The Role of Postoperative Radiation and Chemoradiation in Merkel Cell Carcinoma: A Systematic Review of the Literature

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Abstract

Objective: A systematic review of the literature was undertaken to investigate whether adjuvant radiotherapy and/or chemotherapeutics offered any additional benefit than surgery alone in the treatment of Merkel Cell Carcinoma (MCC).

Methods: A PubMed, MEDLINE search was conducted between 1995 and 2013, to identify reported cases of surgically treated MCC followed by either observation, radiation, or chemoradiation. Patient demographics and outcomes were recorded and compared in a systematic fashion.

Results: Thirty-four studies ( n = 4475) were included. The median age was 73 years, median follow up was 36 months and there was a 1.5:1 ratio of men to women. All 4475 patients had surgery, 1975 had no further treatment, 1689 received postoperative RT, and 301 received postoperative chemoRT. The most common site was face/head/neck, 47.8%. Stage 1 was the most common clinical stage at diagnosis (57%). Three-year local control was 20% (median 10%) in the observation cohort, compared to 65% (62%) with postoperative RT, and 67% (75%) with postoperative chemoRT; these findings were statistically significant ( P < 0.001). Recurrence was found to be 38% (60%) in the observation cohort, compared to 23% (20%) with postoperative RT ( P < 0.001). Three-year overall survival (OS) was found to be 56% (57%) in the observation cohort, compared to 70% (78%) with postoperative RT and 73% (76%) with postoperative chemoRT ( P < 0.001). The observation cohort had a median OS of 44 months compared with 64 months ( P < 0.001) in the postoperative RT cohort. There was no statistically significant difference in any parameters assessed between postoperative radiation and postoperative chemoradiation arms.

Conclusion: The comprehensive collection of retrospective data suggests a survival and control benefit for postoperative radiation in MCC. No differences were noted between adjuvant radiation and chemoradiation. This analysis indicates the need for prospective trials with patients stratified by known prognostic factors.

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Most cited references 44

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Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features.

Michèlle C. Heath, Natalia Jaimes, Bianca Durando Lemos … (2008)

Merkel cell carcinoma (MCC) is an aggressive skin cancer with a mortality of 33%. Advanced disease at diagnosis is a poor prognostic factor, suggesting that earlier detection may improve outcome. No systematic analysis has been published to define the clinical features that are characteristic of MCC. We sought to define the clinical characteristics present at diagnosis to identify features that may aid clinicians in recognizing MCC. We conducted a cohort study of 195 patients given the diagnosis of MCC between 1980 and 2007. Data were collected prospectively in the majority of cases, and medical records were reviewed. An important finding was that 88% of MCCs were asymptomatic (nontender) despite rapid growth in the prior 3 months (63% of lesions) and being red or pink (56%). A majority of MCC lesions (56%) were presumed at biopsy to be benign, with a cyst/acneiform lesion being the single most common diagnosis (32%) given. The median delay from lesion appearance to biopsy was 3 months (range 1-54 months), and median tumor diameter was 1.8 cm. Similar to earlier studies, 81% of primary MCCs occurred on ultraviolet-exposed sites, and our cohort was elderly (90% >50 years), predominantly white (98%), and often profoundly immune suppressed (7.8%). An additional novel finding was that chronic lymphocytic leukemia was more than 30-fold overrepresented among patients with MCC. The study was limited to patients seen at a tertiary care center. Complete clinical data could not be obtained on all patients. This study could not assess the specificity of the clinical characteristics of MCC. To our knowledge, this study is the first to define clinical features that may serve as clues in the diagnosis of MCC. The most significant features can be summarized in an acronym: AEIOU (asymptomatic/lack of tenderness, expanding rapidly, immune suppression, older than 50 years, and ultraviolet-exposed site on a person with fair skin). In our series, 89% of primary MCCs had 3 or more of these findings. Although MCC is uncommon, when present in combination, these features may indicate a concerning process that would warrant biopsy. In particular, a lesion that is red and expanding rapidly yet asymptomatic should be of concern.

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Multimodality treatment of Merkel cell carcinoma: case series and literature review of 1024 cases.

