Non-functional pituitary carcinoma

We present as case to review and present the clinical features, diagnosis and treatment of non-functional pituitary carcinoma (NFPC). We operated on a case of NFPC. After surgery, gamma knife therapy, temozolomide chemotherapy and whole craniospinal irradiation, the patient still had poor tumor control and died 7 months after operation. FPC is very rare. It needs to be diagnosed with a combination of clinical suspicion, imaging and dynamic monitoring. It is necessary to find more effective methods to control the progress of tumor while routine treatment fails.

BRMP-03. Pituitary carcinoma: a case of dramatic response to immunotherapy (ipilimumab + nivolumab) after failure with temozolomide

INTRODUCTION Pituitary carcinoma (PC) accounts for just 0.1% of all pituitary tumors, often recurs following resection, and has a median reported survival of 1 year. Current treatment guidelines are not standardized but combine surgical resection, radiation therapy, and chemotherapy [1]. Temozolomide is the only chemotherapeutic with documented effectiveness, and the only recommended agent for aggressive pituitary carcinomas in ESE clinical guidelines [3]. CASE: A 57-year-old male presented with visual deterioration over a three-month period. Ophthalmologic evaluation revealed bitemporal visual field deficits. MRI brain W/WO demonstrated a sellar mass suspected to be pituitary macroadenoma with displacement of the stalk and optic nerve impingement (Figure 1a). The patient underwent stereotactic endoscopic transsphenoidal resection of the mass [2]. Postoperative MRI demonstrated gross total resection (Figure 1b). Pathology revealed a sparsely granulated corticotroph-adenoma with malignant transformation (early in-situ PC). Immunohistochemistry showed LOE of MLH1 and PMS2 in the tumor cells; Genetic analysis revealed MGMT methylation. Proton therapy was recommended given the elevated Ki67 index (75%) and p53 positivity. Before radiotherapy, there was no evidence of residual tumor or metastasis radiographically. He received 6600cGy of radiation over 33 fractions. Surveillance MRI showed recurrence at 21 months postoperatively, and temozolomide was initiated. However, MRI demonstrated marked progression after 3 cycles, and at 44 months, he developed a new 6th nerve palsy (Figure1c). Next-generation sequencing using the MSK-IMPACT platform identified somatic mutations in MLH1 Y548lfs*9 and TP53 R337C[4]. Immunotherapy with ipilimumab/nivolumab was initiated [5], and the patient noted resolution of his third nerve palsy soon after. MRI demonstrated a dramatic response with only minimal residual tumor burden (Figure1d). CONCLUSION PC is a rare tumor with frequent recurrence and a short median expected length of survival. Here we demonstrate the utility of immunotherapy in a single case report of PC. This treatment helped our patient survive well beyond the expected median life expectancy of this aggressive disease.

Diagnosis and management of adrenocorticotropic hormone-secreting pituitary carcinoma: a case report and review of the literature

Adrenocorticotropic hormone (ACTH)-secreting pituitary carcinomas (PC) are rare. The natural history and management of these carcinomas are poorly understood. We conducted a literature review using The MEDLINE database, including the search terms; ‘ACTH’ and ‘pituitary carcinoma’. We also describe in detail a case of ACTH-secreting PC. A total of 61 case reports were reviewed. Median age of diagnosis was 45 years (IQR: 34–54). Metastases to multiple organs were common (61%). Adjuvant therapy especially radiotherapy (78%), temozolomide (34%) and other medical therapy (29%) were frequently employed. The mortality was 53% with a median time to death from diagnosis of 1 year (IQR: 1–3). In conclusion, ACTH-secreting PC are associated with high mortality and a multidisciplinary team approach is recommended for optimal care due to the emerging modalities with possible efficacy.

Synergism of Checkpoint Inhibitors and Peptide Receptor Radionuclide Therapy in the Treatment of Pituitary Carcinoma

Introduction Aggressive pituitary tumors that have progressed following temozolomide have limited treatment options. Peptide receptor radionuclide therapy and immunotherapy may have a complementary role in the management of these tumors. Methods We provide follow-up data on a previously reported patient with a hypermutated recurrent tumor. The patient in this report provided written informed consent for tumor sequencing and review of medical records on an institutional review board approved research protocol (NCT01775072). Results This patient with a corticotroph pituitary carcinoma with alkylator induced somatic hypermutation has remained on treatment with ipilimumab and nivolumab for 3.5 years and remains clinically well. After an initial partial response to checkpoint inhibitors, she has had several recurrences that have undergone immunoediting of subclonal mutations, which have been effectively treated with continuation of immunotherapy, surgery, external beam radiation, and 177Lu-DOTATATE. Following external beam RT, she had radiographic evidence of an abscopal response at a distant site of disease suggesting a synergism between checkpoint inhibitors and radiotherapy. Following treatment with 177Lu-DOTATATE, the patient had a partial response with a 61% reduction in volume of the target lesion. Conclusion In patients with aggressive pituitary tumors, treatment with checkpoint inhibitors may trigger an abscopal response from radiotherapy. With appropriate selection, an additional efficacious treatment, 177Lu-DOTATATE, may be available for a limited number of patients with aggressive pituitary adenomas, including patients who have progressed on temozolomide and exhibit increased somatostatin receptor expression on 68Ga-DOTATATE PET.