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Journal of Thoracic Oncology:
doi: 10.1097/JTO.0b013e31811f3abb
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Radiation Necrosis Mimicking Progressive Brain Metastasis in a Patient with Non-small Cell Lung Cancer

Ohashi, Kadoaki MD*; Kiura, Kastuyuki MD, PhD*; Takigawa, Nagio MD, PhD*; Umemura, Shigeki MD*; Kondo, Naruhito MD*; Takemoto, Mistuhiro MD, PhD†; Onoda, Kensuke MD, PhD‡; Aoe, Motoi MD, PhD§; Tabata, Masahiro MD, PhD*; Tanimoto, Mistune MD, PhD*

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Departments of *Hematology, Oncology, and Respiratory Medicine; †Radiology; ‡Neurological Surgery; §Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences & Okayama University Hospital, Okayama, Japan.

Disclosure: The authors declare no conflict of interest.

Address for correspondence: Katsuyuki Kiura, MD, PhD, 2-5-1 Shikatacho, Okayama 700-8558, Japan. E-mail:

A 56-year-old Japanese woman presented with adenocarcinoma of the lung in March 2002. The clinical stage was determined to be IIIB (T2N3N0). She had never smoked. She received concomitant chemoradiotherapy consisting of cisplatin/docetaxel and 40 Gy thoracic radiation followed by a right upper lobectomy and mediastinal dissection. Four brain metastatic lesions were detected by gadolinium-enhanced magnetic resonance imaging (Gd-MRI) at 7 months postthoracotomy (Figure 1A). The patient received whole-brain radiation therapy (WBRT) (total 30 Gy) followed by X-knife stereotactic radiotherapy (SRS) (20 Gy) for the treatment of the four lesions. Thereafter, the brain tumors regressed at 1 month after WBRT followed by SRS (Figure 1B). Lung metastasis was detected in the left upper lobe at 15 months postthoracotomy. She received one cycle of systemic chemotherapy consisting of cisplatin, docetaxel, and irinotecan. The lung tumor regressed; however, the brain tumors later regrew. The patient was thereafter treated with gefitinib because L858R mutation at exon 21 of EGFR from the lung biopsy specimen was detected, and gefitinib was considered to be effective for brain metastasis.1 The lung tumor regressed further, and video-assisted thoracic surgery showed a pathologically complete response. However, the largest brain tumor in her right occipital lobe gradually enlarged (Figure 1C). The patient then underwent cyber-knife SRS (20 Gy), but the tumor continued to progress. Hemianopia, visual hallucination, gait disturbance, and unconsciousness developed 6 months after the second SRS (Figure 1D). At that time, the total dose of radiation used to treat the brain tumor was 70 Gy. Subsequently, the brain lesion was surgically removed. No tumor cells were detected on a pathologic examination. The pathological diagnosis was radiation necrosis (Figure 2).2 At the time of this report, the patient is doing well with no tumor recurrence 48 months after the first SRS.

Figure 1
Figure 1
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Figure 2
Figure 2
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In many countries, WBRT, SRS, or combinations of surgery and radiotherapy are still the standard treatment protocol for brain metastases.3 Recently, SRS has become the preferred treatment only for smaller metastases and in single or oligometastases. Practice Guidelines in Oncology v.2.2006 recommends WBRT with or without SRS for selected patients with multiple (more than three) metastatic lesions on computed tomography scan or MRI.4 WBRT followed by SRS did work very well by the early detection of recurrence in the brain, because each brain tumor measured less than 1 cm in diameter. However, the patient had a second recurrence in the lung. A single metastatic lung tumor in this case markedly regressed with gefitinib therapy; however, the brain tumor did not. The conflicting response to gefitinib by the brain tumor seemed to suggest radiation necrosis. This clinical discrepancy is considered to be a significant phenomenon. As a result, this patient might not have needed additional SRS for the enlarged lesion because it might have been the result of radiation necrosis. We should therefore possibly have considered conservative therapy using steroids, glycerol, or hyperbaric oxygen therapy at least initially, although a surgical resection for the progression of brain metastasis has been reported to benefit selected patients with either neurological deficits or steroid dependency.5 Radiation necrosis is thus considered to be important sequelae, even for patients with advanced non-small cell lung cancer. We should therefore include radiation necrosis in the differential diagnosis of enlarged brain tumors demonstrating a ring-like enhancement on Gd-MRI after SRS.

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We thank Dr. Brian Quinn, Kyushu University, for the critical reading of our manuscript.

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1. Hotta K, Kiura K, Ueoka H, et al. Effect of gefitinib (‘Iressa', ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer. Lung Cancer 2004;46:255–261.

2. Tran TA, Fuller GN, Whitman GJ, et al. Delayed cerebral radiation necrosis. AJR Am J Roentgenol 2003;180:70.

3. Langer CJ, Mehta MP. Current management of brain metastases, with a focus on systemic options. J Clin Oncol 2005;23:6207–6219.

4. Non-small cell lung cancer. The National Comprehensive Cancer Network Practice Guidelines in Oncology –v. 2.2006. Available at: Accessed March 14, 2007.

5. Truong MT, St. Clair EG, Donahue BR, et al. Results of surgical resection for progression of brain metastases previously treated by gamma knife radiosurgery. Neurosurgery 2006;59:86–97.

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Japanese Journal of Clinical Oncology
Pseudoprogression of lung cancer after concomitant chemoradiotherapy
Ichihara, E; Kiura, K; Takigawa, N; Omori, M; Aoe, M; Tanimoto, M; Date, H
Japanese Journal of Clinical Oncology, 38(2): 140-142.
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© 2007International Association for the Study of Lung Cancer


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