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CT halo sign as an imaging marker for response to adoptive cell therapy in metastatic melanoma with pulmonary metastases

  • Oncology
  • Published:
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Abstract

Objectives

The halo sign refers to a zone of ground-glass attenuation surrounding a pulmonary nodule. Pulmonary metastatic nodules exhibiting a halo sign are seen mainly in hypervascular tumours. We describe the appearance of a halo sign following treatment of adoptive transfer of autologous tumour-infiltrating lymphocytes (TIL) to melanoma patients with lung metastases.

Methods

The study included 29 melanoma patients with pulmonary metastases who received TIL therapy. Pre- and post-treatment chest CTs were retrospectively reviewed for the presence of a halo sign and its correlation with therapeutic response.

Results

A pulmonary halo sign was not seen in any pre-treatment CT. It was observed in four of 12 patients who responded to the therapy but not in those who failed to respond. Significant differences were found between response ratio in patients in whom post-TIL halo sign appeared compared with those without the halo sign (p = 0.02).

Conclusions

The appearance of a CT halo sign in melanoma with lung metastases following TIL therapy may indicate antitumoral effect and a good response to therapy. Our findings emphasize the importance of applying new assessment criteria for immunological anticancer therapies.

Key Points

• Tumour-infiltrating lymphocytes (TIL) in melanoma patients is a promising novel immunotherapy

• Post-therapy pulmonary halo sign appeared in one-third of TIL responders

• Pulmonary halo sign may serve as an imaging marker for antitumoral activity

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Abbreviations

ACT:

adoptive cell therapy

TIL:

tumour-infiltrating lymphocytes

References

  1. Dreno B, Nguyen JM, Khammari A, Pandolfino MC, Tessier MH, Bercegeay S, Cassidanius A, Lemarre P, Billaudel S, Labarriere N, Jotereau F (2002) Randomized trial of adoptive transfer of melanoma tumor-infiltrating lymphocytes as adjuvant therapy for stage III melanoma. Cancer Immunol Immunother 51:539–546

    Article  CAS  PubMed  Google Scholar 

  2. Rosenberg SA, Dudley ME (2009) Adoptive cell therapy for the treatment of patients with metastatic melanoma. Curr Opin Immunol 21:233–240

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Lee YR, Choi YW, Lee KJ, Jeon SC, Park CK, Heo JN (2005) CT halo sign: the spectrum of pulmonary diseases. Br J Radiol 78:862–865

    Article  CAS  PubMed  Google Scholar 

  4. Primack SL, Hartman TE, Lee KS, Muller NL (1994) Pulmonary nodules and the CT halo sign. Radiology 190:513–515

    CAS  PubMed  Google Scholar 

  5. Kaneria SS, Tarkin J, Williams G, Bain G, Quigley M (2012) Case report: the CT halo sign: a rare manifestation of squamous cell carcinoma of the lung. Clin Radiol 67:613–615

    Article  CAS  PubMed  Google Scholar 

  6. Okita R, Yamashita M, Nakata M, Teramoto N, Bessho A, Mogami H (2005) Multiple ground-glass opacity in metastasis of malignant melanoma diagnosed by lung biopsy. Ann Thorac Surg 79:e1–e2

    Article  PubMed  Google Scholar 

  7. Shapira-Frommer R, Schachter J (2012) Adoptive immunotherapy of advanced melanoma. Curr Treat Options in Oncol 13:340–353

    Article  Google Scholar 

  8. Besser MJ, Shapira-Frommer R, Treves AJ, Zippel D, Itzhaki O, Hershkovitz L, Levy D, Kubi A, Hovav E, Chermoshniuk N, Shalmon B, Hardan I, Catane R, Markel G, Apter S, Ben-Nun A, Kuchuk I, Shimoni A, Nagler A, Schachter J (2010) Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clin Cancer Res 16:2646–2655

    Article  CAS  PubMed  Google Scholar 

  9. 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 (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247

