TECHNICAL STRATEGY
Endoscopic Surgery for Recurrent Undifferentiated Nasopharyngeal Carcinoma Enzo Emanuelli, MD,* Silviu Albu, MD, PhD,† Diego Cazzador, MD,* Barbara Pedruzzi, MD,* Gregorio Babighian, MD, PhD,* and Alessandro Martini, MD, PhD* Abstract: One of the biggest challenges for otolaryngologists is represented by the locally recurrent undifferentiated nasopharyngeal carcinoma (uNPC). Despite improvements in its treatment options, such as modern radiotherapy, chemotherapy, or external surgical approaches, the risk for severe complications, functional disabilities, and even death remains considerable. Over the years, advances in endoscopic surgery have led to a new alternative in the salvage surgery for recurrent uNPC: the nasopharyngeal endoscopic resection (NER). We retrospectively reviewed clinical records of 8 patients (6 men and 2 women), who underwent NER for recurrent T1 (rT1) locally recurrent uNPC between 2008 and 2011. Together with resections for subsequent recurrences, a total of 9 NERs were performed by a single surgeon with curative intent. Negative margins were obtained for the whole group of patients. After a mean follow-up period of 27 months (range, 16–54 mo), all the patients had no evidence of the disease. We had only 1 recurrence after 7 months. Two-year overall survival and disease-free survival rates were 100% and 88.9%, respectively. Only 1 patient presented with a complication, osteitis. Nasopharyngeal endoscopic resection can be considered a valid and promising treatment option for rT1 locally recurrent uNPC, showing encouraging short-term outcomes and complication rate. Long-term follow-up is needed to state the efficacy of NER, together with a larger number of patients. Key Words: Undifferentiated nasopharyngeal carcinoma, recurrence, endoscopic resection, outcomes (J Craniofac Surg 2014;25: 1003–1008)
T
he World Health Organization has classified nasopharyngeal carcinoma (NPC) into 3 histologic types1: keratinizing squamous cell carcinoma (type I), non–keratinizing squamous cell carcinoma (type II), and undifferentiated carcinoma (uNPC; type III), with the latter being the most frequently observed histologic type of NPC. It is well known that uNPC is a high radio-chemosensitive tumor. The mainstay of treatment for primary uNPC is thus given by radiotherapy alone for early-stage tumors or concomitant chemoradiation
From the *Operative Unit of Otolaryngology and Otosurgery, Padua University, Padua, Italy; and †Second Department of Otolaryngology, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, ClujNapoca, Romania. Received November 19, 2013. Accepted for publication January 2, 2014. Address correspondence and reprint requests to Silviu Albu, MD, Second Department of Otolaryngology, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, St Republicii nr. 18, 400015 Cluj-Napoca, Romania; E-mail: [email protected] The authors report no conflicts of interest. Copyright © 2014 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000000698
for advanced lesions.2 In a recent study, this combined treatment modality resulted in an improved control of locoregional disease, together with a reduction of long-term adverse effects, and led to 5-year local control rates of 80% to 85%.3 Nonetheless, the risk for local recurrence is still considerable because its incidence ranges from 8% to 58%.4–6 Curative nasopharyngectomy is considered one of the most effective salvage treatment options for locally recurrent uNPC,7 comprising different kinds of external approaches, such as maxillary swing, mandibulary swing, as well as transpalatal and type C infratemporal approach.8–14 However, such a surgery is one of the most challenging in the head and neck area. In addition, external nasopharyngectomies lead to important functional disabilities, aesthetic problems, and major complications for the patients, deeply compromising their quality of life. Recently, endoscopic endonasal surgery has emerged as a viable option in the management of recurrent uNPC, thus avoiding the morbidity related to external surgery.15–18 The current study presents our experience in the management of recurrent uNPC, aiming to define precise indications for the nasopharyngeal endoscopic resection (NER), to report preliminary outcomes and complications rate and to compare them with those reported previously.
MATERIALS AND METHODS Eight consecutive cases of histologically proven recurrent uNPC were retrospectively reviewed. Between January 2008 and December 2011, all patients underwent NER with curative intent, performed by a single surgeon (E.E.) of a tertiary academic medical center. Primary therapy consisted of radiotherapy only in 5 patients and combined chemoradiotherapy in 2 patients, whereas only 1 patient was directly submitted to NER because he already received radiotherapy intended for a previous medulloblastoma. All patients were carefully investigated through endoscopic examination (Fig. 1), computed tomography (CT), and magnetic resonance scan. Moreover, a preoperative positron emission tomography-CT scan was performed to exclude distant metastasis of the disease. All patients were restaged according to the seventh edition of AJCC Cancer Staging Manual.19 Only recurrent T1 (rT1) cases without regional or distant metastasis were considered eligible for NER. All the operations were performed under hypotensive general anesthesia, in a supine position. The resection was guided by 4-mm– diameter 0-, 30-, and 70-degree–angled endoscopes (Karl-Storz, Tuttlingen, Germany). The nasal cavity was decongested using cotton plugs saturated with pantocaine 2%, oximetazolyne, and epinephrine 1:100.000. The first step consisted of a partial resection of the posterior third of the nasal septum, performed to generate an adequate working place with a better visualization of the surgical field. The sphenopalatine artery was identified and cauterized to prevent further bleeding. A Dornier contact-type diode laser (Dornier Medizin Laser Gmbh, Germering, Germany) with pulse wave (30 W) was set to 10 W during surgery to carry out the mucosal incision, thus creating a bloodless surgical field. A multilayered pattern of resection was performed, removing first the mucosal layer on a subperiosteal
The Journal of Craniofacial Surgery • Volume 25, Number 3, May 2014
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FIGURE 1. Endoscopic view of recurrent nasopharyngeal tumor.
FIGURE 3. En bloc removal of the excised tumor.
surgical plane (Figs. 2–4), followed by drilling of the bone limits using a diamond endonasal drill (Karl-Storz, Tuttlingen, Germany), whenever requested. Tumor resections were classified according to the study of Castelnuovo et al.18 Type I is limited to the posterosuperior nasopharyngeal wall, reaching the floor of the sphenoid sinus and preserving the cartilagineous portion of the Eustachian tube. It always allows the en bloc resection of the tumor. Type II is extended cranially to incorporate the anterior wall of the sphenoid sinus and includes its mucosal stripping together with the drilling of the sphenoid sinus floor. The cartilaginous portion of the Eustachian tube is preserved. Type III is similar to type II, except for the lateral extension because it includes the nasopharyngeal wall up to the parapharyngeal space, not maintaining the cartilagineous portion of the Eustachian tube. Surgical margins were carefully examined with frozen intraoperative sections. The wound was always covered with fibrillary tabotamp for hemostasis and left free to heal by second intention. Nasal packing was performed with a sterile dressing of nonadhesive polyurethane foam (Seton Health Care Group, Oldham, United Kingdom), medicated always with antibiotic. It was removed 72 hours after the operation. All patients were regularly followed up by means of rigid endoscopic evaluation. Imaging studies (computed tomography and magnetic resonance imaging), biopsy, and fine-needle aspiration
cytology were carried out whenever indicated, in accordance with the National Comprehensive Cancer Network guidelines. The cases of local re-recurrence disease were treated with a second NER. The overall survival (OS) and disease-free survival (DFS) were censored at the date of the last follow-up. Survival curves were analyzed using the Kaplan-Meier product limit method. Statistical analyses were performed using MedCalc statistical software (MedCalc Software, Mariakerke, Belgium).
