Curr Oncol Rep (2015) 17:8 DOI 10.1007/s11912-014-0433-x
HEAD AND NECK CANCERS (E HANNA, SECTION EDITOR)
Surgical Salvage of Recurrent Nasopharyngeal Carcinoma Jimmy Yu Wai Chan
# Springer Science+Business Media New York 2015
Abstract Nasopharyngeal carcinoma is a unique tumour which is endemic in southern China including Hong Kong. Whilst the treatment results for the primary cancer has been encouraging, management of recurrent tumours has been challenging. Compared to other surgical approaches, the maxillary swing operation provides wide access to the bilateral nasopharynx and the ipsilateral parapharyngeal space, allowing resection of tumours with adequate margins. Among the 312 patients who had received salvage nasopharyngectomy via the maxillary swing approach, the chance of achieving microscopically clear resection margins was 79.5 %. The overall local recurrence rate after surgery was 13.1 %. Multivariate analysis showed that resection margin status, synchronous nodal recurrence and cavernous sinus invasion were independent prognostic factors for overall survival. For small tumours located in the posterior wall, endoscopic resection, or more recently, the transoral robotic (TORS)-assisted approach, can be performed. Every effort should be made to ensure microscopic clearance of disease as well as to minimize the potential complications of surgery that may adversely affect the subsequent quality of life.
Keywords Recurrent . Nasopharyngeal carcinoma . Nasopharyngectomy . Maxillary swing . Transoral robotic surgery (TORS)
This article is part of the Topical Collection on Head and Neck Cancers J. Y. W. Chan (*) Division of Head and Neck Surgery, Department of Surgery, University of Hong Kong Li Ka Shing Faculty of Medicine, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, SAR, China e-mail: [email protected]
Introduction Nasopharyngeal carcinoma (NPC) is unique among other squamous cell carcinoma of the head and neck regions in its epidemiology, pathology and treatment outcome. It is endemic in southern China, including Hong Kong, affecting 10 to 50 per 100,000 populations per year [1]. According to the Hong Kong Cancer Registry in 2011, NPC ranked seventh in cancer incidence and cancer-related mortality for both genders. More than 95 % of the tumour pathology is undifferentiated, nonkeratinizing carcinoma associated with Epstein-Barr virus (EBV) infection. It is a radiosensitive tumour, making radiotherapy the core treatment of the disease. For advance-staged tumours, studies showed that concurrent chemoradiation confers significant survival benefit [2]. Surgery is reserved for persistent or recurrent tumours after the initial therapy [3]. The local recurrence rate after initial radiotherapy for NPC is approximately 10 % [4]. Management of recurrent NPC has been challenging. Accurate assessment of the extent of the recurrent tumour in the nasopharynx is not easy. Furthermore, re-irradiating the same field may be associated with potentially serious side effects and complications. Surgical salvage is hampered by the anatomical difficulties and the effects of previous radiotherapy. As a result, the choice of therapy for such patients often depends on the availability of expertise in the institute, rather than the reference to the objective comparisons of the outcome of both treatment modalities. Some studies showed that surgery potentially offers better local tumour control and survival [5] as well as less posttreatment morbidities than re-irradiation [6], which may be associated with a risk of major complications as high as 57 % [7]. These include multiple cranial nerve palsies, which lead to dysphagia and aspiration, and hence malnutrition and recurrent pneumonia. Osteoradionecrosis, which is often severe and extensive, is often debilitating and sometimes life-threatening. Internal carotid blow-out is not an infrequent cause of
8
Page 2 of 6
death in these patients, and other complications, such as radiation myelitis, can cause peripheral weakness of limbs, severe hearing loss, and visual impairment. Radiation-induced squamous cell carcinoma and sarcoma, although uncommon, pose a major threat to the long survivors after radiation therapy for NPC. Surgical access to the nasopharynx, however, is not without difficulties. The nasopharynx is deep seated in the central part of the skull. It is obscured by bony structures in all directions, including the cranium, maxilla, palate, mandible and the cervical spine. Over the years, various approaches to the nasopharynx have been described.
Preoperative Assessment Patients after radiotherapy for NPC should have regular endoscopic assessment. In addition, those who complained of new onset symptoms, including nasal obstruction, persistent headache, blood-stained nasal discharge, facial numbness or cranial nerve palsies should have nasopharyngsocopy arranged immediately. Endoscopic diagnosis of early recurrent NPC is often challenging. Any suspicious area should be biopsied under local anaesthesia. Submucosal tumour invasion is not uncommon after radiotherapy, and deep biopsy is often necessary to confirm the diagnosis of tumour recurrence, and sometimes this has to be done under general anaesthesia. Some studies showed that narrow-band imaging (NBI) is potentially useful in such circumstances [8]. It may also guide the extent of resection during salvage nasopharyngectomy for recurrent NPC [9]. Imaging is mandatory to assess the loco-regional extent of the recurrent tumour before surgery is contemplated. It is also helpful in patients with high suspicion of tumour recurrence, and yet repeated nasopharyngeal biopsies are negative. MRI with intravenous contrast provides a better tissue definition than CT scan, which is crucial for the assessment of perineural invasion, prevertebral fascial invasion, parapharyngeal extension and internal carotid artery (ICA) involvement, as well as retropharyngeal lymph node metastasis [10]. The presence of skull base erosion and dural involvement should be identified, and in particular, extension through the foramen rotundum, foramen ovale, foramen lacerum and invasion of the cavernous sinus. The presence of synchronous cervical nodal metastasis should also be noted. Nowadays, [18F]-FDG PET-CT scan allows better systemic staging and should be routinely performed in patients with advance-staged disease. In addition, it is also useful in the diagnosis of isolated retropharyngeal lymph node metastasis after radiotherapy, where imaging-guided biopsy is impossible due to its deepseated location in the parapharyngeal space. Circulating cell free Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) is useful as a molecular marker in the
Curr Oncol Rep (2015) 17:8
monitoring of response after treatment. Chan et al. studied 31 NPC patients, and at a median follow up of 33.7 months, 6 distant and 3 loco-regional failures were detected. Among them, plasma EBV DNA was found to be significantly elevated in 88.9 % of patients with treatment failure. In patients in remission, plasma EBV DNA remained undetectable [11]. In recurrent NPC, the preoperative plasma EBV DNA may predict the chance of resection with clear margins [12], which may help to stratify patients who may benefit from adjuvant treatment after surgery. It is important to note that, however, up to 15.6 % of patients with recurrent NPC have negative plasma EBV DNA before operation, despite the presence of histologically proven, Epstein-Barr virus-encoded RNA (EBER) positive, undifferentiated carcinoma in the nasopharynx. Therefore, a baseline measurement before surgery is important to identify such group of patients, as the molecular marker cannot be used to monitor the treatment response after surgery.
