CASE REPORT
Radiotherapeutic Treatment of a Fighter Pilot with Nasopharyngeal Carcinoma Xian-Rong Xu, Bin-Ru Wang, Yang Zhang, and Zhan-Guo Jin XU X-R, WANG B-R, ZHANG Y, JIN Z-G. Radiotherapeutic treatment CASE REPORT of a fighter pilot with nasopharyngeal carcinoma. Aviat Space EnviThe patient was a 36-yr-old male fighter pilot with ron Med 2014; 85:1056–60. Background: Radiotherapy is the standard and most effective treat1800 h of flight time. In March 2011, he incidentally ment for nasopharyngeal carcinoma (NPC) in its early stages. However, found a painless mass in the left neck. He initially igits application in fighter pilots returning to flying duties with NPC has nored it. During that period, there was no blood in the not been previously reported, presumably due to post-radiotherapeutic nasal mucus and no ear tenderness, tinnitus, hearing complications. Case report: A 36-yr-old male fighter pilot had a painless mass in the left neck for 5 mo. Pathological diagnosis demonstrated loss, or vertigo. However, the mass continued to grow, nonkeratinizing squamous cell carcinoma in the left nasopharynx which so he was admitted to a local hospital at the end of had metastasized to lymph nodes in the left side of the neck. He was August 2011. Nonenhanced CT scan showed a nasophadiagnosed and staged with NPC (T1N2M0) before treatment with radioryngeal mass accompanied with cervical lymph node therapy and adjuvant chemotherapy. The patient suffered from catarrhal otitis media and xerostomia after 3 mo of radiotherapy, but these sympenlargement in the left nasopharynx (Fig. 1). Biopsy of toms resolved. After a total of 8 mo of radiotherapy, he was in remission the mass confirmed that he had NPC with lymph node with no evidence of tumor recurrence or metastasis. He had normal metastasis in the left side of the neck. Therefore, he was Eustachian tube, hearing, and vestibular function before and after hytransferred to our hospital in September 2011. Physical pobaric chamber testing and passed all flight-related physical examinations. Consequently, he was granted a medical waiver and returned examination found a palpable painless mass of approxito flying status in two-seat fighter aircraft, flying for 53 h in a 12-mo pemately 4 3 2 cm, medium to rigid texture, and unclear riod. After passing all flight-related tests again, he was then allowed to boundary at the deep left sternocleidomastoid muscle. fly in single-seat aircraft. At the time of submission of this article, he Nasopharyngeal endoscopy revealed the following: 1) has flown for 147 h and remained on flying status for 26 mo. He will be monitored annually for long-term effects of radiotherapy and/or disthe left Eustachian tubal torus was plumper than the ease recurrence. Conclusions: Fighter pilots with NPC may be safely right one; 2) the left pharyngeal recess was shallower considered for medical waiver with appropriate monitoring after sucthan the right one; 3) a mucosal biopsy-caused white ulcessful treatment. Delivered by Ingenta to: Cornell University Library and 4) no erosion, hemorrhage, or neKeywords: nasopharyngeal carcinoma, radiotherapy , pilots , medical IP: 46.161.59.25 On: Wed,cerated 12 Oct surface; 2016 08:43:10 crosis. Pure tone audiometry showed that: 1) the left ear evolution. Copyright: Aerospace Medical Association
N
ASOPHARYNGEAL carcinoma (NPC) is endemic in southern China with a significantly higher rate of occurrence (800 cases per million) than the rest of the world (, 10 cases per million) (7). Although radiotherapy is not initial treatment for many cancers and is prone to impairing Eustachian tube function, auditory function, and vestibular function, and could result in disqualification of aircrew (12,13), it is currently the standard and most effective treatment for patients with NPC (1,2). We have previously reported two cases of transport pilots who returned to flying duties after treatment with well-recovered function (9). Because transport aircraft are flown by two pilots while fighter aircraft are flown by a single pilot, requirements for a fighter pilot with NPC returning to flying duties after treatment are much stricter. To our knowledge, returning a fighter pilot to flying duties after radiotherapy has not been previously reported in the literature. In this paper, we report one case of a fighter pilot with NPC successfully returned to flying duties.
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had main frequencies of 25 dB and 35 dB at 4 kHz and 8 kHz, respectively; 2) the right ear had a main frequency of 40 dB at 4 kHz; and 3) both ears had other frequencies of 20 dB or less. The results indicated that binaural hearing function was slightly decreased, but it did not affect his aerial communication. A binaural tympanogram showed a Type A curve, indicating that binaural middle ear function was normal. MRI with and without gadolinium contrast of the nasopharynx and neck showed that NPC had metastasized to the left neck lymph nodes (Fig. 2). Review of the pathological slides obtained from the local hospital confirmed nonkeratinizing squamous
From the Center of Clinical Aviation Medicine, General Hospital of PLA Air Force, Beijing, China. This manuscript was received for review in November 2013. It was accepted for publication in July 2014. Address correspondence and reprint requests to: Xian-Rong Xu, M.D., Center of Clinical Aviation Medicine, General Hospital of PLA Air Force, Beijing 100142, China; [email protected]. Reprint & Copyright © by the Aerospace Medical Association, Alexandria, VA. DOI: 10.3357/ASEM.3901.2014
Aviation, Space, and Environmental Medicine x Vol. 85, No. 10 x October 2014
NASOPHARYNGEAL CARCINOMA—XU ET AL.
