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Malignant melanoma of the nasal cavity treated with stereotactic radiotherapy using CyberKnife: report of 2 cases
AM ER IC AN JOURNAL OF OT OLA RYNGOLOGY– H E A D A N D NE CK M E D ICI N E AN D S U RGE RY 3 6 (2 0 1 5) 3 06 – 3 0 9
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/amjoto
Malignant melanoma of the nasal cavity treated with stereotactic radiotherapy using CyberKnife: report of 2 cases☆ Takanori Abe, MD a,⁎, Takeshi Ebara, MD, PhD b , Kazunori Miyaura, MS a , Yu Kumazaki, PhD a , Mitsuhiko Nakahira, MD, PhD c , Masashi Sugasawa, MD, PhD c , Naoto Shikama, MD, PhD a , Shingo Kato, MD, PhD a a b c
Department of Radiation Oncology, Saitama Medical University, International Medical Center, Hidaka, Japan Gunma Prefectural Cancer Center, Ohta, Japan Department of Otolaryngology, Saitama Medical University, International Medical Center, Hidaka, Japan
ARTI CLE I NFO
A BS TRACT
Article history:
Radiotherapy with high doses per fraction may have the potential to control
Received 21 November 2014
radioresistant tumors, such as malignant melanoma. Here we report 2 cases with malignant melanoma of the nasal cavity treated with hypofractionated stereotactic radiotherapy using CyberKnife®. © 2015 Elsevier Inc. All rights reserved.
1.
Introduction
Head and neck malignant melanoma (HNMM) is rare and carries a poor prognosis. Most HNMMs are diagnosed at a late stage [1] because the disease progresses rapidly without symptoms. For advanced disease, surgery with or without adjuvant therapy was considered [2]. However, surgical procedures for advanced disease have a negative impact on patients, because of extensive surgeries, cosmetic problems, and loss of normal function, and high local recurrence rates [3]. Definitive radiotherapy is administered only for few patients because malignant melanoma generally shows a high resistance to radiotherapy [4]. High doses per fraction
☆
may have the potential to control radioresistant tumors; however, such high doses are generally toxic to lateresponding tissues, such as the brain stem and optic nerve. Recently, the CyberKnife® (Accuray, Sunnyvale, California, USA), a new device that combines a robotic arm with a linear accelerator, has been developed for stereotactic radiotherapy (SRT). This device may provide a method of administering an adequate dose to the tumor while decreasing the dose to the surrounding normal tissue. Here we report on 2 cases (3 lesions) of malignant melanoma of the nasal cavity treated with hypofractionated SRT using CyberKnife®. All data were collected after the approval of an institutional review board.
Financial disclosure: None. ⁎ Corresponding author at: Department of Radiation Oncology, Saitama Medical University, International Medical Center, Hidaka-shi, Yamane 1397-1, Saitama 350-1298 Japan. Tel.: +81 42 984 4531; fax: + 81 42 984 4741. E-mail address: [email protected] (T. Abe). http://dx.doi.org/10.1016/j.amjoto.2014.11.010 0196-0709/© 2015 Elsevier Inc. All rights reserved.
AM ER IC AN JOURNAL OF OT OLARYNGOLOGY – H E A D A N D NE CK M E D IC IN E A ND S U RGE RY 3 6 (2 0 1 5) 3 06– 3 0 9
2.
Case reports
2.1.
