ORIGINAL ARTICLE
Treatment outcomes of sinonasal malignant melanoma: a Korean multicenter study Tae-Bin Won, MD, PhD1 , Kyu Young Choi, MD2 , Chae-Seo Rhee, MD, PhD3 , Hong-Ryul Jin, MD, PhD4 , Jong Sook Yi, MD5 , Hun-Jong Dhong, MD, PhD6 , Sung Won Kim, MD, PhD7 , Ji Ho Choi, MD, PhD8 , Jin Kook Kim, MD, PhD9 , Young-Jun Chung, MD, PhD10 , Yong-Min Kim, MD, PhD11 , Sang-Wook Kim, MD, PhD12 , Jung Soo Kim, MD, PhD13 , Sam Hyun Kwon, MD, PhD14 , Sang-Chul Lim, MD, PhD15 and Hwan-Jung Roh, MD, PhD16
Background: The aim of this work was to evaluate factors that influence local recurrence and survival aer surgical resection of sinonasal malignant melanoma, using a large population-based multicenter study in Korea. Methods: Retrospective analysis was performed for 155 newly diagnosed sinonasal malignant melanoma patients gathered from 15 university hospitals throughout Korea. Demographic data, tumor characteristics, surgical approach, adjuvant treatment, recurrence, and outcomes were analyzed. Results: Three-year and 5-year overall survival rates were 48.8% and 40.1%, respectively. Local recurrence rate was 46.6%, with a mean recurrence time of 15.5 months. On multivariate analysis, patients who underwent surgery that included an endoscopic approach showed decreased local recurrence rate (p = 0.042) and increased survival rate (hazard ratio [HR], 1.702; 95% confidence interval [CI], 1.007 to 2.875; p = 0.047) compared to those who underwent an ex-
1 Department
of Otorhinolaryngology–Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea; 2 Department of Otorhinolaryngology–Head and Neck Surgery, Kangnam Sacred Heart Hospital, Seoul, Korea; 3 Department of Otorhinolaryngology–Head and Neck Surgery, Seoul National University Bundang Hospital, Seongnam, Korea; 4 Department of Otorhinolaryngology–Head and Neck Surgery, Seoul National University Boramae Medical Center, Seoul, Korea; 5 Department of Otorhinolaryngology–Head and Neck Surgery, Asan Medical Center, Seoul, Korea; 6 Department of Otorhinolaryngology–Head and Neck Surgery, Samsung Medical Center, Seoul, Korea; 7 Department of Otorhinolaryngology–Head and Neck Surgery, Seoul St. Mary’s Hospital, Seoul, Korea; 8 Department of Otorhinolaryngology–Head and Neck Surgery, Korea University Ansan Hospital, Ansan, Korea; 9 Department of Otorhinolaryngology–Head and Neck Surgery, Konkuk University Hospital, Seoul, Korea; 10 Department of Otorhinolaryngology–Head and Neck Surgery, Dankook University Hospital, Cheonan, Korea; 11 Department of Otorhinolaryngology–Head and Neck Surgery, Chungnam National University Hospital, Daejeon, Korea; 12 Department of
ternal approach. Patients with postoperative radiotherapy showed a decreased local recurrence rate (p = 0.001), but without impact on survival rate. Male gender, tumor beyond the nasal cavity, and presence of distant metastasis were associated with poor survival. Conclusion: An endoscopic-including surgical approach was associated with improved local control and survival in sinonasal malignant melanoma patients. Postoperative raC 2015 diotherapy helped increase the local control rate. ARS-AAOA, LLC.
Key Words: melanoma; nasal cavity; paranasal sinuses; recurrence; survival How to Cite this Article: Won T-B, Choi KY, Rhee C-S, et al. Treatment outcomes of sinonasal malignant melanoma: a Korean multicenter study. Int Forum Allergy Rhinol. 2015;5:950–959.