Fig. 1. CT scans showing pharyngeal recess shallowing and Eustachian tubal torus expanding of left pharynx before radiotherapy.
cell carcinoma at the left nasopharynx and the tumor had metastasized to the lymph nodes on the left side of the neck. He was clinically staged as NPC (T1N2M0) and underwent radiotherapy using a conformal intensity-modulated linear accelerator for 48 d. In addition, he underwent adjuvant chemotherapy with cisplatin. After radiotherapy, he had a severe sore throat, but the size of the mass in the left side of the neck was reduced. Nasopharyngeal endoscopy showed redness on the left side of the Eustachian tube torus with a white ulcerated surface. The pilot underwent ground observation for 3 mo and then returned to our hospital. Nasopharyngeal
endoscopy showed decreased inflammation of the left nasopharyngeal mucous membrane and a slightly rough pharyngeal recess and Eustachian tubal torus. Partial biopsy showed chronic inflammation of the nasopharynx. Using pure tone audiometry it was shown that: 1) the left ear had main frequencies of 25 dB and 45 dB at 4 kHz and 8 kHz, respectively; 2) the right ear had main frequencies of 25 dB and 40 dB at 3 kHz and 4 kHz, respectively; and 3) both ears had other frequencies of 20 dB or less. A binaural tympanogram showed a Type C curve with a left ear pressure of 2175 mm H2O and a right ear pressure of 2200 mm H2O. Plain and contrastenhanced MRI of the nasopharynx and skull base showed reduced left NPC and neck lymph node (2.3 3 0.7 cm), indicating that the binaural Eustachian tube dysfunction did not affect hearing function. The pilot underwent another 5 mo of ground observation and then returned to our hospital. Follow-up at 8 mo after radiotherapy did not find palpable lymph nodes in the left side of the neck. Using pure tone audiometry it was found that: 1) the left ear had a main frequency of 35 dB at 8 kHz; 2) the right ear had main frequencies of 25 dB and 40 dB at 4 kHz and 8 kHz, respectively; and 3) both ears had other frequencies of 20 dB or less. The results indicated that binaural hearing function was restored to the level before radiotherapy. MRI of the nasopharynx and neck (Fig. 3) and whole body organ examination showed no tumor recurrence or metastasis. The indices of all other examinations,
Delivered by Ingenta to: Cornell University Library IP: 46.161.59.25 On: Wed, 12 Oct 2016 08:43:10 Copyright: Aerospace Medical Association
Fig. 2. T1-weighted coronal MR image showing cervical lymph node enlargement, with a size of about 3.7 3 1.8 cm, of the left neck before radiotherapy.
Fig. 3. MRI scans showing the nasopharynx, neck, and other parts were normal after radiotherapy.
Aviation, Space, and Environmental Medicine x Vol. 85, No. 10 x October 2014
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NASOPHARYNGEAL CARCINOMA—XU ET AL. the physiological functions of the microvessels and interfere with oxygen supply and the metabolism of the cochlea and cochlear nerve. Moreover, radiation induced destruction of the outer hair cells and spiral ganglion basal degeneration could result in hearing loss, especially high-frequency hearing loss. Eustachian tube dysfunction could induce catarrhal otitis media, even the decline of bone conduction if the functions of the oval window and the round window are affected, leading to mixed deafness. In this case report, inflammatory edema of the pharyngeal orifice and binaural tympanic negative pressure occurred 3 mo after radiotherapy, suggesting that radiation caused a transient Eustachian tube dysfunction and catarrhal otitis media, which recovered DISCUSSION to normal at 8 mo after radiotherapy. Fortunately, no significant hearing changes occurred before or after raNPC is often first characterized by blood in the mudiotherapy. In addition, no abnormalities were found in cous, cervical lymphadenopathy, a sensation of fullness the distortion-product otoacoustic emissions, or brainin the ear, hearing loss, and cranial nerve involvement. stem and cranial MRI, indicating that radiation did not Because of its invisible localization and atypical early damage the cochlea and auditory nerves. It has been resymptoms, NPC is easily misdiagnosed. For example, in ported that radiation can damage the cochlea. It is well pilots, when the symptoms are nasal congestion and known that cochlea nerve damage has a hysteresis efblood in the mucous, it is often misdiagnosed as aviafect, typically appearing 1-7 yr (average of 2.5 yr) later, tion sinusitis. When the symptoms include ear pain, it is and is generally accompanied by early radiation damoften misdiagnosed as aviation otitis media (6,12). In age to the auditory nerve and auditory center (11). this case, the pilot was admitted to our hospital 5 mo Therefore, long-term follow up of this case is needed to after he first noticed the neck lymphadenectasis, but he monitor for potential delayed hearing changes. continued to fly during this period, which delayed his Vestibular dysfunction: Vestibular function is necessary treatment. for piloting high performance aircraft. Radiotherapy In contrast to many other early stage cancers primarcould damage the peripheral and central vestibular sysily treated with surgery, NPC is treated preferably with tems, leading to autonomic nervous system dysfunction radiotherapy accompanied with chemotherapy and im(airsickness), spatial disorientation (flight illusion), and mune therapy, which often have post-therapeutic comactive movement disorders [benign paroxysmal posiplications such as catarrhal otitis media, sensorineural tional vertigo and alternobaric vertigo (13)]. Studies deafness, sinusitis, nasal adhesions, bleeding nose and have shown that a larger dose of 60Co gamma rays can nasopharynx, optic neuropathy, vestibular dysfunction, cranial nerve injury, temporomandibular arthritis, and cause bilateral utricle and saccule cristae epithelial deDelivered by Ingenta to: Cornell University Library oropharyngeal drying (2,12,13). The following compliand otolith shedding