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18F-FDG PET/CT following chemoradiation of uterine cervix cancer provides powerful prognostic stratification independent of HPV status: a prospective cohort of 105 women with mature survival data

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Abstract

Purpose

To report 5-year outcomes of a prospective registry study investigating posttherapy FDG PET/CT in women with locally advanced cervical cancer. A secondary analysis assessing the prognostic significance of HPV infection was performed.

Methods

Patients underwent definitive chemoradiation followed by a single FDG PET/CT scan for response assessment. A complete metabolic response (CMR) was defined as no evidence of FDG-avid disease. Patients were dichotomized according to HPV infection status into a ‘higher-risk’ group and a ‘lower-risk’ group, with the higher-risk group comprising those with alpha-7 strain HPV (subtypes 18, 39 and 45) and those who were HPV-negative and the lower-risk group comprising those with alpha-9 strain HPV (subtypes 16, 31, 33, 52 and 58) and those with mixed strains. Survival outcomes, patterns of failure and salvage therapy outcomes were investigated for their association with metabolic response and HPV status.

Results

In 105 patients the median prospective follow-up was 5.2 years. The 5-year cancer-specific, overall and progression-free survival rates in patients with a CMR were 97 %, 93 % and 86 %, respectively. In patients without a CMR, the corresponding 5-year survival rates were 36 %, 22 % and 0 % respectively (p < 0.01). PET response was associated with patterns of failure (p < 0.01), with the 5-year freedom from local, nodal and distant failure in patients with a CMR being 94 %, 90 % and 94 %, respectively. Of 16 patients who underwent salvage therapy, 12 had disease detected on the surveillance PET scan, and 8 achieved a post-salvage CMR of whom all were alive at a median of 4.9 years. DNA adequate for HPV analysis was extracted in 68 patients. The likelihood of a PET metabolic response was not influenced by HPV infection status, with 71 % and 75 % of higher-risk and lower-risk patients, respectively, achieving CMR (p = 0.83). Higher-risk patients had a poorer OS (HR 2.6, range 1.0 – 6.6, p = 0.05) in univariable analysis but not multivariable analysis (p = 0.11).

Conclusion

At 5 years CMR remains a powerful factor predicting survival after initial and salvage therapy. Metabolic response was not associated with HPV infection risk. Further studies are required to establish the association with HPV infection risk and survival after chemoradiation.

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References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917. doi:10.1002/ijc.25516.

    Article  CAS  PubMed  Google Scholar 

  2. World Health Organization. Global burden of disease: 2004 update. Geneva: World Health Organization; 2008. p. 30.

    Google Scholar 

  3. Landoni F, Maneo A, Colombo A, Placa F, Milani R, Perego P, et al. Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet. 1997;350:535–40.

    Article  CAS  PubMed  Google Scholar 

  4. Grigsby PW, Siegel BA, Dehdashti F, Rader J, Zoberi I. Posttherapy [18F] fluorodeoxyglucose positron emission tomography in carcinoma of the cervix: response and outcome. J Clin Oncol. 2004;22:2167–71.

    Article  PubMed  Google Scholar 

  5. Grigsby PW, Siegel BA, Dehdashti F, Mutch DG. Posttherapy surveillance monitoring of cervical cancer by FDG-PET. Int J Radiat Oncol Biol Phys. 2003;55:907–13.

    Article  PubMed  Google Scholar 

  6. Siva S, Herschtal A, Thomas JM, Bernshaw DM, Gill S, Hicks RJ, et al. Impact of post-therapy positron emission tomography on prognostic stratification and surveillance after chemoradiotherapy for cervical cancer. Cancer. 2011;117:3981–8. doi:10.1002/cncr.25991.

    Article  PubMed  Google Scholar 

  7. Schwarz JK, Siegel BA, Dehdashti F, Grigsby PW. Metabolic response on post-therapy FDG-PET predicts patterns of failure after radiotherapy for cervical cancer. Int J Radiat Oncol Biol Phys. 2012;83:185–90. doi:10.1016/j.ijrobp.2011.05.053.