Case 1
A 60-year-old male presented to a local clinic with hemoptysis. At presentation, magnetic resonance imaging (MRI) revealed a mass of 2.3 cm × 4.3 cm × 3.5 cm filling the nasal cavity and the frontal, sphenoid, maxillary, and ethmoid sinuses. Extraocular muscles were compressed by the tumor, causing diplopia (Fig. 1). F-18 fluorodeoxyglucose positronemission tomography (FDG-PET) showed abnormal accumulation in the tumor as well as internal jugular lymph nodes. The biopsy confirmed the diagnosis of malignant melanoma; he was diagnosed with cT4aN1M0, stage IVa malignant melanoma of the nasal cavity. Carbon-ion radiotherapy was not indicated because of nodal involvement. Radical surgery was considered unsuitable because of the wide and infiltrative nature of the tumor. Neck dissection was performed for lymph node metastasis, and hypofractionated SRT with CyberKnife® was administered for the primary tumor. A total dose of 39 Gy in 8 fractions was administered and no acute adverse events were observed. Postoperative evaluation revealed 1 positive lymph node among 31 resected lymph nodes. One week after radiotherapy, diplopia improved. The patient received combination chemotherapy consisting of cisplatin, dacarbazine, nimustine, and tamoxifen for a single course. A follow-up CT performed 38 months after initial radiotherapy demonstrated a growing mass in the patient’s right maxillary sinus. Biopsy from the maxillary sinus mass confirmed the diagnosis of malignant melanoma; thus, a diagnosis of recurrent malignant melanoma was made. SRT was administered again with a total dose of 35 Gy in 5
Fig. 2 – CT image taken 51 months after initial treatment showed no evidence of recurrence.
fractions using CyberKnife® (Fig. 1). The patient has not had any adverse events and has shown complete response of disease 51 months after the initial radiotherapy and 11 months after the second radiotherapy (Fig. 2).
2.2.
Case 2
A 76-year-old male presented to a local hospital with a complaint of prolonged nasal congestion. At presentation, endoscopy found a melanomic mass filling the right nasal cavity. Biopsy of the mass confirmed the diagnosis of malignant melanoma. Computed tomography (CT) and MRI revealed no evidence of the invasion of the surrounding structures or lymph node metastasis. In addition, FDG-PET showed no evidence of distant metastasis. As a result, the patient was diagnosed with cT3N0M0, stage III malignant melanoma of the nasal cavity. Treatment options were discussed by the cancer board; it was concluded that extensive surgery was too invasive for this patient because of his age, and the decision was made to administer SRT using CyberKnife®. Patient refused to receive carbon-ion radiotherapy because of financial problem. A total dose of 35 Gy in 5 fractions was administered, and no acute adverse events were observed. The patient refused any adjuvant therapy. Twelve months after treatment, the patient developed lymph node metastasis, but the local tumor remained stable disease, with disappearance of abnormal FDG uptake by positron emission tomography. The patient is alive with lymph node metastasis.
3. Fig. 1 – Treatment plan for recurrent disease of case 1. Planning target volume (PTV) was shown in thick pink line. An isodose line of 35 Gy was shown in orange line which almost covered PTV.
307
Discussion
Dosimetric studies comparing intensity-modulated radiotherapy (IMRT) or SRT with 3-dimensional conformal radiotherapy treatment plans for head and neck cancer reported that IMRT and SRT have a significant advantage in tumor
308
AM ER IC AN JOURNAL OF OT OLA RYNGOLOGY– H E A D A N D NE CK M E D ICI N E AN D S U RGE RY 3 6 (2 0 1 5) 3 06 – 3 0 9
Table 1 – Dose volume parameters. Case 1 Case 2 primary recurrent tumor tumor D max in PTV PTV D90 Tumor volume D max in diseased side optic nerve D max in intact side optic nerve D max in optic chiasm D max in brain stem Skin S 30 GyEQD2
51.6 40.0 44.2 50.0 34.5 0.0 14.3 5.5
Gy Gy ml Gy Gy Gy Gy cm2
44.9 38.8 10.3 5.3 3.5 3.4 6.8 1.2
Gy Gy ml Gy Gy Gy Gy cm2
46.7 33.5 46.9 23.9 17.1 13.0 10.8 15.5
Gy Gy ml Gy Gy Gy Gy cm2
Abbreviations: D max, maximum dose in volume of interest; PTV, planning target volume; D90, The minimum dose delivered to 90 % of the most irradiated volume of interest; V100, % volume that received prescribed dose; Skin S 30 Gy EQD2, the area of skin surface received greater than equivalent dose to 30 Gy at 2 Gy per fraction.
