Medical Oncology

, 35:59 | Cite as

Genital marginal failures after intensity-modulated radiation therapy (IMRT) in squamous cell anal cancer: no higher risk with IMRT when compared to 3DCRT

  • V. Dell’Acqua
  • J. Kobiela
  • F. Kraja
  • M. C. Leonardi
  • A. Surgo
  • M. A. Zerella
  • S. Arculeo
  • C. Fodor
  • R. Ricotti
  • M. G. Zampino
  • S. Ravenda
  • G. Spinoglio
  • R. Biffi
  • A. Bazani
  • R. Luraschi
  • S. Vigorito
  • P. Spychalski
  • R. Orecchia
  • R. Glynne-Jones
  • B. A. Jereczek-Fossa
Original Paper
  • 33 Downloads

Abstract

Intensity-modulated radiotherapy (IMRT) is considered the preferred option in squamous cell canal cancer (SCAC), delivering high doses to tumor volumes while minimizing dose to surrounding normal tissues. IMRT has steep dose gradients, but the technique is more demanding as deep understanding of target structures is required. To evaluate genital marginal failure in a cohort of patients with non-metastatic SCAC treated either with IMRT or 3DCRT and concurrent chemotherapy, 117 patients with SCAC were evaluated: 64 and 53 patients were treated with IMRT and 3DCRT techniques, respectively. All patients underwent clinical and radiological examination during their follow-up. Tumor response was evaluated with response evaluation criteria in solid tumors v1.1 guideline on regular basis. All patients’ data were analyzed, and patients with marginal failure were identified. Concomitant chemotherapy was administered in 97 and 77.4% of patients in the IMRT and 3DCRT groups, respectively. In the IMRT group, the median follow-up was 25 months (range 6–78). Progressive disease was registered in 15.6% of patients; infield recurrence, distant recurrence and both infield recurrence and distant recurrence were identified in 5, 4 and 1 patient, respectively. Two out of 64 patients (3.1%) had marginal failures, localized at vagina/recto-vaginal septum and left perineal region. In the 3DCRT group, the median follow-up was 71.3 months (range 6–194 months). Two out of 53 patients (3.8%) had marginal failures, localized at recto-vaginal septum and perigenital structures. The rate of marginal failures was comparable in IMRT and 3DCRT groups (χ2 test p = 0.85). In this series, the use of IMRT for the treatment of SCAC did not increase the rate of marginal failures offering improved dose conformity to the target. Dose constraints should be applied with caution—particularly in females with involvement of the vagina or the vaginal septum.

Keywords

Radiotherapy Anal cancer Anal carcinoma IMRT Squamous cell anal cancer Genital marginal failures 

Notes

Acknowledgements

This work was partially supported by the research grants from the by ESO Clinical Training Center Programme 2016 Grants to Dr. F. Kraja and Dr. J. Kobiela, Umberto Veronesi Foundation research Grant to Dr. A. Surgo and Accuray Inc. entitled “Data collection and analysis of Tomotherapy and CyberKnife breast clinical studies, breast physics studies and prostate study” to R. Ricotti. Dr: Glynne-Jones receive payment or services from a third party (government, commercial, private foundation, etc.) from Roche, Merck Serono, Amgen, Servier, Sanofi, Eli Lilley, Home Nutrition, Eisai, BMS. Dr Leonardi receive payment or services from a third party (government, commercial, private foundation, etc.) from Accuray. The sponsors did not play any role in the study design, collection, analysis and interpretation of data, nor in the writing of the manuscript, nor in the decision to submit the manuscript for publication.