Surgical Options for Recurrent Nasopharyngeal Carcinoma Although small recurrent tumours in the nasopharynx can be treated by intracavitary [13] or interstitial [14] brachytherapy, majority of the recurrent tumours are managed by formal surgical resection. It is indicated when the disease cannot be managed by brachytherapy, either being too extensive or being located in an unfavourable position, such as the cartilage of the Eustachian tube, where the gold grains cannot be implanted securely. It is also indicated when the parapharyngeal space is invaded by the tumour, where en-bloc removal of the cancer with preservation of the internal carotid artery is crucial. The nasopharynx is located in a deep-seated location such that oncologic extirpation has been a technical challenge. The difficulty of surgical access was addressed by Wilson in 1950 [15]. Over the years, different approaches have been described allowing surgical resection of tumours involving this area. The superior, trans-skull base technique involved lifting and retracting the frontal lobe, allowing the resection of lesions at the clivus, nasopharynx to as low as the second cervical vertebra [16]. However, it may be associated with serious complications such as meningitis, leakage of cerebrospinal fluid, formation of encephalocele and the development of diabetes insipidus [17]. The lateral, infratemporal fossa approach, which was described in 1979 [18], allows resection of tumours involving the ipsilateral nasopharynx. However, exposure is not optimal for tumours involving the contralateral nasopharynx, and patients may develop potential complications such as conductive hearing loss and trigeminal nerve dysfunction. The inferior/transpalatal approach is particularly useful for tumours located in the posterior wall and the roof of the
Curr Oncol Rep (2015) 17:8
nasopharynx [19]. The application of such approach is limited in patients with trismus after previous radiotherapy. Furthermore, the exposure of the parapharyngeal space is limited. If necessary, a combined transcervical approach allows protection of the internal carotid artery and hence, a safer and more complete dissection of the parapharyngeal tumour. Currently, there are two surgical techniques commonly employed for the resection of cancer of the nasopharynx.
Maxillary Swing Nasopharyngectomy The nasopharynx and the anterior skull base are obscured from surgical approach by the maxillary antrum anteriorly. Although it has been reported that the whole maxilla can be removed to facilitate resection of tumours and subsequently reinserting it as a free bone graft [20], nevertheless, in patients with previous radiotherapy, wound healing may be suboptimal and the non-vascularized bone graft may be resorped. It is beneficial to preserve the blood supply to the maxillary antrum by maintaining its soft tissue attachment as an osteocutaneous flap [21]. The surgery involves a Weber Ferguson Longmire incision, osteotomies of the anterior wall, medial wall of the maxillary antrum and the lower portion of the zygomatic arch (Fig. 1). The pterygoid plates are separated from the maxillary tuberosity. The maxillary osteocutaneous unit can then be swung out whilst maintaining its blood supply from the branches of the external carotid artery. This approach provides a complete exposure of the ipsilateral nasopharynx down to the oropharynx inferiorly and the parapharyngeal space postero-laterally. With the removal of the posterior part of the nasal septum, the contralateral nasopharynx can also be exposed. The major limitation of this approach is the access to the contralateral parapharyngeal space. Because of the wide exposure, recurrent cancer of the nasopharynx can be resected with wide margins. Safe resection of tumours invading the parapharyngeal space and those with retropharyngeal lymph Fig. 1 (Left) Patient with recurrent nasopharyngeal carcinoma involving the left nasopharynx. Left maxillary swing nasopharyngectomy was performed via the left Weber Ferguson Longmire incision. (Right) After the osteotomies, the maxillary osteocutaneous unit (MS) was swung out to expose the tumour (T) in the ipsilateral nasopharynx
Page 3 of 6 8
node metastasis can also be performed [22•]. In such circumstances, it is important to resect the tumours en-bloc with the pharyngobasilar fascia to ensure microscopic tumour clearance on the surface of the ICA. The artery can be easily identified and safe-guarded by palpation, intraoperative ultrasound or CT navigation. The exposed artery must then be covered and protected by healthy tissue in order to avoid subsequent blow-out bleeding. Regional flap, such as the temporalis muscle flap, or microvascular free flap, is frequently employed. Upon the completion of surgery, the maxillary osteocutaneous unit was returned into position and the osteotomy sites were fixed with titanium mini plates and screws. A pre-fabricated dental obturator was fitted to ensure accurate dental positioning. Tracheostomy was performed for airway protection, and nasogastric tube was inserted for feeding during the early postoperative period. Between 1989 and 2011, we have performed salvage nasopharyngectomy for 312 patients with recurrent NPC using the maxillary swing approach [3]. Majority (94.6 %) of the tumours were undifferentiated carcinomas that were EpsteinBarr virus-encoded RNA (EBER) positive. The median time for recurrence was 22 months. During surgery, macroscopic tumour clearance was achieved in all patients. Microscopically clear resection margins were achieved in 79.5 % of the subjects. All patients survived the operation, and the mean hospital stay was 12 days. After a median follow up of 54 months, the overall 5-year overall survival was 81 % for rT1 tumours, 68 % for rT2 tumours, 48 % for rT3 tumours and 33 % for rT4 disease. On multivariate analysis, tumour size, resection margin status and gross tumour in the sphenoid sinus were independent prognostic factors for local tumour control. For overall survival, resection margin status, synchronous nodal recurrence and cavernous sinus invasion had a negative influence [23••]. With improving experience, larger tumour can be resected with oncologically satisfactory results. For tumours with encasement of the ICA, erosion of the skull base around the carotid canal, or intracranial extension, the tumour can be removed in staged operations. In the first stage surgery, the
8
Page 4 of 6
Curr Oncol Rep (2015) 17:8
Fig. 2 (Upper, left) Patient with tumour recurrence (arrow) over the left nasopharynx, involving the posterior wall with no parapharyngeal invasion. (Upper, right) The tumour was accessed via the transoral robotic approach. (Lower, left) After the palate was splitted longitudinally, the tumour (arrow) was exposed. (Lower, right) The tumour was manipulated with a 5-mm Maryland grasping forceps mounted to left robotic arm and resected with an 8-mm scissors with monopolar diathermy mounted to the right robotic arm
