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Clinical and Translational Oncology

, Volume 20, Issue 10, pp 1314–1320 | Cite as

The effect of dose escalation for large squamous cell carcinomas of the anal canal

  • R. N. Prasad
  • J. Elson
  • J. Kharofa
Research Article
  • 53 Downloads

Abstract

Purpose

Chemoradiation allows for organ preservation in patients with anal cancer, but patients with large tumors (> 5 cm) have elevated rates of locoregional recurrence. With conformal radiation techniques, there is interest in dose escalation to decrease local recurrence in patients with large tumor size.

Methods/patients

The National Cancer Database (NCDB) was used to identify patients with anal cancer from 2004 to 2013 with tumors > 5 cm. Adult patients who received definitive chemoradiation were included. Patients with prior resection were excluded. High dose was defined as greater than or equal to 5940 cGy. Statistical analyses were performed using logistic regression, Kaplan–Meier, and Cox proportional hazards for overall survival (OS).

Results

In total, 1349 patients were analyzed with 412 (30.5%) receiving high-dose radiation therapy (RT). 5-year OS was 58 and 60% for high and standard dose RT, respectively (p = 0.9887). On univariate analysis, high-dose RT was not associated with improved OS (HR = 0.998, CI 0.805–1.239, p = 0.9887). On multivariate analysis, high-dose RT (HR = 0.948, CI 0.757–1.187, p = 0.6420) was not associated with improved OS but older age (HR = 1.535, CI 1.233–1.911, p = 0.0001), male sex (HR = 1.695, CI 1.382–2.080, p < 0.0001), comorbidities (HR = 1.389, CI 1.097–1.759, p = 0.0064), and long RT (HR = 1.299, CI 1.047–1.611, p = 0.0173) were significantly associated with decreased OS.

Conclusions

There was no observed difference in OS for dose escalation of anal cancers > 5 cm in this population-based analysis. Differences in local control and salvage therapy cannot be assessed through the NCDB. Whether dose escalation of large tumors may improve local control and colostomy-free survival remains an important question and is the subject of ongoing trials.

Keywords

Dose escalation Anal cancer Large tumors Overall survival benefit Squamous cell carcinoma 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest

Ethical approval

This was a retrospective review of population level, aggregated, de-identified data from a national United States cancer database (NCDB). As a result, this study did not involve interaction with any human subjects or sensitive demographic or treatment data from any human subjects that could be tied to any particular patient or treatment center.

