The effect of dose escalation for large squamous cell carcinomas of the anal canal
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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.
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).
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.
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.
KeywordsDose escalation Anal cancer Large tumors Overall survival benefit Squamous cell carcinoma
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest
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.
For this type of study, formal consent is not required
- 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.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
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- 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
- 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