cerebral perfusion is secured using a high-flow, extra-cranial intracranial bypass vascular graft. This is followed by the second stage operation, when the tumour is resected en-bloc, including the petrosal ICA, sphenoid sinus, carotid canal and the cavernous sinus, if necessary, via a combined cranio-facial approach. The resultant defects are usually reconstructed by microvascular free flaps. With such an extended approach, 81.8 % of curative resection rate can be achieved in our reported series of 22 patients [22•]. None of the patients had neurovascular complications after surgery. Except for one patient who was found to have local recurrence and systemic metastasis within 6 months after surgery, the rest of the patients remained disease free to date. The rate of local recurrence after salvage nasopharyngectomy is 13.1 % [24], and the risk of which is significantly higher in patients with positive resection margins at the previous nasopharyngectomy (39.6 vs. 6.9 %, p=0.006). Among them, 63.6 % are amenable for further surgery. The most common reason for inoperability is significant intracranial extension with dural involvement, paraspinal infiltration and the presence of systemic metastases. The most common side effects of surgery included palatal fistula (3.7 %), trismus (9.2 %) and facial numbness (7.4 %) [25]. A longitudinal study using self-reported, health-related quality of life (QOL) questionnaires showed that there was no significant change in the mean global health system scores after surgery [26]. Five functioning domains, including physical, role, emotion, cognitive and social functions, were satisfactory
after surgery, apart from social functioning, which scored slightly lower than the others. The presence of postoperative complications, including palatal fistula and osteoradionecrosis, significantly affects the QOL after surgery. In view of this, a modification of the palatal incision is now adopted [27]. By using a curvilinear incision over the ipsilateral side of the palate, the mucosal incision is no longer overlapping with the osteotomy site, thereby effectively reducing the rate of palatal fistula from 24 to 3.7 %. The presence of osteoradionecrosis (ORN) is associated with significantly more pain, more consumption of analgesics and poorer social contact. To prevent this complication, coverage of the raw bone with well-vascularized flap is mandatory. Small area of exposed bone can be resurfaced by the use of the posteriorly pedicled middle turbinate mucoperiosteal flap [28] or nasal septal mucosal flap [29]. For wide area of raw bone at the clivus and the cervical spine, especially those with exposed ICA, microvascular free flap remains the best option for coverage of all these areas. In general, the QOL is acceptable after salvage nasopharyngectomy using the maxillary swing approach. Attention must be paid to achieve curative resection and to avoid complications, such as palatal fistula and ORN after surgery.
Minimally Invasive Nasopharyngectomy Over the years, with advances in the visualization, instrumentation and technology, surgeons have extended their practice
Curr Oncol Rep (2015) 17:8
from endoscopic sinus surgery to removing tumours of the nasopharynx. After the first report of trans-septal endoscopic nasopharyngectomy by Yoshizaki et al. [30], modification of the techniques are described to improve the exposure for resection, including removing the inferior turbinate [31]. Adequate resection of small tumour located in the posterior wall of the nasopharynx can be achieved with the endoscope approach, and the oncological result has been encouraging. The major advantage of the endoscopic approach is the ability to resect the tumour without an external scar. Furthermore, visualization of the tumour is improved via endoscopic magnification. Resection of tumour is made easier using electric knife with an adjustable angle of knifepoint [32] or laser [33]. However, free manipulation of the instruments within the limited working space in the nasopharynx is difficult, making enbloc resection of larger tumours, especially those located on the lateral wall of the nasopharynx, impossible. The application of transoral robotic surgery (TORS) has received much attention in head and neck surgery, particularly for pathology in the oropharynx [34], supraglottic larynx [35] and upper hypopharynx [36]. Its use in salvage nasopharyngectomy for recurrent NPC has also been described [37]. Access to the nasopharynx is facilitated by a longitudinal split of the soft palate (Fig. 2). The tumour is visualized using a 0° 8-mm dual channel camera introduced transorally, and it is manipulated with a 5-mm Maryland grasping forceps mounted to the left robotic arm and resected with an 8-mm scissors with monopolar diathermy mounted to the right robotic arm. The major advantages of TORS nasopharyngectomy are the outstanding visualization of the tumour with the three-dimensional camera, and the superb manoeuverability of the Endowrist design, which is especially important for working in deep and small area like the nasopharynx. A combined transnasal endoscopic and transoral robotic-assisted approach can be employed when the sphenoid bone has to be removed due to tumour involvement [38]. The major drawback of the TORS nasopharyngectomy is the lack of tactile sensation of open surgery. This is crucial during extensive resection of tumours invading the parapharyngeal space, where the ICA can be inadvertently injured during the process. Currently, the procedure is limited to the resection of small recurrent tumours with minimal parapharyngeal invasion.
Page 5 of 6 8
also be combined with the cranial approach for resecting cancers with skull base erosion and intracranial extension. Every effort should be made to ensure microscopic clearance of tumour as well as to minimize the potential complications that will adversely affect the quality of life after surgery. Compliance with Ethics Guidelines Conflict of Interest Jimmy Yu Wai Chan has received an Area of Excellence Research Grant. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.
2.
3.
4.
5.
6.
7.
8.
Conclusion Surgical salvage for recurrent NPC is effective with acceptable morbidity. Small and centrally located tumours can be removed using the endoscopic or the transoral roboticassisted approach. For tumours with parapharyngeal extension, the maxillary swing approach provides a wide exposure, allowing tumours to be resected with adequate margins. It can
9.
10.
11.