    Article  PubMed  Google Scholar 

  8. Lee Y, Auh SL, Wang Y, Burnette B, Meng Y, Beckett M, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009;114:589–95. doi:10.1182/blood-2009-02-206870.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Mac Manus MP, Hicks RJ, Matthews JP, McKenzie A, Rischin D, Salminen EK, et al. Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small-cell lung cancer. J Clin Oncol. 2003;21:1285–92.

    Article  PubMed  Google Scholar 

  10. Hicks RJ, Mac Manus MP, Matthews JP, Hogg A, Binns D, Rischin D, et al. Early FDG-PET imaging after radical radiotherapy for non–small-cell lung cancer: inflammatory changes in normal tissues correlate with tumor response and do not confound therapeutic response evaluation. Int J Radiat Oncol Biol Phys. 2004;60:412–8.

    Article  PubMed  Google Scholar 

  11. Kalff V, Ware R, Heriot A, Chao M, Drummond E, Hicks RJ. Radiation changes do not interfere with postchemoradiation restaging of patients with rectal cancer by FDG PET/CT before curative surgical therapy. Int J Radiat Oncol Biol Phys. 2009;74:60–6.

    Article  PubMed  Google Scholar 

  12. Rischin D, Young RJ, Fisher R, Fox SB, Le Q-T, Peters LJ, et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol. 2010;28:4142–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Wang CC, Lai CH, Huang YT, Chao A, Chou HH, Hong JH. HPV genotypes predict survival benefits from concurrent chemotherapy and radiation therapy in advanced squamous cell carcinoma of the cervix. Int J Radiat Oncol Biol Phys. 2012;84:e499–506. doi:10.1016/j.ijrobp.2012.06.031.

    Article  PubMed  Google Scholar 

  14. Lindel K, Burri P, Studer H, Altermatt H, Greiner R, Gruber G. Human papillomavirus status in advanced cervical cancer: predictive and prognostic significance for curative radiation treatment. Int J Gynecol Cancer. 2005;15:278–84.

    Article  CAS  PubMed  Google Scholar 

  15. Barnard GA. A new test for 2 × 2 tables. Nature. 1945;156:177.

    Article  Google Scholar 

  16. Barnard GA. Significance tests for 2 × 2 tables. Biometrika. 1947;34:123–38.

    CAS  PubMed  Google Scholar 

  17. Havrilesky LJ, Kulasingam SL, Matchar DB, Myers ER. FDG-PET for management of cervical and ovarian cancer. Gynecol Oncol. 2005;97:183–91.

    Article  PubMed  Google Scholar 

  18. Colombo N, Carinelli S, Colombo A, Marini C, Rollo D, Sessa C. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 Suppl 7:vii27–32.

    PubMed  Google Scholar 

  19. Schwarz JK, Siegel BA, Dehdashti F, Grigsby PW. Association of posttherapy positron emission tomography with tumor response and survival in cervical carcinoma. JAMA. 2007;298:2289–95. doi:10.1001/jama.298.19.2289.

    Article  CAS  PubMed  Google Scholar 

  20. Beriwal S, Kannan N, Sukumvanich P, Richard SD, Kelley JL, Edwards RP, et al. Complete metabolic response after definitive radiation therapy for cervical cancer: patterns and factors predicting for recurrence. Gynecol Oncol. 2012;127:303–6. doi:10.1016/j.ygyno.2012.08.006.

    Article  PubMed  Google Scholar 

  21. De Villiers E-M, Fauquet C, Broker TR, Bernard H-U, zur Hausen H. Classification of papillomaviruses. Virology. 2004;324:17–27.

    Article  PubMed  Google Scholar 

  22. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet. 2007;370:890–907.

