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Published in: Annals of Surgical Oncology 11/2016

01-10-2016 | Radiation Oncology

Radiation Therapy is Associated with Improved Outcomes in Merkel Cell Carcinoma

Authors: Tobin Strom, MD, Michael Carr, MS, Jonathan S. Zager, MD, Arash Naghavi, MD, MS, Franz O. Smith, MD, C. Wayne Cruse, MD, Jane L. Messina, MD, Jeffery Russell, MD, PhD, Nikhil G. Rao, MD, William Fulp, MS, Sungjune Kim, MD, PhD, Javier F. Torres-Roca, MD, Tapan A. Padhya, MD, Vernon K. Sondak, MD, Andy M. Trotti, MD, Louis B. Harrison, MD, FASTRO, Jimmy J. Caudell, MD, PhD

Published in: Annals of Surgical Oncology | Issue 11/2016

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Abstract

Background

Following wide excision of Merkel cell carcinoma (MCC), postoperative radiation therapy (RT) is typically recommended. Controversy remains as to whether RT can be avoided in selected cases, such as those with negative margins. Additionally, there is evidence that RT can influence survival.

Methods

We included 171 patients treated for non-metastatic MCC from 1994 through 2012 at a single institution. Patients without pathologic nodal evaluation (clinical N0 disease) were excluded to reflect modern treatment practice. The endpoints included local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS).

Results

Median follow-up was 33 months. Treatment with RT was associated with improved 3-year LC (91.2 vs. 76.9 %, respectively; p = 0.01), LRC (79.5 vs. 59.1 %; p = 0.004), DFS (57.0 vs. 30.2 %; p < 0.001), and OS (73 vs. 66 %; p = 0.02), and was associated with improved 3-year DSS among node-positive patients (76.2 vs. 48.1 %; p = 0.035), but not node-negative patients (90.1 vs. 80.8 %; p = 0.79). On multivariate analysis, RT was associated with improved LC [hazard ratio (HR) 0.18, 95 % confidence interval (CI) 0.07–0.46; p < 0.001], LRC (HR 0.28, 95 % CI 0.14–0.56; p < 0.001), DFS (HR 0.42, 95 % CI 0.26–0.70; p = 0.001), OS (HR 0.53, 95 % CI 0.31–0.93; p = 0.03), and DSS (HR 0.42, 95 % CI 0.26–0.70; p = 0.001). Patients with negative margins had significant improvements in 3-year LC (90.1 vs. 75.4 %; p < 0.001) with RT. Deaths not attributable to MCC were relatively evenly distributed between the RT and no RT groups (28.5 and 29.3 % of patients, respectively).