in experimental aniIP: 46.161.59.25 On: Wed,generation 12 Oct 2016 08:43:10 cations in aircrew may affect flight safety. mals (10Association ,11), possibly due to the following mechanisms: Copyright: Aerospace Medical Impaired Eustachian tube function and hearing loss: Eu1) radiotherapy could cause lipid peroxidation of inner stachian tube dysfunction and hearing loss are common ear hair cells, vascular degeneration, and microcirculacomplications after radiotherapy. These two complication disorders, injuring vestibular apparatus; 2) radiotions could influence each other and easily lead to catherapy could damage the otolith utricle and saccule, tarrhal otitis media, aural barotrauma, and sensorineural leading to otolith shedding and inducing positional verhearing loss. Radiotherapy could increase the activity of tigo; 3) exudative inflammation and infection of the epithelium secreting cells of the middle ear, decrease the middle ear could induce labyrinthitis inflammation, afsurfactants’ functions in the Eustachian tube, cause carfecting vestibular organs; and 4) radiotherapy could riage dysfunction of the nasopharyngeal cilia, affect sedirectly cause intracranial occlusive endarteritis and cretion discharge, and result in catarrhal otitis media, vascular thickening, resulting in hypoxic ischemic neconductive hearing loss, and even aural barotrauma. crosis of the central vestibular system. We have previRadiotherapy could also induce Eustachian tubal fibroously observed that radical radiotherapy of NPC could sis, neurological levator veil palati muscle and tensor lead to decreased ipsilateral or bilateral vestibular funcveil palati muscle paralysis, glandular atrophy, dried tion, even loss of vestibular function (13). The vestibule scab attachment, and affect Eustachian tubal function, and cochlea respond differently to radiation. Radiationleading to catarrhal otitis media and hearing loss. In adinduced vestibular dysfunction has no clear relationship dition, radioactive tympanic membrane perforation, osto radiation-induced hearing loss (11,13). In this case, sicular chain interruption or hardening, and tympanic the pilot had no nausea, vomiting, vertigo, or flight illumembrane adhesions could cause conductive hearing sions before or after radiotherapy and adapted well to loss. Furthermore, radiation could directly damage the aerial life. Repeat vestibular function tests showed no cochlear hair cells, supporting cells and cochlear nerve, abnormality, suggesting that radiotherapy did not damand induce vascular tissue vasculitis, which could change age vestibular function. including pure tone audiometry and binaural tympanogram before and after hypobaric chamber tests, distortion product acoustic emissions, auditory brainstem response, static and dynamic posturography, the Hallpike caloric test, and the ocular motility test, were normal. He was allowed to fly two-seat aircraft and was scheduled to come back in 3 mo for further evaluation. He flew for 53 h after discharge and returned to limited flying status with no signs or symptoms of deleterious side effects or disease recurrence. Follow-up at 12 and 20 mo after radiotherapy showed no evidence of recurrent or metastatic NPC.
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NASOPHARYNGEAL CARCINOMA—XU ET AL. of 2050 h and flying single-seat aircraft for 250 h after Oropharyngeal xerosis: Radiotherapy could cause ororadiotherapy. It has been reported that the 5-yr local pharyngeal mucosal edema and glandular atrophy or control rate, 5-yr disease-free survival, 5-yr disease-specific necrosis, thus leading to oropharyngeal cavity dryness survival rate, and overall 5-yr survival rate in 144 cases and painful swallowing, which could further affect eatof stage II NPC (UICC2002 standard) after radiotherapy ing and pronunciation, even leading to permanent damwere 93.5%, 79.5%, 91.5%, and 89.5%, respectively (3). age (4,5). Oropharyngeal xerosis in pilots is likely to affect Taking the possibility of NPC recurrence and long-term swallowing and digestion. In addition, breathing pressuradverse reactions of radiotherapy into account, even ized dry oxygen is required during flight, further aggrathough the possibility of NPC recurrence is very small, vating the oropharyngeal xerosis and affecting breathing, the current case needs long-term follow-up at least Eustachian tube function, and communication. In this annually. case, the pilot had apparent oropharyngeal dryness acThe medical evaluation of NPC for flight crew has companied by painful swallowing within 6 mo after not been specifically mentioned in the literature. radiotherapy. Along with saliva function recovery, the Based on our years of experience in aviation medicine oropharyngeal dryness basically disappeared over and specific long-term follow-up of cases such as this time. pilot with NPC, we recommended the Chinese Air The pilot was returned to full flying status in a twoForce adopt the following aeromedical disposition seat aircraft 12 mo after radiotherapy because there were standards for NPC: 1) pilot candidates with skeptical no signs or symptoms of deleterious side effects or disor diagnosed NPC should be unqualified in the priease recurrence and was then allowed to fly single-seat mary examination; 2) flying cadets once diagnosed aircraft. In addition, he was scheduled for re-examination with NPC should be suspended; 3) pilots with NPC in 6 mo for further evaluation. He then flew for another who, after treatment, showed no tumor recurrence 147 h and had good air adaptability. Follow-up at 20 mo and metastasis, and no obvious changes in auditory after radiotherapy showed that he met all flight eligibilfunction, Eustachian tubal function, sinus function, ity criteria and was allowed to continue flying the singleand vestibular function, and other satisfactory physiseat aircraft. He was scheduled for re-examination in 1 cal examination results before and after hypobaric yr. Up to the present, the pilot has been continuously on chamber tests, and no serious sequelae could be alflying duties for 250 h in single-seat aircraft for 26 mo lowed to fly two-seat aircraft 6 mo after successful after radiotherapy. He has been scheduled for annual treatment. If the pilot adapted well to aerial life for re-examination. 