    Article  CAS  PubMed  Google Scholar 

  23. Rautava J, Kuuskoski J, Syrjänen K, Grenman R, Syrjänen S. HPV genotypes and their prognostic significance in head and neck squamous cell carcinomas. J Clin Virol. 2012;53:116–20.

    Article  PubMed  Google Scholar 

  24. Nichols AC, Dhaliwal SS, Palma DA, Basmaji J, Chapeskie C, Dowthwaite S, et al. Does HPV type affect outcome in oropharyngeal cancer? J Otolaryngol Head Neck Surg. 2013;42:9.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Mirghani H, Amen F, Blanchard P, Moreau F, Guigay J, Hartl D, et al. Treatment de‐escalation in HPV-positive oropharyngeal carcinoma: ongoing trials, critical issues and perspectives. Int J Cancer. 2015;136:1494–503.

    Article  CAS  PubMed  Google Scholar 

  26. Bachtiary B, Obermair A, Dreier B, Birner P, Breitenecker G, Knocke TH, et al. Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer. Int J Cancer. 2002;102:237–43.

    Article  CAS  PubMed  Google Scholar 

  27. Harima Y, Sawada S, Nagata K, Sougawa M, Ohnishi T. Human papilloma virus (HPV) DNA associated with prognosis of cervical cancer after radiotherapy. Int J Radiat Oncol Biol Phys. 2002;52:1345–51.

    Article  CAS  PubMed  Google Scholar 

  28. Huang LW, Chao SL, Hwang JL. Human papillomavirus 31 related types predict better survival in cervical carcinoma. Cancer. 2004;100:327–34.

    Article  PubMed  Google Scholar 

  29. Werness BA, Levine AJ, Howley PM. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990;248:76–9.

    Article  CAS  PubMed  Google Scholar 

  30. Lina Villa L, Schlegel R. Differences in transformation activity between HPV-18 and HPV-16 map to the viral LCR-E6-E7 region. Virology. 1991;181:374–7.

    Article  Google Scholar 

  31. Arends M, Wyllie A, Bird C. Human papillomavirus type 18 is associated with less apoptosis in fibroblast tumours than human papillomavirus type 16. Br J Cancer. 1995;72:646–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Wang CC, Lai CH, Huang HJ, Chao A, Chang CJ, Chang TC, et al. Clinical effect of human papillomavirus genotypes in patients with cervical cancer undergoing primary radiotherapy. Int J Radiat Oncol Biol Phys. 2010;78:1111–20. doi:10.1016/j.ijrobp.2009.09.021.

    Article  PubMed  Google Scholar 

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Acknowledgment

The authors acknowledge Prof. Stephen B. Fox for his support in this work.

Compliance with ethical standards

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Funding

This research was supported by a grant from the Peter MacCallum Cancer Centre Foundation.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, St Andrews Street, East Melbourne, 3002, Victoria, Australia

    Shankar Siva, Rodney J. Hicks, Jason Callahan, David Bernshaw & Kailash Narayan

  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia

    Shankar Siva, Rodney J. Hicks, Jason Callahan & Danny Rischin

  3. Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Australia

    Siddhartha Deb

  4. Molecular Therapeutics and Biomarkers Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia

    Richard J. Young

  5. Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne, Australia

    Mathias Bressel

  6. Department of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Australia

    Linda Mileshkin & Danny Rischin

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  1. Shankar Siva
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  2. Siddhartha Deb
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  10. Kailash Narayan
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Correspondence to Shankar Siva.

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Siva, S., Deb, S., Young, R.J. et al. 18F-FDG PET/CT following chemoradiation of uterine cervix cancer provides powerful prognostic stratification independent of HPV status: a prospective cohort of 105 women with mature survival data. Eur J Nucl Med Mol Imaging 42, 1825–1832 (2015). https://doi.org/10.1007/s00259-015-3112-8

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  • DOI: https://doi.org/10.1007/s00259-015-3112-8

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