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

Journal for ImmunoTherapy of Cancer

F Stephen Hodi²  Nikhil H Ramaiya³  Anita Giobbie-Hurder¹  Mizuki Nishino³ 

[1] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston 02215, MA, USA;Department of Medical Oncology and Department of Medicine, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, 450 Brookline Avenue, Boston 02215, MA, USA;Department of Radiology, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston 02215, MA, USA

关键词: RECIST;    Density;    Tumor response;    Anti-angiogenic therapy;    Immunotherapy;    Melanoma;   

Others  :  1133529
DOI  :  10.1186/s40425-014-0040-2

 received in 2014-09-15, accepted in 2014-10-28,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Nishino et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [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.
• [2]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.
• [3]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.
• [4]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.
• [5]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.
• [6]Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, Krainer M, Houede N, Santos R, Mahammedi H, Ng S, Maio M, Franke FA, Sundar S, Agarwal N, Bergman AM, Ciuleanu TE, Korbenfeld E, Sengelov L, Hansen S, Logothetis C, Beer TM, McHenry MB, Gagnier P, Liu D, Gerritsen WR: Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (ca184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 2014, 15:700-712.
• [7]Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M: Safety, activity, and immune correlates of anti-pd-1 antibody in cancer. N Engl J Med 2012, 366:2443-2454.
• [8]Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M: Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013, 369:122-133.
• [9]Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS: Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 2014, 32:1020-1030.
• [10]Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM: Safety and activity of anti-pd-l1 antibody in patients with advanced cancer. N Engl J Med 2012, 366:2455-2465.
• [11]Huang Y, Yuan J, Righi E, Kamoun WS, Ancukiewicz M, Nezivar J, Santosuosso M, Martin JD, Martin MR, Vianello F, Leblanc P, Munn LL, Huang P, Duda DG, Fukumura D, Jain RK, Poznansky MC: Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc Natl Acad Sci U S A 2012, 109:17561-17566.
• [12]Oyama T, Ran S, Ishida T, Nadaf S, Kerr L, Carbone DP, Gabrilovich DI: Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa b activation in hemopoietic progenitor cells. J Immunol 1998, 160:1224-1232.
• [13]Dikov MM, Ohm JE, Ray N, Tchekneva EE, Burlison J, Moghanaki D, Nadaf S, Carbone DP: Differential roles of vascular endothelial growth factor receptors 1 and 2 in dendritic cell differentiation. J Immunol 2005, 174:215-222.
• [14]Yuan J, Zhou J, Dong Z, Tandon S, Kuk D, Panageas KS, Wong P, Wu X, Naidoo J, Page DB, Wolchok JD, Hodi FS: Pretreatment serum vegf is associated with clinical response and overall survival in advanced melanoma patients treated with ipilimumab. Cancer Immunol Res 2014, 2:127-132.
• [15]Hodi FS, Lawrence D, Lezcano C, Wu X, Zhou J, Sasada T, Zeng W, Giobbie-Hurder A, Atkins MB, Ibrahim N, Friedlander P, Flaherty KT, Murphy GF, Rodig S, Velazquez EF, Mihm MC Jr, Russell S, DiPiro PJ, Yap JT, Ramaiya N, Van den Abbeele AD, Gargano M, McDermott D: Bevacizumab plus ipilimumab in patients with metastatic melanoma. Cancer Immunol Res 2014, 2:632-642.
• [16]Nishino M, Jagannathan JP, Krajewski KM, O’Regan K, Hatabu H, Shapiro G, Ramaiya NH: Personalized tumor response assessment in the era of molecular medicine: cancer-specific and therapy-specific response criteria to complement pitfalls of recist. AJR Am J Roentgenol 2012, 198:737-745.
• [17]Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbe C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS: Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009, 15:7412-7420.
• [18]Nishino M, Gargano M, Suda M, Ramaiya NH, Hodi FS: Optimizing immune-related tumor response assessment: does reducing the number of lesions impact response assessment in melanoma patients treated with ipilimumab? J Immunother Cancer 2014, 2:17. BioMed Central Full Text
• [19]Nishino M, Giobbie-Hurder A, Gargano M, Suda M, Ramaiya NH, Hodi FS: Developing a common language for tumor response to immunotherapy: immune-related response criteria using unidimensional measurements. Clin Cancer Res 2013, 19:3936-3943.
• [20]Benjamin RS, Choi H, Macapinlac HA, Burgess MA, Patel SR, Chen LL, Podoloff DA, Charnsangavej C: We should desist using recist, at least in gist. J Clin Oncol 2007, 25:1760-1764.