6-12 mo, he/she could be considered for medical Although NPC is not specifically mentioned, the genwaiver. If the pilot has a recurrence, metastasis, and/ eral discussions about malignancies in the U.S. Air Force or is having serious complications after treatment, Waiver Guide indicate: 1) whether a pilot is qualified for he/she should be permanently grounded. In addiwaiver depends on tumor recurrence, potential for sudtion, aircraft types, flying duties, flying experience, den aerial incapacitation, and side effects of therapies and confidence should also be taken into consider(radiotherapy, chemotherapy, and surgery); and 2) a piation to determine whether the pilot with NPC could lot cannot apply for waiver within 6 mo of formal treatDelivered by Ingenta to: Cornell University Library y after treatment, and the pilot should be required to ment (1). Sethom et al. have reported that a pilot with IP: 46.161.59.25 On: Wed, fl12 Oct 2016 08:43:10 undergo re-examination at least once a year. undifferentiated NPC (T4N2M0) wasCopyright: groundedAerospace due to Medical Association serious post-radiotherapeutic psychological problems ACKNOWLEDGMENT (8). Our decision on fitness to fly with NPC in aircrew Authors and affiliation: Xian-Rong Xu, M.D., Yang Zhang, B.M., (especially in fighter pilots) was based on the following: and Zhan-Guo Jin, M.D., Clinic and Research Center of Aerospace 1) it was diagnosed at an early stage without distant meVertigo, Center of Clinical Aviation Medicine, General Hospital of PLA Air Force, Beijing, China; and Bin-Ru Wang, M.M., Department tastasis; 2) an individualized and prospective treatment of Otolaryngology Head and Neck Surgery, the Third Hospital of plan; 3) no serious complications after radiotherapy to Wuhan, Wuhan, China. Eustachian tubal, auditory, and vestibular functions that REFERENCES affected normal life and flying duties; 4) a low tumor 1. Air Force Surgeon General. Air Force waiver guide [M/OL]. recurrence rate and high long-term survival rate; and 5) Washington: Department of Air Force; 2013. Retrieved August a strong pilot desire to fly again. In this case, once con2013 from http://www.wpafb.af.mil/shared/media/document/ firmed that the patient was at an early stage of NPC, we AFD-130802-026.pdf. 2. Ali H, al-Sarraf M. Nasopharyngeal cancer. Hematol Oncol Clin designed a prospective treatment and follow-up program. North Am 1999; 13:837–47. After the NPC was cured, no flight safety-endangering 3. Feng M, Fan Z, Li J, Zhang P, Li T, et al. Long-term results and complications of Eustachian tube, auditory, and vestibuprognostic factors in 582 nasopharyngeal carcinoma treated by intensity modulated radiotherapy. Chin J Radiat Oncol 2011; lar function occurred. Repeat follow-up within 20 mo 5:369–73. after radiotherapy did not find regional tumor recur4. Ku PK, Yuen EH, Cheung DM, Chan BY, Ahuja A, et al. Early rence, lymph node metastasis, or lung, brain, or other swallowing problems in a cohort of patients with nasopharynorgan metastasis. All flight-related tests were normal. geal carcinoma: symptomatology and videofluoroscopic findings. Laryngoscope 2007; 117:142–6. He then flew safely in a two-seat aircraft for 53 h. With 5. Ng LK, Lee KY, Chiu SN, Ku PK, van Hasselt CA, Tong MC. Silent both physical and psychological recovery, the pilot was aspiration and swallowing physiology after radiotherapy in allowed to fly single-seat aircraft 12 mo after radiotherpatients with nasopharyngeal carcinoma. Head Neck 2011; apy. Up to now, the pilot has been flying for a total 33:1335–9. Aviation, Space, and Environmental Medicine x Vol. 85, No. 10 x October 2014
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NASOPHARYNGEAL CARCINOMA—XU ET AL. 6. Ondrey FG, Greig JR, Herdcher L. Radiation dose to otologic structures during head and neck cancer radiation therapy. Laryngoscope 2000; 110:217–21. 7. Richey LM, Olshan AF, George J, Shores CG, Zanation AM, et al. Incidence and survival rates for young blacks with nasopharyngeal carcinoma in the United States. Arch Otolaryngol Head Neck Surg 2006; 132:1035–40. 8. Sethom A, Ben SS, Ben D, Mrabet A, Souissi A, et al. Head and neck cancer of aircrew personnel in aeronautical medical expertise. Tunis Med 2011; 89:391–3. 9. Tan Z, Xu X, Zhang Y, Jin Z. [Diagnosis, treatment and medical evaluation of head and neck tumors in aircrew.] [Article in Chinese.] Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2011; 25:223–5.
10. Wang J, Shi M, Hsia Y, Luo S, Zhao L, et al. Failure patterns and survival in patients with nasopharyngeal carcinoma treated with intensity modulated radiation in Northwest China: a pilot study. Radiat Oncol 2012; 7:2–8. 11. Wang LF, Kuo WR, Ho KY, Lee KW, Lin CS. A long-term study on hearing status in patients with nasopharyngeal carcinoma after radiotherapy. Otol Neurotol 2004; 25:168–73. 12. Xu X. [Lesions around the Eustachian tube and aural barotrauma.] [Article in Chinese.] Journal of Audiology and Speech Pathology 2008; 16:443–445. 13. Xu XR, Tan ZL, Chen J, Liu HF. [Effects on vestibular function by irradiation in the patients with nasopharyngeal carcinoma.] [Article in Chinese.] Lin Chuang Er Bi Yan Hou Ke Za Zhi 2000; 14:396–7.
ERRATUM Harrington LK, McIntire JP, Hopper DG. Assessing the binocular advantage in aided vision. Aviat Space Environ Med 2014; 85:930–9. DOI: 10.3357/ASEM.3976.2014 The authors of this article recently notified us of an error in the abstract. The fourth sentence that reads: “The selection of a binocular display for use in the F-35 is a current example of this recurring decision process.” should read “The selection of a biocular display for use in the F-35 is a current example of this recurring decision process.” We apologize for the error and any inconvenience.