Informal consent

For this type of study, formal consent is not required

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.CrossRefGoogle Scholar
  2. 2.
    Nelson RA, Levine AM, Bernstein L, Smith DD, Lai LL. Changing patterns of anal canal carcinoma in the United States. J Clin Oncol. 2013;31:1569–75.CrossRefGoogle Scholar
  3. 3.
    Pintor MP, Northover JM, Nicholls RJ. Squamous cell carcinoma of the anus at one hospital from 1948 to 1984. Br J Surg. 1989;76:806–10.CrossRefGoogle Scholar
  4. 4.
    Brown DK, Oglesby AB, Scott DH, Dayton MT. Squamous cell carcinoma of the anus: a twenty-five year retrospective. Am Surg. 1988;54:337–42.PubMedGoogle Scholar
  5. 5.
    Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB, Thomas CR, et al. prognostic factors derived from a prospective database dictate clinical biology of anal cancer: the Intergroup Trial (RTOG 98-11). Cancer [Internet]. 2010; 116. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831519/. Accessed 15 Jan 2018.
  6. 6.
    Kachnic L, Winter K, Myerson R, Goodyear M, Willins J, Esthappan J, et al. RTOG 0529: a phase II evaluation of dose-painted IMRT in combination with 5-fluorouracil and mitomycin-C for reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2009;75:S5.CrossRefGoogle Scholar
  7. 7.
    Gunderson LL, Moughan J, Ajani JA, Pedersen JE, Winter KA, Benson AB, et al. Anal Carcinoma: impact of TN category of disease on survival, disease relapse, and colostomy failure in US Gastrointestinal Intergroup RTOG 98-11 Phase 3 Trial. Int J Radiat Oncol. 2013;87:638–45.CrossRefGoogle Scholar
  8. 8.
    Bentzen AG, Guren MG, Vonen B, Wanderås EH, Frykholm G, Wilsgaard T, et al. Faecal incontinence after chemoradiotherapy in anal cancer survivors: long-term results of a national cohort. Radiother Oncol. 2013;108:55–60.CrossRefGoogle Scholar
  9. 9.
    Peiffert D, Tournier-Rangeard L, Gérard J-P, Lemanski C, François E, Giovannini M, et al. Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 Trial. J Clin Oncol. 2012;30:1941–8.CrossRefGoogle Scholar
  10. 10.
    Ben-Josef E, Moughan J, Ajani JA, Flam M, Gunderson L, Pollock J, et al. Impact of overall treatment time on survival and local control in patients with anal cancer: a pooled data analysis of radiation therapy oncology group trials 87-04 and 98-11. J Clin Oncol. 2010;28:5061–6.CrossRefGoogle Scholar
  11. 11.
    Sebag-Montefiore D, Adams R, Bell S, Berkman L, Gilbert DC, Glynne-Jones R, et al. The Development of an Umbrella Trial (PLATO) to address radiation therapy dose questions in the locoregional management of squamous cell carcinoma of the anus. Int J Radiat Oncol Biol Phys. 2016;96:E164–5.CrossRefGoogle Scholar
  12. 12.
    Nilsson PJ, Lenander C, Rubio C, Auer G, Ljungqvist O, Glimelius B. Prognostic significance of Cyclin A in epidermoid anal cancer. Oncol Rep. 2006;16:443–9.PubMedGoogle Scholar
  13. 13.
    Bruland O, Fluge Ø, Immervoll H, Balteskard L, Myklebust MP, Skarstein A, et al. Gene expression reveals two distinct groups of anal carcinomas with clinical implications. Br J Cancer. 2008;98:1264–73.CrossRefGoogle Scholar
  14. 14.
    Ajani JA, Wang X, Izzo JG, Crane CH, Eng C, Skibber JM, et al. Molecular biomarkers correlate with disease-free survival in patients with anal canal carcinoma treated with chemoradiation. Dig Dis Sci. 2010;55:1098–105.CrossRefGoogle Scholar
  15. 15.
    Das P, Crane CH, Eng C, Ajani JA. Prognostic factors for squamous cell cancer of the anal canal. Gastrointest Cancer Res GCR. 2008;2:10–4.PubMedGoogle Scholar
  16. 16.
    Koerber SA, Schoneweg C, Slynko A, Krug D, Haefner MF, Herfarth K, et al. Influence of human papillomavirus and p16INK4a on treatment outcome of patients with anal cancer. Radiother Oncol. 2014;113:331–6.CrossRefGoogle Scholar
  17. 17.
    Yhim H-Y, Lee N-R, Song E-K, Kwak J-Y, Lee ST, Kim JH, et al. The prognostic significance of tumor human papillomavirus status for patients with anal squamous cell carcinoma treated with combined chemoradiotherapy. Int J Cancer. 2011;129:1752–60.CrossRefGoogle Scholar
  18. 18.
    Mai S, Welzel G, Ottstadt M, Lohr F, Severa S, Prigge E-S, et al. Prognostic relevance of HPV infection and p16 overexpression in squamous cell anal cancer. Int J Radiat Oncol Biol Phys. 2015;93:819–27.CrossRefGoogle Scholar
  19. 19.
    Serup-Hansen E, Linnemann D, Skovrider-Ruminski W, Høgdall E, Geertsen PF, Havsteen H. Human papillomavirus genotyping and p16 expression as prognostic factors for patients with American Joint Committee on Cancer stages I to III carcinoma of the anal canal. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32:1812–7.CrossRefGoogle Scholar
  20. 20.
    Blumetti J, Bastawrous AL. Epidermoid cancers of the anal canal: current treatment. Clin Colon Rectal Surg. 2009;22:77–83.CrossRefGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  1. 1.Department of Radiation Oncology, UC Health Barrett Cancer CenterUniversity of CincinnatiCincinnatiUSA

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