CASE REPORT
Peter Andersen, MD, Section Editor
Single-fraction stereotactic body radiation therapy for sinonasal malignant melanoma Daniel J. Bourgeois III, MD, MPH, Anurag K. Singh, MD* University at Buffalo School of Medicine, Roswell Park Cancer Institute, Buffalo, New York.
Accepted 28 May 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23788
ABSTRACT: Background. A rare head and neck disease that may benefit from definitive or palliative stereotactic body radiation therapy (SBRT) is sinonasal malignant melanoma. These tumors can be very aggressive and often lead to severe epistaxis and significant mass effect. Results from only a handful of head and neck sinonasal malignant melanoma treated with SBRT are available in the current literature. Methods. The following reports on 2 cases of sinonasal malignant melanoma that recurred postoperatively and were subsequently treated at Roswell Park with SBRT. Both were treated with a single fraction of 15 Gy.
Results. Nearly instant relief of their chronic epistaxis and complete responses were seen in both patients. One patient is alive and free of disease 7 years after radiation. Conclusion. These patients with sinonasal malignant melanoma achieved symptomatic relief of severe bleeding and airway issues from singlefraction SBRT. SBRT should be considered as a treatment option in C 2014 Wiley patients with unresectable sinonasal malignant melanoma. V Periodicals, Inc. Head Neck 00: 000–000, 2014
INTRODUCTION
CASE REPORT
Over the last 5 years, several centers have begun using stereotactic body radiation therapy (SBRT) to treat patients with primary, recurrent, previously irradiated, or metastatic lesions in patients who were deemed ineligible for or declined fractionated radiotherapy and other recommended modalities of treatment.1–3 The majority of these cases were either squamous cell carcinoma or metastatic lesions. One aggressive head and neck malignancy that may benefit from definitive or palliative SBRT is sinonasal malignant melanoma. These tumors are rare histologically and anatomically in the head and neck (1% and 3.6%, respectively).4 Sinonasal malignant melanoma can be very aggressive and lead to severe epistaxis and mass effect with a high risk of airway compromise. Because of the demonstrated resistance to fractionated radiation of melanoma cells, surgery has remained the standard of care.5 Nevertheless, with highly invasive disease in complex anatomic locations, a tolerable and effective regimen of radiation therapy would be an attractive treatment option.6 The following is a report of 2 cases of sinonasal malignant melanoma that recurred locally in the postoperative setting and were subsequently treated at Roswell Park Cancer Institute (RPCI) with single-fraction SBRT. This retrospective review was authorized by our institutional review board.
Case 1
*Corresponding author: A. K. Singh, University at Buffalo School of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo NY 14263. E-mail: [email protected]
KEY WORDS: stereotactic body radiation therapy (SBRT), sinonasal, mucosal, melanoma, single-fraction
A 60-year-old man presented to an otolaryngologist in 2006 after 1 year of progressive unilateral nasal occlusion that was refractory to antibiotic therapy. He subsequently underwent an excisional biopsy that confirmed sinonasal malignant melanoma, followed by an endoscopic excision of a right-sided nasal mass with a right medial maxillectomy. Although margins were deemed positive after the latter procedure, it was noted that widespread melanosis made it difficult to rule out the presence of disease within these margins. Approximately 1 year later, when found to have a large mass again occluding his nares and causing severe epistaxis and fullness in his ears, the patient was referred to RPCI. A biopsy confirmed recurrent sinonasal malignant melanoma, and imaging showed a destructive mass extending from the nasal septum through both hard and soft palates. The tumor had invaded through his maxillary, ethmoid, and frontal sinuses. Furthermore, his positron emission tomography imaging revealed a metabolically active lesion in the posterior myocardium of his left ventricle. Discussion of the case at a multidisciplinary conference revealed no enthusiasm for further palliative surgery or chemotherapy given the patient’s deteriorating condition. Given a dearth of options, a course of SBRT to 15 Gy in a single fraction for palliation was chosen. At this point, the patient had lost a significant amount of weight and was having chronic bleeding from bilateral nares requiring hospitalization. HEAD & NECK—DOI 10.1002/HED