Delivered by Ingenta to: Cornell University Library IP: 46.161.59.25 On: Wed, 12 Oct 2016 08:43:10 Copyright: Aerospace Medical Association
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Aviation, Space, and Environmental Medicine x Vol. 85, No. 10 x October 2014
Radiotherapeutic Treatment of a Fighter Pilot with Nasopharyngeal Carcinoma Xian-Rong Xu, Bin-Ru Wang, Yang Zhang, and Zhan-Guo Jin XU X-R, WANG B-R, ZHANG Y, JIN Z-G. Radiotherapeutic treatment CASE REPORT of a fighter pilot with nasopharyngeal carcinoma. Aviat Space EnviThe patient was a 36-yr-old male fighter pilot with ron Med 2014; 85:1056–60. Background: Radiotherapy is the standard and most effective treat1800 h of flight time. In March 2011, he incidentally ment for nasopharyngeal carcinoma (NPC) in its early stages. However, found a painless mass in the left neck. He initially igits application in fighter pilots returning to flying duties with NPC has nored it. During that period, there was no blood in the not been previously reported, presumably due to post-radiotherapeutic nasal mucus and no ear tenderness, tinnitus, hearing complications. Case report: A 36-yr-old male fighter pilot had a painless mass in the left neck for 5 mo. Pathological diagnosis demonstrated loss, or vertigo. However, the mass continued to grow, nonkeratinizing squamous cell carcinoma in the left nasopharynx which so he was admitted to a local hospital at the end of had metastasized to lymph nodes in the left side of the neck. He was August 2011. Nonenhanced CT scan showed a nasophadiagnosed and staged with NPC (T1N2M0) before treatment with radioryngeal mass accompanied with cervical lymph node therapy and adjuvant chemotherapy. The patient suffered from catarrhal otitis media and xerostomia after 3 mo of radiotherapy, but these sympenlargement in the left nasopharynx (Fig. 1). Biopsy of toms resolved. After a total of 8 mo of radiotherapy, he was in remission the mass confirmed that he had NPC with lymph node with no evidence of tumor recurrence or metastasis. He had normal metastasis in the left side of the neck. Therefore, he was Eustachian tube, hearing, and vestibular function before and after hytransferred to our hospital in September 2011. Physical pobaric chamber testing and passed all flight-related physical examinations. Consequently, he was granted a medical waiver and returned examination found a palpable painless mass of approxito flying status in two-seat fighter aircraft, flying for 53 h in a 12-mo pemately 4 3 2 cm, medium to rigid texture, and unclear riod. After passing all flight-related tests again, he was then allowed to boundary at the deep left sternocleidomastoid muscle. fly in single-seat aircraft. At the time of submission of this article, he Nasopharyngeal endoscopy revealed the following: 1) has flown for 147 h and remained on flying status for 26 mo. He will be monitored annually for long-term effects of radiotherapy and/or disthe left Eustachian tubal torus was plumper than the ease recurrence. Conclusions: Fighter pilots with NPC may be safely right one; 2) the left pharyngeal recess was shallower considered for medical waiver with appropriate monitoring after sucthan the right one; 3) a mucosal biopsy-caused white ulcessful treatment. Delivered by Ingenta to: Cornell University Library and 4) no erosion, hemorrhage, or neKeywords: nasopharyngeal carcinoma, radiotherapy , pilots , medical IP: 46.161.59.25 On: Wed,cerated 12 Oct surface; 2016 08:43:10 crosis. Pure tone audiometry showed that: 1) the left ear evolution. Copyright: Aerospace Medical Association
N
ASOPHARYNGEAL carcinoma (NPC) is endemic in southern China with a significantly higher rate of occurrence (800 cases per million) than the rest of the world (, 10 cases per million) (7). Although radiotherapy is not initial treatment for many cancers and is prone to impairing Eustachian tube function, auditory function, and vestibular function, and could result in disqualification of aircrew (12,13), it is currently the standard and most effective treatment for patients with NPC (1,2). We have previously reported two cases of transport pilots who returned to flying duties after treatment with well-recovered function (9). Because transport aircraft are flown by two pilots while fighter aircraft are flown by a single pilot, requirements for a fighter pilot with NPC returning to flying duties after treatment are much stricter. To our knowledge, returning a fighter pilot to flying duties after radiotherapy has not been previously reported in the literature. In this paper, we report one case of a fighter pilot with NPC successfully returned to flying duties.
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had main frequencies of 25 dB and 35 dB at 4 kHz and 8 kHz, respectively; 2) the right ear had a main frequency of 40 dB at 4 kHz; and 3) both ears had other frequencies of 20 dB or less. The results indicated that binaural hearing function was slightly decreased, but it did not affect his aerial communication. A binaural tympanogram showed a Type A curve, indicating that binaural middle ear function was normal. MRI with and without gadolinium contrast of the nasopharynx and neck showed that NPC had metastasized to the left neck lymph nodes (Fig. 2). Review of the pathological slides obtained from the local hospital confirmed nonkeratinizing squamous
From the Center of Clinical Aviation Medicine, General Hospital of PLA Air Force, Beijing, China. This manuscript was received for review in November 2013. It was accepted for publication in July 2014. Address correspondence and reprint requests to: Xian-Rong Xu, M.D., Center of Clinical Aviation Medicine, General Hospital of PLA Air Force, Beijing 100142, China; [email protected]. Reprint & Copyright © by the Aerospace Medical Association, Alexandria, VA. DOI: 10.3357/ASEM.3901.2014
Aviation, Space, and Environmental Medicine x Vol. 85, No. 10 x October 2014
NASOPHARYNGEAL CARCINOMA—XU ET AL.