coverage and normal organ sparing [5]. CyberKnife® is one of the most flexible treatment devices in the field of photonbeam therapy, and may allow more conformable dose delivery. In both cases, the prescribed dose adequately covered PTV while sparing the surrounding normal tissue, such as the optic nerves on the contralateral side, skin, optic chiasm, and brain stem. As shown in Table 1, maximum point doses for these OAR are lower than the reported tolerance dose [6,7]. Radiobiological studies demonstrated radio-resistant nature of the melanoma cells caused by the repair of sublethal DNA damage [4]. However, high dose per fraction may have a potential to control radio-resistant tumor [8–10]. Overgaard
et al. investigated the relationship between doses per fraction and response rate in 600 metastatic melanoma cases and reported that a cutoff value of 120 Gy, which was calculated as a biologically effective dose (BED), was associated with improved response rate [9]. Ozyigit et al. reported that 4 cases of HNMM showed favorable outcomes with a total dose of 35 Gy in 5 fractions using CyberKnife® [10]. The relationship between doses per fraction and treatment outcome in the literature is summarized in Table 2. On the basis of this background, we administered a total of 39 Gy in 8 fractions or 35 Gy in 5 fractions using CyberKnife®, which is equal to a BED of 115 Gy or 133 Gy. So far, 2 of the 3 lesions show complete response and 1 lesion shows stable disease. Our prescribed dose seems to be adequate for these cases. No acute and late adverse events greater than grade 2 were observed in this study. Acute skin and mucosal reactions are major issues in the radiotherapy for head and neck cancer [7]. Lee et al. reported that doses of 30 Gy administered to a 100-cm2 field of skin surface produced a moderate acute skin reaction, and higher doses, such as 40 Gy administered to a 100-cm2 field of skin surface, produced exudative radiation dermatitis [7]. A dose equivalent to 30 Gy at 2 Gy per fraction (30 GyEQD2) is approximately equal to 25 Gy in 8 fractions or 21 Gy in 5 fractions; this is calculated using BED assuming an α/β ratio of 3 Gy. In our study, the maximum mean area of the skin surface that received more than 30 GyEQD2 was 15.5 cm2. The CyberKnife® treatment-planning software, Mutil plan® version 4.0.3 (Accuray, Sunnyvale, California, USA), provides an inverse planning ability that allows decreasing the dose to OARs. Using inverse planning, we were able to decrease the dose to the skin. The multibeam application and inverse planning using CyberKnife® for SRT may provide an advantage in terms of minimizing the dose to skin surface.
Table 2 – Review of the literature. Author
No. of patients
Treatment site
Radiotherapy Total dose (Gy) Dose per fraction (Gy/fr)
Treatment outcome
Sause et al. [11]
62
Skin = 38, lymph node =6, Others = 6
CR = 24.2% PR = 35.5%.
Temam et al. [12]
69
Sinonasal cavity = 46, oral cavity = 19, pharynx–larynx = 4
Gilligan et al. [13]
28
Nasal cavity = 16, Paranasal sinuses = 4, both = 8
Wada et al. [14]
66
Krengli et al. [15]
74
Yanagi et al. [16]
72
Nasal cavity = 16, paranasal sinuses = 7, hard palate = 3, pharynx = 2, others = 3 (middle ear, gingiva, orbit) Nasal cavity = 31, oral cavity = 12, paranasal sinuses = 5, parynx = 1, multiple sites = 25 Nasal cavity = 44, paranasal sinuses = 16, Oral cavity = 7, pharynx = 5
Electrons 32 Gy 8 Gy/fr Photons 50–70 Gy 2 Gy/fr Photons 45–55 Gy 3–6 Gy/fr Photons 32–64 Gy 1.5–13.8 Gy/fr Photons, brachytherapy 5–70 Gy 1.3–5.0 Gy/fr Carbon ions 57.6–64 Gy 3.6–4 Gy/fr
5-year OS = 20% LR = 54% LC = 61% 3-year OS = 49% 5-year OS = 17.9% LR = 41.9% 5-year DSS = 33% LR = 31% 5-year OS = 28% 5-year LC = 81.9% 5-year DSS = 39.6%
Abbreviations: CR = complete response; PR = partial response; fr = fraction; OS = overall survival; LR = local relapse; LC = local control; DSS = disease specific survival.