References

  1. 1.
    Vinayan A, Glynne-Jones R. Anal cancer—What is the optimum chemoradiotherapy? Best Pract Res Clin Gastroenterol. 2016;30(4):641–53.CrossRefPubMedGoogle Scholar
  2. 2.
    Esiashvili N, Landry J, Matthews RH. Carcinoma of the anus: strategies in management. Oncologist. 2002;7(3):188–99.CrossRefPubMedGoogle Scholar
  3. 3.
    Mitchell MP, Abboud M, Eng C, Beddar AS, et al. Intensity-modulated radiation therapy with concurrent chemotherapy for anal cancer: outcomes and toxicity. Am J Clin Oncol. 2014;37(5):461–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Call JA, Prendergast BM, Jensen LG, et al. Intensity-modulated radiation therapy for anal cancer: results from a multi-institutional retrospective cohort study. Am J Clin Oncol. 2016;39(1):8–12.CrossRefPubMedGoogle Scholar
  5. 5.
    Kachnic LA, Winter K, Myerson RJ, et al. RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2013;86(1):27–33.CrossRefPubMedGoogle Scholar
  6. 6.
    Han K, Cummings BJ, Lindsay P, et al. Prospective evaluation of acute toxicity and quality of life after IMRT and concurrent chemotherapy for anal canal and perianal cancer. Int J Radiat Oncol Biol Phys. 2014;90(3):587–94.CrossRefPubMedGoogle Scholar
  7. 7.
    Milano MT, Jani AB, Farrey KJ, et al. Intensity-modulated radiation therapy (IMRT) in the treatment of anal cancer: toxicity and clinical outcome. Int J Radiat Oncol Biol Phys. 2005;63(2):354–61.CrossRefPubMedGoogle Scholar
  8. 8.
    Menkarios C, Azria D, Laliberté B, et al. Optimal organ-sparing intensity-modulated radiation therapy (IMRT) regimen for the treatment of locally advanced anal canal carcinoma: a comparison of conventional and IMRT plans. Radiat Oncol. 2007;15(2):41.CrossRefGoogle Scholar
  9. 9.
    Brooks CJ, Lee YK, Aitken K, et al. Organ-sparing Intensity-modulated radiotherapy for anal cancer using the ACTII schedule: a comparison of conventional and intensity-modulated radiotherapy plans. Clin Oncol (R Coll Radiol). 2013;25(3):155–61.CrossRefGoogle Scholar
  10. 10.
    Zimmermann M, Beer J, Bodis S, et al. PET-CT guided SIB-IMRT combined with concurrent 5-FU/MMC for the treatment of anal cancer. Acta Oncol. 2017;30:1–7.Google Scholar
  11. 11.
    Koeck J, Lohr F, Buergy D, et al. Genital invasion or perigenital spread may pose a risk of marginal misses for Intensity Modulated Radiotherapy (IMRT) in anal cancer. Radiat Oncol. 2016;4(11):53.CrossRefGoogle Scholar
  12. 12.
    Mai S, Welzel G, Ottstadt M, et al. Prognostic relevance of HPV infection and p16 overexpression in squamous cell anal cancer. Int J Radiat Oncol Biol Phys. 2015;93(4):819–27.CrossRefPubMedGoogle Scholar
  13. 13.
    Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRefPubMedGoogle Scholar
  14. 14.
    Dawson LA, Anzai Y, Marsh L, et al. Patterns of local-regional recurrence following parotid-sparing conformal and segmental intensity-modulated radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 2000;46(5):1117–26.CrossRefPubMedGoogle Scholar
  15. 15.
    Ng M, Leong T, Chander S, Chu J, et al. Australasian gastrointestinal trials group (AGITG) contouring atlas and planning guidelines for intensity-modulated radiotherapy in anal cancer. Int J Radiat Oncol Biol Phys. 2012;83(5):1455–62.CrossRefPubMedGoogle Scholar
  16. 16.
    Viswanathan AN, Moughan J, Miller BE, et al. NRG Oncology/RTOG 0921: a phase 2 study of postoperative intensity-modulated radiotherapy with concurrent cisplatin and bevacizumab followed by carboplatin and paclitaxel for patients with endometrial cancer. Cancer. 2015;121(13):2156–63.CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    The International Commission on radiation units and measurements, ICRU report no. 83. Prescribing, recording and reporting photon-beam intensity modulated radiation therapy (IMRT). J ICRU. 2010;10(1) report 83. Oxford University Press.  https://doi.org/10.1093/jicru/ndq001.
  18. 18.
    Salati SA, Al Kadi A. Anal cancer—a review. Int J Health Sci (Qassim). 2012;6(2):206–30.CrossRefGoogle Scholar
  19. 19.
    Haddock MG, Martenson JA. Chapter 39: anal carcinoma. In: Gunderson LL, Tepper JE, editors. Clinical radiation oncology. Pennsylvania: Churchill Livingstone; 2000. p. 747–61.Google Scholar
  20. 20.