The study group consisted of 8 patients, 6 men and 2 women, with a mean age at surgery of 59 years and a median age of 53.5 years (range, 45–83 y). Table 1 reports a detailed list of the patient's characteristics. The mean time from the primary treatment to local recurrence was 57.7 months (range, 36–114 mo). All lesions were classified rT1 (stage I) according to the seventh edition of American Joint Committee on Cancer Staging Manual.19 The whole group of patients underwent NER with curative intent. Type I NER was performed in 5 cases; type II, in 2 cases; and type III, in 2 cases. One patient developed a recurrent tumor 7 months after the first endoscopic salvage treatment (NER, type I). Consequently, he was submitted to a second more extensive NER (type III) and is still alive without evidences of the disease.
FIGURE 2. Mucosal incision using the diode laser.
FIGURE 4. Endoscopic view of the nasopharynx after the tumor removal.
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RESULTS
© 2014 Mutaz B. Habal, MD
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The Journal of Craniofacial Surgery • Volume 25, Number 3, May 2014
Endoscopic Surgery for uNPC
TABLE 1. Patients Included in the Study
Patient Age Sex 1 2 3 4 5 6 7 8
45 53 47 70 83 54 69 52
F M M M M F M M
Stage at Diagnosis*
Primary Treatment
Time to First Recurrence (mo)
Stage at Recurrence*
Time to Second Recurrence (mo)
NER
Postoperative Treatment
T2N0M0 T3N0M0 T1N0M0 T2N0M0 T1N0M0 T1N0M0 T1N2bM0 T1N0M0
— RT RT RT RT RT RT+CT RT+CT
45 42 62 56 68 114 39 36 —
rT1 rT1 rT1 rT1 rT1 rT1 rT1 rT1 rT1
— — — — — — — — 7
2 2 1 1 1 3 1 1 3
RT — — — — — — — —
Follow-up (mo) Results 22 25 17 54 25 35 16 7 14
NED NED NED NED NED NED NED rec NED
*According to the 2010 AJCC TNM staging system classification. F, female; M, male; NED, no evidence of the disease; rec, local recurrence.
Nasopharyngeal endoscopic resections were successfully performed through the endonasal approach, and no conversions to external approaches were necessary. Negative margins were obtained in 100% of cases. The mean operating time was 140 minutes (range, 40–210 min). No patients required blood transfusions. One patient received a prophylactic selective modified type III radical neck dissection after the endoscopic approach. Only one patient received postoperative radiotherapy, the one previously diagnosed with medulloblastoma. No intraoperative complications were observed. Postoperatively, we encountered one case of osteitis of the sphenoid basis, which resolved in 3 weeks under antibiotic therapy treatment. The overall complication rate was consequently 11% (1/9 procedures). Each patient had exactly a 3-day hospitalization time. All patients were discharged with systemic antibiotic therapy and nasal irrigation with physiological solution. The mean follow-up time was 27 months (range, 16–54 mo). The patients developed neither lymphatic nor distant metastasis during this time. The 2-year OS and DFS rates are 100% and 88.9%, respectively. Local recurrence rate is 12.5%.
DISCUSSION Despite an adequate primary treatment, local recurrence represents an important problem in uNPC. Feasible salvage options consist of re-irradiation and surgery, the choice of which depends on tumor features, such as location and size, patient's condition, as well as previous primary treatment.4 Chemotherapy alone is used for palliation, being indicated for patients not suitable to other curative therapy options.4 A second course of external RT might be unsafe because of the high risk for complications, such as cerebral necrosis, hypothalamic-pituitary failure, deafness, retinopathy, transverse myelitis, and cranial nerve dysfunction.7,12–14 The incidence of reirradiation morbidity varies between 6% and 85% depending on the radiation dose intensity, whereas the mortality rate is between 1.8% and 20%.4,20–22 Alternatively, surgery is recommended in the treatment of recurrent uNPC, having the advantage of avoiding re-irradiation toxicities. Moreover, it provides better local control and survival rates than does re-irradiation alone.20–26 Salvage nasopharyngectomy was initially performed using an external approach. An analysis of the literature on external nasopharyngectomy is reassumed in Table 2. As one can see, surgery provides 5-year OS rates between 30% and 60%3–14 as well as a local control rate between 43% and 74%.20–26 External salvage surgery is associated with serious and potentially fatal complications, that is, massive hemorrhage, as result
of internal carotid artery injury,3,9,10 or intracranial complications such as meningitis and osteoradionecrosis.4–11 This approach, being very aggressive and invasive, may also compromise vital functions, thus resulting in functional disabilities such as severe trismus, oronasal fistula, and palatal dehiscence, leading to dysphagia and malnutrition, significantly decreasing the patient's quality of life.3–14 Moreover, external scarring may also compromise the aesthetical aspect of the patient. Improvement in the endoscopic armamentarium, coupled with high-definition monitors and increasing experience in endoscopic surgery, has led to an extension of the indications of endoscopic approaches. As a consequence, NER emerged as a viable salvage treatment.27–32 Published results of NER are outlined in Table 3. We report 8 cases of rT1 uNPC, with no intraoperative complications and no treatment-related mortality. Only 1 patient presented a postoperative complication, osteomyelitis, and received antibiotic treatment. Nasopharyngeal endoscopic resection was performed following the principle of multilayer centripetal resection, which has shown excellent oncological results in the treatment of sinus tumors.33 This surgical technique allows the achievement of clear surgical margins, contrasting the en bloc resection theory. Within a mean follow-up of 27 months, only 1 local recurrence was registered. The patient was endoscopically re-treated, resulting to be free of the disease at the time of writing. Neither regional nor distant metastasis occurred. At 2 years, we calculated OS, DFS, and local control rate of 100%, 88.9%, and 83.3%, respectively. Our survival rates reflect that reported in other published series.22–32 According to the literature, NER is indicated for early recurrent disease, achieving good results for rT1 cases.22–32 Regarding recurrent T2 (rT2) lesions, the outcome mostly depends on the invasion of the parapharyngeal space.22 With tumors extending far laterally, the likelihood of achieving negative margins decreases because of the proximity of internal carotid artery, with the associated risk for injuring during the resection. Positive surgical margins are associated with dismal prognosis and have an independent negative influence on DFS and OS.34 Therefore, when the distance between tumor and internal carotid artery is less than 1 cm, an open approach is recommended, such as the maxillary swing or the type C infratemporal approach.22,27 Only a few cases of recurrent T3 (rT3) NPC are reported.17,18,27 Four cases were reported by Chen et al27 and Ho et al17; each of them had sphenoid sinus extension and received a radical endoscopic resection, but 3 of the 4 cases developed distant metastasis. In the study of Castelnuovo et al,18 2 patients were alive with disease, whereas 1 died of the disease. The role of NER for rT3 lesions has still to be clearly defined. Given the increasing experience in the endoscopic treatment of anterior skull base tumors, highly selected cases
