Expert Panel Recommendations for the Management of Patients with Recurrent or Persistent Cushing’s Disease

Presentation Number: SUN 430
Date of Presentation: April 2nd, 2017

Eliza B. Geer*1, Ismat Shafiq2, Murray B. Gordon3, Vivien Bonert4, Alejandro Raul Ayala5, Ronald S. Swerdloff6, Laurence Katznelson7, Ekaterina Manuylova2, John D. Carmichael8, Vijaya Surampudi6, Michael S. Broder9, Dasha Cherepanov9, Jackie Lee9, Qayyim Said10, Savita Nandal10 and Beverly M.K. Biller11
1Memorial Sloan Kettering, New York, NY, 2University of Rochester School of Medicine and Dentistry, Rochester, NY, 3Allegheny Neuroendocrinology Center, Allegheny General Hospital, Pittsburgh, PA, 4Cedars-Sinai Medical Center, Los Angeles, CA, 5University of Miami and Jackson Memorial Hospital, Miami, FL, 6Harbor-UCLA Medical Center, Los Angeles, CA, 7Stanford University School of Medicine, Stanford, CA, 8Keck School of Medicine of USC, Los Angeles, CA, 9Partnership for Health Analytic Research, LLC, Beverly Hills, CA, 10Novartis Pharmaceuticals Corporation, East Hanover, NJ, 11Massachusetts General Hospital, Boston, MA


BACKGROUND: Management of Cushing’s disease (CD) is complex, particularly in the setting of recurrent or persistent disease.

OBJECTIVE: To develop consensus statements on the management of patients with persistent or recurrent CD.

METHODS: The study used the RAND/UCLA modified Delphi process. A panel of 11 expert endocrinologists from diverse US locations and several practice types rated 708 unique patient scenarios twice: once on their own and once following a day-long, professionally moderated, panel discussion to clarify definitions. For each scenario (e.g., a hypopituitary patient with severe hypercortisolism without fulminant CD and a macroadenoma), panelists rated appropriateness for different treatment options on a 1-9 scale as the first intervention after it was determined that the patient had residual or recurrent tumor. Responses were grouped as appropriate (median rating of 7-9 with no disagreement between panelists), least desirable (median rating of 1-3 with no disagreement), or uncertain (median rating of 4-6 with no disagreement). Scenarios with >2 ratings from 1-3 and >2 from 7-9 range were considered to have disagreements between panelists.

RESULTS: Panelists had practiced medicine a median of 29 years, and spent about 50% of their time in clinical care and 25% conducting research; panelists reported seeing on average about 30 unique CD patients per year. The majority were from academic/tertiary settings. Agreement about which treatment would be ideal vs. undesirable for individual treatment scenarios increased following the panel discussion from 82.1% (581 scenarios) to 97.5% (690) in the final ratings, with 43.4% of the treatment options in specific scenarios rated appropriate, 21.6% rated uncertain, and 32.5% rated least desirable. Consensus statements were developed based on the final ratings with input from the panel. These include: 1) If residual tumor is identified, and an expert pituitary surgeon believes it is operable, repeat pituitary surgery can be considered; 2) Medical therapy can be used as initial treatment of nearly all cases of recurrent or persistent CD; 3) Radiotherapy can be used as an initial treatment option in recurrent or persistent CD when combined with medical therapy.

CONCLUSIONS: Using the RAND/UCLA modified Delphi method, a panel of expert endocrinologists developed consensus recommendations for recurrent or persistent CD. The panel emphasized that the optimal treatment approach involves shared decision-making with the patient, endocrinologist, and neurosurgeon, and requires weighing multiple factors, including patient preferences; size, location and characteristics of residual tumor; concurrent medication use; drug interactions; cost; and the availability of expert care.


Disclosure: EBG: Consultant, Novartis Pharmaceuticals, Investigator, Novartis Pharmaceuticals, Advisory Group Member, Strongbridge, Advisory Group Member, Chiasma, Consultant, Ionis. IS: Investigator, Novartis Pharmaceuticals. MBG: Principal Investigator, Novartis Pharmaceuticals, Principal Investigator, Corcept. ARA: Advisory Group Member, Novartis Pharmaceuticals, Consultant, NHT theapeutics. RSS: Investigator, Clarus, Principal Investigator, Novartis Pharmaceuticals. LK: Ad Hoc Consultant, Corcept, Investigator, Novartis Pharmaceuticals. EM: Clinician, Novartis Pharmaceuticals. JDC: Advisory Group Member, Pfizer, Inc., Advisory Group Member, Novartis Pharmaceuticals, Advisory Group Member, Chiasma, Advisory Group Member, Ionis Pharmaceuticals, Principal Investigator, Novo Nordisk, Principal Investigator, Novartis Pharmaceuticals, Principal Investigator, Pfizer, Inc., Principal Investigator, Chiasma, Principal Investigator, Strong bridge Biopharma, Coinvestigator, Novartis Pharmaceuticals. MSB: Researcher, Novartis Pharmaceuticals. DC: Researcher, Novartis Pharmaceuticals. JL: Researcher, Novartis Pharmaceuticals. QS: Employee, Novartis Pharmaceuticals. SN: reviewer, Novartis Pharmaceuticals. BMKB: Principal Investigator, Cortendo - Strongbridge, Ad Hoc Consultant, Cortendo - Strongbridge, Ad Hoc Consultant, Ipsen, Principal Investigator, Novartis Pharmaceuticals, Ad Hoc Consultant, Novartis Pharmaceuticals. Nothing to Disclose: VB, VS