MONTH 2014
1
BOURGEOIS AND SINGH
FIGURE 1. Dose-volume histogram for case 1. The black arrow shows the planned tumor volume (PTV) 78% coverage with the prescribed dose (minimum dose 5 4.4 Gy). The white arrow shows the brain stem, optic chiasm, bilateral optic nerves, brain, and spinal cord (in descending order by average dose). Dose delivered to all critical structures was maintained below institutional tolerance levels. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
The single-fraction SBRT was delivered via intensitymodulated radiation therapy to treat a gross tumor volume (GTV) of 62.5 cm3 with 10 static beams. This volume was expanded by 3 mm to create a planned tumor volume (PTV) of 111.75 cm3. A prescription dose of 15 Gy was delivered to >95% of the GTV while adhering to a strict optic chiasm dose constraint of 8 Gy. The maximum dose was within the PTV, and the cumulative volume of all tissues outside of the PTV receiving a dose >105% of prescription dose was kept below 15% of the PTV. The ratio of 50% prescription isodose volume to the PTV (R50) was 3.485, and the maximum dose at 2 cm from the PTV in any direction (D2 cm) was 12.6 Gy. A dose-volume histogram and the sagittal dose distribution of case 1 are shown in Figures 1 and 2, respectively. SBRT was tolerated extremely well. In the acute setting, the patient’s persistent epistaxis resolved within 1 day, which provided significant relief for him and his family. The tumor subsequently grew dry and necrotic. Pieces began to slough off after 3 days, and the residual disease regressed completely over the next few months. Dacarbazine was also initiated a month later for the suspicious lesion in the cardiac muscle, but it was discontinued because of side effects. This patient is now followed annually at RPCI with surveillance imaging, which, as of his most recent examinations in 2013, remain clear of any masses or lesions. Figure 3 provides CT images from his pretreatment simulation and the latest follow-up scan for comparison. The patient is now living comfortably without disease 7 years after SBRT.
Case 2 In 2012, advanced sinonasal malignant melanoma was diagnosed in an 85-year-old woman with a large, right nasopharyngeal mass expanding into the maxillary, ethmoid, and sphenoid sinuses. Her symptoms had progressed to persistent epistaxis and difficulty breathing 2
HEAD & NECK—DOI 10.1002/HED
MONTH 2014
FIGURE 2. Sagittal CT isodose distribution for case 1. The arrow shows the 7.5 Gy dose distribution. A maximum dose of 15.828 Gy delivered within gross tumor volume (GTV) minimum dose 5 6.894 Gy; GTV mean dose 5 15.172). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
over 2 years. Discussion of the case at a multidisciplinary conference did not recommend further palliative surgery or chemotherapy given the patient’s advanced age, poor performance status, and extensive disease. Consequently, after considering the acute and durable efficacy of the aforementioned sinonasal malignant melanoma case, a course of SBRT to 15 Gy in a single fraction for palliation was chosen. Case 2 was also treated via intensity-modulated radiation therapy, however, volumetric-modulated arc therapy was used to treat the 133.3 cm3 GTV with 4 arc fields. The GTV was expanded with a 3 mm margin to create a PTV of 194.46 cm3, and a dose of 15 Gy was prescribed to this volume at the 100% isodose line. The same constraints and guidelines used in case 1 were again utilized for this treatment. The R50 was 2.645, and D2 cm was 12.6 Gy. After SBRT, there was a gradual regression of the destructive disease and sloughing of necrotic pieces of
FIGURE 3. Left 5 Pretreatment CT scan showing destructive mass extending from the nasal septum through both hard and soft palates. The lesion measured approximately 10 cm at its greatest dimension. Right 5 7-year follow-up CT scan showing no evidence of disease.