© 2014 Mutaz B. Habal, MD
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TABLE 2. Results of External Nasopharyngectomy
Author (year) King et al13 (2000)
Surgical Approach 11 transpalatal
Group (mean age, y) rT Stage* 31 (43)
11 mandibular swing 9 maxillary swing Shu et al35 (2000)
Hsu et al24 (2001)
To et al11 (2002)
Maxillary swing + other
28 maxillary swing 11 transpalatal
28 (53)
60 (50.8)
rT1 - 15 rT1N1 - 1 rT2a - 3 rT2bN0 - 5 rT2bN1 - 1 rT3 - 2 rT4 - 1 rT1 - 10 rT2 - 18
—
29.3
6 facial translocation 5 maxillary swing
11 (55)
Danesi et al9 (2007)
Infratemporal fossa type C
11 (45)
53 (50.6)
—
21 (75)
—
DFS - 32.1% (4.3)
27.7
—
11% c.n. paralysis 11% osteonecrosis 7% trismus 3% choanal stenosis 7% other OS - 56% (2); 30% (5) 18% oronasal fistula DFS - 60% (2); 40% (5) 18% palatal incompetence other (otitis media, trismus)
—
—
22 (71%)
28.5
DFS - 58% (2.4)
6% perioperative meningitis
—
63%
30 (79%)
26.8
OS - 60% (3) lcr - 72.8% (3)
13.2% morbidity
—
100%
—
69.8
4/11 DOD 1/11 AWD
100%
—
48
83%
36 (68%)
—
64 (66.7%): 47.9% clear, 18.8% close margins
86%
44 (62%)
rT3/4
—
—
—
94.6%
248 (79.5%)
rT4 - 10 rT1 - 7 rT2 - 13 rT3 - 2 rT4 - 9 rT1 - 16 rT2b - 4 rT3 - 11 rT4 - 7 rT1 - 3 rT2 - 5 rT3 - 3 rT1 - 2
Bridger et al36 (2005)
DFS - 42% (5) lcr - 43% (5)
Complications 64% otitis media with effusion 52% palatal fistula 48% trismus 39% dysphagia 14% ICA blowout
43.1
10 transmandibular 17 midfacial degloving 31 (49.5) 10 maxillary swing 4 mandibular swing Facial translocation 38 (48.8) (12 with a combined NCH approach)
OS - 47% (5)
—
rT3 - 22
rT2 - 6 rT3 - 2 rT4 - 1 rT1 - 27 rT2 - 9
—
—
DFS - 72% (2)
27% wound infection 27% trismus
—
37.1
OS - 48.7% (5) lcr - 53.6% (5)
11.3% morbidity
—
—
OS - 51.9% (5) LRFS - 46.7 (5) lcr - 62.8% (5)
47% morbidity 15% ectropion 11% palatal fistula 10% palatal dehiscence 10% other 22.5% morbidity 10% trismus 8% palatal fistula 4% submandible necrosis 63.6% trismus 4.5% fistula
—
rT3 - 9
Vlantis et al34 (2010)
38 maxillary swing 97 (47.7) 35 midfacial degloving 24 transpalatal
Bian et al26 (2011)
33 maxillary swing 38 other
Chan JYet al37 Maxillary swing + (2012) free flap reconstruction 31 Chan et al Maxillary swing (2012)
90%
Mean Hospitalization Time, d
82%
11 transmaxillary
33 facial translocation 18 craniofacial resection 2 endoscopic nasopharyngectomy
UC, %
rT2 - 9 rT3 – 2
Chang et al14 (2004)
Hao et al30 (2008)
rT1 - 20
Negative Median Survival Rate (years Margins, % Follow-up, mo of assessment)
71 (46)
22 (48.2)
312 (52)
rT4 - 8 rT1 - 53 rT2 - 32 rT3/4 - 12
rT1 rT2 rT3 rT4
-
27 19 14 11
30
lcr - 61.9% (2) lrc - 53.5% (5)
38.8
1/22 local and distant recurrent disease
34
OS - 62% (5) DFS - 56% (5) lcr - 74% (5)
20% trismus 15.7% palatal fistula
—
8.6
12
rT, recurrent tumor; UC, undifferentiated carcinoma; lcr, local control rate; ICA, internal carotid artery; cn, cranial nerves; NCH, neurosurgical; DOD, died of disease; AWD, alive with disease; LRFS, local relapse free survival; UICC, Union for International Cancer Control; AJCC, American Joint Committee on Cancer. *according to the American Joint Committee on Cancer.
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The Journal of Craniofacial Surgery • Volume 25, Number 3, May 2014
Endoscopic Surgery for uNPC
TABLE 3. Nasopharyngeal Endoscopic Resection: Published Results
Author (year)
rT Stage*
Yoshizaki et al15 (2005)
rT2 rT1 - 3 rT2a - 3 rT1 - 17 rT2a - 4 rT2b - 14 rT3 - 2 rT1 - 12
Chen et al16 (2007) Chen et al27 (2009)
Ko et al32 (2009)
Median Follow-up (months)
Recurrence
Survival Rate, % (years of assessment)
4 6 (49)
— 100%
— 29
25% 16.7%
— lcr: 83.3% (2)
37 (47)
94.6%
24
13.5%
OS 84.2% (2) DFS 86.3% (2) pfs 82.6% (2)
28 (51)
89%
27
35.7%
Patient Number (mean age, y)*
Negative margins
rT2aN0 - 14
Rohaizam et al38 (2009) Castelnuovo et al18 (2010)
rT2aN1 - 2 rT1 - 6
6
100%
7
0
—
23
0 (rT1-2a); 100% rT3
13 (55.7)
78.9%
24
30.8%
8 (53.5)
100%
27
12.5%
rT1 - 4
8 (52.5)
Ho et al17 (2012)
rT2a - 1 rT3N0 - 2 rT3N1 - 1 rT1 - 6
Our patient series
rT2a - 3 rT2b - 2 rT3 - 2 rT1† - 8
OS (2) rT1 = 90.9; rT2 = 38.5 LDFS (2) rT1 = 100; rT2 = 41.7 OS 100% (2)
Major Complications, %
Mean Hospitalization Time, d
— 17% orn
— —
2.7% intracranial infection
11% orn
5
—
11% XII palsy
Flap necrosis 50%; orn 17%
—
No recurrence in rT1, rT2a rT3: 2 AWD, 1 DOD
0%
4
OS 100 (2) DFS 69.2 (2)
0%
0.3
OS 100% (2) DFS 88.9% (2) lcr 83.3% (2)
12.5% osteomyelitis
3
AWD, alive with disease; DOD, dead of disease; lcr, local control rate; LDFS, local disease-free survival; orn, osteoradionecrosis; pfs, progression-free survival. *UICC/AJCC TNM staging system classification. †UICC/AJCC TNM staging system classification.
of sphenoid sinus tumor invasion may be treated achieving negative margins. Compared with the results of external approaches, NER seems to have favorable local control and survival outcomes and demonstrates to be a very good surgical technique in terms of postoperative morbidity, patient's quality of life, and hospitalization time.27–32 According to the literature, negative margins were achieved in 71.6% of external nasopharyngectomies,3–14 whereas they were obtained in 93.75% of endoscopic procedures.15–32 These results probably depend on the magnification ability of the endoscopes and the possibility of a precise local control of the limits of the lesion. Despite the small size of our cohort, the outcomes reveal that NER is a safe and feasible surgical procedure in selected earlystage recurrent uNPC. Better results are obtained for rT1 lesions. Contraindications to NER include extensive parapharyngeal space invasion, carotid artery encasement, severe perineural infiltration, as well as infratemporal fossa, dural, brain, or cavernous sinus involvement. The endoscopic approach to the nasopharynx leads to low morbidity and no postoperative mortality. It is moreover indicated even in cases of local re-recurrence of the disease, when early diagnosed. That is the reason why a close surveillance is required with careful endoscopic and radiologic evaluations, accompanied by biopsy of any suspicious lesion.