AM ER IC AN JOURNAL OF OT OLARYNGOLOGY – H E A D A N D NE CK M E D IC IN E A ND S U RGE RY 3 6 (2 0 1 5) 3 06– 3 0 9
In this study, 1 patient had lymph node metastasis. Treatment for such advanced HNMM remains a challenge. In our patient, we first performed neck lymph node dissection and then administered definitive radiotherapy for the primary tumor using CyberKnife®. Thus far, the patient has shown good disease control with no cosmetic problems or loss of normal function. For the neck lymph node-positive patients who are inoperable or refuse extensive surgery, neck dissection and SRT for the primary tumor using CyberKnife® may be an option.
4.
Conclusion
Stereotactic radiotherapy using CyberKnife® administered adequate dose to the target while decreasing the dose to the surrounding normal tissue. It may be an option for advanced HNMM.
REFERENCES
[1] Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1998;83:1664–78. [2] Wagner M, Morris CG, Werning JW, et al. Mucosal melanoma of the head and neck. Am J Clin Oncol 2008;31:43–8. [3] Patel SG, Prasad ML, Escrig M, et al. Primary mucosal malignant melanoma of the head and neck. Head Neck 2002; 24:247–57. [4] Overgaard J, Overgaard M, Hansen V, et al. Some factors of importance in the radiation treatment of malignant melanoma. Radiother Oncol 1986;5:183–92.
309
[5] Levendag PC, Lagerwaard FJ, de Pan C, et al. High-dose, high-precision treatment options for boosting cancer of the nasopharynx. Radiother Oncol 2002;63:67–74. [6] Timmerman RD. An overview of hypofractionation and introduction to this issue of seminars in radiation oncology. Semin Radiat Oncol 2008;18:215–22. [7] Lee N, Chuang C, Quivey JM, et al. Skin toxicity due to intensity-modulated radiotherapy for head-and-neck carcinoma. Int J Radiat Oncol Biol Phys 2002;53:630–7. [8] Fowler JF. The linear–quadratic formula and progress in fractionated radiotherapy. Br J Radiol 1989;62:679–94. [9] Overgaard J. The role of radiotherapy in recurrent and metastatic malignant melanoma: a clinical radiobiological study. Int J Radiat Oncol Biol Phys 1986;12:867–72. [10] Ozyigit G, Cengiz M, Yazici G, et al. Robotic stereotactic body radiotherapy in the treatment of sinonasal mucosal melanoma: report of four cases. Head Neck 2013;35: 69–73. [11] Sause W, Cooper JS, Rush S, et al. Fraction size in external beam radiation therapy in the treatment of melanoma. Int J Radiat Oncol Biol Phys 1991;20:429–32. [12] Temam S, Mamelle G, Marandas P, et al. Postoperative radiotherapy for primary mucosal melanoma of the head and neck. Cancer 2005;103:313–9. [13] Gilligan D, Slevin NJ. Radical radiotherapy for 28 cases of mucosal melanoma in the nasal cavity and sinuses. Br J Radiol 1991;64:1147–50. [14] Wada H, Nemoto K, Ogawa Y, et al. A multi-institutional retrospective analysis of external radiotherapy for mucosal melanoma of the head and neck in Northern Japan. Int J Radiat Oncol Biol Phys 2004;59:495–500. [15] Krengli M, Masini L, Kaanders JH, et al. Radiotherapy in the treatment of mucosal melanoma of the upper aerodigestive tract: analysis of 74 cases. A Rare Cancer Network study. Int J Radiat Oncol Biol Phys 2006;65:751–9. [16] Yanagi T, Mizoe JE, Hasegawa A, et al. Mucosal malignant melanoma of the head and neck treated by carbon ion radiotherapy. Int J Radiat Oncol Biol Phys 2009;74:15–20.