Fig. 1. CT scans showing pharyngeal recess shallowing and Eustachian tubal torus expanding of left pharynx before radiotherapy.
cell carcinoma at the left nasopharynx and the tumor had metastasized to the lymph nodes on the left side of the neck. He was clinically staged as NPC (T1N2M0) and underwent radiotherapy using a conformal intensity-modulated linear accelerator for 48 d. In addition, he underwent adjuvant chemotherapy with cisplatin. After radiotherapy, he had a severe sore throat, but the size of the mass in the left side of the neck was reduced. Nasopharyngeal endoscopy showed redness on the left side of the Eustachian tube torus with a white ulcerated surface. The pilot underwent ground observation for 3 mo and then returned to our hospital. Nasopharyngeal
endoscopy showed decreased inflammation of the left nasopharyngeal mucous membrane and a slightly rough pharyngeal recess and Eustachian tubal torus. Partial biopsy showed chronic inflammation of the nasopharynx. Using pure tone audiometry it was shown that: 1) the left ear had main frequencies of 25 dB and 45 dB at 4 kHz and 8 kHz, respectively; 2) the right ear had main frequencies of 25 dB and 40 dB at 3 kHz and 4 kHz, respectively; and 3) both ears had other frequencies of 20 dB or less. A binaural tympanogram showed a Type C curve with a left ear pressure of 2175 mm H2O and a right ear pressure of 2200 mm H2O. Plain and contrastenhanced MRI of the nasopharynx and skull base showed reduced left NPC and neck lymph node (2.3 3 0.7 cm), indicating that the binaural Eustachian tube dysfunction did not affect hearing function. The pilot underwent another 5 mo of ground observation and then returned to our hospital. Follow-up at 8 mo after radiotherapy did not find palpable lymph nodes in the left side of the neck. Using pure tone audiometry it was found that: 1) the left ear had a main frequency of 35 dB at 8 kHz; 2) the right ear had main frequencies of 25 dB and 40 dB at 4 kHz and 8 kHz, respectively; and 3) both ears had other frequencies of 20 dB or less. The results indicated that binaural hearing function was restored to the level before radiotherapy. MRI of the nasopharynx and neck (Fig. 3) and whole body organ examination showed no tumor recurrence or metastasis. The indices of all other examinations,
Delivered by Ingenta to: Cornell University Library IP: 46.161.59.25 On: Wed, 12 Oct 2016 08:43:10 Copyright: Aerospace Medical Association
Fig. 2. T1-weighted coronal MR image showing cervical lymph node enlargement, with a size of about 3.7 3 1.8 cm, of the left neck before radiotherapy.
Fig. 3. MRI scans showing the nasopharynx, neck, and other parts were normal after radiotherapy.
Aviation, Space, and Environmental Medicine x Vol. 85, No. 10 x October 2014
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NASOPHARYNGEAL CARCINOMA—XU ET AL. the physiological functions of the microvessels and interfere with oxygen supply and the metabolism of the cochlea and cochlear nerve. Moreover, radiation induced destruction of the outer hair cells and spiral ganglion basal degeneration could result in hearing loss, especially high-frequency hearing loss. Eustachian tube dysfunction could induce catarrhal otitis media, even the decline of bone conduction if the functions of the oval window and the round window are affected, leading to mixed deafness. In this case report, inflammatory edema of the pharyngeal orifice and binaural tympanic negative pressure occurred 3 mo after radiotherapy, suggesting that radiation caused a transient Eustachian tube dysfunction and catarrhal otitis media, which recovered DISCUSSION to normal at 8 mo after radiotherapy. Fortunately, no significant hearing changes occurred before or after raNPC is often first characterized by blood in the mudiotherapy. In addition, no abnormalities were found in cous, cervical lymphadenopathy, a sensation of fullness the distortion-product otoacoustic emissions, or brainin the ear, hearing loss, and cranial nerve involvement. stem and cranial MRI, indicating that radiation did not Because of its invisible localization and atypical early damage the cochlea and auditory nerves. It has been resymptoms, NPC is easily misdiagnosed. For example, in ported that radiation can damage the cochlea. It is well pilots, when the symptoms are nasal congestion and known that cochlea nerve damage has a hysteresis efblood in the mucous, it is often misdiagnosed as aviafect, typically appearing 1-7 yr (average of 2.5 yr) later, tion sinusitis. When the symptoms include ear pain, it is and is generally accompanied by early radiation damoften misdiagnosed as aviation otitis media (6,12). In age to the auditory nerve and auditory center (11). this case, the pilot was admitted to our hospital 5 mo Therefore, long-term follow up of this case is needed to after he first noticed the neck lymphadenectasis, but he monitor for potential delayed hearing changes. continued to fly during this period, which delayed his Vestibular dysfunction: Vestibular function is necessary treatment. for piloting high performance aircraft. Radiotherapy In contrast to many other early stage cancers primarcould damage the peripheral and central vestibular sysily treated with surgery, NPC is treated preferably with tems, leading to autonomic nervous system dysfunction radiotherapy accompanied with chemotherapy and im(airsickness), spatial disorientation (flight illusion), and mune therapy, which often have post-therapeutic comactive movement disorders [benign paroxysmal posiplications such as catarrhal otitis media, sensorineural tional vertigo and alternobaric vertigo (13)]. Studies deafness, sinusitis, nasal adhesions, bleeding nose and have shown that a larger dose of 60Co gamma rays can nasopharynx, optic neuropathy, vestibular dysfunction, cranial nerve injury, temporomandibular arthritis, and cause bilateral utricle and saccule cristae epithelial deDelivered by Ingenta to: Cornell University Library oropharyngeal drying (2,12,13). The following compliand otolith shedding in experimental aniIP: 46.161.59.25 On: Wed,generation 12 Oct 