Conclusions

RT for MCC was associated with improved LRC and survival. RT appeared to be beneficial regardless of margin status.
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Literature
2.
go back to reference Pectasides D, Pectasides M, Economopoulos T. Merkel cell cancer of the skin. Ann Oncol. 2006;17:1489–95.CrossRefPubMed Pectasides D, Pectasides M, Economopoulos T. Merkel cell cancer of the skin. Ann Oncol. 2006;17:1489–95.CrossRefPubMed
3.
go back to reference Rollison DE, Giuliano AR, Becker JC. New virus associated with merkel cell carcinoma development. J Natl Compr Canc Netw. 2010;8:874–80.PubMed Rollison DE, Giuliano AR, Becker JC. New virus associated with merkel cell carcinoma development. J Natl Compr Canc Netw. 2010;8:874–80.PubMed
5.
go back to reference Lyhne D, Lock-Andersen J, Dahlstrom K, et al. Rising incidence of Merkel cell carcinoma. J Plast Surg Hand Surg. 2011;45:274–80.CrossRefPubMed Lyhne D, Lock-Andersen J, Dahlstrom K, et al. Rising incidence of Merkel cell carcinoma. J Plast Surg Hand Surg. 2011;45:274–80.CrossRefPubMed
6.
go back to reference Allen PJ, Bowne WB, Jaques DP, Brennan MF, Busam K, Coit DG. Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol. 2005;23:2300–9.CrossRefPubMed Allen PJ, Bowne WB, Jaques DP, Brennan MF, Busam K, Coit DG. Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol. 2005;23:2300–9.CrossRefPubMed
7.
go back to reference Bichakjian CK, Lowe L, Lao CD, et al. Merkel cell carcinoma: critical review with guidelines for multidisciplinary management. Cancer. 2007;110:1–12.CrossRefPubMed Bichakjian CK, Lowe L, Lao CD, et al. Merkel cell carcinoma: critical review with guidelines for multidisciplinary management. Cancer. 2007;110:1–12.CrossRefPubMed
8.
go back to reference Lemos BD, Storer BE, Iyer JG, et al. Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system. J Am Acad Dermatol. 2010;63:751–61.CrossRefPubMedPubMedCentral Lemos BD, Storer BE, Iyer JG, et al. Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system. J Am Acad Dermatol. 2010;63:751–61.CrossRefPubMedPubMedCentral
9.
go back to reference Henness S, Vereecken P. Management of Merkel tumours: an evidence-based review. Curr Opin Oncol. 2008;20: 280–6.CrossRefPubMed Henness S, Vereecken P. Management of Merkel tumours: an evidence-based review. Curr Opin Oncol. 2008;20: 280–6.CrossRefPubMed
10.
go back to reference Al-Ghazal SK, Arora DS, Simpson RH, Saxby P. Merkel cell carcinoma of the skin. Br J Plast Surg. 1996;49: 491–6.CrossRefPubMed Al-Ghazal SK, Arora DS, Simpson RH, Saxby P. Merkel cell carcinoma of the skin. Br J Plast Surg. 1996;49: 491–6.CrossRefPubMed
12.
go back to reference Hitchcock CL, Bland KI, Laney RG 3rd, Franzini D, Harris B, Copeland EM 3rd. Neuroendocrine (Merkel cell) carcinoma of the skin. Its natural history, diagnosis, and treatment. Ann Surg. 1988;207:201–7.CrossRefPubMedPubMedCentral Hitchcock CL, Bland KI, Laney RG 3rd, Franzini D, Harris B, Copeland EM 3rd. Neuroendocrine (Merkel cell) carcinoma of the skin. Its natural history, diagnosis, and treatment. Ann Surg. 1988;207:201–7.CrossRefPubMedPubMedCentral
13.
go back to reference Miller SJ, Alam M, Andersen J, et al. Merkel cell carcinoma. J Natl Compr Cancer Netw. 2009;7:322–32. Miller SJ, Alam M, Andersen J, et al. Merkel cell carcinoma. J Natl Compr Cancer Netw. 2009;7:322–32.
15.
go back to reference Kang SH, Haydu LE, Goh RY, Fogarty GB. Radiotherapy is associated with significant improvement in local and regional control in Merkel cell carcinoma. Radiat Oncol. 2012;7:171.CrossRefPubMedPubMedCentral Kang SH, Haydu LE, Goh RY, Fogarty GB. Radiotherapy is associated with significant improvement in local and regional control in Merkel cell carcinoma. Radiat Oncol. 2012;7:171.CrossRefPubMedPubMedCentral
16.
go back to reference Lewis KG, Weinstock MA, Weaver AL, Otley CC. Adjuvant local irradiation for Merkel cell carcinoma. Arch Dermatol. 2006;142:693–700.PubMed Lewis KG, Weinstock MA, Weaver AL, Otley CC. Adjuvant local irradiation for Merkel cell carcinoma. Arch Dermatol. 2006;142:693–700.PubMed
17.
go back to reference Gillenwater AM, Hessel AC, Morrison WH, et al. Merkel cell carcinoma of the head and neck: effect of surgical excision and radiation on recurrence and survival. Arch Otolaryngol Head Neck Surg. 2001;127:149–54.CrossRefPubMed Gillenwater AM, Hessel AC, Morrison WH, et al. Merkel cell carcinoma of the head and neck: effect of surgical excision and radiation on recurrence and survival. Arch Otolaryngol Head Neck Surg. 2001;127:149–54.CrossRefPubMed
18.