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/amjoto
Malignant melanoma of the nasal cavity treated with stereotactic radiotherapy using CyberKnife: report of 2 cases☆ Takanori Abe, MD a,⁎, Takeshi Ebara, MD, PhD b , Kazunori Miyaura, MS a , Yu Kumazaki, PhD a , Mitsuhiko Nakahira, MD, PhD c , Masashi Sugasawa, MD, PhD c , Naoto Shikama, MD, PhD a , Shingo Kato, MD, PhD a a b c
Department of Radiation Oncology, Saitama Medical University, International Medical Center, Hidaka, Japan Gunma Prefectural Cancer Center, Ohta, Japan Department of Otolaryngology, Saitama Medical University, International Medical Center, Hidaka, Japan
ARTI CLE I NFO
A BS TRACT
Article history:
Radiotherapy with high doses per fraction may have the potential to control
Received 21 November 2014
radioresistant tumors, such as malignant melanoma. Here we report 2 cases with malignant melanoma of the nasal cavity treated with hypofractionated stereotactic radiotherapy using CyberKnife®. © 2015 Elsevier Inc. All rights reserved.
1.
Introduction
Head and neck malignant melanoma (HNMM) is rare and carries a poor prognosis. Most HNMMs are diagnosed at a late stage [1] because the disease progresses rapidly without symptoms. For advanced disease, surgery with or without adjuvant therapy was considered [2]. However, surgical procedures for advanced disease have a negative impact on patients, because of extensive surgeries, cosmetic problems, and loss of normal function, and high local recurrence rates [3]. Definitive radiotherapy is administered only for few patients because malignant melanoma generally shows a high resistance to radiotherapy [4]. High doses per fraction
☆
may have the potential to control radioresistant tumors; however, such high doses are generally toxic to lateresponding tissues, such as the brain stem and optic nerve. Recently, the CyberKnife® (Accuray, Sunnyvale, California, USA), a new device that combines a robotic arm with a linear accelerator, has been developed for stereotactic radiotherapy (SRT). This device may provide a method of administering an adequate dose to the tumor while decreasing the dose to the surrounding normal tissue. Here we report on 2 cases (3 lesions) of malignant melanoma of the nasal cavity treated with hypofractionated SRT using CyberKnife®. All data were collected after the approval of an institutional review board.
Financial disclosure: None. ⁎ Corresponding author at: Department of Radiation Oncology, Saitama Medical University, International Medical Center, Hidaka-shi, Yamane 1397-1, Saitama 350-1298 Japan. Tel.: +81 42 984 4531; fax: + 81 42 984 4741. E-mail address: [email protected] (T. Abe). http://dx.doi.org/10.1016/j.amjoto.2014.11.010 0196-0709/© 2015 Elsevier Inc. All rights reserved.
AM ER IC AN JOURNAL OF OT OLARYNGOLOGY – H E A D A N D NE CK M E D IC IN E A ND S U RGE RY 3 6 (2 0 1 5) 3 06– 3 0 9
2.
Case reports
2.1.