Humberto Medina-Cortina, M M Urist, D Heslin … (2001)

Merkel cell carcinoma (MCC) is an unusual and potentially aggressive cancer of the skin. There is no consensus regarding the optimal therapeutic approach, and the relative roles of surgery, radiotherapy, and chemotherapy still are controversial The aim of this study is to analyze the roles of these therapeutic options. The medical records of 16 patients with a diagnosis of localized, primary MCC treated at the University of Alabama at Birmingham were reviewed. An extensive review of the English-language literature also was performed. The Kaplan-Meier method was used to develop the survival curves. Comparisons were made using Fisher's exact test. Significance was defined as P < .05. MCC presented primarily in Caucasians (98.3%) with a median age of 69 years. Immunosuppressive therapy appeared to play a role in the development of this cancer. In the UAB experience, 3-year actuarial survival was 31%. The only factor significantly associated with overall survival was the stage of disease at presentation: median survivals were 97 vs. 15 months for stages I and II, respectively (log-rank, P = .02). From the literature review, adjuvant radiotherapy was associated with a reduced risk of local recurrence (P < .00001). MCC is an aggressive cancer, with a high tendency for local recurrence and distant spread. Surgery and adjuvant radiotherapy appear to provide optimal local control. The role of chemotherapy remains to be defined.

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Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases.

J M Tonita, Francis J. Gilchrist, P. Tai … (2000)

To study the use of chemotherapy for Merkel cell carcinoma (MCC) of the skin. Twenty-five cases of MCC were treated at the London Regional Cancer Center between 1987 and 1997. Thirteen cases treated with chemotherapy were reviewed with 191 cases from the literature. At presentation, 24 patients had localized skin lesions (stage I) and one had locoregional involvement (stage II). Among the nine cases with recurrent nodal disease, six had chemotherapy as a component of salvage treatment. They were all free of disease at a median of 19 months (range, 12 to 37 months). In contrast, two patients who had salvage radiotherapy alone died of disease. Overall survival (OS) and disease-free survival (DFS) were 59% and 43%, respectively, at two years. Median OS and DFS were 29 months (range, 1 to 133 months) and 9 months (range, 1 to 133 months), respectively. Nodal disease developed in 12 (50%) of 24 patients with stage I disease, and distant metastases developed in six (25%) of 24. Including those from the literature, there were 204 cases treated with chemotherapy. Cyclophosphamide/doxorubicin (or epirubicin)/vincristine combination +/- prednisone was the most commonly used chemotherapy regimen (47 cases), with an overall response rate of 75.7% (35.1% complete, 35. 1% partial, and 5.4% minor responses). Etoposide/cisplatin (or carboplatin) was the next most commonly used regimen (27 cases), with an overall response rate of 60% (36% complete and 24% partial responses). The difference in response rate was not statistically significant (P =.19). Among the 204 cases, there were seven (3.4%) toxic deaths. Chemoradiation for locally recurrent or advanced disease may be an option for patients with a good performance status.

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Contributors

: URI : http://frontiersin.org/people/u/105731

: URI : http://frontiersin.org/people/u/119997

: URI : http://frontiersin.org/people/u/119256

Journal

Journal ID (nlm-ta): Front Oncol

Journal ID (iso-abbrev): Front Oncol

Journal ID (publisher-id): Front. Oncol.

Title: Frontiers in Oncology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 2234-943X

Publication date (Electronic): 14 November 2013

Publication date Collection: 2013

Volume: 3

Electronic Location Identifier: 276

Affiliations

[1] ¹College of Osteopathic Medicine, Nova Southeastern University , Fort Lauderdale, FL, USA

[2] ²Department of Neuroscience, Yale University , Hartford, CT, USA

[3] ³Department of Radiation Oncology, University Hospitals at Case Western , Cleveland, OH, USA

Author notes

Edited by: Ajay Bhatnagar, University of Pittsburgh School of Medicine, USA

Reviewed by: Shisuo Du, New York University, USA; Christopher Schultz, Medical College of Wisconsin, USA

*Correspondence: Shaakir Hasan, College of Osteopathic Medicine, Nova Southeastern University, 3301 College Avenue, Fort Lauderdale, FL 33314, USA e-mail: sh1055@ 123456nova.edu

This article was submitted to Radiation Oncology, a section of the journal Frontiers in Oncology.

Article

DOI: 10.3389/fonc.2013.00276

PMC ID: 3827544

PubMed ID: 24294591

SO-VID: 88b49422-5455-47bd-8927-c31f5db373db

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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 15 September 2013

Date accepted : 25 October 2013

Page count

Figures: 3, Tables: 4, Equations: 0, References: 51, Pages: 9, Words: 6127

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The Role of Postoperative Radiation and Chemoradiation in Merkel Cell Carcinoma: A Systematic Review of the Literature

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Most cited references 44

Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features.

Multimodality treatment of Merkel cell carcinoma: case series and literature review of 1024 cases.

Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases.

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