HEAD & NECK—DOI 10.1002/HED
MONTH 2014
SBRT
SRS
Carbon ion RT
Surgery 6 adjuvant EBRT
RR 5 16.1% DM 5 35.5% 50–70 Gy in 2 5-y OS 5 20% Gy/fx (BED LR 5 54% 5 216–303 Gy) DM 5 68% Photons (49) 5-y OS 5 28% 5–70 Gy in 1.3–5.0 Gy 5-y DSS 5 47% Brachytherapy (4) 5-y DFS 5 28% 42–66 Gy LR 5 31% (9–19 d) RR 5 29% DM 5 28% 30 Gy in 6 Local failure – 57.9% vs Gy/fx (over 3 wk) 26.3% (p 5 .0991). (BED 5 330 Gy) Regional metastasis – 57.9% vs 21% (p 5 .0448). DM – 52.6% vs 47.3% (p 5 1.000). 52.8–64 GyE in 5-y LC – 84.1% 16 fxs (over 4 wk) 5-y OS – 27% 5-y DSS – 39.6% 15 Gy in 1 fx at the Significant tumor 50% isodose line reduction at 7-mo follow-up 30 Gy in 3 fx or 35 - LC 5 100% Gy in 5 fx - CR in 3 of 4 patients (BED 5 443–530) - Only partial response (80%) achieved in 4th patient, but no evidence of disease found at 2-y follow-up
5-y DSS 5 33% LR 5 41.9%
LR 5 45 vs 17% DM 5 50 vs 46%
LC 5 61% 3-y OS 5 49% 5-y OS 5 17.9% DM 5 64% 5-y Actuarial OS 5 20 vs 50% LR 5 100 vs 71% DM 5 46% 5-y OS 5 45 vs 29%
Results
- One patient required interventions for perforation of her hard palate. - Two patients without evidence of disease at 2-y follow-up, and the other 2 had DM.
- Significantly worse 5-y OS with sinonasal malignant melanoma compared to oral malignant melanoma (0 vs 38.4%; p 5 .0228). - No grade 3 or higher toxicity in late phase. - Tumor volume 118 Gy found as favorable prognostic indicators. - Two late, fatal complications (ulcer and bleeding) noted in hypofractionated group - Early T classification lesions (p 5 .004) and those that received adjuvant EBRT (p 5 .05) had longer local DFS.
- All DM occurred in patients with local treatment failure. - Those who received postoperative RT appeared to have done better with increased disease-free intervals and prolonged OS. - The addition of RT tended to decrease LR (p 5 .13), but did not improve OS (p 5 .73) because of the high rate of DM.
- All sinonasal malignant melanoma patients. - Initial complete regression in 22 of 28 patients treated. - Suggest influence of dose-per-fraction.
Notes
Abbreviations: RT, radiation therapy; EBRT, external beam radiation therapy; BED, biologic equivalent dose calculated when possible with published dose/fractions schemes using a/b50.6 Gy and linear quadratic model; LC, local control; OS, overall survival; DM, distant metastasis; LR, local recurrence; DSS, disease-specific survival; RR, regional recurrence; DFS, disease-free survival; SRS, stereotactic radiosurgery; CR, complete response.
4
Ozyigit et al19 (2013)
42
Meleti et al16 (2008)
1
74
Krengli, et al. (2006)15
Horie et al18 (2002)
69
Tenam, et al. (2005)14
72
Surgery 6 adjuvant RT vs RT alone vs chemoimmunotherapy
31
Wada et al10 (2004)
Yanagi et al17 (2009)
Surgery 6 adjuvant EBRT
48
Owens et al13 (2003)
45–55 Gy in 3.0–6 Gy/fx (BED 325–460 Gy)
RT dose/fractionation
30–62 Gy in 2–6 Gy/fx (BED 270–330 Gy) Surgery 6 adjuvant EBRT 60 Gy in 2 Gy/fx for sinonasal lesions (BED 5 260 Gy) 30 Gy in 6 Gy/fx for oral lesions (BED 5 330 Gy) Definitive EBRT or surgery 32–64 Gy in 1.5–13.8 1 adjuvant EBRT Gy/fx (2–5 d/wk)
Surgery 6 adjuvant EBRT
17
Kingdom et al12 (1995)
Definitive EBRT
Treatment modality
28
No. of patients
Gilligan et al11 (1991)
Author
TABLE 1. Review of the head and neck mucosal malignant melanoma literature.