Case 1
A 60-year-old male presented to a local clinic with hemoptysis. At presentation, magnetic resonance imaging (MRI) revealed a mass of 2.3 cm × 4.3 cm × 3.5 cm filling the nasal cavity and the frontal, sphenoid, maxillary, and ethmoid sinuses. Extraocular muscles were compressed by the tumor, causing diplopia (Fig. 1). F-18 fluorodeoxyglucose positronemission tomography (FDG-PET) showed abnormal accumulation in the tumor as well as internal jugular lymph nodes. The biopsy confirmed the diagnosis of malignant melanoma; he was diagnosed with cT4aN1M0, stage IVa malignant melanoma of the nasal cavity. Carbon-ion radiotherapy was not indicated because of nodal involvement. Radical surgery was considered unsuitable because of the wide and infiltrative nature of the tumor. Neck dissection was performed for lymph node metastasis, and hypofractionated SRT with CyberKnife® was administered for the primary tumor. A total dose of 39 Gy in 8 fractions was administered and no acute adverse events were observed. Postoperative evaluation revealed 1 positive lymph node among 31 resected lymph nodes. One week after radiotherapy, diplopia improved. The patient received combination chemotherapy consisting of cisplatin, dacarbazine, nimustine, and tamoxifen for a single course. A follow-up CT performed 38 months after initial radiotherapy demonstrated a growing mass in the patient’s right maxillary sinus. Biopsy from the maxillary sinus mass confirmed the diagnosis of malignant melanoma; thus, a diagnosis of recurrent malignant melanoma was made. SRT was administered again with a total dose of 35 Gy in 5
Fig. 2 – CT image taken 51 months after initial treatment showed no evidence of recurrence.
fractions using CyberKnife® (Fig. 1). The patient has not had any adverse events and has shown complete response of disease 51 months after the initial radiotherapy and 11 months after the second radiotherapy (Fig. 2).
2.2.
Case 2
A 76-year-old male presented to a local hospital with a complaint of prolonged nasal congestion. At presentation, endoscopy found a melanomic mass filling the right nasal cavity. Biopsy of the mass confirmed the diagnosis of malignant melanoma. Computed tomography (CT) and MRI revealed no evidence of the invasion of the surrounding structures or lymph node metastasis. In addition, FDG-PET showed no evidence of distant metastasis. As a result, the patient was diagnosed with cT3N0M0, stage III malignant melanoma of the nasal cavity. Treatment options were discussed by the cancer board; it was concluded that extensive surgery was too invasive for this patient because of his age, and the decision was made to administer SRT using CyberKnife®. Patient refused to receive carbon-ion radiotherapy because of financial problem. A total dose of 35 Gy in 5 fractions was administered, and no acute adverse events were observed. The patient refused any adjuvant therapy. Twelve months after treatment, the patient developed lymph node metastasis, but the local tumor remained stable disease, with disappearance of abnormal FDG uptake by positron emission tomography. The patient is alive with lymph node metastasis.
3. Fig. 1 – Treatment plan for recurrent disease of case 1. Planning target volume (PTV) was shown in thick pink line. An isodose line of 35 Gy was shown in orange line which almost covered PTV.
307
Discussion
Dosimetric studies comparing intensity-modulated radiotherapy (IMRT) or SRT with 3-dimensional conformal radiotherapy treatment plans for head and neck cancer reported that IMRT and SRT have a significant advantage in tumor
308
AM ER IC AN JOURNAL OF OT OLA RYNGOLOGY– H E A D A N D NE CK M E D ICI N E AN D S U RGE RY 3 6 (2 0 1 5) 3 06 – 3 0 9
Table 1 – Dose volume parameters. Case 1 Case 2 primary recurrent tumor tumor D max in PTV PTV D90 Tumor volume D max in diseased side optic nerve D max in intact side optic nerve D max in optic chiasm D max in brain stem Skin S 30 GyEQD2
51.6 40.0 44.2 50.0 34.5 0.0 14.3 5.5
Gy Gy ml Gy Gy Gy Gy cm2
44.9 38.8 10.3 5.3 3.5 3.4 6.8 1.2
Gy Gy ml Gy Gy Gy Gy cm2
46.7 33.5 46.9 23.9 17.1 13.0 10.8 15.5
Gy Gy ml Gy Gy Gy Gy cm2
Abbreviations: D max, maximum dose in volume of interest; PTV, planning target volume; D90, The minimum dose delivered to 90 % of the most irradiated volume of interest; V100, % volume that received prescribed dose; Skin S 30 Gy EQD2, the area of skin surface received greater than equivalent dose to 30 Gy at 2 Gy per fraction.
