Comparison of Radiographic Approaches to Assess Treatment Response in Pituitary Adenomas

Is RECIST or RANO Good Enough?

Brandon S. Imber; Andrew L. Lin; Zhigang Zhang; Krishna Nand Keshavamurthy; Amy Robin Deipolyi; Kathryn Beal; Marc A. Cohen; Viviane Tabar; Lisa M. DeAngelis; Eliza B. Geer; T. Jonathan Yang; Robert J. Young


J Endo Soc. 2019;3(9):1693-1706. 

In This Article

Abstract and Introduction


Context: Pituitary adenomas (PA) are often irregularly shaped, particularly posttreatment. There are no standardized radiographic criteria for assessing treatment response, substantially complicating interpretation of prospective outcome data. Existing imaging frameworks for intracranial tumors assume perfectly spherical targets and may be suboptimal.

Objective: To compare a three-dimensional (3D) volumetric approach against accepted surrogate measurements to assess PA posttreatment response (PTR).

Design: Retrospective review of patients with available pre- and postradiotherapy (RT) imaging. A neuroradiologist determined tumor sizes in one dimensional (1D) per Response Evaluation in Solid Tumors (RECIST) criteria, two dimensional (2D) per Response Assessment in Neuro-Oncology (RANO) criteria, and 3D estimates assuming a perfect sphere or perfect ellipsoid. Each tumor was manually segmented for 3D volumetric measurements. The Hakon Wadell method was used to calculate sphericity.

Setting: Tertiary cancer center.

Patients or Other Participants: Patients (n = 34, median age = 50 years; 50% male) with PA and MRI scans before and after sellar RT.

Interventions: Patients received sellar RT for intact or surgically resected lesions.

Main Outcome Measure(s): Radiographic PTR, defined as percent tumor size change.

Results: Using 3D volumetrics, mean sphericity = 0.63 pre-RT and 0.60 post-RT. With all approaches, most patients had stable disease on post-RT scan. PTR for 1D, 2D, and 3D spherical measurements were moderately well correlated with 3D volumetrics (e.g., for 1D: 0.66, P < 0.0001) and were superior to 3D ellipsoid. Intraclass correlation coefficient demonstrated moderate to good reliability for 1D, 2D, and 3D sphere (P < 0.001); 3D ellipsoid was inferior (P = 0.009). 3D volumetrics identified more potential partially responding and progressive lesions.

Conclusions: Although PAs are irregularly shaped, 1D and 2D approaches are adequately correlated with volumetric assessment.


Pituitary tumors represent the third most common primary tumor in the adult head after gliomas and meningiomas, accounting for ~15% of cases.[1] Although pituitary adenomas (PAs) are typically benign and slow-growing, their clinical course can vary widely; those that are hormonally active or located in the proximity of sensitive parasellar structures such as the cavernous sinuses, optic chiasm, and hypothalamus often cause the greatest morbidity.[2,3] With the exception of prolactinomas, surgery remains the preferred initial treatment, and subtotally resected and recurrent tumors often require multimodality treatment including medication and radiotherapy (RT).[4] Despite the current treatment efforts, a subset of these tumors progress.

Clinical trials investigating the role of cytotoxic chemotherapy, targeted therapy, and immunotherapy are needed to improve the treatment of PAs.[5,6] Emerging retrospective data support the use of the alkylator chemotherapy, temozolomide, in the treatment of aggressive PAs. One challenge is that the field has not agreed on a standardized response criterion; for this reason, authors have defined meaningful responses to temozolomide as reductions of anywhere from 20% to 80%. Further complicating interpretation is heterogeneity in how a reduction in tumor size is defined. For example, sometimes regression refers to a decrease in tumor volume and sometimes a decrease in longest diameter (or the product of diameters).[7] For reference, a 65% decrease in volume, assuming tumor sphericity, translates to a 50% decrease in the product of the diameters and a 30% change in the longest diameter.[8] Thus, differences in how regression is defined can be meaningful in terms of overall interpretation.

Going forward, the ability to compare temozolomide and other therapies reliably necessitates confidence that overall response rates are generated comparably. As the number of experimental protocols for both medical therapies and RT continues to increase,[9,10] there is an increasing need to establish a standardized approach to imaging interpretation.

There are imaging response criteria that have been validated for other tumor types. Response Evaluation Criteria in Solid Tumors (RECIST)[11] measures tumors in one dimension and is used in clinical trials to define radiographic response for most malignancies outside of the central nervous system. For central nervous system malignancies, a two-dimensional criteria, Response Assessment in Neuro-Oncology (RANO),[12] is used most commonly. Two different volumetric approaches have been proposed: (i) an approach that uses geometric formulas that assume that intracranial tumors are either perfectly spherical or ellipsoid and (ii) computer-based approaches which allow tumor volume measurements based on three-dimensional (3D) voxel-based segmentation of relevant cross-sectional imaging sequences. Segmentation can be performed either manually by a radiologist or using semi- or fully automated approaches. The 3D volumetric approach has been adopted in several contexts within neuro-oncology, e.g., in glioblastoma, with promising results.[13,14] Although 3D volumetric measurement is believed to be the most accurate reflection of tumor response, its correct application requires operator expertise and more neuroradiology time/resources per scan.

Importantly, there have not been formal validations of any of these imaging frameworks for pituitary tumors. We hypothesized that because of the irregular morphology of pituitary tumors, particularly after surgical resection, one dimensional (1D) and two dimensional (2D) as well as 3D spherical or ellipsoid surrogate measurement strategies are inadequate. In this study, we generated 3D volumetric measurements in patients receiving conventionally fractionated RT for PAs and compared the post-RT response with the other more standard neuro-oncological imaging response criteria.