SBRT FOR SINONASAL MALIGNANT MELANOMA
3
BOURGEOIS AND SINGH
the mass. Again, the chronic epistaxis resolved nearly immediately. During one of her most recent visits, her nares were clear of any visible masses, bleeding, and discharge. Furthermore, imaging showed marked interval decrease in the size of her disease. At this 2-month follow-up, the patient reported an improved energy level, breathing, mood, and appetite. Unfortunately, her nasal mass recurred aggressively 8 months later. Although it had been discussed with the patient and family that repeat-SBRT was feasible should the tumor recur, the patient decided not to pursue any further therapy without discussion with her physicians, and died under hospice care.
DISCUSSION Two cases of sinonasal malignant melanoma treated with single-fraction SBRT to 15 Gy both demonstrated rapid epistaxis control without any significant side effects. This suggests that single-fraction SBRT to 15 Gy produces rapid palliation. In case 1, durable cure was achieved and provides the longest follow-up in any case of single-fraction SBRT for sinonasal malignant melanoma; the patient remains without evidence of disease after 7 years. A 1985 randomized trial by Overgaard et al7 showed significantly improved responses of recurrent and metastatic melanoma to radiation at doses greater than 3 to 4 Gy per fraction. Additionally, radiation biology studies have measured an a/b ratio of malignant melanoma of 0.6 Gy and reported favorable tumor responses with a biologically effective dose (BED) greater than 118 Gy.8– 10 Our treatment of these 2 cases provided a BED of 390 Gy, and that of other reported radiation regimens are listed in Table 1. Our experience is consistent with the scant literature listed in Table 1 regarding the efficacy of radiation therapy in sinonasal malignant melanoma. Of these reports, only two used SBRT doses. Horie et al18 reported a partial response with stereotactic radiosurgery (SRS) at a single fraction dose of 15 Gy. Ozyigit et al19 presented 4 sinonasal malignant melanoma cases that were treated with SBRT from 2007 to 2009, and all were alive by the time of publication in 2011. Doses used were 30 Gy in 3 fractions and 35 Gy in 5 fractions. Three of the 4 patients experienced a complete response with the fourth achieving a partial response with a median follow-up of 26 months. However, the reported case that had a partial radiographic response was initially without evidence of disease at her 2-year follow-up. Another patient was also without disease after 2 years, but had developed a perforation of her hard palate requiring medical and hyperbaric intervention. The other 2 patients remained without local recurrence but developed distant metastases.
4
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CONCLUSION Single fraction SBRT to 15 Gy produced rapid resolution of epistaxis and mass effect symptoms without any notable toxicity in 2 patients with sinonasal malignant melanoma. One patient remains without evidence of disease or toxicity 7 years later. One patient recurred and may have been benefited from further therapy. SBRT should be considered as a treatment option in patients with unresectable sinonasal malignant melanoma.
REFERENCES 1. Siddiqui F, Patel M, Khan M, et al. Stereotactic body radiation therapy for primary, recurrent, and metastatic tumors in the head-and-neck region. Int J Radiat Oncol Biol Phys 2009;74:1047–1053. 2. Heron DE, Ferris RL, Karamouzis M, et al. Stereotactic body radiotherapy for recurrent squamous cell carcinoma of the head and neck: results of a phase I dose-escalation trial. Int J Radiat Oncol Biol Phys 2009;75:1493– 1500. 3. Vargo JA, Wegner RE, Heron DE, et al. Stereotactic body radiation therapy for locally recurrent, previously irradiated nonsquamous cell cancers of the head and neck. Head Neck 2012;34:1153–1161. 4. 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;83:1664–1678. 5. Dewey DL. The radiosensitivity of melanoma cells in culture. Br J Radiol 1971;44:816–817. 6. Khan N, Khan MK, Almasan A, Singh AD, Macklis R. The evolving role of radiation therapy in the management of malignant melanoma. Int J Radiat Oncol Biol Phys 2011;80:645–654. 7. Overgaard J, von der Maase H, Overgaard M. A randomized study comparing two high-dose per fraction radiation schedules in recurrent or metastatic malignant melanoma. Int J Radiat Oncol Biol Phys 1985;11:1837–1839. 