    Article  CAS  PubMed  Google Scholar 

  10. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van GM, van Oosterom AT, Christian MC, Gwyther SG (2000) 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 92:205–216

    Article  CAS  PubMed  Google Scholar 

  11. Marten K, Rummeny EJ, Engelke C (2004) The CT halo: a new sign in active pulmonary sarcoidosis. Br J Radiol 77:1042–1045

    Article  CAS  PubMed  Google Scholar 

  12. Cole DJ, Taubenberger JK, Pockaj BA, Yannelli JR, Carter C, Carrasquillo J, Leitman S, Steinberg SM, Rosenberg SA, Yang YC (1994) Histopathological analysis of metastatic melanoma deposits in patients receiving adoptive immunotherapy with tumor-infiltrating lymphocytes. Cancer Immunol Immunother 38:299–303

    Article  CAS  PubMed  Google Scholar 

  13. Fisher B, Packard BS, Read EJ, Carrasquillo JA, Carter CS, Topalian SL, Yang JC, Yolles P, Larson SM, Rosenberg SA (1989) Tumor localization of adoptively transferred indium-111 labeled tumor infiltrating lymphocytes in patients with metastatic melanoma. J Clin Oncol 7:250–261

    CAS  PubMed  Google Scholar 

  14. Griffith KD, Read EJ, Carrasquillo JA, Carter CS, Yang JC, Fisher B, Aebersold P, Packard BS, Yu MY, Rosenberg SA (1989) In vivo distribution of adoptively transferred indium-111-labeled tumor infiltrating lymphocytes and peripheral blood lymphocytes in patients with metastatic melanoma. J Natl Cancer Inst 81:1709–1717

    Article  CAS  PubMed  Google Scholar 

  15. Pockaj BA, Sherry RM, Wei JP, Yannelli JR, Carter CS, Leitman SF, Carasquillo JA, Steinberg SM, Rosenberg SA, Yang JC (1994) Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy. Augmentation with cyclophosphamide and correlation with response. Cancer 73:1731–1737

    Article  CAS  PubMed  Google Scholar 

  16. Zhou J, Dudley ME, Rosenberg SA, Robbins PF (2005) Persistence of multiple tumor-specific T-cell clones is associated with complete tumor regression in a melanoma patient receiving adoptive cell transfer therapy. J Immunother 28:53–62

    Article  PubMed Central  PubMed  Google Scholar 

  17. Hoos A, Eggermont AM, Janetzki S, Hodi FS, Ibrahim R, Anderson A, Humphrey R, Blumenstein B, Old L, Wolchok J (2010) Improved endpoints for cancer immunotherapy trials. J Natl Cancer Inst 102:1388–1397

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

The scientific guarantor of this publication is Prof. Sara Apter. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. The authors state that this work has not received any funding. No complex statistical methods were necessary for this paper. Institutional review board approval was obtained. Written informed consent was waived by the institutional review board. Methodology: retrospective, observational, performed at one institution.

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Authors and Affiliations

  1. Department of Diagnostic Imaging, Sheba Medical Center, Tel-Hashomer, 2 Sheba Rd, Tel Hashomer 52621, Israel, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel

    Shai Shrot & Sara Apter

  2. The Ella Institute for Melanoma Research and Treatment, Sheba Medical Center, Tel-Hashomer, 2 Sheba Rd, Tel Hashomer, 52621, Israel

    Jacob Schachter, Ronnie Shapira-Frommer & Michal J. Besser

  3. Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Michal J. Besser

Authors
  1. Shai Shrot
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  2. Jacob Schachter
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  3. Ronnie Shapira-Frommer
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  4. Michal J. Besser
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  5. Sara Apter
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Correspondence to Shai Shrot.

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Shrot, S., Schachter, J., Shapira-Frommer, R. et al. CT halo sign as an imaging marker for response to adoptive cell therapy in metastatic melanoma with pulmonary metastases. Eur Radiol 24, 1251–1256 (2014). https://doi.org/10.1007/s00330-014-3129-6

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  • DOI: https://doi.org/10.1007/s00330-014-3129-6

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