Luo J, Chia KS, Chia SE, et al. Secular trends of nasopharyngeal carcinoma incidence in Singapore, Hong Kong and Los Angeles Chinese population, 1973–1997. Eur J Epidemiol. 2007;22:513– 21. Lin JC, Jan JS, Hsu CY, et al. Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. J Clin Oncol. 2003;21:631–7. Chan JY, Wei WI. Critical appraisal of maxillary swing approach for nasopharyngeal carcinoma. Expert Opin Ther Targets. 2012;16 Suppl 1:S111–7. Yu KH, Leung SF, Tung SY, Zee B, Chua DT, Sze WM, 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(5):397–405. Fee Jr W, Moir M, Choi EC, et al. Nasopharyngectomy for recurrent nasopharyngeal cancer: a 2- to 17-year follow-up. Arch Otolaryngol Head Neck Surg. 2002;128:280–4. Wu SX, Chua DT, Deng ML, et al. Outcome of fractionated stereostatic radiotherapy for 90 patients with locally persistent and recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2007;69:761–9. Leung TW, Tung SY, Sze WK, Sze WM, Wong VY, Wong CS, et al. Salvage radiation therapy for locally recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2000;48:1331–8. Lin YC, Wang WH. Narrow-band imaging for detecting early recurrent nasopharyngeal carcinoma. Head Neck. 2011;33(4):591–4. Wang WH, Lin YC, Chen WC, Chen MF, Chen CC, Lee KF. Detection of mucosal recurrent nasopharyngeal carcinomas after radiotherapy with narrow-band imaging endoscopy. Int J Radiat Oncol Biol Phys. 2012;83(4):1213–9. King AD, Bhatia KS. Magnetic resonance imaging staging of nasopharyngeal carcinoma in the head and neck. World J Radiol. 2010;2(5):159–65. Chan AT, Ma BB, Lo YM, et al. Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal
8
Curr Oncol Rep (2015) 17:8
Page 6 of 6
carcinoma: therapeutic monitoring with plasma Epstein-Barr virus DNA. J Clin Oncol. 2004;22:3053–60. 12. Chan JY, Chow VL, Mok VW, Ho AC, Wei WI. Prediction of surgical outcome using plasma Epstein-Barr virus DNA and 18FFDG PET-CT scan in recurrent nasopharyngeal carcinoma. Head Neck. 2012;34(4):541–5. 13. Wang CC, Busse J, Gitterman M. A simple afterloading applicator for intracavitary irradiation of carcinoma of the nasopharynx. Radiology. 1975;115(3):737–8. 14. Harrison LB, Weissberg JB. A technique for interstitial nasopharyngeal brachytherapy. Int J Radiat Oncol Biol Phys. 1987;13(3): 451–3. 15. Wilson CP. The approach to the nasopharynx. Proc R Soc Med. 1951;44:353–8. 16. Derome PJ. The transbasal approach to tumours invading the base of the skull. In: Schmidek HH, Sweet WH, editors. Operative neurosurgical techniques, vol. I. New York: Grune and Stratton; 1982. p. 357–9. 17. Van Buren JM, Ommaya AK, Ketcham AS. Ten years’ experience with radical combined craniofacial resection of malignant tumors of the paranasal sinuses. J Neurosurg. 1968;28:341–50. 18. Fish U. The infratemporal fossa approach for nasopharyngeal tumors. Laryngoscope. 1983;93(1):36–44. 19. Morton RP, Liavaag PG, McLean M, Freeman JL. Transcervicomandibulo-palatal approach for surgical salvage of recurrent nasopharyngeal carcinoma. Head Neck. 1996;18(4):352–8. 20. Schuller DE, Goodman JH, Brown BL, Frank JE, Ervin-Miller KJ. Maxillary removal and reinsertion for improved access to anterior cranial base tumors. Laryngoscope. 1992;102:203–12. 21. Wei WI, Lam KH, Shan JS. New approach to the nasopharynx: the maxillary swing approach. Head Neck. 1991;13(3):200–7. 22.• Chan JY, Chow VLY, Tsang RKY, Wei WI. Nasopharyngectomy for locally advanced recurrent nasopharyngeal carcinoma: exploring the limits. Head Neck. 2012;34(7):923–8. The article describes the need for resecting the advanced tumour en-bloc with the fascia on the surface of the internal carotid artery in order to achieve a clear margin. Traditionally these cancers are associated with a poor local control after surgery because of the inadequate resection. 23.•• Chan JY, To VS, Chow VL, Wong ST, Wei WI. Multivariate analysis of prognostic factors for salvage nasopharyngectomy via the maxillary swing approach. Head Neck. 2014;36(7):1013–7. The article reports on the prognostic factors for salvage nasopharyngectomy for recurrent NPC. Distant failure is the major limit in outcome after surgery for recurrent T4 tumours in the nasopharynx.
24.
Chan JY, Wei WI. Recurrent nasopharyngeal carcinoma after salvage nasopharyngectomy. Arch Otolaryngol Head Neck Surg. 2012;138(6):572–6. 25. Chan JY, Tsang RK, Wei WI. Morbidities after maxillary swing nasopharyngectomy for recurrent nasopharyngeal carcinoma. Head Neck. 2014. doi:10.1002/hed.23633. 26. Chan JY, Chow VL, Wei WI. Quality of life of patients after salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma. Cancer. 2012;118(15):3710–8. 27. Ng RW, Wei WI. Elimination of palatal fistula after maxillary swing procedure. Head Neck. 2005;27:608–12. 28. Chen MY, Hua YJ, Wan XB, et al. A posteriorly pedicled middle turbinate mucoperiosteal flap resurfacing nasopharynx after endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma. Otolaryngol Head Neck Surg. 2012;146(3):409–11. 29. Chen MY, Wang SL, Zhu YL, et al. Use of a posterior pedicle nasal septum and floor mucoperiosteum flap to resurface the nasopharynx after endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma. Head Neck. 2012;34(10):1383–8. 30. Yoshizaki T, Wakisaka N, Nurono S, Shimizu Y, Furukawa M. Endoscopic nasopharyngectomy for patients with recurrent nasopharyngeal carcinoma at the primary site. Laryngoscope. 2005;115: 1517–9. 31. Chen MK, Lai JC, Chang CC, Liu MT. Minimally invasive endoscopic nasopharyngectomy in the treatment of recurrent T1-2a nasopharyngeal carcinoma. Laryngoscope. 2007;117:894–6. 32. Chen MY, Wen WP, Guo X, et al. Endoscopic nasopharyngectomy for locally recurrent nasopharyngeal carcinoma. Laryngoscope. 2009;119:516–22. 33. Ko JY, Wang CP, Ting LL, Yang TL, Tan CT. Endoscopic nasopharyngectomy with potassium-titanyl-phosphate (KTP) laser for early locally recurrent nasopharyngeal carcinoma. Head Neck. 2009;331(10):1309–15. 34. Wrinstein GS, O’Malley Jr BW, Snyder W, Sherman E, Quon H. Transoral robotic surgery: radical tonsillectomy. Arch Otolaryngol Head Neck Surg. 2007;133:1220–6. 35. Weinstein GS, O’Malley Jr BW, Snyder W, Hockstein NG. Transoral robotic surgery: supraglottic partial laryngectomy. Ann Otol Rhinol Laryngol. 2007;116:19–23. 36. Park YM, Lee WJ, Lee JG, et al. Transoral robotic surgery (TORS) in laryngeal and hypopharyngeal cancer. J Laparoendosc Adv Surg Tech A. 2009;69:S125–8. 37. Wei WI, Ho WK. Transoral robotic resection of recurrent nasopharyngeal carcinoma. Laryngoscope. 2010;120:2011–4. 38. Tsang RK, Ho WK, Wei WI. Combined transnasal endoscopic and transoral robotic resection of recurrent nasopharyngeal carcinoma. Head Neck. 2012;34:1190–3.