REFERENCES 1. Barnes L. WHO histological classification of tumours of the nasal cavity and paranasal sinuses. In: Barnes E, Eveson J, Reichart P, et al, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Head and Neck Tumours. Lyon: IARC Press, 2005:205–211
2. Chan AT, Teo PM, Huang DP. Pathogenesis and treatment of nasopharyngeal carcinoma. Semin Oncol 2004;31:794–801 3. Wei WI, Kwong DL. Current management strategy of nasopharyngeal carcinoma. Clin Exp Otorhinolaryngol 2010;3:1–12 4. Suarez C, Rodrigo JP, Rinaldo A, et al. Current treatment options for recurrent nasopharyngeal cancer. Eur Arch Otorhinolaryngol 2010;267:1811–1824 5. Ma J, Mai HQ, Hong MH, et al. Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol 2001;19:1350–1357 6. Lin JC, Liang WM, Jan JS, et al. Another way to estimate outcome of advanced nasopharyngeal carcinoma—is concurrent chemoradiotherapy adequate? Int J Radiat Oncol Biol Phys 2004;60:156–164 7. Yu KH, Leung SF, Tung SY, et al. Survival outcome of patients with nasopharyngeal carcinoma with first local failure: a study by the Hong Kong Nasopharyngeal Carcinoma Study Group. Head Neck 2005;27:397–405 8. Fisch U. The infratemporal fossa approach for nasopharyngeal tumors. Laryngoscope 1983;93:36–44 9. Danesi G, Zanoletti E, Mazzoni A. Salvage surgery for recurrent nasopharyngeal carcinoma. Skull Base 2007;17:173–180 10. Morton RP, Liavaag PG, McLean M, et al. Transcervico-mandibulo-palatal approach for surgical salvage of recurrent nasopharyngeal cancer. Head Neck 1996;18:352–358 11. To EW, Lai EC, Cheng JH, et al. Nasopharyngectomy for recurrent nasopharyngeal carcinoma: a review of 31 patients and prognostic factors. Laryngoscope 2002;112:1877–1882 12. Wei WI, Ho CM, Yuen PW, et al. Maxillary swing approach for resection of tumors in and around the nasopharynx. Arch Otolaryngol Head Neck Surg 1995;121:638–642
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Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
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13. King WW, Ku PK, Mok CO, et al. Nasopharyngectomy in the treatment of recurrent nasopharyngeal carcinoma: a twelve-year experience. Head Neck 2000;22:215–222 14. Chang KP, Hao SP, Tsang NM, et al. Salvage surgery for locally recurrent nasopharyngeal carcinoma—a 10-year experience. Otolaryngol Head Neck Surg 2004;131:497–502 15. Yoshizaki T, Wakisaka N, Murono S, et al. Endoscopic nasopharyngectomy for patients with recurrent nasopharyngeal carcinoma at the primary site. Laryngoscope 2005;115:1517–1519 16. Chen MK, Lai JC, Chang CC, et al. Minimally invasive endoscopic nasopharyngectomy in the treatment of recurrent T1-2a nasopharyngeal carcinoma. Laryngoscope 2007;117:894–896 17. Ho AS, Kaplan MJ, Fee WE Jr, et al. Targeted endoscopic salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma. Int Forum Allergy Rhinol 2012;2:166–173 18. Castelnuovo P, Dallan I, Bignami M, et al. Nasopharyngeal endoscopic resection in the management of selected malignancies: ten-year experience. Rhinology 2010;48:84–89 19. Edge SB, Byrd DR, Compton CC, et al AJCC Cancer Staging Manual. 7th ed. New York: Springer, 2010 20. Lee AW, Sze WM, Au JS, et al. Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys 2005;61:1107–1116 21. Vlantis AC, Yu BK, Kam MK, et al. Nasopharyngectomy: does the approach to the nasopharynx influence survival? Otolaryngol Head Neck Surg 2008;139:40–46 22. Ong YK, Solares CA, Lee S, et al. Endoscopic nasopharyngectomy and its role in managing locally recurrent nasopharyngeal carcinoma. Otolaryngol Clin North Am 2011;44:1141–1154 23. Wei WI, Chan JY, Ng RW, et al. Surgical salvage of persistent or recurrent nasopharyngeal carcinoma with maxillary swing approach—critical appraisal after 2 decades. Head Neck 2011;33:969–975 24. Hsu MM, Hong RL, Ting LL, et al. Factors affecting the overall survival after salvage surgery in patients with recurrent nasopharyngeal carcinoma at the primary site: experience with 60 cases. Arch Otolaryngol Head Neck Surg 2001;127:798–802 25. Hao SP, Tsang NM, Chang CN. Salvage surgery for recurrent nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg 2002;128:63–67
1008
26. Bian X, Chen H, Liao L. A retrospective study of salvage surgery for recurrent nasopharyngeal carcinoma. Int J Clin Oncol 2012;17:212–217 27. Chen MY, Wen WP, Guo X, et al Endoscopic nasopharyngectomy for locally recurrent nasopharyngeal carcinoma. Laryngoscope 2009;119:516–522 28. To EW, Teo PM, Ku PK, et al. Nasopharyngectomy for recurrent nasopharyngeal carcinoma: an innovative transnasal approach through a mid-face deglove incision with stereotactic navigation guidance. Br J Oral Maxillofac Surg 2001;39:55–62 29. Tu GY, Hu YH, Xu GZ, et al. Salvage surgery for nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg 1988;114:328–329 30. Hao SP, Tsang NM, Chang KP, et al. Nasopharyngectomy for recurrent nasopharyngeal carcinoma: a review of 53 patients and prognostic factors. Acta Otolaryngol 2008;128:473–481 31. Chan JY, Chow VL, Tsang R, et al. Nasopharyngectomy for locally advanced recurrent nasopharyngeal carcinoma: exploring the limits. Head Neck 2012;34:923–928 32. Ko JY, Wang CP, Ting LL, et al. Endoscopic nasopharyngectomy with potassium-titanyl-phosphate (KTP) laser for early locally recurrent nasopharyngeal carcinoma. Head Neck 2009;31: 1309–1315 33. Nicolai P, Battaglia P, Bignami M, et al. Endoscopic surgery for malignant tumors of the sinonasal tract and adjacent skull base: a 10-year experience. Am J Rhinol 2008;22:308–316 34. Vlantis AC, Chan HS, Tong MC, et al. Surgical salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma: a multivariate analysis of prognostic factors. Head Neck 2011;33:1126–1131 35. Shu CH, Cheng H, Lirng JF, et al. Salvage surgery for recurrent nasopharyngeal carcinoma. Laryngoscope 2000;110:1483–1488 36. Bridger GP, Smee R, Baldwin MA, et al. Salvage nasopharyngectomy for radiation recurrences. ANZ J Surg 2005;75:1065–1069 37. Chan JY, Wei WI. Recurrent nasopharyngeal carcinoma after salvage nasopharyngectomy. Arch Otolaryngol Head Neck Surg 2012;138:572–576 38. Rohaizam J, Subramaniam SK, Vikneswaran T, et al. Endoscopic nasopharyngectomy: the Sarawak experience. Med J Malaysia 2009;64:213–215
© 2014 Mutaz B. Habal, MD
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
Endoscopic Surgery for Recurrent Undifferentiated Nasopharyngeal Carcinoma Enzo Emanuelli, MD,* Silviu Albu, MD, PhD,† Diego Cazzador, MD,* Barbara Pedruzzi, MD,* Gregorio Babighian, MD, PhD,* and Alessandro Martini, MD, PhD* Abstract: One of the biggest challenges for otolaryngologists is represented by the locally recurrent undifferentiated nasopharyngeal carcinoma (uNPC). Despite improvements in its treatment options, such as modern radiotherapy, chemotherapy, or external surgical approaches, the risk for severe complications, functional disabilities, and even death remains considerable. Over the years, advances in endoscopic surgery have led to a new alternative in the salvage surgery for recurrent uNPC: the nasopharyngeal endoscopic resection (NER). We retrospectively reviewed clinical records of 8 patients (6 men and 2 women), who underwent NER for recurrent T1 (rT1) locally recurrent uNPC between 2008 and 2011. Together with resections for subsequent recurrences, a total of 9 NERs were performed by a single surgeon with curative intent. Negative margins were obtained for the whole group of patients. After a mean follow-up period of 27 months (range, 16–54 mo), all the patients had no evidence of the disease. We had only 1 recurrence after 7 months. Two-year overall survival and disease-free survival rates were 100% and 88.9%, respectively. Only 1 patient presented with a complication, osteitis. Nasopharyngeal endoscopic resection can be considered a valid and promising treatment option for rT1 locally recurrent uNPC, showing encouraging short-term outcomes and complication rate. Long-term follow-up is needed to state the efficacy of NER, together with a larger number of patients. Key Words: Undifferentiated nasopharyngeal carcinoma, recurrence, endoscopic resection, outcomes (J Craniofac Surg 2014;25: 1003–1008)
