PMC7553601_01
Summary of the treatment course in this case report. Arrows indicate the target lesions in the imaging studies.
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However, tumor recurrence occurred 3 months later, with a new left lower lung tumor, bone (left clavicle and right femur) and brain (left cerebral frontal lobe) metastases (Figure 1). Because of the chemoresistant nature of PPC, the patient received an aggressive multidisciplinary approach including lung tumor resection (S6 segmentectomy) in February 2018, radiation to the bone metastases (35 Gy in five fractions to the left clavicle and right femur) in February 2018, and brain tumor resection in March 2018 followed by radiation to the brain tumor bed (18 Gy in a single fraction) (Figure 1). TKIs persisted until November 2018, although new lung tumors emerged in the right upper and lower lobes (Figure 1). The lung tumor, bone, and renal metastases responded well during follow-up (last image study in June 2020 as showed in Figure 1), except a pseudoprogression of the left frontal lobe brain tumor occurring in March 2019, which was confirmed as radiation necrosis after surgical resection (Figure 3). Recurrence of radiation necrosis was noted 3 months after surgery, and it later spontaneously resolved. The patient is still under lorlatinib therapy since November 2018 with a sustained systemic partial remission. The total treatment course is summarized in Figure 1.
The left lower lobe tumor showed a pleomorphic carcinoma characterized by large, pleomorphic tumor cells (A) and spindle cells (B). These tumor cells demonstrated co-expression of TTF-1 (C) and vimentin (D) immunoreactivities, indicating an adenocarcinoma with sarcomatoid transformation. The tumor cells were negative for ROS1 (E) while using the D4D6 assay, and positive for ROS1 (F) with the SP384 assay.
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The pathologic findings of the lung (Figure 2A) and brain tumors showed pleomorphic carcinoma (Figure 2B) arising in an adenocarcinoma, which was positive for thyroid transcription factor 1 (Figure 2C) and vimentin (Figure 2D) and negative for CK7. Using a more sensitive ROS-1 antibody (SP384), we disclosed both resected lung tumor and brain tumor had ROS-1 protein expression (Figure 2F).
(A) Magnetic Resonance Imaging (MRI) of a new brain tumor 12 months after brain metastasis resection. (B) Surgical resection specimen pathology confirmed radiation necrosis via hematoxylin and eosin stain with foamy histiocyte aggregation, hyalinized vascular walls, and no viable tumor cells. (C) Brain CT showed postoperative changes and no relapse of the brain metastasis.
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The lung tumor, bone, and renal metastases responded well during follow-up (last image study in June 2020 as showed in Figure 1), except a pseudoprogression of the left frontal lobe brain tumor occurring in March 2019, which was confirmed as radiation necrosis after surgical resection (Figure 3). Recurrence of radiation necrosis was noted 3 months after surgery, and it later spontaneously resolved. The patient is still under lorlatinib therapy since November 2018 with a sustained systemic partial remission. The total treatment course is summarized in Figure 1.