Sai-Hong Ignatius Ou1, Samuel J Klempner2, Michele C Azada3, Veronica Rausei-Mills4, Christopher Duma5. 1. Department of Medicine, Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, CA 92868, United States; Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA 92868, United States. Electronic address: Ignatius.ou@uci.edu. 2. Department of Medicine, Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, CA 92868, United States; Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA 92868, United States. 3. Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA 92868, United States. 4. Department of Pathology, Hoag Memorial Hospital Presbyterian, One Hoag Drive, Newport Beach, CA 92658, United States. 5. Hoag Neurosciences Institute, Director, Hoag Brain Tumor Program, Hoag Memorial Hospital Presbyterian, Newport Beach, CA 92663, United States.
Abstract
OBJECTIVES: Radiation necrosis presenting as pseudoprogression (PsP) is relatively common after radiation and temozolomide (TMZ) treatment in glioblastoma multiforme (GBM), especially among patients with GBM that harbors intrinsic increased responsiveness to TMZ (methylated O6-methylguanine-DNA methyltransferase [MGMT] promoter). Alectinib is a second generation ALK inhibitor that has significant CNS activity against brain metastases in anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: We report 2 ALK+ NSCLC patients who met RECIST criteria for progressive disease by central radiologic review due to increased in size from increased contrast enhancement in previously stereotactically radiated brain metastases with ongoing extra-cranial response to alectinib. In both patients alectinib was started within 4 months of completing stereotactic radiosurgery (SRS). The enlarging lesions in both patients were resected and found to have undergone extensive necrosis with no residual tumor pathologically. PsP was incorrectly classified as progressive disease even by central independent imaging review. CONCLUSIONS: Treatment-related necrosis of previously SRS-treated brain metastasis during alectinib treatment can present as PsP. It may be impossible to distinguish PsP from true disease progression without a pathologic examination from resected sample. High degree of clinical suspicion, close monitoring and more sensitive imaging modalities may be needed to distinguish PsP versus progression in radiated brain lesions during alectinib treatment especially if there is no progression extra-cranially.
OBJECTIVES:Radiation necrosis presenting as pseudoprogression (PsP) is relatively common after radiation and temozolomide (TMZ) treatment in glioblastoma multiforme (GBM), especially among patients with GBM that harbors intrinsic increased responsiveness to TMZ (methylated O6-methylguanine-DNA methyltransferase [MGMT] promoter). Alectinib is a second generation ALK inhibitor that has significant CNS activity against brain metastases in anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: We report 2 ALK+ NSCLCpatients who met RECIST criteria for progressive disease by central radiologic review due to increased in size from increased contrast enhancement in previously stereotactically radiated brain metastases with ongoing extra-cranial response to alectinib. In both patientsalectinib was started within 4 months of completing stereotactic radiosurgery (SRS). The enlarging lesions in both patients were resected and found to have undergone extensive necrosis with no residual tumor pathologically. PsP was incorrectly classified as progressive disease even by central independent imaging review. CONCLUSIONS: Treatment-related necrosis of previously SRS-treated brain metastasis during alectinib treatment can present as PsP. It may be impossible to distinguish PsP from true disease progression without a pathologic examination from resected sample. High degree of clinical suspicion, close monitoring and more sensitive imaging modalities may be needed to distinguish PsP versus progression in radiated brain lesions during alectinib treatment especially if there is no progression extra-cranially.
Authors: Jessica J Lin; Ginger Y Jiang; Nencyben Joshipura; Jennifer Ackil; Subba R Digumarthy; Sandra P Rincon; Beow Y Yeap; Justin F Gainor; Alice T Shaw Journal: J Thorac Oncol Date: 2018-12-07 Impact factor: 15.609