8. Overgaard J. The role of radiotherapy in recurrent and metastatic malignant melanoma: a clinical radiobiological study. Int J Radiat Oncol Biol Phys 1986;12:867–872. 9. Bentzen SM, Overgaard J, Thames HD, et al. Clinical radiobiology of malignant melanoma. Radiother Oncol 1989;16:169–182. 10. 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. 11. Gilligan D, Slevin NJ. Radical radiotherapy for 28 cases of mucosal melanoma in the nasal cavity and sinuses. Br J Radiol 1991;64:1147–1150. 12. Kingdom TT, Kaplan MJ. Mucosal melanoma of the nasal cavity and paranasal sinuses. Head Neck 1995;17:184–189. 13. Owens JM, Roberts DB, Myers JN. The role of postoperative adjuvant radiation therapy in the treatment of mucosal melanomas of the head and neck region. Arch Otolaryngol Head Neck Surg 2003;129:864–868. 14. Temam S, Mamelle G, Marandas P, et al. Postoperative radiotherapy for primary mucosal melanoma of the head and neck. Cancer 2005;103:313–319. 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– 759. 16. Meleti M, Leemans CR, de Bree R, Vescovi P, Sesenna E, van der Waal I. Head and neck mucosal melanoma: experience with 42 patients, with emphasis on the role of postoperative radiotherapy. Head Neck 2008;30: 1543–1551. 17. 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. 18. Horie N. Takahashi N, Furuichi S, Mori K, Shibata S. Gamma knife radiosurgery for malignant melanoma in the paranasal sinuses: case report [in Japanese]. No Shinkei Geka 2002;30:753–757. 19. Ozyigit G, Cengiz M, Yazici G, et al. Robotic stereotactic body radiotherapy in the treatment of sinonasal melanoma: report of four cases. Head Neck 2013;35:E69–E73.
Peter Andersen, MD, Section Editor
Single-fraction stereotactic body radiation therapy for sinonasal malignant melanoma Daniel J. Bourgeois III, MD, MPH, Anurag K. Singh, MD* University at Buffalo School of Medicine, Roswell Park Cancer Institute, Buffalo, New York.
Accepted 28 May 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23788
ABSTRACT: Background. A rare head and neck disease that may benefit from definitive or palliative stereotactic body radiation therapy (SBRT) is sinonasal malignant melanoma. These tumors can be very aggressive and often lead to severe epistaxis and significant mass effect. Results from only a handful of head and neck sinonasal malignant melanoma treated with SBRT are available in the current literature. Methods. The following reports on 2 cases of sinonasal malignant melanoma that recurred postoperatively and were subsequently treated at Roswell Park with SBRT. Both were treated with a single fraction of 15 Gy.
Results. Nearly instant relief of their chronic epistaxis and complete responses were seen in both patients. One patient is alive and free of disease 7 years after radiation. Conclusion. These patients with sinonasal malignant melanoma achieved symptomatic relief of severe bleeding and airway issues from singlefraction SBRT. SBRT should be considered as a treatment option in C 2014 Wiley patients with unresectable sinonasal malignant melanoma. V Periodicals, Inc. Head Neck 00: 000–000, 2014
INTRODUCTION
CASE REPORT
Over the last 5 years, several centers have begun using stereotactic body radiation therapy (SBRT) to treat patients with primary, recurrent, previously irradiated, or metastatic lesions in patients who were deemed ineligible for or declined fractionated radiotherapy and other recommended modalities of treatment.1–3 The majority of these cases were either squamous cell carcinoma or metastatic lesions. One aggressive head and neck malignancy that may benefit from definitive or palliative SBRT is sinonasal malignant melanoma. These tumors are rare histologically and anatomically in the head and neck (1% and 3.6%, respectively).4 Sinonasal malignant melanoma can be very aggressive and lead to severe epistaxis and mass effect with a high risk of airway compromise. Because of the demonstrated resistance to fractionated radiation of melanoma cells, surgery has remained the standard of care.5 Nevertheless, with highly invasive disease in complex anatomic locations, a tolerable and effective regimen of radiation therapy would be an attractive treatment option.6 The following is a report of 2 cases of sinonasal malignant melanoma that recurred locally in the postoperative setting and were subsequently treated at Roswell Park Cancer Institute (RPCI) with single-fraction SBRT. This retrospective review was authorized by our institutional review board.