T
he World Health Organization has classified nasopharyngeal carcinoma (NPC) into 3 histologic types1: keratinizing squamous cell carcinoma (type I), non–keratinizing squamous cell carcinoma (type II), and undifferentiated carcinoma (uNPC; type III), with the latter being the most frequently observed histologic type of NPC. It is well known that uNPC is a high radio-chemosensitive tumor. The mainstay of treatment for primary uNPC is thus given by radiotherapy alone for early-stage tumors or concomitant chemoradiation
From the *Operative Unit of Otolaryngology and Otosurgery, Padua University, Padua, Italy; and †Second Department of Otolaryngology, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, ClujNapoca, Romania. Received November 19, 2013. Accepted for publication January 2, 2014. Address correspondence and reprint requests to Silviu Albu, MD, Second Department of Otolaryngology, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, St Republicii nr. 18, 400015 Cluj-Napoca, Romania; E-mail: [email protected] The authors report no conflicts of interest. Copyright © 2014 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000000698
for advanced lesions.2 In a recent study, this combined treatment modality resulted in an improved control of locoregional disease, together with a reduction of long-term adverse effects, and led to 5-year local control rates of 80% to 85%.3 Nonetheless, the risk for local recurrence is still considerable because its incidence ranges from 8% to 58%.4–6 Curative nasopharyngectomy is considered one of the most effective salvage treatment options for locally recurrent uNPC,7 comprising different kinds of external approaches, such as maxillary swing, mandibulary swing, as well as transpalatal and type C infratemporal approach.8–14 However, such a surgery is one of the most challenging in the head and neck area. In addition, external nasopharyngectomies lead to important functional disabilities, aesthetic problems, and major complications for the patients, deeply compromising their quality of life. Recently, endoscopic endonasal surgery has emerged as a viable option in the management of recurrent uNPC, thus avoiding the morbidity related to external surgery.15–18 The current study presents our experience in the management of recurrent uNPC, aiming to define precise indications for the nasopharyngeal endoscopic resection (NER), to report preliminary outcomes and complications rate and to compare them with those reported previously.
MATERIALS AND METHODS Eight consecutive cases of histologically proven recurrent uNPC were retrospectively reviewed. Between January 2008 and December 2011, all patients underwent NER with curative intent, performed by a single surgeon (E.E.) of a tertiary academic medical center. Primary therapy consisted of radiotherapy only in 5 patients and combined chemoradiotherapy in 2 patients, whereas only 1 patient was directly submitted to NER because he already received radiotherapy intended for a previous medulloblastoma. All patients were carefully investigated through endoscopic examination (Fig. 1), computed tomography (CT), and magnetic resonance scan. Moreover, a preoperative positron emission tomography-CT scan was performed to exclude distant metastasis of the disease. All patients were restaged according to the seventh edition of AJCC Cancer Staging Manual.19 Only recurrent T1 (rT1) cases without regional or distant metastasis were considered eligible for NER. All the operations were performed under hypotensive general anesthesia, in a supine position. The resection was guided by 4-mm– diameter 0-, 30-, and 70-degree–angled endoscopes (Karl-Storz, Tuttlingen, Germany). The nasal cavity was decongested using cotton plugs saturated with pantocaine 2%, oximetazolyne, and epinephrine 1:100.000. The first step consisted of a partial resection of the posterior third of the nasal septum, performed to generate an adequate working place with a better visualization of the surgical field. The sphenopalatine artery was identified and cauterized to prevent further bleeding. A Dornier contact-type diode laser (Dornier Medizin Laser Gmbh, Germering, Germany) with pulse wave (30 W) was set to 10 W during surgery to carry out the mucosal incision, thus creating a bloodless surgical field. A multilayered pattern of resection was performed, removing first the mucosal layer on a subperiosteal
The Journal of Craniofacial Surgery • Volume 25, Number 3, May 2014
Copyright © 2014 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
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FIGURE 1. Endoscopic view of recurrent nasopharyngeal tumor.
FIGURE 3. En bloc removal of the excised tumor.
surgical plane (Figs. 2–4), followed by drilling of the bone limits using a diamond endonasal drill (Karl-Storz, Tuttlingen, Germany), whenever requested. Tumor resections were classified according to the study of Castelnuovo et al.18 Type I is limited to the posterosuperior nasopharyngeal wall, reaching the floor of the sphenoid sinus and preserving the cartilagineous portion of the Eustachian tube. It always allows the en bloc resection of the tumor. Type II is extended cranially to incorporate the anterior wall of the sphenoid sinus and includes its mucosal stripping together with the drilling of the sphenoid sinus floor. The cartilaginous portion of the Eustachian tube is preserved. Type III is similar to type II, except for the lateral extension because it includes the nasopharyngeal wall up to the parapharyngeal space, not maintaining the cartilagineous portion of the Eustachian tube. Surgical margins were carefully examined with frozen intraoperative sections. The wound was always covered with fibrillary tabotamp for hemostasis and left free to heal by second intention. Nasal packing was performed with a sterile dressing of nonadhesive polyurethane foam (Seton Health Care Group, Oldham, United Kingdom), medicated always with antibiotic. It was removed 72 hours after the operation. All patients were regularly followed up by means of rigid endoscopic evaluation. Imaging studies (computed tomography and magnetic resonance imaging), biopsy, and fine-needle aspiration
cytology were carried out whenever indicated, in accordance with the National Comprehensive Cancer Network guidelines. The cases of local re-recurrence disease were treated with a second NER. The overall survival (OS) and disease-free survival (DFS) were censored at the date of the last follow-up. Survival curves were analyzed using the Kaplan-Meier product limit method. Statistical analyses were performed using MedCalc statistical software (MedCalc Software, Mariakerke, Belgium).
