Skip to main content
Top
Published in: Clinical and Translational Oncology 10/2018

01-10-2018 | Research Article

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

Authors: R. N. Prasad, J. Elson, J. Kharofa

Published in: Clinical and Translational Oncology | Issue 10/2018

Login to get access

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.
Literature
1.
go back to reference Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.CrossRef Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.CrossRef
2.
go back to reference 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.CrossRef 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.CrossRef
3.
go back to reference 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.CrossRef 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.CrossRef
4.
go back to reference 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.PubMed 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.PubMed
6.
go back to reference 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.CrossRef 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.CrossRef
7.
go back to reference 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.CrossRef 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.CrossRef
8.
go back to reference 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.CrossRef 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.CrossRef
9.
go back to reference 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.CrossRef 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.CrossRef
10.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference 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.CrossRef 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.CrossRef
12.
go back to reference 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.PubMed 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.PubMed
13.
go back to reference 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.CrossRef 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.CrossRef
14.
go back to reference 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.CrossRef 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.CrossRef
15.
go back to reference 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.PubMed 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.PubMed
16.
go back to reference 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.CrossRef 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.CrossRef
17.
go back to reference 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.CrossRef 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.CrossRef
18.
go back to reference 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.CrossRef 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.CrossRef
19.
go back to reference 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.CrossRef 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.CrossRef
20.
go back to reference Blumetti J, Bastawrous AL. Epidermoid cancers of the anal canal: current treatment. Clin Colon Rectal Surg. 2009;22:77–83.CrossRef Blumetti J, Bastawrous AL. Epidermoid cancers of the anal canal: current treatment. Clin Colon Rectal Surg. 2009;22:77–83.CrossRef
Metadata
Title
The effect of dose escalation for large squamous cell carcinomas of the anal canal
Authors
R. N. Prasad
J. Elson
J. Kharofa
Publication date
01-10-2018
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 10/2018
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-018-1863-y

Other articles of this Issue 10/2018

Clinical and Translational Oncology 10/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine