Jpn J Clin Oncol 2014;44(8)736 – 742 doi:10.1093/jjco/hyu062 Advance Access Publication 19 May 2014
Radiation-induced Brachial Plexus Injury After Radiotherapy for Nasopharyngeal Carcinoma Beibei Gu1,†, Zhihua Yang2,†, Shixiong Huang3, Songhua Xiao1, Bei Zhang4, Lianhong Yang1, Jia Zhao1, Zhongyan Zhao3, Jun Shen1 and Jun Liu1,* 1
Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong, Guangzhou, Department of Neurology, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, 3Department of Neurology, Hainan Provincial People’s Hospital, Haikou and 4Department of Neurology, The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, China 2
Received February 12, 2014; accepted April 17, 2014
Objective: Radiation-induced brachial plexus injury is a devastating complication that occurs after radiotherapy in the vicinity of the brachial plexus. Nasopharyngeal carcinoma, the most common type of cancer in Guangdong Province, is primarily treated with radiotherapy with subsequent side effects. However, radiation-induced brachial plexus injury is rarely reported in nasopharyngeal carcinoma. To draw attention to this correlation, we analyzed the clinical characteristics including the imaging findings of 10 patients suffering from radiation-induced brachial plexus injury for nasopharyngeal carcinoma. Methods: We considered the patients’ medical histories, analyzed their clinical characteristics, and monitored the long-term efficacy of treatment. Results: The total irradiation dose of the nasopharynx ranged from 66.6 to 74 Gy, and that of the supraclavicular fossa ranged from 60 to 70 Gy. The mean latency was 8.2 + 5.5 years. Seven patients initially complained of bilateral weakness, and three patients complained of isolated pain. The injuries of eight patients reached Grade 3 or worse. Magnetic resonance imaging showed a low signal on T1-weighted images and a high signal on short tau inversion recovery sequences in all cases. Swollen nerve fibers were clearly displayed in magnetic resonance diffusion tensor imaging. Electromyography showed myokymia in three patients. With conservative therapy, only one patient was temporarily relieved of pain, while the conditions of others were not ameliorated. Conclusions: Radiation-induced brachial plexus injury is a late but catastrophic complication in patients with nasopharyngeal carcinoma. Clinicians should be aware of radiation-induced brachial plexus injury when deciding on treatment and should give them regular follow-up post radiotherapy. Key words: radiation-induced brachial plexus injury – nasopharyngeal carcinoma – neurological manifestations – MRI – electromyography
# The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
*For reprints and all correspondence: Jun Liu, Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong 510120, China. E-mail: [email protected] † These authors contributed equally to this work.
Jpn J Clin Oncol 2014;44(8)
INTRODUCTION
Table 1. Modified LENT/SOMA scale Grade Symptoms 1
Mild sensory deficits, no pain, no treatment required
2
Moderate sensory deficits, tolerable pain, mild arm weakness
3
Continuous paresthesia with incomplete paresis, pain medication required
4
Complete paresis, excruciating pain, muscle atrophy, regular pain medication required
LENT/SOMA, late effects of normal tissues conference/subjective, objective, management, and analytic.
DIAGNOSIS AND ASSESSMENT OF RIBP For patients with NPC who had previously received radiotherapy, RIBP was diagnosed based on the detailed history, as well as physical MRI and electrophysiological examination, on the condition that all other causes are excluded. The severity of RIBP was assessed based on a modified late effects of normal tissues conference/subjective, objective, management, and analytic (LENT/SOMA) score (6,7), the details of which are shown in Table 1.
RESULTS CLINICAL CHARACTERISTICS OF NPC
PATIENTS AND METHODS PARTICIPANTS From January 2007 to December 2012, 1209 patients at Sun Yat-sen Memorial Hospital of Sun Yat-sen University displayed various radiation-related complications after receiving radiotherapy for NPC. These patients were periodically evaluated at 6-month intervals after they were discharged from the hospital. Ten patients (0.83%) could not be contacted, so they were excluded from this study. Through this review, we found 10 patients (four males and six females) who suffered from RIBP, and obtained details from their clinical materials.
AUXILIARY EXAMINATION In this retrospective study, all the patients were assessed by certified neurologists. The latency of RIBP was evaluated from the end of radiotherapy to the onset of the symptoms. MRI, including conventional T1-weighted enhanced images and short tau inversion recovery sequences (STIR) using 3T magnets, was performed to confirm the diagnosis and to distinguish RIBP from tumor metastases. Diffusion tensor imaging (DTI) and maximum intensity projection (MIP) were used to show edema of the brachial plexus more clearly. Electromyography (EMG) was also performed to confirm the brachial plexus injury.
All 10 patients were definitely diagnosed with NPC according to their pathological manifestations. Tumor staging was performed according to the 2002 tumor, node, and metastasis classification system of the American Joint Committee on Cancer (AJCC). They all suffered from regionally (Nþ: 100%) advanced tumors. Three of them had stage T1, two had stage T2, four had stage T3 and one had stage T4. Nodal involvement was N1 in three patients, N2 in six patients and N3 in one patient, and there were no distant metastases. The pathological subtypes included seven keratinizing squamous cell carcinomas (KSCC), two undifferentiated nonkeratinizing carcinomas (UD-NKC), and one differentiated non-keratinizing carcinoma (D-NKC). The detailed information is listed in Table 2. All patients underwent conventional external beam radiotherapy comprised of a three-field facial technique encompassing the nasopharynx and immediate risk areas, and a single matched anterior split neck field. Two large bilateral opposed fields were used to treat the nasopharynx and the upper neck, and an anterior port was applied to the rest of the neck and the supraclavicular fossa (8,9). Conventional radiotherapy was given in 2 –3 different phases. The target dose to the nasopharynx and upper neck ranged from 66.6 to 74 Gy (70.5 + 1.9). The lower neck and supraclavicular fossa received a dose of 60 to 70 Gy (64.2 + 3.3). Treatment was completed in 1.8–2.0 Gy fractions daily five times per week. In addition, seven patients with advanced stage T3–T4 or N2–N3 NPC were treated with five or more cycles of neoadjuvant chemotherapy.
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
Nasopharyngeal carcinoma (NPC) is the most common type of cancer in the Guangdong province of China. The incidence of NPC in Guangdong Province is the highest in the world, which is .30 per 100 000 people among males (1). Due to its special pathological features, radiotherapy is the primary treatment for NPC. However, radiation exposure may cause serious side effects in normal tissues. Radiation-induced brachial plexus injury (RIBP) is a rare but severe complication in patients who have received radiation in the vicinity of the brachial plexus (2,3). RIBP usually begins months to years after the end of radiotherapy (4). Symptoms of RIBP including motor and sensory disorders in the bilateral upper extremities, may largely affect the quality of life for each patient. RIBP is most commonly observed in breast and lung cancers, yet it is seldom reported in patients with NPC (5). Recent improvements in radiation techniques have resulted in longer survival time; thus, patients with NPC have more opportunities to develop RIBP, which means that more attention should be given to RIBP, despite the rarity of reports. In the present study, we report on 10 patients who suffered from RIBP after receiving radiotherapy for NPC. Studying the clinical characteristics of RIBP may increase awareness of RIBP and offer an opportunity to explore strategies to prevent or ameliorate this side effect.
737
738
RIBP for NPC
Table 2. Characteristics of nasopharyngeal carcinoma patients with radiation-induced brachial plexus injury Patient number
Pathological classification
Tumor stage
Dose of irradiation (nasopharynx)
Dose of irradiation (supraclavicular fossa)
Adjuvant treatments
Latency period (years)
1
34/F
D-NKC
T1N2M0/III
66.6 Gy/37F
61.2 Gy/34F
Yes
2
58/F
UD-NKC
T3N2M0/III
70 Gy/35F
64 Gy/32F
Yes
17
Pain
Bilateral
III
3
59/F
KSCC
T2N1M0/II
70 Gy/35F
60 Gy/30F
No
7
Pain
Bilateral
III
4
52/M
KSCC
T4N1M0/IV
74 Gy/37F
66 Gy/33F
Yes
12
Weakness
Bilateral
III
5
43/M
UD-NKC
T3N2M0/III
72 Gy/36F
64 Gy/32F
Yes
1
Weakness
Unilateral
III
6
60/M
KSCC
T1N2M0/III
70 Gy/35F
63 Gy/35F
No
9
Weakness and numbness
Bilateral
II
7
54/F
KSCC
T1N2M0/III
70 Gy/35F
60 Gy/33F
Yes
12
Pain and weakness
Bilateral
III
8
60/F
KSCC
T3N2M0/III
70 Gy/35F
70 Gy/35F
Yes
14
Pain
Bilateral
IV
9
48/F
KSCC
T2N1M0/II
70 Gy/35F
66 Gy/33F
No
5
Weakness and paresthesia
Bilateral
III
10
46/M
KSCC
T3N3M0/IV
72 Gy/36F
68 Gy/34F
Yes
3
Weakness
Bilateral
IV
1.8
First symptoms
Involvement
Scales of clinical manifestation
Weakness and hypesthesia
Bilateral
II
NKC, non-keratinizing carcinoma; D-NKC, differentiated NKC; UD-NKC, undifferentiated NKC; KSCC, keratinizing squamous cell carcinoma.
NEUROLOGICAL MANIFESTATIONS The first onset of clinical manifestations ranged between 34 and 60 (51.4 + 8.6) years of age. The latency of RIBP encompassed a large time span, which was from 1 to 17 (8.2 + 5.5) years. There were nine bilateral and one unilateral RIBP patients in our report. Seven patients complained of weakness, including disorders in shoulder abduction, arm raising, elbow bending and forearm rotation, yet their wrist and finger movements remained normal. The other three patients simply presented with isolated but intense pain in the upper limbs throughout the entire course. Among the former seven patients, only one suffered single motor symptoms, two combined with hyposthesia, one with numbness, and the remaining three with persistent but tolerable pain localized in the proximal arm. In addition, one of the 10 patients experienced significant atrophy in the deltoid muscle, biceps, and interosseous muscle 17 years after radiation. The symptoms of eight patients reached Grade 3 or 4 of the LENT/SOMA score.
and median nerve were exhibited in all patients. As an indication of neurogenic damage, broadened and increased motor unit action potentials (MUAPs) in the deltoid, biceps brachii and first dorsal interosseous muscles, were observed in each patient, supporting the injury of C5 – C7 nerve plexus (Fig. 2). Myokymia, an important symbol of radiation plexopathy, was observed in three patients. TREATMENT AND PROGNOSIS All 10 patients were medicated with drugs including glucocorticoids, mannitol, gangliosides, nerve growth factors and anticoagulants. Furthermore, pregabalin and/or neurotropin were used to alleviate neuropathic pain. Unfortunately, through all these active treatments, only one patient experienced temporary relief of pain, while symptoms of other patients increased continuously.
MRI EXAMINATION
DISCUSSION
Obvious swelling of bilateral nerve plexus from cervical 5 to thoracic 1 (C5 – T1), especially C5 – C7, was observed in all patients, which showed a low signal on T1-weighted MRI and a high signal on STIR (Fig. 1A). Peripheral enhancement of the nerve plexus was observed on T1-weighted enhanced images (Fig. 1B). Edema of brachial plexus fibers was clearly and completely displayed on MIP (Fig. 1C) and DTI (Fig. 1D).
RIBP, first recognized in 1966 by Stoll and Andrews, was considered a disastrous complication after radiotherapy for breast and lung cancer (10). NPC is the most common type of cancer in the Guangdong province, which has the highest incidence in the world (11,12). The treatment strategy for NPC has always been a challenge to radiation oncologists because of its unique histological features, strategic location, and high radiosensitivity, which distinguishes it from other head and neck cancers. With improvements in radiotherapy techniques, the 5-year survival rate of patients with NPC is up to 80% or more (13). Along this prolonged lifetime, the complications of radiotherapy have begun to garner the attention of specialists
ELECTROMYOGRAPHY Reduced sensory and motor nerve conduction velocity, prolonged latency, and decreased amplitude in the radial nerve
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
Age/ sex
Jpn J Clin Oncol 2014;44(8)
739
and scholars. Even so, there have been almost no reports on RIBP in patients with NPC until now, likely due to various aspects. First, the radiation field of NPC is further from the brachial plexus than in breast and lung cancer, so the brachial plexus is not often involved, which makes it a neglected area of research. Second, the long interval between irradiation and the onset of RIBP renders clinical follow-up more difficult. Finally, clinicians often have no awareness of RIBP, and patients with symptoms in the upper extremities are often misdiagnosed with tumor metastasis or other diseases. The mechanism of RIBP remains elusive. Brian C. Bowen divided RIBP into acute plexopathy and classic delayed injury (14). Acute injury develops several days to 6 months after the completion of radiotherapy. The main pathological of acute injury is inflammatory edema due to the direct neurotoxicity of radiation. Abnormal radiosensitivity of a genetic origin is the possible cause of acute onset. However, all the cases here suffered delayed injury. Delayed injury occurs 6 months or later, it may be caused by the late toxicity of accumulated rays within neighboring tissues. The vascular lesions and fibrosis of connective tissues surrounding the brachial plexus may ultimately result in ischemia as well as nerve demyelination. Some degree of recovery following the 3-month use of anticoagulant agents was reported in radiation injuries of peripheral nerves, which may be a support of blood vessel injury (15,16). In addition, our previous experiment demonstrated
that basic fibroblast growth factor (bFGF) could protect neurons from late radiation injury in vitro via the ERK1/2 signal transduction pathway, which may identify a new direction in neural regeneration for future research on the mechanism of RIBP (17,18). As the pathogenesis of neuroinjury after irradiation is a slow, gradual process, the incidence of RIBP is likely to increase over time. Typical RIBP occurs in patients with the following risk factors: high dose per fraction and total irradiation dose, overlapping fields, increased dose in axilla, as well as concurrent chemotherapy (19). High-dose radiation could bring damage to nuclear chromosomes and mitochondria, then leads to declination of cellular regeneration and aggravation of hypoxia. Historical data gathered mostly on breast cancer patients suggested that the 5% RIBP risk at 5 years was .60 Gy and that the 50% risk at 5 years was nearly 75 Gy, respectively (4). The incidence of brachial plexus injury significantly increased with doses .2 Gy per fraction (20). In our study, the total radiation dose of the nasopharynx ranged from 66.6 to 74 Gy, that of the supraclavicular fossa ranged from 60 to 70 Gy, and the per fraction dose of most patients reached 2.0 Gy. On the basis of the literature, they were all within the range of risk exposure that could result in RIBI. Cytotoxic chemotherapy is likely to bind to tubulin in the axoplasm and reduce the anterograde axoplasmic transport. It may be neurotoxic due to treatment-related immunosuppression and
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
Figure 1. Coronal magnetic resonance (MR) image of one patient. Female, 48 years old, 9 years after radiotherapy of NPC, the bilateral damage of C5 – T1 nerve plexus. (A) Swelling of nerve plexus, high signal on short tau inversion recovery sequences; (B) significantly strengthen of nerve plexus on T1-weighted magnetic resonance imaging enhanced images; (C and D) maximum intensity projection and diffusion tensor imaging showed injuries of brachial plexus fibers clearly and completely.
740
RIBP for NPC
subsequent impaired cellular response to damaged tissue (21). High-dose irradiation and concomitant chemotherapy were also shown to contribute to the severity of neurological injury. In this study, the total dose of eight patients whose symptoms reached Grade 3 or 4 received irradiation dose of .70 Gy, and six patients who received chemotherapy suffered injuries reaching Grade 3 or 4. The symptoms of our patients were predominantly distributed in the bilateral upper brachial plexus, mainly involving the C5 – C7 nerve plexus. This is quite different from the plexopathy caused by tumor infiltration, in which muscle weakness could begin unilaterally and is always limited in a C8 to T1 (lower plexus) distribution (3,19). As for the lower risk for lower trunk of brachial plexus injury, we speculate it may be
explained by the following reasons: Firstly, the supraclavicular region, where the lower trunk distributes, receives a lower radiation dose (64.2 + 3.3 Gy) than the upper neck region (70.5 + 1.9 Gy) when the neck was treated, therefore, the lower trunk may be at lower risk of RIBP than the upper trunk. Secondly, the ray could be attenuated when it passes through the high-density clavicle, then it may be less invasive to the lower trunk of brachial plexus (19,22). While the upper trunk traces a longer course through the radiation field and has less protection due to a smaller amount of tissue within the occipital triangle (19). MRI is a momentous application for the diagnosis of RIBP. Bilbey et al. (23) reported that delayed radiation injury or fibrosis were usually isointense or hypointense relative to
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
Figure 2. Electromyography examination of one patient. Male, 46-years-old, 3 years after radiotherapy of NPC, the injury of right brachial plexus. (A) The first dorsal interosseous, 15 MUAPs were analyzed and 1(6.67%) of them was polyphasic; (B) The deltoid, 12 MUAPs were analyzed and 6(50.00%) of them was polyphasic.