Otorhinolaryngology–Head and Neck Surgery, Gyeongsang National University Hospital, Jinju, Korea; 13 Department of Otorhinolaryngology–Head and Neck Surgery, Kyungpook National University Hospital, Daegu, Korea; 14 Department of Otorhinolaryngology–Head and Neck Surgery, Chonbuk National University Hospital, Jeonju, Korea; 15 Department of Otorhinolaryngology–Head and Neck Surgery, Chonnam National University Hwasun Hospital, Gwangju, Korea; 16 Department of Otorhinolaryngology–Head and Neck Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea Correspondence to: Hwan-Jung Roh, MD, PhD, Department of Otorhinolaryngology–Head and Neck Surgery, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, Yangsan 626-770, Korea; e-mail: [email protected] T.B.W. and K.Y.C. contributed equally to this work. Potential conflict of interest: None provided. Received: 20 January 2015; Revised: 7 April 2015; Accepted: 28 April 2015 DOI: 10.1002/alr.21558 View this article online at wileyonlinelibrary.com.
International Forum of Allergy & Rhinology, Vol. 5, No. 10, October 2015
950
Sinonasal malignant melanoma
S
inonasal malignant melanoma (SNMM) is a rare clinical entity that accounts for about 4% of sinonasal malignancies.1 The reported incidence rates range from 0.018 to 0.051 per 100000 per year.2–4 Prognosis is poor and worse than cutaneous malignant melanoma, with reported 5-year survival rates ranging from 19% to 46%.5 The grave prognosis is a consequence of the aggressive biological behavior of the disease, resulting from high local recurrence (31–85%) and distant metastasis (25–50%).6, 7 Difficulties in performing curative surgery in the sinonasal tract also contribute to the poor prognosis of the disease. The prognostic factors of SNMM have been reported heterogeneously, including tumor size, tumor location, lymph node involvement,8 positive margin,9, 10 local recurrence, and distant metastasis.11, 12 As for tumor location, tumors involving the paranasal sinuses have been reported to have poor prognoses,12, 13 whereas tumors located in the nasal septum have been reported to have better outcome.7 Various staging systems have been proposed for SNMM, because of the heterogeneous behavior of the tumor.11, 14, 15 The 7th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual has revised the staging system for mucosal melanoma of the head and neck, which has shown its efficacy in providing reliable prognostic information.13, 16 The mainstay of treatment has been surgical resection; adjuvant radiotherapy and elective neck dissection have not showed a significant survival benefit.17 Recently, in light of the trend toward endoscopic techniques, studies have revealed favorable outcomes for endoscopic removal compared to open approaches.8, 12 The aim of this study was to provide a comprehensive analysis of SNMM and to evaluate predictors for local recurrence and survival outcome through a large populationbased multicenter study in Korea.
Patients and methods A multicenter study regarding SNMM was initiated by the sinonasal tumor study division of the Korean Rhinologic Society. From April 1994 to June 2013, patients newly diagnosed for SNMM with a follow-up period of at least 1 year were included. Subsequently, patients who had initially been treated surgically with curative intent were analyzed for local recurrence and survival. Retrospective review of prospectively collected medical records was carried out according to the unified data collection system developed by the study division. Among 155 newly diagnosed patients from 15 different university hospitals, surgical excision had been performed in 141 patients, in which 133 cases were surgery for curative intent. The data included demographic information that included gender, age (at symptom onset), smoking status, presenting symptom and its duration (prior to diagnosis), and tumor characteristics, which included size, morphology, presence of skip lesions (multiple pigmented lesions), and presence of pigmentation. Diagnosis of SNMM was confirmed through pathological reports in all
951
International Forum of Allergy & Rhinology, Vol. 5, No. 10, October 2015
