Metastatic Melanoma: Lactate Dehydrogenase Levels and CT Imaging Findings of Tumor Devascularization Allow Accurate Prediction of Survival in Patients Treated with Bevacizumab

Abstract

Purpose To predict survival in patients with metastatic melanoma by evaluating a combination of serum lactate dehydrogenase (LDH) level and initial computed tomographic (CT) findings of tumor devascularization after antiangiogenic therapy. Materials and Methods Consent was waived for this institutional review board–approved, retrospective, secondary analysis. Forty-four patients with metastatic melanoma received bevacizumab therapy in a randomized prospective phase II trial. Target lesions on the initial posttherapy CT images were evaluated by using Response Evaluation Criteria in Solid Tumors, the Choi criteria, and Morphology, Attenuation, Size, and Structure (MASS) criteria. Cox proportional hazards models were used to assess the association of baseline clinical variables including serum LDH and imaging findings with progression-free and overall survival. The receiver operating characteristic curve with area under the curve (AUC) was used to evaluate accuracy. Results In multivariate analysis, a high baseline serum LDH level was associated with decreased progression-free survival (hazard ratio = 1.29 for each increase of 100 IU/L; P = .002) and overall survival (hazard ratio = 1.44 for each increase of 100 IU/L; P = .001). Evaluation with MASS criteria of the first CT examination after therapy strongly predicted progression-free (P < .001) and overall (P < .001) survival. Baseline serum LDH level was moderately accurate for predicting progression-free survival at 9 months (AUC = 0.793) and overall survival at 18 months (AUC = 0.689). The combination of baseline serum LDH levels and evaluation with MASS criteria at the first CT examination after therapy had significantly higher accuracy for predicting progression-free survival at 9 months (AUC = 0.969) and overall survival at 18 months (AUC = 0.813) than did baseline serum LDH levels alone for prediction of progression-free survival (P = .020). Conclusion A combination of baseline serum LDH levels and evaluation with MASS criteria at the first CT examination after bevacizumab therapy had the highest accuracy for predicting survival in patients with metastatic melanoma.

Response assessment in metastatic melanoma treated with ipilimumab and bevacizumab: CT tumor size and density as markers for response and outcome

“…While density decrease is a relatively common phenomenon in advanced melanoma treated with ipilimumab plus bevacizumab, further studies are needed to define its role in assessing anti-cancer activity and therapeutic benefit of the agents and to identify objective imaging marker that can predict outcome during the combined immunotherapy and anti-angiogenic therapy. The degree of diameter and density changes in our cohort were similar to the previous report by Gray et al in their study of metastatic melanoma patients treated with bevacizumab with or without interferon, which reported the average of 2% diameter change and −7% density change [26]. No lesions or patients in our study met the density response criteria by MASS, indicating that such a marked decrease in density is a rare phenomenon among melanoma patients receiving ipilimumab plus bevacizumab.…”

Cancer immunotherapy and immune-related response assessment: The role of radiologists in the new arena of cancer treatment

“…In advanced RCC treated with anti-angiogenic therapy, MASS (morphology, attenuation, size, and structure) criteria propose to define response as ≥20% diameter decrease, or ≥40HU density decrease, or marked central necrosis in predominantly solid enhancing lesion 54 . Gray et al recently studied 44 metastatic melanoma patients treated with bevacizumab with or without interferon, and demonstrated that the assessment by MASS criteria on the first follow-up CT in combination with baseline serum lactate dehydrogenase (LDH) level accurately predicted progression-free survival and overall survival 57 . In another study in 21 advanced melanoma patients treated with ipilimumab plus bevacizumab (VEGF inhibitor), one-third of the patients had CT tumor density decrease ≥15% (defined as density response by Choi criteria for GIST 55 ), indicating that CT tumor density decrease is a relatively common phenomenon during immunotherapy, while its role in evaluating anti-cancer activity and therapeutic benefit remain to be determined 52 .…”

Response assessment in metastatic melanoma treated with ipilimumab and bevacizumab: CT tumor size and density as markers for response and outcome

“…In RCC treated with anti-angiogenic therapy, another modified criteria called MASS (morphology, attenuation, size, and structure) criteria has been proposed, and define response as ≥20% diameter decrease, or ≥40HU density decrease, or marked central necrosis in predominantly solid enhancing lesion(s) [ 16 , 25 ]. MASS criteria were recently studied in metastatic melanoma treated with bevacizumab with or without interferon, and shown to strongly predict progression-free survival (PFS) and OS [ 26 ]. Given these prior observations and the recent promising phase 1 trial results, it is worthwhile to study tumor diameter and density changes, in addition to conventional tumor diameter changes, during the combined therapy of ipilimumab and bevacizumab in capturing tumor response and predicting outcome.…”