Jpn J Clin Oncol 2014;44(8)
CONCLUSIONS RIBP is a scarce but devastating complication of radiotherapy that may lead to upper limb disability in patients with NPC. To date, the mechanism of RIBP has been unclear. Medical providers should be aware of this side effect when developing a radiotherapeutic plan for patients with NPC and should maintain regular clinical follow-up with these patients after radiotherapy.
Funding This study was supported by grants to Jun Liu from the National Natural Science Foundation of China (no.81372919) and the Guangdong Natural Science Foundation (no. S2013010013964).
Conflict of interest statement None declared.
References 1. Zhao Z, Lan Y, Bai S, et al. Late-onset radiation-induced optic neuropathy after radiotherapy for nasopharyngeal carcinoma. J Clin Neurosci 2013;20:702– 6. 2. Ferrante MA. Brachial plexopathies: classification, causes, and consequences. Muscle Nerve 2004;30:547– 68. 3. Jaeckle KA. Neurological manifestations of neoplastic and radiationinduced plexopathies. Semin Neurol 2004;24:385– 93. 4. Fathers E, Thrush D, Huson SM, Norman A. Radiation-induced brachial plexopathy in women treated for carcinoma of the breast. Clin Rehabil 2002;16:160–5. 5. Bajrovic A, Rades D, Fehlauer F, et al. Is there a life-long risk of brachial plexopathy after radiotherapy of supraclavicular lymph nodes in breast cancer patients? Radiother Oncol 2004;71:297– 301. 6. Johansson S, Svensson H, Larsson LG, Denekamp J. Brachial plexopathy after postoperative radiotherapy of breast cancer patients—a long-term follow-up. Acta Oncol 2000;39:373–82. 7. Fehlauer F, Tribius S, Holler U, et al. Long-term radiation sequelae after breast-conserving therapy in women with early-stage breast cancer: an observational study using the LENT-SOMA scoring system. Int J Radiat Oncol Biol Phys 2003;55:651–8. 8. Tuan JK, Ha TC, Ong WS, et al. Late toxicities after conventional radiation therapy alone for nasopharyngeal carcinoma. Radiother Oncol 2012;104:305 –11. 9. Jen YM, Shih R, Lin YS, et al. Parotid gland-sparing 3-dimensional conformal radiotherapy results in less severe dry mouth in nasopharyngeal cancer patients: a dosimetric and clinical comparison with conventional radiotherapy. Radiother Oncol 2005;75:204– 9. 10. Wouter VEH, Engelen AM, Witkamp TD, Ramos LM, Feldberg MA. Radiation-induced brachial plexopathy: MR imaging. Skeletal Radiol 1997;26:284– 8. 11. Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev 2006;15:1765– 77. 12. Chen J, Dassarath M, Yin Z, Liu H, Yang K, Wu G. Radiation induced temporal lobe necrosis in patients with nasopharyngeal carcinoma: a review of new avenues in its management. Radiat Oncol 2011;6:128. 13. Lee AW, Sze WM, Au JS, et al. Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys 2005;61:1107– 16. 14. Bowen BC, Verma A, Brandon AH, Fiedler JA. Radiation-induced brachial plexopathy: MR and clinical findings. AJNR Am J Neuroradiol 1996;17:1932 –6. 15. Soto O. Radiation-induced conduction block: resolution following anticoagulant therapy. Muscle Nerve 2005;31:642– 5. 16. Tung TH, Liu DZ, Mackinnon SE. Nerve transfer for elbow flexion in radiation-induced brachial plexopathy: a case report. Hand (N Y) 2009;4:123– 8. 17. Luan P, Zhou HH, Zhang B, et al. Basic fibroblast growth factor protects C17.2 cells from radiation-induced injury through ERK1/2. CNS Neurosci Ther 2012;18:767– 72. 18. Zhao ZY, Luan P, Huang SX, et al. Edaravone protects HT22 neurons from H2O2-induced apoptosis by inhibiting the MAPK signaling pathway. CNS Neurosci Ther 2013;19:163– 9. 19. Gosk J, Rutowski R, Reichert P, Rabczynski J. Radiation-induced brachial plexus neuropathy—aetiopathogenesis, risk factors, differential
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