cases; when tumor cells (epithelioid, spindle cell, mixed, or undifferentiated) arranged in various histological patterns (pseudopapillary, peritheliomatous, sarcoid, etc.) were found in the specimen with or without melanin pigment. Immunohistochemistry (S-100, HMB-45, Melan-A, tyrosinase, cytokeratin, etc.) was used necessarily, especially when melanin pigment was not visible.15 Involved site or sites was determined by endoscopic and radiological findings, which included computed tomography (CT) and/or magnetic resonance imaging (MRI) reports. Size of the tumor was measured by either imaging reports or endoscopic findings, which was matched for surgical specimen. Patients were staged according to the 7th edition of the AJCC Cancer Staging Manual for mucosal melanoma of the head and neck.16 Because no general criteria for surgical methods exist in treatment of SNMM, endoscopic or open approaches (or combination) had been chosen freely by the corresponding surgeon in each individual cases. Surgical approach was designated as an exclusively endoscopic approach, an exclusively external approach, or a combination of both. Adjuvant treatment as well as treatment results were analyzed. Involved sites of tumors were categorized into 11 sites (maxillary sinus, nasal cavity, ethmoid sinus, frontal sinus, sphenoid sinus, septum, skull base, orbit, nasopharynx, nasolacrimal duct, and skin), and subsites were categorized for maxillary sinus (medial/lateral/superior/inferior/anterior/posterior portion), ethmoid sinus (anterior/posterior), nasal cavity (superior turbinate/middle turbinate/inferior turbinate/vestibule/nasal floor/Eustachian tube area, excluding nasopharyngeal lesion/choana), and skull base (dura/brain). Subjects were analyzed and compared for local recurrence and survival according to various clinical factors. The research was approved by the institutional review boards of each hospital. Data were recorded and collected using Microsoft Excel software (Microsoft Corp., Redmond, WA), and statistical analysis was performed using IBM SPSS Statistics version 20 (IBM Corporation, Armonk, NY). Fisher’s exact test or Pearson’s chi-square (χ 2 ) analysis were used to assess the associations between the variables (including surgical approaches) and tumor recurrences. Multivariate analysis was performed for factors affecting local recurrence (showing a p value of less than 0.1) by binary logistic regression. An overall survival curve was made using the Kaplan-Meier method, and the log rank test was used to compare survival between each group, followed by a multivariate analysis with the Cox proportional hazards method. Values of p < 0.05 were considered statistically significant.
Results Clinicopathological features Among the newly diagnosed 155 patients, 81 were male (52%) and 74 were female (48%). The mean age at the time of the first visit was 63.3 years (range, 28–92 years),
Won et al.
TABLE 1. Tumor characteristics of newly diagnosed
sinonasal malignant melanoma patients (n = 155)
Characteristics
TABLE 2. Survival period and rate, according to treatment
modality and stage of the newly diagnosed sinonasal malignant melanoma patients from our series (n = 155)
Sinonasal malignant melanoma Median overall survival period
3-year overall
(months)
survival (%)
Without surgery (11)
36
42.4
With surgery (144)
44
49.2
Size in greatest length
Treatment outcomes of sinonasal malignant melanoma: a Korean multicenter study Tae-Bin Won, MD, PhD1 , Kyu Young Choi, MD2 , Chae-Seo Rhee, MD, PhD3 , Hong-Ryul Jin, MD, PhD4 , Jong Sook Yi, MD5 , Hun-Jong Dhong, MD, PhD6 , Sung Won Kim, MD, PhD7 , Ji Ho Choi, MD, PhD8 , Jin Kook Kim, MD, PhD9 , Young-Jun Chung, MD, PhD10 , Yong-Min Kim, MD, PhD11 , Sang-Wook Kim, MD, PhD12 , Jung Soo Kim, MD, PhD13 , Sam Hyun Kwon, MD, PhD14 , Sang-Chul Lim, MD, PhD15 and Hwan-Jung Roh, MD, PhD16
Background: The aim of this work was to evaluate factors that influence local recurrence and survival aer surgical resection of sinonasal malignant melanoma, using a large population-based multicenter study in Korea. Methods: Retrospective analysis was performed for 155 newly diagnosed sinonasal malignant melanoma patients gathered from 15 university hospitals throughout Korea. Demographic data, tumor characteristics, surgical approach, adjuvant treatment, recurrence, and outcomes were analyzed. Results: Three-year and 5-year overall survival rates were 48.8% and 40.1%, respectively. Local recurrence rate was 46.6%, with a mean recurrence time of 15.5 months. On multivariate analysis, patients who underwent surgery that included an endoscopic approach showed decreased local recurrence rate (p = 0.042) and increased survival rate (hazard ratio [HR], 1.702; 95% confidence interval [CI], 1.007 to 2.875; p = 0.047) compared to those who underwent an ex-
1 Department