2016 08:43:10 cations in aircrew may affect flight safety. mals (10Association ,11), possibly due to the following mechanisms: Copyright: Aerospace Medical Impaired Eustachian tube function and hearing loss: Eu1) radiotherapy could cause lipid peroxidation of inner stachian tube dysfunction and hearing loss are common ear hair cells, vascular degeneration, and microcirculacomplications after radiotherapy. These two complication disorders, injuring vestibular apparatus; 2) radiotions could influence each other and easily lead to catherapy could damage the otolith utricle and saccule, tarrhal otitis media, aural barotrauma, and sensorineural leading to otolith shedding and inducing positional verhearing loss. Radiotherapy could increase the activity of tigo; 3) exudative inflammation and infection of the epithelium secreting cells of the middle ear, decrease the middle ear could induce labyrinthitis inflammation, afsurfactants’ functions in the Eustachian tube, cause carfecting vestibular organs; and 4) radiotherapy could riage dysfunction of the nasopharyngeal cilia, affect sedirectly cause intracranial occlusive endarteritis and cretion discharge, and result in catarrhal otitis media, vascular thickening, resulting in hypoxic ischemic neconductive hearing loss, and even aural barotrauma. crosis of the central vestibular system. We have previRadiotherapy could also induce Eustachian tubal fibroously observed that radical radiotherapy of NPC could sis, neurological levator veil palati muscle and tensor lead to decreased ipsilateral or bilateral vestibular funcveil palati muscle paralysis, glandular atrophy, dried tion, even loss of vestibular function (13). The vestibule scab attachment, and affect Eustachian tubal function, and cochlea respond differently to radiation. Radiationleading to catarrhal otitis media and hearing loss. In adinduced vestibular dysfunction has no clear relationship dition, radioactive tympanic membrane perforation, osto radiation-induced hearing loss (11,13). In this case, sicular chain interruption or hardening, and tympanic the pilot had no nausea, vomiting, vertigo, or flight illumembrane adhesions could cause conductive hearing sions before or after radiotherapy and adapted well to loss. Furthermore, radiation could directly damage the aerial life. Repeat vestibular function tests showed no cochlear hair cells, supporting cells and cochlear nerve, abnormality, suggesting that radiotherapy did not damand induce vascular tissue vasculitis, which could change age vestibular function. including pure tone audiometry and binaural tympanogram before and after hypobaric chamber tests, distortion product acoustic emissions, auditory brainstem response, static and dynamic posturography, the Hallpike caloric test, and the ocular motility test, were normal. He was allowed to fly two-seat aircraft and was scheduled to come back in 3 mo for further evaluation. He flew for 53 h after discharge and returned to limited flying status with no signs or symptoms of deleterious side effects or disease recurrence. Follow-up at 12 and 20 mo after radiotherapy showed no evidence of recurrent or metastatic NPC.
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NASOPHARYNGEAL CARCINOMA—XU ET AL. of 2050 h and flying single-seat aircraft for 250 h after Oropharyngeal xerosis: Radiotherapy could cause ororadiotherapy. It has been reported that the 5-yr local pharyngeal mucosal edema and glandular atrophy or control rate, 5-yr disease-free survival, 5-yr disease-specific necrosis, thus leading to oropharyngeal cavity dryness survival rate, and overall 5-yr survival rate in 144 cases and painful swallowing, which could further affect eatof stage II NPC (UICC2002 standard) after radiotherapy ing and pronunciation, even leading to permanent damwere 93.5%, 79.5%, 91.5%, and 89.5%, respectively (3). age (4,5). Oropharyngeal xerosis in pilots is likely to affect Taking the possibility of NPC recurrence and long-term swallowing and digestion. In addition, breathing pressuradverse reactions of radiotherapy into account, even ized dry oxygen is required during flight, further aggrathough the possibility of NPC recurrence is very small, vating the oropharyngeal xerosis and affecting breathing, the current case needs long-term follow-up at least Eustachian tube function, and communication. In this annually. case, the pilot had apparent oropharyngeal dryness acThe medical evaluation of NPC for flight crew has companied by painful swallowing within 6 mo after not been specifically mentioned in the literature. radiotherapy. Along with saliva function recovery, the Based on our years of experience in aviation medicine oropharyngeal dryness basically disappeared over and specific long-term follow-up of cases such as this time. pilot with NPC, we recommended the Chinese Air The pilot was returned to full flying status in a twoForce adopt the following aeromedical disposition seat aircraft 12 mo after radiotherapy because there were standards for NPC: 1) pilot candidates with skeptical no signs or symptoms of deleterious side effects or disor diagnosed NPC should be unqualified in the priease recurrence and was then allowed to fly single-seat mary examination; 2) flying cadets once diagnosed aircraft. In addition, he was scheduled for re-examination with NPC should be suspended; 3) pilots with NPC in 6 mo for further evaluation. He then flew for another who, after treatment, showed no tumor recurrence 147 h and had good air adaptability. Follow-up at 20 mo and metastasis, and no obvious changes in auditory after radiotherapy showed that he met all flight eligibilfunction, Eustachian tubal function, sinus function, ity criteria and was allowed to continue flying the singleand vestibular function, and other satisfactory physiseat aircraft. He was scheduled for re-examination in 1 cal examination results before and after hypobaric yr. Up to the present, the pilot has been continuously on chamber tests, and no serious sequelae could be alflying duties for 250 h in single-seat aircraft for 26 mo lowed to fly two-seat aircraft 6 mo after successful after radiotherapy. He has been scheduled for annual treatment. If the pilot adapted well to aerial life for re-examination. 