Case 1
*Corresponding author: A. K. Singh, University at Buffalo School of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo NY 14263. E-mail: [email protected]
KEY WORDS: stereotactic body radiation therapy (SBRT), sinonasal, mucosal, melanoma, single-fraction
A 60-year-old man presented to an otolaryngologist in 2006 after 1 year of progressive unilateral nasal occlusion that was refractory to antibiotic therapy. He subsequently underwent an excisional biopsy that confirmed sinonasal malignant melanoma, followed by an endoscopic excision of a right-sided nasal mass with a right medial maxillectomy. Although margins were deemed positive after the latter procedure, it was noted that widespread melanosis made it difficult to rule out the presence of disease within these margins. Approximately 1 year later, when found to have a large mass again occluding his nares and causing severe epistaxis and fullness in his ears, the patient was referred to RPCI. A biopsy confirmed recurrent sinonasal malignant melanoma, and imaging showed a destructive mass extending from the nasal septum through both hard and soft palates. The tumor had invaded through his maxillary, ethmoid, and frontal sinuses. Furthermore, his positron emission tomography imaging revealed a metabolically active lesion in the posterior myocardium of his left ventricle. Discussion of the case at a multidisciplinary conference revealed no enthusiasm for further palliative surgery or chemotherapy given the patient’s deteriorating condition. Given a dearth of options, a course of SBRT to 15 Gy in a single fraction for palliation was chosen. At this point, the patient had lost a significant amount of weight and was having chronic bleeding from bilateral nares requiring hospitalization. HEAD & NECK—DOI 10.1002/HED
MONTH 2014
1
BOURGEOIS AND SINGH
FIGURE 1. Dose-volume histogram for case 1. The black arrow shows the planned tumor volume (PTV) 78% coverage with the prescribed dose (minimum dose 5 4.4 Gy). The white arrow shows the brain stem, optic chiasm, bilateral optic nerves, brain, and spinal cord (in descending order by average dose). Dose delivered to all critical structures was maintained below institutional tolerance levels. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
The single-fraction SBRT was delivered via intensitymodulated radiation therapy to treat a gross tumor volume (GTV) of 62.5 cm3 with 10 static beams. This volume was expanded by 3 mm to create a planned tumor volume (PTV) of 111.75 cm3. A prescription dose of 15 Gy was delivered to >95% of the GTV while adhering to a strict optic chiasm dose constraint of 8 Gy. The maximum dose was within the PTV, and the cumulative volume of all tissues outside of the PTV receiving a dose >105% of prescription dose was kept below 15% of the PTV. The ratio of 50% prescription isodose volume to the PTV (R50) was 3.485, and the maximum dose at 2 cm from the PTV in any direction (D2 cm) was 12.6 Gy. A dose-volume histogram and the sagittal dose distribution of case 1 are shown in Figures 1 and 2, respectively. SBRT was tolerated extremely well. In the acute setting, the patient’s persistent epistaxis resolved within 1 day, which provided significant relief for him and his family. The tumor subsequently grew dry and necrotic. Pieces began to slough off after 3 days, and the residual disease regressed completely over the next few months. Dacarbazine was also initiated a month later for the suspicious lesion in the cardiac muscle, but it was discontinued because of side effects. This patient is now followed annually at RPCI with surveillance imaging, which, as of his most recent examinations in 2013, remain clear of any masses or lesions. Figure 3 provides CT images from his pretreatment simulation and the latest follow-up scan for comparison. The patient is now living comfortably without disease 7 years after SBRT.