go back to reference Meeuwissen JA, Bourne RG, Kearsley JH. The importance of postoperative radiation therapy in the treatment of Merkel cell carcinoma. Int J Radiat Oncol Biol Phys. 1995;31:325–31.CrossRef Meeuwissen JA, Bourne RG, Kearsley JH. The importance of postoperative radiation therapy in the treatment of Merkel cell carcinoma. Int J Radiat Oncol Biol Phys. 1995;31:325–31.CrossRef
19.
go back to reference Hui AC, Stillie AL, Seel M, Ainslie J. Merkel cell carcinoma: 27-year experience at the Peter MacCallum Cancer Centre. Int J Radiat Oncol Biol Phys. 2011;80:1430–5.CrossRef Hui AC, Stillie AL, Seel M, Ainslie J. Merkel cell carcinoma: 27-year experience at the Peter MacCallum Cancer Centre. Int J Radiat Oncol Biol Phys. 2011;80:1430–5.CrossRef
20.
go back to reference Ghadjar P, Kaanders JH, Poortmans P, et al. The essential role of radiotherapy in the treatment of Merkel cell carcinoma: a study from the Rare Cancer Network. Int J Radiat Oncol Biol Phys. 2011;81:e583–91.CrossRef Ghadjar P, Kaanders JH, Poortmans P, et al. The essential role of radiotherapy in the treatment of Merkel cell carcinoma: a study from the Rare Cancer Network. Int J Radiat Oncol Biol Phys. 2011;81:e583–91.CrossRef
21.
go back to reference Morrison WH, Peters LJ, Silva EG, Wendt CD, Ang KK, Goepfert H. The essential role of radiation therapy in securing locoregional control of Merkel cell carcinoma. Int J Radiat Oncol Biol Phys. 1990;19:583–91.CrossRef Morrison WH, Peters LJ, Silva EG, Wendt CD, Ang KK, Goepfert H. The essential role of radiation therapy in securing locoregional control of Merkel cell carcinoma. Int J Radiat Oncol Biol Phys. 1990;19:583–91.CrossRef
22.
go back to reference Eng TY, Boersma MG, Fuller CD, Cavanaugh SX, Valenzuela F, Herman TS. Treatment of merkel cell carcinoma. Am J Clin Oncol. 2004;27:510–5.CrossRefPubMed Eng TY, Boersma MG, Fuller CD, Cavanaugh SX, Valenzuela F, Herman TS. Treatment of merkel cell carcinoma. Am J Clin Oncol. 2004;27:510–5.CrossRefPubMed
23.
go back to reference Eich HT, Eich D, Staar S, et al. Role of postoperative radiotherapy in the management of Merkel cell carcinoma. Am J Clin Oncol. 2002;25:50–6.CrossRefPubMed Eich HT, Eich D, Staar S, et al. Role of postoperative radiotherapy in the management of Merkel cell carcinoma. Am J Clin Oncol. 2002;25:50–6.CrossRefPubMed
24.
go back to reference Bishop AJ, Garden AS, Gunn GB, et al. Merkel cell carcinoma of the head and neck: favorable outcomes with radiotherapy. Head Neck. 2016;38(Suppl 1):E452–8.CrossRefPubMed Bishop AJ, Garden AS, Gunn GB, et al. Merkel cell carcinoma of the head and neck: favorable outcomes with radiotherapy. Head Neck. 2016;38(Suppl 1):E452–8.CrossRefPubMed
25.
go back to reference Mojica P, Smith D, Ellenhorn JD. Adjuvant radiation therapy is associated with improved survival in Merkel cell carcinoma of the skin. J Clin Oncol. 2007;25:1043–7.CrossRefPubMed Mojica P, Smith D, Ellenhorn JD. Adjuvant radiation therapy is associated with improved survival in Merkel cell carcinoma of the skin. J Clin Oncol. 2007;25:1043–7.CrossRefPubMed
26.
go back to reference Jouary T, Leyral C, Dreno B, et al. Adjuvant prophylactic regional radiotherapy versus observation in stage I Merkel cell carcinoma: a multicentric prospective randomized study. Ann Oncol. 2012;23:1074–80.CrossRefPubMed Jouary T, Leyral C, Dreno B, et al. Adjuvant prophylactic regional radiotherapy versus observation in stage I Merkel cell carcinoma: a multicentric prospective randomized study. Ann Oncol. 2012;23:1074–80.CrossRefPubMed
27.
go back to reference Kim JA, Choi AH. Effect of radiation therapy on survival in patients with resected Merkel cell carcinoma: a propensity score surveillance, epidemiology, and end results database analysis. JAMA Dermatol. 2013;149: 831–8.CrossRefPubMed Kim JA, Choi AH. Effect of radiation therapy on survival in patients with resected Merkel cell carcinoma: a propensity score surveillance, epidemiology, and end results database analysis. JAMA Dermatol. 2013;149: 831–8.CrossRefPubMed
Metadata
Title
Radiation Therapy is Associated with Improved Outcomes in Merkel Cell Carcinoma
Authors
Tobin Strom, MD
Michael Carr, MS
Jonathan S. Zager, MD
Arash Naghavi, MD, MS
Franz O. Smith, MD
C. Wayne Cruse, MD
Jane L. Messina, MD
Jeffery Russell, MD, PhD
Nikhil G. Rao, MD
William Fulp, MS
Sungjune Kim, MD, PhD
Javier F. Torres-Roca, MD
Tapan A. Padhya, MD
Vernon K. Sondak, MD
Andy M. Trotti, MD
Louis B. Harrison, MD, FASTRO
Jimmy J. Caudell, MD, PhD
Publication date
01-10-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 11/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5293-1

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