6-12 mo, he/she could be considered for medical Although NPC is not specifically mentioned, the genwaiver. If the pilot has a recurrence, metastasis, and/ eral discussions about malignancies in the U.S. Air Force or is having serious complications after treatment, Waiver Guide indicate: 1) whether a pilot is qualified for he/she should be permanently grounded. In addiwaiver depends on tumor recurrence, potential for sudtion, aircraft types, flying duties, flying experience, den aerial incapacitation, and side effects of therapies and confidence should also be taken into consider(radiotherapy, chemotherapy, and surgery); and 2) a piation to determine whether the pilot with NPC could lot cannot apply for waiver within 6 mo of formal treatDelivered by Ingenta to: Cornell University Library y after treatment, and the pilot should be required to ment (1). Sethom et al. have reported that a pilot with IP: 46.161.59.25 On: Wed, fl12 Oct 2016 08:43:10 undergo re-examination at least once a year. undifferentiated NPC (T4N2M0) wasCopyright: groundedAerospace due to Medical Association serious post-radiotherapeutic psychological problems ACKNOWLEDGMENT (8). Our decision on fitness to fly with NPC in aircrew Authors and affiliation: Xian-Rong Xu, M.D., Yang Zhang, B.M., (especially in fighter pilots) was based on the following: and Zhan-Guo Jin, M.D., Clinic and Research Center of Aerospace 1) it was diagnosed at an early stage without distant meVertigo, Center of Clinical Aviation Medicine, General Hospital of PLA Air Force, Beijing, China; and Bin-Ru Wang, M.M., Department tastasis; 2) an individualized and prospective treatment of Otolaryngology Head and Neck Surgery, the Third Hospital of plan; 3) no serious complications after radiotherapy to Wuhan, Wuhan, China. Eustachian tubal, auditory, and vestibular functions that REFERENCES affected normal life and flying duties; 4) a low tumor 1. Air Force Surgeon General. Air Force waiver guide [M/OL]. recurrence rate and high long-term survival rate; and 5) Washington: Department of Air Force; 2013. Retrieved August a strong pilot desire to fly again. In this case, once con2013 from http://www.wpafb.af.mil/shared/media/document/ firmed that the patient was at an early stage of NPC, we AFD-130802-026.pdf. 2. Ali H, al-Sarraf M. Nasopharyngeal cancer. Hematol Oncol Clin designed a prospective treatment and follow-up program. North Am 1999; 13:837–47. After the NPC was cured, no flight safety-endangering 3. Feng M, Fan Z, Li J, Zhang P, Li T, et al. Long-term results and complications of Eustachian tube, auditory, and vestibuprognostic factors in 582 nasopharyngeal carcinoma treated by intensity modulated radiotherapy. Chin J Radiat Oncol 2011; lar function occurred. Repeat follow-up within 20 mo 5:369–73. after radiotherapy did not find regional tumor recur4. Ku PK, Yuen EH, Cheung DM, Chan BY, Ahuja A, et al. Early rence, lymph node metastasis, or lung, brain, or other swallowing problems in a cohort of patients with nasopharynorgan metastasis. All flight-related tests were normal. geal carcinoma: symptomatology and videofluoroscopic findings. Laryngoscope 2007; 117:142–6. He then flew safely in a two-seat aircraft for 53 h. With 5. Ng LK, Lee KY, Chiu SN, Ku PK, van Hasselt CA, Tong MC. Silent both physical and psychological recovery, the pilot was aspiration and swallowing physiology after radiotherapy in allowed to fly single-seat aircraft 12 mo after radiotherpatients with nasopharyngeal carcinoma. Head Neck 2011; apy. Up to now, the pilot has been flying for a total 33:1335–9. Aviation, Space, and Environmental Medicine x Vol. 85, No. 10 x October 2014
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NASOPHARYNGEAL CARCINOMA—XU ET AL. 6. Ondrey FG, Greig JR, Herdcher L. Radiation dose to otologic structures during head and neck cancer radiation therapy. Laryngoscope 2000; 110:217–21. 7. Richey LM, Olshan AF, George J, Shores CG, Zanation AM, et al. Incidence and survival rates for young blacks with nasopharyngeal carcinoma in the United States. Arch Otolaryngol Head Neck Surg 2006; 132:1035–40. 8. Sethom A, Ben SS, Ben D, Mrabet A, Souissi A, et al. Head and neck cancer of aircrew personnel in aeronautical medical expertise. Tunis Med 2011; 89:391–3. 9. Tan Z, Xu X, Zhang Y, Jin Z. [Diagnosis, treatment and medical evaluation of head and neck tumors in aircrew.] [Article in Chinese.] Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2011; 25:223–5.
10. Wang J, Shi M, Hsia Y, Luo S, Zhao L, et al. Failure patterns and survival in patients with nasopharyngeal carcinoma treated with intensity modulated radiation in Northwest China: a pilot study. Radiat Oncol 2012; 7:2–8. 11. Wang LF, Kuo WR, Ho KY, Lee KW, Lin CS. A long-term study on hearing status in patients with nasopharyngeal carcinoma after radiotherapy. Otol Neurotol 2004; 25:168–73. 12. Xu X. [Lesions around the Eustachian tube and aural barotrauma.] [Article in Chinese.] Journal of Audiology and Speech Pathology 2008; 16:443–445. 13. Xu XR, Tan ZL, Chen J, Liu HF. [Effects on vestibular function by irradiation in the patients with nasopharyngeal carcinoma.] [Article in Chinese.] Lin Chuang Er Bi Yan Hou Ke Za Zhi 2000; 14:396–7.
ERRATUM Harrington LK, McIntire JP, Hopper DG. Assessing the binocular advantage in aided vision. Aviat Space Environ Med 2014; 85:930–9. DOI: 10.3357/ASEM.3976.2014 The authors of this article recently notified us of an error in the abstract. The fourth sentence that reads: “The selection of a binocular display for use in the F-35 is a current example of this recurring decision process.” should read “The selection of a biocular display for use in the F-35 is a current example of this recurring decision process.” We apologize for the error and any inconvenience.
Delivered by Ingenta to: Cornell University Library IP: 46.161.59.25 On: Wed, 12 Oct 2016 08:43:10 Copyright: Aerospace Medical Association
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