of Otorhinolaryngology–Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea; 2 Department of Otorhinolaryngology–Head and Neck Surgery, Kangnam Sacred Heart Hospital, Seoul, Korea; 3 Department of Otorhinolaryngology–Head and Neck Surgery, Seoul National University Bundang Hospital, Seongnam, Korea; 4 Department of Otorhinolaryngology–Head and Neck Surgery, Seoul National University Boramae Medical Center, Seoul, Korea; 5 Department of Otorhinolaryngology–Head and Neck Surgery, Asan Medical Center, Seoul, Korea; 6 Department of Otorhinolaryngology–Head and Neck Surgery, Samsung Medical Center, Seoul, Korea; 7 Department of Otorhinolaryngology–Head and Neck Surgery, Seoul St. Mary’s Hospital, Seoul, Korea; 8 Department of Otorhinolaryngology–Head and Neck Surgery, Korea University Ansan Hospital, Ansan, Korea; 9 Department of Otorhinolaryngology–Head and Neck Surgery, Konkuk University Hospital, Seoul, Korea; 10 Department of Otorhinolaryngology–Head and Neck Surgery, Dankook University Hospital, Cheonan, Korea; 11 Department of Otorhinolaryngology–Head and Neck Surgery, Chungnam National University Hospital, Daejeon, Korea; 12 Department of
ternal approach. Patients with postoperative radiotherapy showed a decreased local recurrence rate (p = 0.001), but without impact on survival rate. Male gender, tumor beyond the nasal cavity, and presence of distant metastasis were associated with poor survival. Conclusion: An endoscopic-including surgical approach was associated with improved local control and survival in sinonasal malignant melanoma patients. Postoperative raC 2015 diotherapy helped increase the local control rate. ARS-AAOA, LLC.
Key Words: melanoma; nasal cavity; paranasal sinuses; recurrence; survival How to Cite this Article: Won T-B, Choi KY, Rhee C-S, et al. Treatment outcomes of sinonasal malignant melanoma: a Korean multicenter study. Int Forum Allergy Rhinol. 2015;5:950–959.
Otorhinolaryngology–Head and Neck Surgery, Gyeongsang National University Hospital, Jinju, Korea; 13 Department of Otorhinolaryngology–Head and Neck Surgery, Kyungpook National University Hospital, Daegu, Korea; 14 Department of Otorhinolaryngology–Head and Neck Surgery, Chonbuk National University Hospital, Jeonju, Korea; 15 Department of Otorhinolaryngology–Head and Neck Surgery, Chonnam National University Hwasun Hospital, Gwangju, Korea; 16 Department of Otorhinolaryngology–Head and Neck Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea Correspondence to: Hwan-Jung Roh, MD, PhD, Department of Otorhinolaryngology–Head and Neck Surgery, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, Yangsan 626-770, Korea; e-mail: [email protected] T.B.W. and K.Y.C. contributed equally to this work. Potential conflict of interest: None provided. Received: 20 January 2015; Revised: 7 April 2015; Accepted: 28 April 2015 DOI: 10.1002/alr.21558 View this article online at wileyonlinelibrary.com.
International Forum of Allergy & Rhinology, Vol. 5, No. 10, October 2015
950
Sinonasal malignant melanoma
S
inonasal malignant melanoma (SNMM) is a rare clinical entity that accounts for about 4% of sinonasal malignancies.1 The reported incidence rates range from 0.018 to 0.051 per 100000 per year.2–4 Prognosis is poor and worse than cutaneous malignant melanoma, with reported 5-year survival rates ranging from 19% to 46%.5 The grave prognosis is a consequence of the aggressive biological behavior of the disease, resulting from high local recurrence (31–85%) and distant metastasis (25–50%).6, 7 Difficulties in performing curative surgery in the sinonasal tract also contribute to the poor prognosis of the disease. The prognostic factors of SNMM have been reported heterogeneously, including tumor size, tumor location, lymph node involvement,8 positive margin,9, 10 local recurrence, and distant metastasis.11, 12 As for tumor location, tumors involving the paranasal sinuses have been reported to have poor prognoses,12, 13 whereas tumors located in the nasal septum have been reported to have better outcome.7 Various staging systems have been proposed for SNMM, because of the heterogeneous behavior of the tumor.11, 14, 15 The 7th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual has revised the staging system for mucosal melanoma of the head and neck, which has shown its efficacy in providing reliable prognostic information.13, 16 The mainstay of treatment has been surgical resection; adjuvant radiotherapy and elective neck dissection have not showed a significant survival benefit.17 Recently, in light of the trend toward endoscopic techniques, studies have revealed favorable outcomes for endoscopic removal compared to open approaches.8, 12 The aim of this study was to provide a comprehensive analysis of SNMM and to evaluate predictors for local recurrence and survival outcome through a large populationbased multicenter study in Korea.
