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. 2014 Nov 18;2(1):40.
doi: 10.1186/s40425-014-0040-2. eCollection 2014.

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

Mizuki Nishino  1 , Anita Giobbie-Hurder  2 , Nikhil H Ramaiya  1 , F Stephen Hodi  3
Affiliations

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

Mizuki Nishino et al. J Immunother Cancer. .

Abstract

Background: Investigate the tumor diameter and density changes in advanced melanoma patients treated with ipilimumab plus bevacizumab, compare response rates based on different response criteria, and study association between these measures and survival.

Methods: Twenty-one advanced melanoma patients with 59 measurable lesions treated in a phase 1 trial of ipilimumab plus bevacizumab were retrospectively studied. Tumor diameter and density were measured on baseline and first follow-up CT. Responses were assigned using RECIST, MASS and Choi criteria. Diameter and density measures and responses by these criteria were studied for the association with survival.

Results: Twenty-three (39%) lesions and 7 (33%) patients met the Choi density criteria for response (≥15% density decrease) at the first follow-up. The response rates were 14% (3/21, 95% CI: 3-36%) by RECIST and MASS, and 52% (11/21, 95% CI: 30-74%) by Choi criteria, when both size and density criteria were used. Larger baseline tumor diameter was significantly associated with shorter progression-free survival (PFS) and overall survival (OS) (log-rank p = 0.001 and 0.003; respectively). Diameter or density changes, or responses by RECIST, MASS or Choi criteria at the first follow-up, were not associated with PFS or OS.

Conclusion: Tumor density decrease meeting Choi criteria was noted in one-third of advanced melanoma patients at the first follow-up scan during ipilimumab plus bevacizumab therapy. While larger baseline tumor diameter was strongly associated with shorter survival, changes of diameter or density, or responses by three criteria did not predict survival. The role of density changes in evaluating response during ipilimumab and bevacizumab therapy for advanced melanoma remains to be further established.

Keywords: Anti-angiogenic therapy; Density; Immunotherapy; Melanoma; RECIST; Tumor response.

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Figures

Figure 1
Figure 1
Scatter plot of the percent changes of the tumor diameter and density on the first follow-up CT compared to the baseline CT in 59 lesions. The cut-off values for response are indicated by the yellow dashed line for RECIST (≥30% diameter decrease), by the orange dashed line for MASS (≥20% diameter decrease), and by the purple dashed lines for Choi (≥10% diameter decrease or ≥15% density decrease) criteria. No lesions met the density response criteria by MASS.
Figure 2
Figure 2
Scatter plot of the percent changes of the tumor diameter and density on the first follow-up CT compared to the baseline CT in 21 patients. The cut-off values for response are indicated by the yellow dashed line for RECIST (≥30% diameter decrease), by the orange dashed line for MASS (≥20% diameter decrease), and by the purple dashed lines for Choi (≥10% diameter decrease or ≥15% density decrease) criteria. No patients met the density response criteria by MASS.
Figure 3
Figure 3
A 61-year-old male with metastatic melanoma. Contrast-enhanced CT scan of the chest at baseline (A) demonstrate a lobulated right lower lobe mass measuring 37 mm and 54.3 HU (A, arrow). The follow-up scan (B) at 11.4 weeks of ipilimumab and bevacizumab therapy demonstrated the lesion measuring 36 mm and 44.4 HU (B, arrow). While the percent decrease of diameter was only 2%, CT density decreased by 18% comparing to baseline, meeting the Choi response criteria.
Figure 4
Figure 4
Progression-free survival in patients dichotomized using the median baseline diameter (38 mm).
Figure 5
Figure 5
Overall survival in patients dichotomized using the median baseline diameter (38 mm).
Figure 6
Figure 6
Intra- and inter-observer variability of diameter and density measurements. Bland-Altman plots demonstrate the variability of density and diameter measurements (A, B for intra-observer, C, D for inter-observer, respectively). The relative difference (%) in two independent measurements for each patient is plotted against the first measurement by Radiologist 1. The straight lines represent the mean relative difference (%), and the dotted lines represent the upper and lower 95% limits of agreement (%).
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References

    1. Hodi FS, Mihm MC, Soiffer RJ, Haluska FG, Butler M, Seiden MV, Davis T, Henry-Spires R, MacRae S, Willman A, Padera R, Jaklitsch MT, Shankar S, Chen TC, Korman A, Allison JP, Dranoff G. Biologic activity of cytotoxic t lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci U S A. 2003;100:4712–4717. doi: 10.1073/pnas.0830997100. - DOI - PMC - PubMed
    1. Hodi FS, Oble DA, Drappatz J, Velazquez EF, Ramaiya N, Ramakrishna N, Day AL, Kruse A, Mac Rae S, Hoos A, Mihm M. Ctla-4 blockade with ipilimumab induces significant clinical benefit in a female with melanoma metastases to the cns. Nat Clin Pract Oncol. 2008;5:557–561. doi: 10.1038/ncponc1183. - DOI - PubMed
    1. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–723. doi: 10.1056/NEJMoa1003466. - DOI - PMC - PubMed
    1. Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage iiib/iv non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase ii study. J Clin Oncol. 2012;30:2046–2054. doi: 10.1200/JCO.2011.38.4032. - DOI - PubMed
    1. Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013;24:75–83. doi: 10.1093/annonc/mds213. - DOI - PubMed