metastases received whole brain irradiation (WBRT). The radiotherapy with radical dose at primary tumour was delivered to 27 patients with limited disease and they got 4-6 cycles of chemotherapy. Median overall survival (OS) of 34 patients with brain metastases was 9 months (95% CI 6-12) while OS of 153 patients with metastases in other locations was 11 months (95% CI 10-12); the difference did not reach the level of significance (p = 0.62). As expected, the OS of patients without metastases at the time of primary diagnosis turned out to be significantly better compared to the survival of patients with either brain or other location metastases at the primary diagnosis (15 months vs 9 and 11 months, respectively, p < 0.001).

The prognosis of patients with extensive SCLS with brain metastases at the primary diagnosis treated with chemotherapy and WBRT was not significantly worse compared to the prognosis of patients with extensive SCLC and metastases outside the brain. In extensive SCLC brain metastases were not a negative prognostic factor per se if the patients were able to be treated appropriately. However, the survival rates of extensive SCLC with or without brain metastases remained poor and novel treatment approaches are needed. The major strength of this study is that it has been done on a population of patients treated in a routine clinical setting 1).

2000

In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m(2) was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain.

One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P<.001). Time to progression in the brain was longer in the combined-modality group (P=.005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P=.087).

Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different 2).

1987

429 patients with small cell lung cancer were reviewed. Forty-three patients (10%) presented with brain metastases. In 18 patients the brain was the only site of metastatic disease, whereas the remaining 25 patients had at least one additional metastatic site. Forty-one of forty-three patients were treated with combination chemotherapy and cranial radiotherapy. Systemic response rates were similar for both groups. Twenty-seven patients underwent repeat central nervous system staging: 19 (70%) had a complete response, 4 (15%) a partial response, and 4 (15%) no response. Median survival of patients with only one site of metastatic disease was 11 months; patients with additional sites lived 5 months (p = 0.153). Survival in patients with only one site is similar to that in patients with limited disease (11 compared with 13 months; p = 0.074) 3).

Small Cell Lung Carcinoma Metastasis To Atypical Meningioma: The Importance Of Perfusion Mri Graphics In Differential Diagnosis 4).


1)
Lekic M, Kovac V, Triller N, Knez L, Sadikov A, Cufer T. Outcome of small cell lung cancer (SCLC) patients with brain metastases in a routine clinical setting. Radiol Oncol. 2012 Mar;46(1):54-9. doi: 10.2478/v10019-012-0007-1. Epub 2012 Jan 2. PubMed PMID: 22933980; PubMed Central PMCID: PMC3423766.
2)
Postmus PE, Haaxma-Reiche H, Smit EF, Groen HJ, Karnicka H, Lewinski T, van Meerbeeck J, Clerico M, Gregor A, Curran D, Sahmoud T, Kirkpatrick A, Giaccone G. Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy–a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol. 2000 Oct 1;18(19):3400-8. PubMed PMID: 11013281.
3)
Giannone L, Johnson DH, Hande KR, Greco FA. Favorable prognosis of brain metastases in small cell lung cancer. Ann Intern Med. 1987 Mar;106(3):386-9. PubMed PMID: 3028222.
4)
Danisman Specialist MÇ, Koplay M, Paksoy Y, Keleşoğlu KS, Karabağlı P, Köktekir E. Small Cell Lung Carcinoma Metastasis To Atypical Meningioma: The Importance Of Perfusion Mri Graphics In Differential Diagnosis. World Neurosurg. 2019 Jan 28. pii: S1878-8750(19)30182-2. doi: 10.1016/j.wneu.2019.01.084. [Epub ahead of print] PubMed PMID: 30703595.
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