The study group consisted of 8 patients, 6 men and 2 women, with a mean age at surgery of 59 years and a median age of 53.5 years (range, 45–83 y). Table 1 reports a detailed list of the patient's characteristics. The mean time from the primary treatment to local recurrence was 57.7 months (range, 36–114 mo). All lesions were classified rT1 (stage I) according to the seventh edition of American Joint Committee on Cancer Staging Manual.19 The whole group of patients underwent NER with curative intent. Type I NER was performed in 5 cases; type II, in 2 cases; and type III, in 2 cases. One patient developed a recurrent tumor 7 months after the first endoscopic salvage treatment (NER, type I). Consequently, he was submitted to a second more extensive NER (type III) and is still alive without evidences of the disease.
FIGURE 2. Mucosal incision using the diode laser.
FIGURE 4. Endoscopic view of the nasopharynx after the tumor removal.
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RESULTS
© 2014 Mutaz B. Habal, MD
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The Journal of Craniofacial Surgery • Volume 25, Number 3, May 2014
Endoscopic Surgery for uNPC
TABLE 1. Patients Included in the Study
Patient Age Sex 1 2 3 4 5 6 7 8
45 53 47 70 83 54 69 52
F M M M M F M M
Stage at Diagnosis*
Primary Treatment
Time to First Recurrence (mo)
Stage at Recurrence*
Time to Second Recurrence (mo)
NER
Postoperative Treatment
T2N0M0 T3N0M0 T1N0M0 T2N0M0 T1N0M0 T1N0M0 T1N2bM0 T1N0M0
— RT RT RT RT RT RT+CT RT+CT
45 42 62 56 68 114 39 36 —
rT1 rT1 rT1 rT1 rT1 rT1 rT1 rT1 rT1
— — — — — — — — 7
2 2 1 1 1 3 1 1 3
RT — — — — — — — —
Follow-up (mo) Results 22 25 17 54 25 35 16 7 14
NED NED NED NED NED NED NED rec NED
*According to the 2010 AJCC TNM staging system classification. F, female; M, male; NED, no evidence of the disease; rec, local recurrence.
Nasopharyngeal endoscopic resections were successfully performed through the endonasal approach, and no conversions to external approaches were necessary. Negative margins were obtained in 100% of cases. The mean operating time was 140 minutes (range, 40–210 min). No patients required blood transfusions. One patient received a prophylactic selective modified type III radical neck dissection after the endoscopic approach. Only one patient received postoperative radiotherapy, the one previously diagnosed with medulloblastoma. No intraoperative complications were observed. Postoperatively, we encountered one case of osteitis of the sphenoid basis, which resolved in 3 weeks under antibiotic therapy treatment. The overall complication rate was consequently 11% (1/9 procedures). Each patient had exactly a 3-day hospitalization time. All patients were discharged with systemic antibiotic therapy and nasal irrigation with physiological solution. The mean follow-up time was 27 months (range, 16–54 mo). The patients developed neither lymphatic nor distant metastasis during this time. The 2-year OS and DFS rates are 100% and 88.9%, respectively. Local recurrence rate is 12.5%.
DISCUSSION Despite an adequate primary treatment, local recurrence represents an important problem in uNPC. Feasible salvage options consist of re-irradiation and surgery, the choice of which depends on tumor features, such as location and size, patient's condition, as well as previous primary treatment.4 Chemotherapy alone is used for palliation, being indicated for patients not suitable to other curative therapy options.4 A second course of external RT might be unsafe because of the high risk for complications, such as cerebral necrosis, hypothalamic-pituitary failure, deafness, retinopathy, transverse myelitis, and cranial nerve dysfunction.7,12–14 The incidence of reirradiation morbidity varies between 6% and 85% depending on the radiation dose intensity, whereas the mortality rate is between 1.8% and 20%.4,20–22 Alternatively, surgery is recommended in the treatment of recurrent uNPC, having the advantage of avoiding re-irradiation toxicities. Moreover, it provides better local control and survival rates than does re-irradiation alone.20–26 Salvage nasopharyngectomy was initially performed using an external approach. An analysis of the literature on external nasopharyngectomy is reassumed in Table 2. As one can see, surgery provides 5-year OS rates between 30% and 60%3–14 as well as a local control rate between 43% and 74%.20–26 External salvage surgery is associated with serious and potentially fatal complications, that is, massive hemorrhage, as result
of internal carotid artery injury,3,9,10 or intracranial complications such as meningitis and osteoradionecrosis.4–11 This approach, being very aggressive and invasive, may also compromise vital functions, thus resulting in functional disabilities such as severe trismus, oronasal fistula, and palatal dehiscence, leading to dysphagia and malnutrition, significantly decreasing the patient's quality of life.3–14 Moreover, external scarring may also compromise the aesthetical aspect of the patient. Improvement in the endoscopic armamentarium, coupled with high-definition monitors and increasing experience in endoscopic surgery, has led to an extension of the indications of endoscopic approaches. As a consequence, NER emerged as a viable salvage treatment.27–32 Published results of NER are outlined in Table 3. We report 8 cases of rT1 uNPC, with no intraoperative complications and no treatment-related mortality. Only 1 patient presented a postoperative complication, osteomyelitis, and received antibiotic treatment. Nasopharyngeal endoscopic resection was performed following the principle of multilayer centripetal resection, which has shown excellent oncological results in the treatment of sinus tumors.33 This surgical technique allows the achievement of clear surgical margins, contrasting the en bloc resection theory. Within a mean follow-up of 27 months, only 1 local recurrence was registered. The patient was endoscopically re-treated, resulting to be free of the disease at the time of writing. Neither regional nor distant metastasis occurred. At 2 years, we calculated OS, DFS, and local control rate of 100%, 88.9%, and 83.3%, respectively. Our survival rates reflect that reported in other published series.22–32 According to the literature, NER is indicated for early recurrent disease, achieving good results for rT1 cases.22–32 Regarding recurrent T2 (rT2) lesions, the outcome mostly depends on the invasion of the parapharyngeal space.22 With tumors extending far laterally, the likelihood of achieving negative margins decreases because of the proximity of internal carotid artery, with the associated risk for injuring during the resection. Positive surgical margins are associated with dismal prognosis and have an independent negative influence on DFS and OS.34 Therefore, when the distance between tumor and internal carotid artery is less than 1 cm, an open approach is recommended, such as the maxillary swing or the type C infratemporal approach.22,27 Only a few cases of recurrent T3 (rT3) NPC are reported.17,18,27 Four cases were reported by Chen et al27 and Ho et al17; each of them had sphenoid sinus extension and received a radical endoscopic resection, but 3 of the 4 cases developed distant metastasis. In the study of Castelnuovo et al,18 2 patients were alive with disease, whereas 1 died of the disease. The role of NER for rT3 lesions has still to be clearly defined. Given the increasing experience in the endoscopic treatment of anterior skull base tumors, highly selected cases