coverage and normal organ sparing [5]. CyberKnife® is one of the most flexible treatment devices in the field of photonbeam therapy, and may allow more conformable dose delivery. In both cases, the prescribed dose adequately covered PTV while sparing the surrounding normal tissue, such as the optic nerves on the contralateral side, skin, optic chiasm, and brain stem. As shown in Table 1, maximum point doses for these OAR are lower than the reported tolerance dose [6,7]. Radiobiological studies demonstrated radio-resistant nature of the melanoma cells caused by the repair of sublethal DNA damage [4]. However, high dose per fraction may have a potential to control radio-resistant tumor [8–10]. Overgaard
et al. investigated the relationship between doses per fraction and response rate in 600 metastatic melanoma cases and reported that a cutoff value of 120 Gy, which was calculated as a biologically effective dose (BED), was associated with improved response rate [9]. Ozyigit et al. reported that 4 cases of HNMM showed favorable outcomes with a total dose of 35 Gy in 5 fractions using CyberKnife® [10]. The relationship between doses per fraction and treatment outcome in the literature is summarized in Table 2. On the basis of this background, we administered a total of 39 Gy in 8 fractions or 35 Gy in 5 fractions using CyberKnife®, which is equal to a BED of 115 Gy or 133 Gy. So far, 2 of the 3 lesions show complete response and 1 lesion shows stable disease. Our prescribed dose seems to be adequate for these cases. No acute and late adverse events greater than grade 2 were observed in this study. Acute skin and mucosal reactions are major issues in the radiotherapy for head and neck cancer [7]. Lee et al. reported that doses of 30 Gy administered to a 100-cm2 field of skin surface produced a moderate acute skin reaction, and higher doses, such as 40 Gy administered to a 100-cm2 field of skin surface, produced exudative radiation dermatitis [7]. A dose equivalent to 30 Gy at 2 Gy per fraction (30 GyEQD2) is approximately equal to 25 Gy in 8 fractions or 21 Gy in 5 fractions; this is calculated using BED assuming an α/β ratio of 3 Gy. In our study, the maximum mean area of the skin surface that received more than 30 GyEQD2 was 15.5 cm2. The CyberKnife® treatment-planning software, Mutil plan® version 4.0.3 (Accuray, Sunnyvale, California, USA), provides an inverse planning ability that allows decreasing the dose to OARs. Using inverse planning, we were able to decrease the dose to the skin. The multibeam application and inverse planning using CyberKnife® for SRT may provide an advantage in terms of minimizing the dose to skin surface.
Table 2 – Review of the literature. Author
No. of patients
Treatment site
Radiotherapy Total dose (Gy) Dose per fraction (Gy/fr)
Treatment outcome
Sause et al. [11]
62
Skin = 38, lymph node =6, Others = 6
CR = 24.2% PR = 35.5%.
Temam et al. [12]
69
Sinonasal cavity = 46, oral cavity = 19, pharynx–larynx = 4
Gilligan et al. [13]
28
Nasal cavity = 16, Paranasal sinuses = 4, both = 8
Wada et al. [14]
66
Krengli et al. [15]
74
Yanagi et al. [16]
72
Nasal cavity = 16, paranasal sinuses = 7, hard palate = 3, pharynx = 2, others = 3 (middle ear, gingiva, orbit) Nasal cavity = 31, oral cavity = 12, paranasal sinuses = 5, parynx = 1, multiple sites = 25 Nasal cavity = 44, paranasal sinuses = 16, Oral cavity = 7, pharynx = 5
Electrons 32 Gy 8 Gy/fr Photons 50–70 Gy 2 Gy/fr Photons 45–55 Gy 3–6 Gy/fr Photons 32–64 Gy 1.5–13.8 Gy/fr Photons, brachytherapy 5–70 Gy 1.3–5.0 Gy/fr Carbon ions 57.6–64 Gy 3.6–4 Gy/fr
5-year OS = 20% LR = 54% LC = 61% 3-year OS = 49% 5-year OS = 17.9% LR = 41.9% 5-year DSS = 33% LR = 31% 5-year OS = 28% 5-year LC = 81.9% 5-year DSS = 39.6%
Abbreviations: CR = complete response; PR = partial response; fr = fraction; OS = overall survival; LR = local relapse; LC = local control; DSS = disease specific survival.