HEAD AND NECK CANCERS (E HANNA, SECTION EDITOR)
Surgical Salvage of Recurrent Nasopharyngeal Carcinoma Jimmy Yu Wai Chan
# Springer Science+Business Media New York 2015
Abstract Nasopharyngeal carcinoma is a unique tumour which is endemic in southern China including Hong Kong. Whilst the treatment results for the primary cancer has been encouraging, management of recurrent tumours has been challenging. Compared to other surgical approaches, the maxillary swing operation provides wide access to the bilateral nasopharynx and the ipsilateral parapharyngeal space, allowing resection of tumours with adequate margins. Among the 312 patients who had received salvage nasopharyngectomy via the maxillary swing approach, the chance of achieving microscopically clear resection margins was 79.5 %. The overall local recurrence rate after surgery was 13.1 %. Multivariate analysis showed that resection margin status, synchronous nodal recurrence and cavernous sinus invasion were independent prognostic factors for overall survival. For small tumours located in the posterior wall, endoscopic resection, or more recently, the transoral robotic (TORS)-assisted approach, can be performed. Every effort should be made to ensure microscopic clearance of disease as well as to minimize the potential complications of surgery that may adversely affect the subsequent quality of life.
Keywords Recurrent . Nasopharyngeal carcinoma . Nasopharyngectomy . Maxillary swing . Transoral robotic surgery (TORS)
This article is part of the Topical Collection on Head and Neck Cancers J. Y. W. Chan (*) Division of Head and Neck Surgery, Department of Surgery, University of Hong Kong Li Ka Shing Faculty of Medicine, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, SAR, China e-mail: [email protected]
Introduction Nasopharyngeal carcinoma (NPC) is unique among other squamous cell carcinoma of the head and neck regions in its epidemiology, pathology and treatment outcome. It is endemic in southern China, including Hong Kong, affecting 10 to 50 per 100,000 populations per year [1]. According to the Hong Kong Cancer Registry in 2011, NPC ranked seventh in cancer incidence and cancer-related mortality for both genders. More than 95 % of the tumour pathology is undifferentiated, nonkeratinizing carcinoma associated with Epstein-Barr virus (EBV) infection. It is a radiosensitive tumour, making radiotherapy the core treatment of the disease. For advance-staged tumours, studies showed that concurrent chemoradiation confers significant survival benefit [2]. Surgery is reserved for persistent or recurrent tumours after the initial therapy [3]. The local recurrence rate after initial radiotherapy for NPC is approximately 10 % [4]. Management of recurrent NPC has been challenging. Accurate assessment of the extent of the recurrent tumour in the nasopharynx is not easy. Furthermore, re-irradiating the same field may be associated with potentially serious side effects and complications. Surgical salvage is hampered by the anatomical difficulties and the effects of previous radiotherapy. As a result, the choice of therapy for such patients often depends on the availability of expertise in the institute, rather than the reference to the objective comparisons of the outcome of both treatment modalities. Some studies showed that surgery potentially offers better local tumour control and survival [5] as well as less posttreatment morbidities than re-irradiation [6], which may be associated with a risk of major complications as high as 57 % [7]. These include multiple cranial nerve palsies, which lead to dysphagia and aspiration, and hence malnutrition and recurrent pneumonia. Osteoradionecrosis, which is often severe and extensive, is often debilitating and sometimes life-threatening. Internal carotid blow-out is not an infrequent cause of
8
Page 2 of 6
death in these patients, and other complications, such as radiation myelitis, can cause peripheral weakness of limbs, severe hearing loss, and visual impairment. Radiation-induced squamous cell carcinoma and sarcoma, although uncommon, pose a major threat to the long survivors after radiation therapy for NPC. Surgical access to the nasopharynx, however, is not without difficulties. The nasopharynx is deep seated in the central part of the skull. It is obscured by bony structures in all directions, including the cranium, maxilla, palate, mandible and the cervical spine. Over the years, various approaches to the nasopharynx have been described.
Preoperative Assessment Patients after radiotherapy for NPC should have regular endoscopic assessment. In addition, those who complained of new onset symptoms, including nasal obstruction, persistent headache, blood-stained nasal discharge, facial numbness or cranial nerve palsies should have nasopharyngsocopy arranged immediately. Endoscopic diagnosis of early recurrent NPC is often challenging. Any suspicious area should be biopsied under local anaesthesia. Submucosal tumour invasion is not uncommon after radiotherapy, and deep biopsy is often necessary to confirm the diagnosis of tumour recurrence, and sometimes this has to be done under general anaesthesia. Some studies showed that narrow-band imaging (NBI) is potentially useful in such circumstances [8]. It may also guide the extent of resection during salvage nasopharyngectomy for recurrent NPC [9]. Imaging is mandatory to assess the loco-regional extent of the recurrent tumour before surgery is contemplated. It is also helpful in patients with high suspicion of tumour recurrence, and yet repeated nasopharyngeal biopsies are negative. MRI with intravenous contrast provides a better tissue definition than CT scan, which is crucial for the assessment of perineural invasion, prevertebral fascial invasion, parapharyngeal extension and internal carotid artery (ICA) involvement, as well as retropharyngeal lymph node metastasis [10]. The presence of skull base erosion and dural involvement should be identified, and in particular, extension through the foramen rotundum, foramen ovale, foramen lacerum and invasion of the cavernous sinus. The presence of synchronous cervical nodal metastasis should also be noted. Nowadays, [18F]-FDG PET-CT scan allows better systemic staging and should be routinely performed in patients with advance-staged disease. In addition, it is also useful in the diagnosis of isolated retropharyngeal lymph node metastasis after radiotherapy, where imaging-guided biopsy is impossible due to its deepseated location in the parapharyngeal space. Circulating cell free Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) is useful as a molecular marker in the
Curr Oncol Rep (2015) 17:8
monitoring of response after treatment. Chan et al. studied 31 NPC patients, and at a median follow up of 33.7 months, 6 distant and 3 loco-regional failures were detected. Among them, plasma EBV DNA was found to be significantly elevated in 88.9 % of patients with treatment failure. In patients in remission, plasma EBV DNA remained undetectable [11]. In recurrent NPC, the preoperative plasma EBV DNA may predict the chance of resection with clear margins [12], which may help to stratify patients who may benefit from adjuvant treatment after surgery. It is important to note that, however, up to 15.6 % of patients with recurrent NPC have negative plasma EBV DNA before operation, despite the presence of histologically proven, Epstein-Barr virus-encoded RNA (EBER) positive, undifferentiated carcinoma in the nasopharynx. Therefore, a baseline measurement before surgery is important to identify such group of patients, as the molecular marker cannot be used to monitor the treatment response after surgery.
Surgical Options for Recurrent Nasopharyngeal Carcinoma Although small recurrent tumours in the nasopharynx can be treated by intracavitary [13] or interstitial [14] brachytherapy, majority of the recurrent tumours are managed by formal surgical resection. It is indicated when the disease cannot be managed by brachytherapy, either being too extensive or being located in an unfavourable position, such as the cartilage of the Eustachian tube, where the gold grains cannot be implanted securely. It is also indicated when the parapharyngeal space is invaded by the tumour, where en-bloc removal of the cancer with preservation of the internal carotid artery is crucial. The nasopharynx is located in a deep-seated location such that oncologic extirpation has been a technical challenge. The difficulty of surgical access was addressed by Wilson in 1950 [15]. Over the years, different approaches have been described allowing surgical resection of tumours involving this area. The superior, trans-skull base technique involved lifting and retracting the frontal lobe, allowing the resection of lesions at the clivus, nasopharynx to as low as the second cervical vertebra [16]. However, it may be associated with serious complications such as meningitis, leakage of cerebrospinal fluid, formation of encephalocele and the development of diabetes insipidus [17]. The lateral, infratemporal fossa approach, which was described in 1979 [18], allows resection of tumours involving the ipsilateral nasopharynx. However, exposure is not optimal for tumours involving the contralateral nasopharynx, and patients may develop potential complications such as conductive hearing loss and trigeminal nerve dysfunction. The inferior/transpalatal approach is particularly useful for tumours located in the posterior wall and the roof of the
Curr Oncol Rep (2015) 17:8
nasopharynx [19]. The application of such approach is limited in patients with trismus after previous radiotherapy. Furthermore, the exposure of the parapharyngeal space is limited. If necessary, a combined transcervical approach allows protection of the internal carotid artery and hence, a safer and more complete dissection of the parapharyngeal tumour. Currently, there are two surgical techniques commonly employed for the resection of cancer of the nasopharynx.
Maxillary Swing Nasopharyngectomy The nasopharynx and the anterior skull base are obscured from surgical approach by the maxillary antrum anteriorly. Although it has been reported that the whole maxilla can be removed to facilitate resection of tumours and subsequently reinserting it as a free bone graft [20], nevertheless, in patients with previous radiotherapy, wound healing may be suboptimal and the non-vascularized bone graft may be resorped. It is beneficial to preserve the blood supply to the maxillary antrum by maintaining its soft tissue attachment as an osteocutaneous flap [21]. The surgery involves a Weber Ferguson Longmire incision, osteotomies of the anterior wall, medial wall of the maxillary antrum and the lower portion of the zygomatic arch (Fig. 1). The pterygoid plates are separated from the maxillary tuberosity. The maxillary osteocutaneous unit can then be swung out whilst maintaining its blood supply from the branches of the external carotid artery. This approach provides a complete exposure of the ipsilateral nasopharynx down to the oropharynx inferiorly and the parapharyngeal space postero-laterally. With the removal of the posterior part of the nasal septum, the contralateral nasopharynx can also be exposed. The major limitation of this approach is the access to the contralateral parapharyngeal space. Because of the wide exposure, recurrent cancer of the nasopharynx can be resected with wide margins. Safe resection of tumours invading the parapharyngeal space and those with retropharyngeal lymph Fig. 1 (Left) Patient with recurrent nasopharyngeal carcinoma involving the left nasopharynx. Left maxillary swing nasopharyngectomy was performed via the left Weber Ferguson Longmire incision. (Right) After the osteotomies, the maxillary osteocutaneous unit (MS) was swung out to expose the tumour (T) in the ipsilateral nasopharynx
Page 3 of 6 8
node metastasis can also be performed [22•]. In such circumstances, it is important to resect the tumours en-bloc with the pharyngobasilar fascia to ensure microscopic tumour clearance on the surface of the ICA. The artery can be easily identified and safe-guarded by palpation, intraoperative ultrasound or CT navigation. The exposed artery must then be covered and protected by healthy tissue in order to avoid subsequent blow-out bleeding. Regional flap, such as the temporalis muscle flap, or microvascular free flap, is frequently employed. Upon the completion of surgery, the maxillary osteocutaneous unit was returned into position and the osteotomy sites were fixed with titanium mini plates and screws. A pre-fabricated dental obturator was fitted to ensure accurate dental positioning. Tracheostomy was performed for airway protection, and nasogastric tube was inserted for feeding during the early postoperative period. Between 1989 and 2011, we have performed salvage nasopharyngectomy for 312 patients with recurrent NPC using the maxillary swing approach [3]. Majority (94.6 %) of the tumours were undifferentiated carcinomas that were EpsteinBarr virus-encoded RNA (EBER) positive. The median time for recurrence was 22 months. During surgery, macroscopic tumour clearance was achieved in all patients. Microscopically clear resection margins were achieved in 79.5 % of the subjects. All patients survived the operation, and the mean hospital stay was 12 days. After a median follow up of 54 months, the overall 5-year overall survival was 81 % for rT1 tumours, 68 % for rT2 tumours, 48 % for rT3 tumours and 33 % for rT4 disease. On multivariate analysis, tumour size, resection margin status and gross tumour in the sphenoid sinus were independent prognostic factors for local tumour control. For overall survival, resection margin status, synchronous nodal recurrence and cavernous sinus invasion had a negative influence [23••]. With improving experience, larger tumour can be resected with oncologically satisfactory results. For tumours with encasement of the ICA, erosion of the skull base around the carotid canal, or intracranial extension, the tumour can be removed in staged operations. In the first stage surgery, the
8
Page 4 of 6
Curr Oncol Rep (2015) 17:8
Fig. 2 (Upper, left) Patient with tumour recurrence (arrow) over the left nasopharynx, involving the posterior wall with no parapharyngeal invasion. (Upper, right) The tumour was accessed via the transoral robotic approach. (Lower, left) After the palate was splitted longitudinally, the tumour (arrow) was exposed. (Lower, right) The tumour was manipulated with a 5-mm Maryland grasping forceps mounted to left robotic arm and resected with an 8-mm scissors with monopolar diathermy mounted to the right robotic arm