    Vuong T, Devic S, Belliveau P, et al. Contribution of conformal therapy in the treatment of anal canal carcinoma with combined chemotherapy and radiotherapy: results of a phase II study. Int J Radiat Oncol Biol Phys. 2003;56(3):823–31.CrossRefPubMedGoogle Scholar
  21. 21.
    Beriwal S, Heron DE, Kim H, et al. Intensity-modulated radiotherapy for the treatment of vulvar carcinoma: a comparative dosimetric study with early clinical outcome. Int J Radiat Oncol Biol Phys. 2006;64(5):1395–400.CrossRefPubMedGoogle Scholar
  22. 22.
    Brooks C, Hansen VN, Riddell A, et al. Proposed genitalia contouring guidelines in anal cancer intensity-modulated radiotherapy. Br J Radiol. 2015;88(1051):20150032.CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Chen AM, Farwell DG, Luu Q, et al. Marginal misses after postoperative intensity-modulated radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 2011;80(5):1423–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Franco P, Arcadipane F, Ragona R, et al. Locally advanced (T3–T4 or N+) anal cancer treated with simultaneous integrated boost radiotherapy and concurrent chemotherapy. Anticancer Res. 2016;36(4):2027–32.PubMedGoogle Scholar
  25. 25.
    Franco P, Arcadipane F, Ragona R, et al. Early-stage node-negative (T1-T2N0) anal cancer treated with simultaneous integrated boost radiotherapy and concurrent chemotherapy. Anticancer Res. 2016;36(4):1943–8.PubMedGoogle Scholar
  26. 26.
    Bagshaw HP, Sause WT, Gawlick U, et al. Vulvar recurrences after intensity-modulated radiation therapy for squamous cell carcinoma of the anus. Am J Clin Oncol. 2016. [Epub ahead of print].Google Scholar
  27. 27.
    Das P, Bhatia S, Eng C, et al. Predictors and patterns of recurrence after definitive chemoradiation for anal cancer. Int J Radiat Oncol Biol Phys. 2007;68(3):794–800.CrossRefPubMedGoogle Scholar
  28. 28.
    Sischy B, Doggett RL, Krall JM, et al. Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on radiation therapy oncology group study no. 8314. J Natl Cancer Inst. 1989;81(11):850–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Glynne-Jones R, Nilsson PJ, Aschele C, et al. European society for medical oncology (ESMO); European society of surgical oncology (ESSO); European society of radiotherapy and oncology (ESTRO). Anal cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Eur J Surg Oncol. 2014;40(10):1165–76.CrossRefPubMedGoogle Scholar
  30. 30.
    Bartelink H, Roelofsen F, Eschwege F, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European organization for research and treatment of cancer radiotherapy and gastrointestinal cooperative groups. J Clin Oncol. 1997;15(5):2040–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Wright JL, Patil SM, Temple LK, et al. Squamous cell carcinoma of the anal canal: patterns and predictors of failure and implications for intensity-modulated radiation treatment planning. Int J Radiat Oncol Biol Phys. 2010;78(4):1064–72.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • V. Dell’Acqua
    • 1
  • J. Kobiela
    • 2
  • F. Kraja
    • 3
  • M. C. Leonardi
    • 1
  • A. Surgo
    • 1
  • M. A. Zerella
    • 1
    • 4
  • S. Arculeo
    • 1
    • 4
  • C. Fodor
    • 1
  • R. Ricotti
    • 1
  • M. G. Zampino
    • 5
  • S. Ravenda
    • 5
  • G. Spinoglio
    • 6
  • R. Biffi
    • 7
  • A. Bazani
    • 8
  • R. Luraschi
    • 8
  • S. Vigorito
    • 8
  • P. Spychalski
    • 2
  • R. Orecchia
    • 9
  • R. Glynne-Jones
    • 10
  • B. A. Jereczek-Fossa
    • 1
    • 4
  1. 1.Department of RadiotherapyEuropean Institute of OncologyMilanItaly
  2. 2.Department of General, Endocrine and Transplant SurgeryMedical University of GdanskGdańskPoland
  3. 3.Division of OncologyUniversity Hospital Centre “Mother Theresa”TiranaAlbania
  4. 4.Department of Oncology and Hemato-OncologyUniversity of MilanMilanItaly
  5. 5.Division of Gastrointestinal Medical Oncology and Neuroendocrine TumorsEuropean Institute of OncologyMilanItaly
  6. 6.Division of Digestive SurgeryMilanItaly
  7. 7.Unit of Peritoneal Cancer SurgeryEuropean Institute of OncologyMilanItaly
  8. 8.Unit of Medical PhysicsEuropean Institute of OncologyMilanItaly
  9. 9.Scientific DirectorateEuropean Institute of OncologyMilanItaly
  10. 10.Mount Vernon Centre for Cancer TreatmentNorthwood, MiddlesexUK

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