Differentiation of brain metastases from small and non-small lung cancers using apparent diffusion coefficient (ADC) maps

Abstract

Background: Brain metastases are particularly common in patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC showing a less aggressive clinical course and lower chemo- and radio sensitivity compared to SCLC. Early adequate therapy is highly desirable and depends on a reliable classification of tumor type. The apparent diffusion coefficient is a noninvasive neuroimaging marker with the potential to differentiate between major histological subtypes. Here we determine the sensitivity and specificity of the apparent diffusion coefficient to distinguish between NSCLC and SCLC.

Methods: We enrolled all NSCLC and SCLC patients diagnosed between 2008 and 2019 at the University Medical Center Göttingen. Cranial MR scans were visually inspected for brain metastases and the ratio of the apparent diffusion coefficient (ADC) was calculated by dividing the ADC measured within the solid part of a metastasis by a reference ADC extracted from an equivalent region in unaffected tissue on the contralateral hemisphere.

Results: Out of 411 enrolled patients, we detected 129 patients (83 NSCLC, 46 SCLC) with sufficiently large brain metastases with histologically classified lung cancer and no hemorrhage. We analyzed 185 brain metastases, 84 of SCLC and 101 of NSCLC. SCLC brain metastases showed an ADC ratio of 0.68 ± 0.12 SD, and NSCLC brain metastases showed an ADC ratio of 1.47 ± 0.31 SD. Receiver operating curve statistics differentiated brain metastases of NSCLC from SCLC with an area under the curve of 0.99 and a 95% CI of 0.98 to 1, p < 0.001. Youden's J cut-point is 0.97 at a sensitivity of 0.989 and a specificity of 0.988.

Conclusions: In patients with lung cancer and brain metastases with solid tumor parts, ADC ratio enables an ad hoc differentiation of SCLC and NSCLC, easily achieved during routine neuroradiological examination. Non-invasive MR imaging enables an early-individualized management of brain metastases from lung cancer.

Trial registration: The study was registered in the German Clinical Trials Register (DRKS00023016).

Keywords: ADC; Brain metastases; Diffusion; NSCLC; SCLC.

Fig. 1

Two examples of ADC-ratios of brain metastasis in 3-T MRI (T1 with contrast agent and ADC map): left: typical SCLC with ADC ratio of 484/819 = 0.59, right: NSCLC with ADC ratio of 812/478 = 1.70. SCLC small cell lung cancer, NSCLC non-small cell lung cancer, ADC apparent diffusion coefficient

Fig. 2

Participant flow chart. AC adenocarcinoma, ADC apparent diffusion coefficient, CA contrast agent, NSCLC non-small cell lung cancer, SCC squamous cell carcinoma, SCLC small cell lung cancer

Fig. 3

Overview results—a Pie charts of the patient cohort: distribution of patients with measurable brain metastases of lung cancer, and d distribution of only pre-therapeutic patients. b Histogram: distribution of ADC ratio of all measured metastases and, e only pre-therapeutic metastases of small cell lung cancer (left) and non-small cell lung cancer (right, contains only squamous cell carcinoma and adenocarcinoma). c Whisker-Box-Plot of ADC ratios grouped by histologies. f Receiver operating characteristics curve and area und curve of all, pre- and post-therapeutic patients with confidence interval. AC adenocarcinoma, SCC squamous cell carcinoma, SCLC small cell lung cancer