Bevacizumab is Effective for Recurrent Papillary Tumor of the Pineal Region: First Report
A 31-year-old right-handed man was referred for treatment of recurrent PTPR in the posterior fossa with symptoms including headache, inability to open his eyes, confusion, and obstructive hydrocephalus. He originally presented at 24 years of age with obstructive hydrocephalus and a 1.5-cm enhancing pineal mass. Following placement of a ventriculoperitoneal shunt and a nondiagnostic biopsy, he underwent craniotomy and resection. The pathology report showed a papillary neoplasm negative for GFAP, synaptophysin, PLAF, and MEC, and positive for CAM 5.2 and cytokeratin 3. The MIB-1 index was 15%. The pathology was reviewed at Johns Hopkins University and has subsequently been reviewed by us; the diagnosis has been confirmed to be PTPR (fig. ). Because of residual tumor, he received 5,940 cGy of radiotherapy in 33 fractions.\nSeven months later, he developed a new 1-cm enhancing mass in the left lateral ventricle that increased in size over 3 months. New lesions also developed in the posterior fossa, and he was treated with Gamma Knife to 5 locations. Eighteen months later, he had Gamma Knife to 4 additional posterior fossa lesions, resulting in shrinkage of the lesions on MRI and decreased steroid requirement. Over the next 2 years, he had waxing and waning enhancement over the right inferior temporal lobe that was treated as radiation necrosis with pentoxifylline and vitamins, with subsequent resolution of the enhancement.\nBy the age of 28, he had increased edema and mass effect in the left cerebellum and underwent a posterior fossa craniotomy. The specimen was about 70% necrosis and gliosis and 30% viable PTPR. Because of residual enhancement, dose-dense temozolomide (75 mg/m2 for 21 days of a 28-day cycle) was given for 11 cycles. He then developed increased enhancement and worsening balance while on the temozolomide and was treated with 2 cycles of PCV and 2 cycles of carboplatin and etoposide.\nHis MRI then showed stable 1-cm lesions in the occipital lobe but an enlarging 4.6 × 3.2 × 2.8-cm mass in the midline posterior cerebellum and a 1.7 × 1 × 2.8-cm mass abutting the fourth ventricle, both with surrounding edema and mass effect, and he was referred to the University of Utah (fig. ). An extraventricular drain was placed, followed by a ventriculoperitoneal shunt. Reirradiation was recommended, but the patient declined due to prior toxicity.\nTwelve days later, at the age of 31, he began bevacizumab 10 mg/kg every 2 weeks. The enhancing midline cerebellar mass decreased in size to 2 × 1.4 × 2.8 cm (80% decrease in the cross-sectional area) and the periventricular mass decreased to 1.7 × 0.8 × 0.9 cm in 1 month (20% decrease in the cross-sectional area), and both remained stable for 13 months. The FLAIR signal remained decreased as well (fig. ). His dexamethasone dose remained at 2 mg daily for 6 months and then was tapered off.\nAfter 13 months, both masses increased in size to 3.1 × 1.9 cm (120%) and 2.2 × 1.1 cm (84%) in cross-sectional area, respectively (fig. ). Oral etoposide 50 mg/m2 for 21 out of 28 days was added, and his mass remained stable on MRI at 2, 5 (fig. : white arrow indicates tumor; black arrow indicates shunt), and 7 months. After 7 months of bevacizumab and etoposide, he had increased dysarthria and ataxia, and MRI demonstrated growth of the masses by 220% in cross-sectional area to 5.6 × 3.5 cm and by 100% to 3.1 × 1.7 cm. He again declined radiation and has continued on bevacizumab and etoposide. His dexamethasone dose has varied between 1 and 2 mg per day.