cerebral perfusion is secured using a high-flow, extra-cranial intracranial bypass vascular graft. This is followed by the second stage operation, when the tumour is resected en-bloc, including the petrosal ICA, sphenoid sinus, carotid canal and the cavernous sinus, if necessary, via a combined cranio-facial approach. The resultant defects are usually reconstructed by microvascular free flaps. With such an extended approach, 81.8 % of curative resection rate can be achieved in our reported series of 22 patients [22•]. None of the patients had neurovascular complications after surgery. Except for one patient who was found to have local recurrence and systemic metastasis within 6 months after surgery, the rest of the patients remained disease free to date. The rate of local recurrence after salvage nasopharyngectomy is 13.1 % [24], and the risk of which is significantly higher in patients with positive resection margins at the previous nasopharyngectomy (39.6 vs. 6.9 %, p=0.006). Among them, 63.6 % are amenable for further surgery. The most common reason for inoperability is significant intracranial extension with dural involvement, paraspinal infiltration and the presence of systemic metastases. The most common side effects of surgery included palatal fistula (3.7 %), trismus (9.2 %) and facial numbness (7.4 %) [25]. A longitudinal study using self-reported, health-related quality of life (QOL) questionnaires showed that there was no significant change in the mean global health system scores after surgery [26]. Five functioning domains, including physical, role, emotion, cognitive and social functions, were satisfactory
after surgery, apart from social functioning, which scored slightly lower than the others. The presence of postoperative complications, including palatal fistula and osteoradionecrosis, significantly affects the QOL after surgery. In view of this, a modification of the palatal incision is now adopted [27]. By using a curvilinear incision over the ipsilateral side of the palate, the mucosal incision is no longer overlapping with the osteotomy site, thereby effectively reducing the rate of palatal fistula from 24 to 3.7 %. The presence of osteoradionecrosis (ORN) is associated with significantly more pain, more consumption of analgesics and poorer social contact. To prevent this complication, coverage of the raw bone with well-vascularized flap is mandatory. Small area of exposed bone can be resurfaced by the use of the posteriorly pedicled middle turbinate mucoperiosteal flap [28] or nasal septal mucosal flap [29]. For wide area of raw bone at the clivus and the cervical spine, especially those with exposed ICA, microvascular free flap remains the best option for coverage of all these areas. In general, the QOL is acceptable after salvage nasopharyngectomy using the maxillary swing approach. Attention must be paid to achieve curative resection and to avoid complications, such as palatal fistula and ORN after surgery.
Minimally Invasive Nasopharyngectomy Over the years, with advances in the visualization, instrumentation and technology, surgeons have extended their practice
Curr Oncol Rep (2015) 17:8
from endoscopic sinus surgery to removing tumours of the nasopharynx. After the first report of trans-septal endoscopic nasopharyngectomy by Yoshizaki et al. [30], modification of the techniques are described to improve the exposure for resection, including removing the inferior turbinate [31]. Adequate resection of small tumour located in the posterior wall of the nasopharynx can be achieved with the endoscope approach, and the oncological result has been encouraging. The major advantage of the endoscopic approach is the ability to resect the tumour without an external scar. Furthermore, visualization of the tumour is improved via endoscopic magnification. Resection of tumour is made easier using electric knife with an adjustable angle of knifepoint [32] or laser [33]. However, free manipulation of the instruments within the limited working space in the nasopharynx is difficult, making enbloc resection of larger tumours, especially those located on the lateral wall of the nasopharynx, impossible. The application of transoral robotic surgery (TORS) has received much attention in head and neck surgery, particularly for pathology in the oropharynx [34], supraglottic larynx [35] and upper hypopharynx [36]. Its use in salvage nasopharyngectomy for recurrent NPC has also been described [37]. Access to the nasopharynx is facilitated by a longitudinal split of the soft palate (Fig. 2). The tumour is visualized using a 0° 8-mm dual channel camera introduced transorally, and it is manipulated with a 5-mm Maryland grasping forceps mounted to the left robotic arm and resected with an 8-mm scissors with monopolar diathermy mounted to the right robotic arm. The major advantages of TORS nasopharyngectomy are the outstanding visualization of the tumour with the three-dimensional camera, and the superb manoeuverability of the Endowrist design, which is especially important for working in deep and small area like the nasopharynx. A combined transnasal endoscopic and transoral robotic-assisted approach can be employed when the sphenoid bone has to be removed due to tumour involvement [38]. The major drawback of the TORS nasopharyngectomy is the lack of tactile sensation of open surgery. This is crucial during extensive resection of tumours invading the parapharyngeal space, where the ICA can be inadvertently injured during the process. Currently, the procedure is limited to the resection of small recurrent tumours with minimal parapharyngeal invasion.
Page 5 of 6 8
also be combined with the cranial approach for resecting cancers with skull base erosion and intracranial extension. Every effort should be made to ensure microscopic clearance of tumour as well as to minimize the potential complications that will adversely affect the quality of life after surgery. Compliance with Ethics Guidelines Conflict of Interest Jimmy Yu Wai Chan has received an Area of Excellence Research Grant. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.
2.
3.
4.
5.
6.
7.
8.
Conclusion Surgical salvage for recurrent NPC is effective with acceptable morbidity. Small and centrally located tumours can be removed using the endoscopic or the transoral roboticassisted approach. For tumours with parapharyngeal extension, the maxillary swing approach provides a wide exposure, allowing tumours to be resected with adequate margins. It can
9.
10.
11.