© 2014 Mutaz B. Habal, MD
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TABLE 2. Results of External Nasopharyngectomy
Author (year) King et al13 (2000)
Surgical Approach 11 transpalatal
Group (mean age, y) rT Stage* 31 (43)
11 mandibular swing 9 maxillary swing Shu et al35 (2000)
Hsu et al24 (2001)
To et al11 (2002)
Maxillary swing + other
28 maxillary swing 11 transpalatal
28 (53)
60 (50.8)
rT1 - 15 rT1N1 - 1 rT2a - 3 rT2bN0 - 5 rT2bN1 - 1 rT3 - 2 rT4 - 1 rT1 - 10 rT2 - 18
—
29.3
6 facial translocation 5 maxillary swing
11 (55)
Danesi et al9 (2007)
Infratemporal fossa type C
11 (45)
53 (50.6)
—
21 (75)
—
DFS - 32.1% (4.3)
27.7
—
11% c.n. paralysis 11% osteonecrosis 7% trismus 3% choanal stenosis 7% other OS - 56% (2); 30% (5) 18% oronasal fistula DFS - 60% (2); 40% (5) 18% palatal incompetence other (otitis media, trismus)
—
—
22 (71%)
28.5
DFS - 58% (2.4)
6% perioperative meningitis
—
63%
30 (79%)
26.8
OS - 60% (3) lcr - 72.8% (3)
13.2% morbidity
—
100%
—
69.8
4/11 DOD 1/11 AWD
100%
—
48
83%
36 (68%)
—
64 (66.7%): 47.9% clear, 18.8% close margins
86%
44 (62%)
rT3/4
—
—
—
94.6%
248 (79.5%)
rT4 - 10 rT1 - 7 rT2 - 13 rT3 - 2 rT4 - 9 rT1 - 16 rT2b - 4 rT3 - 11 rT4 - 7 rT1 - 3 rT2 - 5 rT3 - 3 rT1 - 2
Bridger et al36 (2005)
DFS - 42% (5) lcr - 43% (5)
Complications 64% otitis media with effusion 52% palatal fistula 48% trismus 39% dysphagia 14% ICA blowout
43.1
10 transmandibular 17 midfacial degloving 31 (49.5) 10 maxillary swing 4 mandibular swing Facial translocation 38 (48.8) (12 with a combined NCH approach)
OS - 47% (5)
—
rT3 - 22
rT2 - 6 rT3 - 2 rT4 - 1 rT1 - 27 rT2 - 9
—
—
DFS - 72% (2)
27% wound infection 27% trismus
—
37.1
OS - 48.7% (5) lcr - 53.6% (5)
11.3% morbidity
—
—
OS - 51.9% (5) LRFS - 46.7 (5) lcr - 62.8% (5)
47% morbidity 15% ectropion 11% palatal fistula 10% palatal dehiscence 10% other 22.5% morbidity 10% trismus 8% palatal fistula 4% submandible necrosis 63.6% trismus 4.5% fistula
—
rT3 - 9
Vlantis et al34 (2010)
38 maxillary swing 97 (47.7) 35 midfacial degloving 24 transpalatal
Bian et al26 (2011)
33 maxillary swing 38 other
Chan JYet al37 Maxillary swing + (2012) free flap reconstruction 31 Chan et al Maxillary swing (2012)
90%
Mean Hospitalization Time, d
82%
11 transmaxillary
33 facial translocation 18 craniofacial resection 2 endoscopic nasopharyngectomy
UC, %
rT2 - 9 rT3 – 2
Chang et al14 (2004)
Hao et al30 (2008)
rT1 - 20
Negative Median Survival Rate (years Margins, % Follow-up, mo of assessment)
71 (46)
22 (48.2)
312 (52)
rT4 - 8 rT1 - 53 rT2 - 32 rT3/4 - 12
rT1 rT2 rT3 rT4
-
27 19 14 11
30
lcr - 61.9% (2) lrc - 53.5% (5)
38.8
1/22 local and distant recurrent disease
34
OS - 62% (5) DFS - 56% (5) lcr - 74% (5)
20% trismus 15.7% palatal fistula
—
8.6
12
rT, recurrent tumor; UC, undifferentiated carcinoma; lcr, local control rate; ICA, internal carotid artery; cn, cranial nerves; NCH, neurosurgical; DOD, died of disease; AWD, alive with disease; LRFS, local relapse free survival; UICC, Union for International Cancer Control; AJCC, American Joint Committee on Cancer. *according to the American Joint Committee on Cancer.
1006
© 2014 Mutaz B. Habal, MD
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The Journal of Craniofacial Surgery • Volume 25, Number 3, May 2014
Endoscopic Surgery for uNPC
TABLE 3. Nasopharyngeal Endoscopic Resection: Published Results
Author (year)
rT Stage*
Yoshizaki et al15 (2005)
rT2 rT1 - 3 rT2a - 3 rT1 - 17 rT2a - 4 rT2b - 14 rT3 - 2 rT1 - 12
Chen et al16 (2007) Chen et al27 (2009)
Ko et al32 (2009)
Median Follow-up (months)
Recurrence
Survival Rate, % (years of assessment)
4 6 (49)
— 100%
— 29
25% 16.7%
— lcr: 83.3% (2)
37 (47)
94.6%
24
13.5%
OS 84.2% (2) DFS 86.3% (2) pfs 82.6% (2)
28 (51)
89%
27
35.7%
Patient Number (mean age, y)*
Negative margins
rT2aN0 - 14
Rohaizam et al38 (2009) Castelnuovo et al18 (2010)
rT2aN1 - 2 rT1 - 6
6
100%
7
0
—
23
0 (rT1-2a); 100% rT3
13 (55.7)
78.9%
24
30.8%
8 (53.5)
100%
27
12.5%
rT1 - 4
8 (52.5)
Ho et al17 (2012)
rT2a - 1 rT3N0 - 2 rT3N1 - 1 rT1 - 6
Our patient series
rT2a - 3 rT2b - 2 rT3 - 2 rT1† - 8
OS (2) rT1 = 90.9; rT2 = 38.5 LDFS (2) rT1 = 100; rT2 = 41.7 OS 100% (2)
Major Complications, %
Mean Hospitalization Time, d
— 17% orn
— —
2.7% intracranial infection
11% orn
5
—
11% XII palsy
Flap necrosis 50%; orn 17%
—
No recurrence in rT1, rT2a rT3: 2 AWD, 1 DOD
0%
4
OS 100 (2) DFS 69.2 (2)
0%
0.3
OS 100% (2) DFS 88.9% (2) lcr 83.3% (2)
12.5% osteomyelitis
3
AWD, alive with disease; DOD, dead of disease; lcr, local control rate; LDFS, local disease-free survival; orn, osteoradionecrosis; pfs, progression-free survival. *UICC/AJCC TNM staging system classification. †UICC/AJCC TNM staging system classification.
of sphenoid sinus tumor invasion may be treated achieving negative margins. Compared with the results of external approaches, NER seems to have favorable local control and survival outcomes and demonstrates to be a very good surgical technique in terms of postoperative morbidity, patient's quality of life, and hospitalization time.27–32 According to the literature, negative margins were achieved in 71.6% of external nasopharyngectomies,3–14 whereas they were obtained in 93.75% of endoscopic procedures.15–32 These results probably depend on the magnification ability of the endoscopes and the possibility of a precise local control of the limits of the lesion. Despite the small size of our cohort, the outcomes reveal that NER is a safe and feasible surgical procedure in selected earlystage recurrent uNPC. Better results are obtained for rT1 lesions. Contraindications to NER include extensive parapharyngeal space invasion, carotid artery encasement, severe perineural infiltration, as well as infratemporal fossa, dural, brain, or cavernous sinus involvement. The endoscopic approach to the nasopharynx leads to low morbidity and no postoperative mortality. It is moreover indicated even in cases of local re-recurrence of the disease, when early diagnosed. That is the reason why a close surveillance is required with careful endoscopic and radiologic evaluations, accompanied by biopsy of any suspicious lesion.