• [21]Choi H, Charnsangavej C, de Castro FS, Tamm EP, Benjamin RS, Johnson MM, Macapinlac HA, Podoloff DA: Ct evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: a quantitative analysis correlated with fdg pet findings. AJR Am J Roentgenol 2004, 183:1619-1628.
• [22]Choi H, Charnsangavej C, Faria SC, Macapinlac HA, Burgess MA, Patel SR, Chen LL, Podoloff DA, Benjamin RS: Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol 2007, 25:1753-1759.
• [23]Faivre S, Zappa M, Vilgrain V, Boucher E, Douillard JY, Lim HY, Kim JS, Im SA, Kang YK, Bouattour M, Dokmak S, Dreyer C, Sablin MP, Serrate C, Cheng AL, Lanzalone S, Lin X, Lechuga MJ, Raymond E: Changes in tumor density in patients with advanced hepatocellular carcinoma treated with sunitinib. Clin Cancer Res 2011, 17:4504-4512.
• [24]van der Veldt AA, Meijerink MR, van den Eertwegh AJ, Haanen JB, Boven E: Choi response criteria for early prediction of clinical outcome in patients with metastatic renal cell cancer treated with sunitinib. Br J Cancer 2010, 102:803-809.
• [25]Smith AD, Shah SN, Rini BI, Lieber ML, Remer EM: Morphology, attenuation, size, and structure (mass) criteria: assessing response and predicting clinical outcome in metastatic renal cell carcinoma on antiangiogenic targeted therapy. AJR Am J Roentgenol 2010, 194:1470-1478.
• [26]Gray MR, Martin del Campo S, Zhang X, Zhang H, Souza FF, Carson WE 3rd, Smith AD: Metastatic melanoma: lactate dehydrogenase levels and ct imaging findings of tumor devascularization allow accurate prediction of survival in patients treated with bevacizumab. Radiology 2014, 270:425-434.
• [27]Nishino M, Hatabu H, Johnson BE, McLoud TC: State of the art: response assessment in lung cancer in the era of genomic medicine. Radiology 2014, 271:6-27.
• [28]Menzies AM, Haydu LE, Carlino MS, Azer MW, Carr PJ, Kefford RF, Long GV: Inter- and intra-patient heterogeneity of response and progression to targeted therapy in metastatic melanoma. PLoS One 2014, 9:e85004.
• [29]Tirkes T, Hollar MA, Tann M, Kohli MD, Akisik F, Sandrasegaran K: Response criteria in oncologic imaging: review of traditional and new criteria. Radiographics 2013, 33:1323-1341.
• [30]Erasmus JJ, Gladish GW, Broemeling L, Sabloff BS, Truong MT, Herbst RS, Munden RF: Interobserver and intraobserver variability in measurement of non-small-cell carcinoma lung lesions: implications for assessment of tumor response. J Clin Oncol 2003, 21:2574-2582.
• [31]Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J: New response evaluation criteria in solid tumours: revised recist guideline (version 1.1). Eur J Cancer 2009, 45:228-247.
• [32]Nishino M, Jagannathan JP, Ramaiya NH, Van den Abbeele AD: Revised recist guideline version 1.1: What oncologists want to know and what radiologists need to know? AJR Am J Roentgenol 2010, 195:281-289.
• [33]Nishino M, Cardarella S, Jackman DM, Ramaiya NH, Rabin MS, Hatabu H, Janne PA, Johnson BE: Recist 1.1 in nsclc patients with egfr mutations treated with egfr tyrosine kinase inhibitors: comparison with recist 1.0. AJR Am J Roentgenol 2013, 201:W64-W71.
• [34]Araki T, Sholl LM, Gerbaudo VH, Hatabu H, Nishino M: Imaging characteristics of pathologically proven thymic hyperplasia: identifying features that can differentiate true from lymphoid hyperplasia. AJR Am J Roentgenol 2014, 202:471-478.
• [35]Nishino M, Dahlberg SE, Cardarella S, Jackman DM, Rabin MS, Hatabu H, Janne PA, Johnson BE: Tumor volume decrease at 8 weeks is associated with longer survival in egfr-mutant advanced non-small-cell lung cancer patients treated with egfr tki. J Thorac Oncol 2013, 8:1059-1068.
• [36]Krajewski KM, Nishino M, Franchetti Y, Ramaiya NH, Van den Abbeele AD, Choueiri TK: Intraobserver and interobserver variability in computed tomography size and attenuation measurements in patients with renal cell carcinoma receiving antiangiogenic therapy: implications for alternative response criteria. Cancer 2014, 120:711-721.
• [37]Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000, 92:205-216.
• [38]Smith AD, Lieber ML, Shah SN: Assessing tumor response and detecting recurrence in metastatic renal cell carcinoma on targeted therapy: importance of size and attenuation on contrast-enhanced ct. AJR Am J Roentgenol 2010, 194:157-165.
• [39]Nishino M, Guo M, Jackman DM, DiPiro PJ, Yap JT, Ho TK, Hatabu H, Janne PA, Van den Abbeele AD, Johnson BE: Ct tumor volume measurement in advanced non-small-cell lung cancer: performance characteristics of an emerging clinical tool. Acad Radiol 2011, 18:54-62.
• [40]Lin LI: A concordance correlation coefficient to evaluate reproducibility. Biometrics 1989, 45:255-268.
• [41]Bland JM, Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986, 1:307-310.