Luo J, Chia KS, Chia SE, et al. Secular trends of nasopharyngeal carcinoma incidence in Singapore, Hong Kong and Los Angeles Chinese population, 1973–1997. Eur J Epidemiol. 2007;22:513– 21. Lin JC, Jan JS, Hsu CY, et al. Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. J Clin Oncol. 2003;21:631–7. Chan JY, Wei WI. Critical appraisal of maxillary swing approach for nasopharyngeal carcinoma. Expert Opin Ther Targets. 2012;16 Suppl 1:S111–7. Yu KH, Leung SF, Tung SY, Zee B, Chua DT, Sze WM, 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(5):397–405. Fee Jr W, Moir M, Choi EC, et al. Nasopharyngectomy for recurrent nasopharyngeal cancer: a 2- to 17-year follow-up. Arch Otolaryngol Head Neck Surg. 2002;128:280–4. Wu SX, Chua DT, Deng ML, et al. Outcome of fractionated stereostatic radiotherapy for 90 patients with locally persistent and recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2007;69:761–9. Leung TW, Tung SY, Sze WK, Sze WM, Wong VY, Wong CS, et al. Salvage radiation therapy for locally recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2000;48:1331–8. Lin YC, Wang WH. Narrow-band imaging for detecting early recurrent nasopharyngeal carcinoma. Head Neck. 2011;33(4):591–4. Wang WH, Lin YC, Chen WC, Chen MF, Chen CC, Lee KF. Detection of mucosal recurrent nasopharyngeal carcinomas after radiotherapy with narrow-band imaging endoscopy. Int J Radiat Oncol Biol Phys. 2012;83(4):1213–9. King AD, Bhatia KS. Magnetic resonance imaging staging of nasopharyngeal carcinoma in the head and neck. World J Radiol. 2010;2(5):159–65. Chan AT, Ma BB, Lo YM, et al. Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal
8
Curr Oncol Rep (2015) 17:8
Page 6 of 6
carcinoma: therapeutic monitoring with plasma Epstein-Barr virus DNA. J Clin Oncol. 2004;22:3053–60. 12. Chan JY, Chow VL, Mok VW, Ho AC, Wei WI. Prediction of surgical outcome using plasma Epstein-Barr virus DNA and 18FFDG PET-CT scan in recurrent nasopharyngeal carcinoma. Head Neck. 2012;34(4):541–5. 13. Wang CC, Busse J, Gitterman M. A simple afterloading applicator for intracavitary irradiation of carcinoma of the nasopharynx. Radiology. 1975;115(3):737–8. 14. Harrison LB, Weissberg JB. A technique for interstitial nasopharyngeal brachytherapy. Int J Radiat Oncol Biol Phys. 1987;13(3): 451–3. 15. Wilson CP. The approach to the nasopharynx. Proc R Soc Med. 1951;44:353–8. 16. Derome PJ. The transbasal approach to tumours invading the base of the skull. In: Schmidek HH, Sweet WH, editors. Operative neurosurgical techniques, vol. I. New York: Grune and Stratton; 1982. p. 357–9. 17. Van Buren JM, Ommaya AK, Ketcham AS. Ten years’ experience with radical combined craniofacial resection of malignant tumors of the paranasal sinuses. J Neurosurg. 1968;28:341–50. 18. Fish U. The infratemporal fossa approach for nasopharyngeal tumors. Laryngoscope. 1983;93(1):36–44. 19. Morton RP, Liavaag PG, McLean M, Freeman JL. Transcervicomandibulo-palatal approach for surgical salvage of recurrent nasopharyngeal carcinoma. Head Neck. 1996;18(4):352–8. 20. Schuller DE, Goodman JH, Brown BL, Frank JE, Ervin-Miller KJ. Maxillary removal and reinsertion for improved access to anterior cranial base tumors. Laryngoscope. 1992;102:203–12. 21. Wei WI, Lam KH, Shan JS. New approach to the nasopharynx: the maxillary swing approach. Head Neck. 1991;13(3):200–7. 22.• Chan JY, Chow VLY, Tsang RKY, Wei WI. Nasopharyngectomy for locally advanced recurrent nasopharyngeal carcinoma: exploring the limits. Head Neck. 2012;34(7):923–8. The article describes the need for resecting the advanced tumour en-bloc with the fascia on the surface of the internal carotid artery in order to achieve a clear margin. Traditionally these cancers are associated with a poor local control after surgery because of the inadequate resection. 23.•• Chan JY, To VS, Chow VL, Wong ST, Wei WI. Multivariate analysis of prognostic factors for salvage nasopharyngectomy via the maxillary swing approach. Head Neck. 2014;36(7):1013–7. The article reports on the prognostic factors for salvage nasopharyngectomy for recurrent NPC. Distant failure is the major limit in outcome after surgery for recurrent T4 tumours in the nasopharynx.
24.
Chan JY, Wei WI. Recurrent nasopharyngeal carcinoma after salvage nasopharyngectomy. Arch Otolaryngol Head Neck Surg. 2012;138(6):572–6. 25. Chan JY, Tsang RK, Wei WI. Morbidities after maxillary swing nasopharyngectomy for recurrent nasopharyngeal carcinoma. Head Neck. 2014. doi:10.1002/hed.23633. 26. Chan JY, Chow VL, Wei WI. Quality of life of patients after salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma. Cancer. 2012;118(15):3710–8. 27. Ng RW, Wei WI. Elimination of palatal fistula after maxillary swing procedure. Head Neck. 2005;27:608–12. 28. Chen MY, Hua YJ, Wan XB, et al. A posteriorly pedicled middle turbinate mucoperiosteal flap resurfacing nasopharynx after endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma. Otolaryngol Head Neck Surg. 2012;146(3):409–11. 29. Chen MY, Wang SL, Zhu YL, et al. Use of a posterior pedicle nasal septum and floor mucoperiosteum flap to resurface the nasopharynx after endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma. Head Neck. 2012;34(10):1383–8. 30. Yoshizaki T, Wakisaka N, Nurono S, Shimizu Y, Furukawa M. Endoscopic nasopharyngectomy for patients with recurrent nasopharyngeal carcinoma at the primary site. Laryngoscope. 2005;115: 1517–9. 31. Chen MK, Lai JC, Chang CC, Liu MT. Minimally invasive endoscopic nasopharyngectomy in the treatment of recurrent T1-2a nasopharyngeal carcinoma. Laryngoscope. 2007;117:894–6. 32. Chen MY, Wen WP, Guo X, et al. Endoscopic nasopharyngectomy for locally recurrent nasopharyngeal carcinoma. Laryngoscope. 2009;119:516–22. 33. Ko JY, Wang CP, Ting LL, Yang TL, Tan CT. Endoscopic nasopharyngectomy with potassium-titanyl-phosphate (KTP) laser for early locally recurrent nasopharyngeal carcinoma. Head Neck. 2009;331(10):1309–15. 34. Wrinstein GS, O’Malley Jr BW, Snyder W, Sherman E, Quon H. Transoral robotic surgery: radical tonsillectomy. Arch Otolaryngol Head Neck Surg. 2007;133:1220–6. 35. Weinstein GS, O’Malley Jr BW, Snyder W, Hockstein NG. Transoral robotic surgery: supraglottic partial laryngectomy. Ann Otol Rhinol Laryngol. 2007;116:19–23. 36. Park YM, Lee WJ, Lee JG, et al. Transoral robotic surgery (TORS) in laryngeal and hypopharyngeal cancer. J Laparoendosc Adv Surg Tech A. 2009;69:S125–8. 37. Wei WI, Ho WK. Transoral robotic resection of recurrent nasopharyngeal carcinoma. Laryngoscope. 2010;120:2011–4. 38. Tsang RK, Ho WK, Wei WI. Combined transnasal endoscopic and transoral robotic resection of recurrent nasopharyngeal carcinoma. Head Neck. 2012;34:1190–3.