Case 2 In 2012, advanced sinonasal malignant melanoma was diagnosed in an 85-year-old woman with a large, right nasopharyngeal mass expanding into the maxillary, ethmoid, and sphenoid sinuses. Her symptoms had progressed to persistent epistaxis and difficulty breathing 2
HEAD & NECK—DOI 10.1002/HED
MONTH 2014
FIGURE 2. Sagittal CT isodose distribution for case 1. The arrow shows the 7.5 Gy dose distribution. A maximum dose of 15.828 Gy delivered within gross tumor volume (GTV) minimum dose 5 6.894 Gy; GTV mean dose 5 15.172). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
over 2 years. Discussion of the case at a multidisciplinary conference did not recommend further palliative surgery or chemotherapy given the patient’s advanced age, poor performance status, and extensive disease. Consequently, after considering the acute and durable efficacy of the aforementioned sinonasal malignant melanoma case, a course of SBRT to 15 Gy in a single fraction for palliation was chosen. Case 2 was also treated via intensity-modulated radiation therapy, however, volumetric-modulated arc therapy was used to treat the 133.3 cm3 GTV with 4 arc fields. The GTV was expanded with a 3 mm margin to create a PTV of 194.46 cm3, and a dose of 15 Gy was prescribed to this volume at the 100% isodose line. The same constraints and guidelines used in case 1 were again utilized for this treatment. The R50 was 2.645, and D2 cm was 12.6 Gy. After SBRT, there was a gradual regression of the destructive disease and sloughing of necrotic pieces of
FIGURE 3. Left 5 Pretreatment CT scan showing destructive mass extending from the nasal septum through both hard and soft palates. The lesion measured approximately 10 cm at its greatest dimension. Right 5 7-year follow-up CT scan showing no evidence of disease.
HEAD & NECK—DOI 10.1002/HED
MONTH 2014
SBRT
SRS
Carbon ion RT
Surgery 6 adjuvant EBRT
RR 5 16.1% DM 5 35.5% 50–70 Gy in 2 5-y OS 5 20% Gy/fx (BED LR 5 54% 5 216–303 Gy) DM 5 68% Photons (49) 5-y OS 5 28% 5–70 Gy in 1.3–5.0 Gy 5-y DSS 5 47% Brachytherapy (4) 5-y DFS 5 28% 42–66 Gy LR 5 31% (9–19 d) RR 5 29% DM 5 28% 30 Gy in 6 Local failure – 57.9% vs Gy/fx (over 3 wk) 26.3% (p 5 .0991). (BED 5 330 Gy) Regional metastasis – 57.9% vs 21% (p 5 .0448). DM – 52.6% vs 47.3% (p 5 1.000). 52.8–64 GyE in 5-y LC – 84.1% 16 fxs (over 4 wk) 5-y OS – 27% 5-y DSS – 39.6% 15 Gy in 1 fx at the Significant tumor 50% isodose line reduction at 7-mo follow-up 30 Gy in 3 fx or 35 - LC 5 100% Gy in 5 fx - CR in 3 of 4 patients (BED 5 443–530) - Only partial response (80%) achieved in 4th patient, but no evidence of disease found at 2-y follow-up
5-y DSS 5 33% LR 5 41.9%
LR 5 45 vs 17% DM 5 50 vs 46%
LC 5 61% 3-y OS 5 49% 5-y OS 5 17.9% DM 5 64% 5-y Actuarial OS 5 20 vs 50% LR 5 100 vs 71% DM 5 46% 5-y OS 5 45 vs 29%
Results
- One patient required interventions for perforation of her hard palate. - Two patients without evidence of disease at 2-y follow-up, and the other 2 had DM.
- Significantly worse 5-y OS with sinonasal malignant melanoma compared to oral malignant melanoma (0 vs 38.4%; p 5 .0228). - No grade 3 or higher toxicity in late phase. - Tumor volume 118 Gy found as favorable prognostic indicators. - Two late, fatal complications (ulcer and bleeding) noted in hypofractionated group - Early T classification lesions (p 5 .004) and those that received adjuvant EBRT (p 5 .05) had longer local DFS.
- All DM occurred in patients with local treatment failure. - Those who received postoperative RT appeared to have done better with increased disease-free intervals and prolonged OS. - The addition of RT tended to decrease LR (p 5 .13), but did not improve OS (p 5 .73) because of the high rate of DM.
- All sinonasal malignant melanoma patients. - Initial complete regression in 22 of 28 patients treated. - Suggest influence of dose-per-fraction.
Notes
Abbreviations: RT, radiation therapy; EBRT, external beam radiation therapy; BED, biologic equivalent dose calculated when possible with published dose/fractions schemes using a/b50.6 Gy and linear quadratic model; LC, local control; OS, overall survival; DM, distant metastasis; LR, local recurrence; DSS, disease-specific survival; RR, regional recurrence; DFS, disease-free survival; SRS, stereotactic radiosurgery; CR, complete response.
