Rapid tumor doubling in the CNS

Abstract

We quantify a three day tumor doubling time for small cell lung cancer metastatic to the brain in a case of a 61 yearold woman with a 30 pack-year smoking history. She was diagnosed with extensive stage small cell lung carcinoma with bone metastases and was treated with four cycles of carboplatin and etoposide. After four cycles of chemotherapy, a restaging body CT scan demonstrated a partial response with near-total resolution of right hilar nodules, but retained residual diffuse patchy bony metastases. The patient also underwent an MRI of the brain, which demonstrated no evidence of disease (Figure, image c, d, and g includes Axial T1 MRI images using a 1.5 Tesla magnet with Gadolinium contrast and TI flair image). Thirty-nine days after the MRI of the brain, the patient presented with complaints of headache, nausea and vomiting, blurred and double vision, and severe dizziness. Neurological examination was unremarkable. An MRI study demonstrated multiple areas of high attenuation lesions throughout the meninges, cortex, and grey-white matter junction (image a, b, and f, axial T1 with contrast and T1 flair). She was treated with whole brain irradiation, at a total dose of 30 Gy in 3 Gy fractions and oral dexamethasone 4 mg three times a day, and her neurologic symptoms improved. A repeat MRI study two weeks following the completion of radiation therapy (image e and h, axial T1 with contrast and T1 flair from a 3.0 GE Tesla magnet), demonstrated a complete response, but the response was not enduring. The patient elected to enroll in a palliative care program six weeks following her last radiation treatment and soon passed away. The development of demonstrable new disease within thirty-nine days allowed us to calculate a tumor growth doubling time based on volume. Although the first MRI study did not demonstrate disease, we estimated the initial tumor size (diameter) to be the limit of spatial resolution of our GE 1.5 Tesla scanner, which is 0.7 mm. Approximate tumor doubling times were then calculated based on the diameter from the second MRI study using the formula: VDT = (t 9 log2) / (log (Vt/Vo)), where t = the interval between two CT scans, Vt = the tumor volume at the second MRI scan and Vo = the tumor volume at the initial MRI scan [1]. The calculations only provide lower ranges of the tumor doubling time, as the actual and upper range are unknown. Using this equation, the tumor doubling times were calculated to be three days for the two largest parenchymal brain metastases and four days for the next three largest lesions. Interest in tumor doubling times has been rekindled with improved imaging studies used in screening for lung and liver cancers, and with the use of volumetric doubling to determine treatment plans and to assess the malignant potential of various small lesions [1–5]. Factors affecting tumor volume doubling include the type of cancer, local environment, the rate of cell death, and the cell-cycling time [6]. For small cell lung cancer the mean volume doubling times reported range from 30 to 97 days, however, as median survival without treatment is only 3 to 1.5 months depending on limited or extensive stage, respectively, the disease is clinically aggressive [1, 7–9]. J. A. Christensen L. Bressler K. Bath S. Chichili J. L. Villano (&) Section of Hematology/Oncology, Neurology, and Department of Pharmacy Practice, University of Illinois at Chicago, 909 S. Wolcott Av. M/C 734, Chicago, IL 60612, USA e-mail: jvillano@uic.edu