AM ER IC AN JOURNAL OF OT OLARYNGOLOGY – H E A D A N D NE CK M E D IC IN E A ND S U RGE RY 3 6 (2 0 1 5) 3 06– 3 0 9
In this study, 1 patient had lymph node metastasis. Treatment for such advanced HNMM remains a challenge. In our patient, we first performed neck lymph node dissection and then administered definitive radiotherapy for the primary tumor using CyberKnife®. Thus far, the patient has shown good disease control with no cosmetic problems or loss of normal function. For the neck lymph node-positive patients who are inoperable or refuse extensive surgery, neck dissection and SRT for the primary tumor using CyberKnife® may be an option.
4.
Conclusion
Stereotactic radiotherapy using CyberKnife® administered adequate dose to the target while decreasing the dose to the surrounding normal tissue. It may be an option for advanced HNMM.
REFERENCES
[1] Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1998;83:1664–78. [2] Wagner M, Morris CG, Werning JW, et al. Mucosal melanoma of the head and neck. Am J Clin Oncol 2008;31:43–8. [3] Patel SG, Prasad ML, Escrig M, et al. Primary mucosal malignant melanoma of the head and neck. Head Neck 2002; 24:247–57. [4] Overgaard J, Overgaard M, Hansen V, et al. Some factors of importance in the radiation treatment of malignant melanoma. Radiother Oncol 1986;5:183–92.
309
[5] Levendag PC, Lagerwaard FJ, de Pan C, et al. High-dose, high-precision treatment options for boosting cancer of the nasopharynx. Radiother Oncol 2002;63:67–74. [6] Timmerman RD. An overview of hypofractionation and introduction to this issue of seminars in radiation oncology. Semin Radiat Oncol 2008;18:215–22. [7] Lee N, Chuang C, Quivey JM, et al. Skin toxicity due to intensity-modulated radiotherapy for head-and-neck carcinoma. Int J Radiat Oncol Biol Phys 2002;53:630–7. [8] Fowler JF. The linear–quadratic formula and progress in fractionated radiotherapy. Br J Radiol 1989;62:679–94. [9] Overgaard J. The role of radiotherapy in recurrent and metastatic malignant melanoma: a clinical radiobiological study. Int J Radiat Oncol Biol Phys 1986;12:867–72. [10] Ozyigit G, Cengiz M, Yazici G, et al. Robotic stereotactic body radiotherapy in the treatment of sinonasal mucosal melanoma: report of four cases. Head Neck 2013;35: 69–73. [11] Sause W, Cooper JS, Rush S, et al. Fraction size in external beam radiation therapy in the treatment of melanoma. Int J Radiat Oncol Biol Phys 1991;20:429–32. [12] Temam S, Mamelle G, Marandas P, et al. Postoperative radiotherapy for primary mucosal melanoma of the head and neck. Cancer 2005;103:313–9. [13] Gilligan D, Slevin NJ. Radical radiotherapy for 28 cases of mucosal melanoma in the nasal cavity and sinuses. Br J Radiol 1991;64:1147–50. [14] Wada H, Nemoto K, Ogawa Y, et al. A multi-institutional retrospective analysis of external radiotherapy for mucosal melanoma of the head and neck in Northern Japan. Int J Radiat Oncol Biol Phys 2004;59:495–500. [15] Krengli M, Masini L, Kaanders JH, et al. Radiotherapy in the treatment of mucosal melanoma of the upper aerodigestive tract: analysis of 74 cases. A Rare Cancer Network study. Int J Radiat Oncol Biol Phys 2006;65:751–9. [16] Yanagi T, Mizoe JE, Hasegawa A, et al. Mucosal malignant melanoma of the head and neck treated by carbon ion radiotherapy. Int J Radiat Oncol Biol Phys 2009;74:15–20.