Patients and methods A multicenter study regarding SNMM was initiated by the sinonasal tumor study division of the Korean Rhinologic Society. From April 1994 to June 2013, patients newly diagnosed for SNMM with a follow-up period of at least 1 year were included. Subsequently, patients who had initially been treated surgically with curative intent were analyzed for local recurrence and survival. Retrospective review of prospectively collected medical records was carried out according to the unified data collection system developed by the study division. Among 155 newly diagnosed patients from 15 different university hospitals, surgical excision had been performed in 141 patients, in which 133 cases were surgery for curative intent. The data included demographic information that included gender, age (at symptom onset), smoking status, presenting symptom and its duration (prior to diagnosis), and tumor characteristics, which included size, morphology, presence of skip lesions (multiple pigmented lesions), and presence of pigmentation. Diagnosis of SNMM was confirmed through pathological reports in all
951
International Forum of Allergy & Rhinology, Vol. 5, No. 10, October 2015
cases; when tumor cells (epithelioid, spindle cell, mixed, or undifferentiated) arranged in various histological patterns (pseudopapillary, peritheliomatous, sarcoid, etc.) were found in the specimen with or without melanin pigment. Immunohistochemistry (S-100, HMB-45, Melan-A, tyrosinase, cytokeratin, etc.) was used necessarily, especially when melanin pigment was not visible.15 Involved site or sites was determined by endoscopic and radiological findings, which included computed tomography (CT) and/or magnetic resonance imaging (MRI) reports. Size of the tumor was measured by either imaging reports or endoscopic findings, which was matched for surgical specimen. Patients were staged according to the 7th edition of the AJCC Cancer Staging Manual for mucosal melanoma of the head and neck.16 Because no general criteria for surgical methods exist in treatment of SNMM, endoscopic or open approaches (or combination) had been chosen freely by the corresponding surgeon in each individual cases. Surgical approach was designated as an exclusively endoscopic approach, an exclusively external approach, or a combination of both. Adjuvant treatment as well as treatment results were analyzed. Involved sites of tumors were categorized into 11 sites (maxillary sinus, nasal cavity, ethmoid sinus, frontal sinus, sphenoid sinus, septum, skull base, orbit, nasopharynx, nasolacrimal duct, and skin), and subsites were categorized for maxillary sinus (medial/lateral/superior/inferior/anterior/posterior portion), ethmoid sinus (anterior/posterior), nasal cavity (superior turbinate/middle turbinate/inferior turbinate/vestibule/nasal floor/Eustachian tube area, excluding nasopharyngeal lesion/choana), and skull base (dura/brain). Subjects were analyzed and compared for local recurrence and survival according to various clinical factors. The research was approved by the institutional review boards of each hospital. Data were recorded and collected using Microsoft Excel software (Microsoft Corp., Redmond, WA), and statistical analysis was performed using IBM SPSS Statistics version 20 (IBM Corporation, Armonk, NY). Fisher’s exact test or Pearson’s chi-square (χ 2 ) analysis were used to assess the associations between the variables (including surgical approaches) and tumor recurrences. Multivariate analysis was performed for factors affecting local recurrence (showing a p value of less than 0.1) by binary logistic regression. An overall survival curve was made using the Kaplan-Meier method, and the log rank test was used to compare survival between each group, followed by a multivariate analysis with the Cox proportional hazards method. Values of p < 0.05 were considered statistically significant.
Results Clinicopathological features Among the newly diagnosed 155 patients, 81 were male (52%) and 74 were female (48%). The mean age at the time of the first visit was 63.3 years (range, 28–92 years),
Won et al.
TABLE 1. Tumor characteristics of newly diagnosed
sinonasal malignant melanoma patients (n = 155)
Characteristics
TABLE 2. Survival period and rate, according to treatment
modality and stage of the newly diagnosed sinonasal malignant melanoma patients from our series (n = 155)
Sinonasal malignant melanoma Median overall survival period
3-year overall
(months)
survival (%)
Without surgery (11)
36
42.4
With surgery (144)
44
49.2
Size in greatest length