4
Ozyigit et al19 (2013)
42
Meleti et al16 (2008)
1
74
Krengli, et al. (2006)15
Horie et al18 (2002)
69
Tenam, et al. (2005)14
72
Surgery 6 adjuvant RT vs RT alone vs chemoimmunotherapy
31
Wada et al10 (2004)
Yanagi et al17 (2009)
Surgery 6 adjuvant EBRT
48
Owens et al13 (2003)
45–55 Gy in 3.0–6 Gy/fx (BED 325–460 Gy)
RT dose/fractionation
30–62 Gy in 2–6 Gy/fx (BED 270–330 Gy) Surgery 6 adjuvant EBRT 60 Gy in 2 Gy/fx for sinonasal lesions (BED 5 260 Gy) 30 Gy in 6 Gy/fx for oral lesions (BED 5 330 Gy) Definitive EBRT or surgery 32–64 Gy in 1.5–13.8 1 adjuvant EBRT Gy/fx (2–5 d/wk)
Surgery 6 adjuvant EBRT
17
Kingdom et al12 (1995)
Definitive EBRT
Treatment modality
28
No. of patients
Gilligan et al11 (1991)
Author
TABLE 1. Review of the head and neck mucosal malignant melanoma literature.
SBRT FOR SINONASAL MALIGNANT MELANOMA
3
BOURGEOIS AND SINGH
the mass. Again, the chronic epistaxis resolved nearly immediately. During one of her most recent visits, her nares were clear of any visible masses, bleeding, and discharge. Furthermore, imaging showed marked interval decrease in the size of her disease. At this 2-month follow-up, the patient reported an improved energy level, breathing, mood, and appetite. Unfortunately, her nasal mass recurred aggressively 8 months later. Although it had been discussed with the patient and family that repeat-SBRT was feasible should the tumor recur, the patient decided not to pursue any further therapy without discussion with her physicians, and died under hospice care.
DISCUSSION Two cases of sinonasal malignant melanoma treated with single-fraction SBRT to 15 Gy both demonstrated rapid epistaxis control without any significant side effects. This suggests that single-fraction SBRT to 15 Gy produces rapid palliation. In case 1, durable cure was achieved and provides the longest follow-up in any case of single-fraction SBRT for sinonasal malignant melanoma; the patient remains without evidence of disease after 7 years. A 1985 randomized trial by Overgaard et al7 showed significantly improved responses of recurrent and metastatic melanoma to radiation at doses greater than 3 to 4 Gy per fraction. Additionally, radiation biology studies have measured an a/b ratio of malignant melanoma of 0.6 Gy and reported favorable tumor responses with a biologically effective dose (BED) greater than 118 Gy.8– 10 Our treatment of these 2 cases provided a BED of 390 Gy, and that of other reported radiation regimens are listed in Table 1. Our experience is consistent with the scant literature listed in Table 1 regarding the efficacy of radiation therapy in sinonasal malignant melanoma. Of these reports, only two used SBRT doses. Horie et al18 reported a partial response with stereotactic radiosurgery (SRS) at a single fraction dose of 15 Gy. Ozyigit et al19 presented 4 sinonasal malignant melanoma cases that were treated with SBRT from 2007 to 2009, and all were alive by the time of publication in 2011. Doses used were 30 Gy in 3 fractions and 35 Gy in 5 fractions. Three of the 4 patients experienced a complete response with the fourth achieving a partial response with a median follow-up of 26 months. However, the reported case that had a partial radiographic response was initially without evidence of disease at her 2-year follow-up. Another patient was also without disease after 2 years, but had developed a perforation of her hard palate requiring medical and hyperbaric intervention. The other 2 patients remained without local recurrence but developed distant metastases.
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HEAD & NECK—DOI 10.1002/HED
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CONCLUSION Single fraction SBRT to 15 Gy produced rapid resolution of epistaxis and mass effect symptoms without any notable toxicity in 2 patients with sinonasal malignant melanoma. One patient remains without evidence of disease or toxicity 7 years later. One patient recurred and may have been benefited from further therapy. SBRT should be considered as a treatment option in patients with unresectable sinonasal malignant melanoma.
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