REFERENCES 1. Barnes L. WHO histological classification of tumours of the nasal cavity and paranasal sinuses. In: Barnes E, Eveson J, Reichart P, et al, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Head and Neck Tumours. Lyon: IARC Press, 2005:205–211
2. Chan AT, Teo PM, Huang DP. Pathogenesis and treatment of nasopharyngeal carcinoma. Semin Oncol 2004;31:794–801 3. Wei WI, Kwong DL. Current management strategy of nasopharyngeal carcinoma. Clin Exp Otorhinolaryngol 2010;3:1–12 4. Suarez C, Rodrigo JP, Rinaldo A, et al. Current treatment options for recurrent nasopharyngeal cancer. Eur Arch Otorhinolaryngol 2010;267:1811–1824 5. Ma J, Mai HQ, Hong MH, et al. Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol 2001;19:1350–1357 6. Lin JC, Liang WM, Jan JS, et al. Another way to estimate outcome of advanced nasopharyngeal carcinoma—is concurrent chemoradiotherapy adequate? Int J Radiat Oncol Biol Phys 2004;60:156–164 7. Yu KH, Leung SF, Tung SY, et al. Survival outcome of patients with nasopharyngeal carcinoma with first local failure: a study by the Hong Kong Nasopharyngeal Carcinoma Study Group. Head Neck 2005;27:397–405 8. Fisch U. The infratemporal fossa approach for nasopharyngeal tumors. Laryngoscope 1983;93:36–44 9. Danesi G, Zanoletti E, Mazzoni A. Salvage surgery for recurrent nasopharyngeal carcinoma. Skull Base 2007;17:173–180 10. Morton RP, Liavaag PG, McLean M, et al. Transcervico-mandibulo-palatal approach for surgical salvage of recurrent nasopharyngeal cancer. Head Neck 1996;18:352–358 11. To EW, Lai EC, Cheng JH, et al. Nasopharyngectomy for recurrent nasopharyngeal carcinoma: a review of 31 patients and prognostic factors. Laryngoscope 2002;112:1877–1882 12. Wei WI, Ho CM, Yuen PW, et al. Maxillary swing approach for resection of tumors in and around the nasopharynx. Arch Otolaryngol Head Neck Surg 1995;121:638–642
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13. King WW, Ku PK, Mok CO, et al. Nasopharyngectomy in the treatment of recurrent nasopharyngeal carcinoma: a twelve-year experience. Head Neck 2000;22:215–222 14. Chang KP, Hao SP, Tsang NM, et al. Salvage surgery for locally recurrent nasopharyngeal carcinoma—a 10-year experience. Otolaryngol Head Neck Surg 2004;131:497–502 15. Yoshizaki T, Wakisaka N, Murono S, et al. Endoscopic nasopharyngectomy for patients with recurrent nasopharyngeal carcinoma at the primary site. Laryngoscope 2005;115:1517–1519 16. Chen MK, Lai JC, Chang CC, et al. Minimally invasive endoscopic nasopharyngectomy in the treatment of recurrent T1-2a nasopharyngeal carcinoma. Laryngoscope 2007;117:894–896 17. Ho AS, Kaplan MJ, Fee WE Jr, et al. Targeted endoscopic salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma. Int Forum Allergy Rhinol 2012;2:166–173 18. Castelnuovo P, Dallan I, Bignami M, et al. Nasopharyngeal endoscopic resection in the management of selected malignancies: ten-year experience. Rhinology 2010;48:84–89 19. Edge SB, Byrd DR, Compton CC, et al AJCC Cancer Staging Manual. 7th ed. New York: Springer, 2010 20. Lee AW, Sze WM, Au JS, et al. Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys 2005;61:1107–1116 21. Vlantis AC, Yu BK, Kam MK, et al. Nasopharyngectomy: does the approach to the nasopharynx influence survival? Otolaryngol Head Neck Surg 2008;139:40–46 22. Ong YK, Solares CA, Lee S, et al. Endoscopic nasopharyngectomy and its role in managing locally recurrent nasopharyngeal carcinoma. Otolaryngol Clin North Am 2011;44:1141–1154 23. Wei WI, Chan JY, Ng RW, et al. Surgical salvage of persistent or recurrent nasopharyngeal carcinoma with maxillary swing approach—critical appraisal after 2 decades. Head Neck 2011;33:969–975 24. Hsu MM, Hong RL, Ting LL, et al. Factors affecting the overall survival after salvage surgery in patients with recurrent nasopharyngeal carcinoma at the primary site: experience with 60 cases. Arch Otolaryngol Head Neck Surg 2001;127:798–802 25. Hao SP, Tsang NM, Chang CN. Salvage surgery for recurrent nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg 2002;128:63–67
1008
26. Bian X, Chen H, Liao L. A retrospective study of salvage surgery for recurrent nasopharyngeal carcinoma. Int J Clin Oncol 2012;17:212–217 27. Chen MY, Wen WP, Guo X, et al Endoscopic nasopharyngectomy for locally recurrent nasopharyngeal carcinoma. Laryngoscope 2009;119:516–522 28. To EW, Teo PM, Ku PK, et al. Nasopharyngectomy for recurrent nasopharyngeal carcinoma: an innovative transnasal approach through a mid-face deglove incision with stereotactic navigation guidance. Br J Oral Maxillofac Surg 2001;39:55–62 29. Tu GY, Hu YH, Xu GZ, et al. Salvage surgery for nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg 1988;114:328–329 30. Hao SP, Tsang NM, Chang KP, et al. Nasopharyngectomy for recurrent nasopharyngeal carcinoma: a review of 53 patients and prognostic factors. Acta Otolaryngol 2008;128:473–481 31. Chan JY, Chow VL, Tsang R, et al. Nasopharyngectomy for locally advanced recurrent nasopharyngeal carcinoma: exploring the limits. Head Neck 2012;34:923–928 32. Ko JY, Wang CP, Ting LL, et al. Endoscopic nasopharyngectomy with potassium-titanyl-phosphate (KTP) laser for early locally recurrent nasopharyngeal carcinoma. Head Neck 2009;31: 1309–1315 33. Nicolai P, Battaglia P, Bignami M, et al. Endoscopic surgery for malignant tumors of the sinonasal tract and adjacent skull base: a 10-year experience. Am J Rhinol 2008;22:308–316 34. Vlantis AC, Chan HS, Tong MC, et al. Surgical salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma: a multivariate analysis of prognostic factors. Head Neck 2011;33:1126–1131 35. Shu CH, Cheng H, Lirng JF, et al. Salvage surgery for recurrent nasopharyngeal carcinoma. Laryngoscope 2000;110:1483–1488 36. Bridger GP, Smee R, Baldwin MA, et al. Salvage nasopharyngectomy for radiation recurrences. ANZ J Surg 2005;75:1065–1069 37. Chan JY, Wei WI. Recurrent nasopharyngeal carcinoma after salvage nasopharyngectomy. Arch Otolaryngol Head Neck Surg 2012;138:572–576 38. Rohaizam J, Subramaniam SK, Vikneswaran T, et al. Endoscopic nasopharyngectomy: the Sarawak experience. Med J Malaysia 2009;64:213–215
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