MON-407 Tumor Control after Radiotherapy and Temozolomide in a Cushing's Disease Patient with Giant Aggressive Pituitary Tumor

Abstract

Introduction: Typical ACTH-producing pituitary adenomas are benign tumors, microadenomas, successfully treated by neurosurgery. However, 10-20% of Cushing’s disease (CD) patients have macroadenomas, sometimes invasive and aggressive cases with poorer surgical prognosis needing additional approaches. Temozolomide (TMZ), second generation alkylating agent, has been used alone or in combination to other medications/radiotherapy (RTX) for tumor control of aggressive pituitary adenomas and carcinomas. We report one patient with giant aggressive corticotropinoma that presented control tumor with RTX and TMZ after four pituitary surgeries unable to uncontroll tumor growth. Clinical Case: A 18-year-old female patient presented with weight gain, red moon face, supraclavicular fullness, dorsal hump, large purple striae, acanthosis nigricans, secondary amenorrhea, frontotemporal headache, visual impairment and right palpebral ptosis. Hormonal analysis confirmed ACTH-dependent Cushing's syndrome. Pituitary MRI showed the presence of a large selar and suprasellar expansive lesion of 5.2X5.1X4.0 cm with displacement of third ventricle, hypothalamus and lateral ventricles. The patient was submitted to the first neurosurgery (transsphenoidal route) with partial resection. Pathological analyses confirmed pituitary adenoma positive for ACTH, Ki-67 8%, negative p53 and 7 mitoses/10 field of great increase. Subsequent surgery was done by craniotomy with partial resection. Cabergoline 2 mg/week was started but the tumor keeps growing with worsening of visual complaints and increase of cortisol levels. At admission in our center, we planned new surgeries do remove the maximal tumor possible (debulking) and subsequent RTX and TMZ. She was submitted to third surgery by transsphenoidal route and the last surgical procedure by craniotomy. MRI pre-RTX done three months after the 4th surgery showed remnant tumor of 3.5X3.0X3.0 cm. Fractioned stereotaxic radiotherapy was done with linear accelerator in a total of 54 Gy divided in 30 sessions. TMZ was initiated in a dose of 150 m2/day, cycles of five days/month, using for 14 months. Pituitary MRI 3, 6 and 10 months after TMZ showed a small reduction of tumor with increase of intratumor cystic areas. Conclusion: The combined use of TMZ and radiotherapy is an important approach for the treatment of rapidly growing, aggressive pituitary ACTH-secreting tumors resistant to conventional treatment.