muscle on T 2-weighted images (T2 WI). Wouter et al. (10), however, noted that swelling and diffuse infiltration of the brachial plexus showed slight hyperintensity or hyperintensity on T 2WI. Radiation is known to cause a connective tissue response ranging from edema and acute inflammation to chronic inflammation, progressive fibrosis and neovascularization. These diverse pathological changes could account for the different signal abnormalities. All our patients suffered delayed injury and showed obvious hyperintensity on T2WI or STIR sequences. In particular, as an advanced MRI technique, DTI is performed to clearly visualize the injured nerve fibers and detect radiation injury earlier. EMG is another valid means to diagnose RIBP. Myokymia may be a significant distinction between radiation-induced and neoplastic brachial plexopathy (24,25). As for a differential diagnosis, not only tumor infiltration but also chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) should be considered. Patients with neuropathy of otherwise unknown etiology are more likely to have CIDP. The following clinical factors are suggestive of CIDP: classical symmetrical distal weakness in upper and lower extremities, sensory disturbance at nerve roots distributing areas, cranial nerve involvement and a favorable response to therapy (26). When the classical clinical features are present, the distinguished diagnosis between RIBP and CIDP can be straightforward. With active medications, almost no patients in our study obtained significant relief of their symptoms. It is not difficult to explain with respect to the mechanisms mentioned above. All patients here suffered delayed injury, which was considered caused by the compression of surrounding tissues. This nerve compression could not be removed via pharmacotherapy, so necrosis would eventually occur, and finally, the neurological function would be lost inevitably. Therefore, some surgical procedures, including neurolysis and omentoplasty, have been attempted for patients whose injuries reached Grades 3 or 4 on the modified LENT/SOMA scale (19,27). Pathogenesis of radiation injury is a chronic process. Recent publications have shown the progressively increasing morbidity of RIBP over the entire 34-year follow-up after aggressive telecobalt therapy (28). From our data, the latency of RIBP in NPC patients encompassed a long time span from 1 to 17 years, which indicates the importance of regular follow-up after radiotherapy for NPC.
741
742
20. 21. 22. 23.
RIBP for NPC
diagnostics, symptoms and treatment. Folia Neuropathol 2007;45: 26 – 30. Wittenberg KH, Adkins MC. MR imaging of nontraumatic brachial plexopathies: frequency and spectrum of findings. Radiographics 2000;20:1023–32. Chambless LB, Angel FB, Abel TW, Xia F, Weaver KD. Delayed cerebral radiation necrosis following treatment for a plasmacytoma of the skull. Surg Neurol Int 2010;1:65. Brennan MJ. Breast cancer recurrence in a patient with a previous history of radiation injury of the brachial plexus: a case report. Arch Phys Med Rehabil 1995;76:974–6. Bilbey JH, Lamond RG, Mattrey RF. MR imaging of disorders of the brachial plexus. J Magn Reson Imaging 1994;4:13– 8.
24. Shimazaki H, Nakano I. Radiation myelopathy and plexopathy. Brain Nerve 2008;60:115– 21. 25. Ko K, Sung DH, Kang MJ, et al. Clinical, electrophysiological findings in adult patients with non-traumatic plexopathies. Ann Rehabil Med 2011;35:807–15. 26. Brannagan TR. Current diagnosis of CIDP: the need for biomarkers. J Peripher Nerv Syst 2011;16(Suppl 1):3 –13. 27. Gosk J, Rutowski R, Urban M, Wiecek R, Rabczynski J. Brachial plexus injuries after radiotherapy—analysis of 6 cases. Folia Neuropathol 2007;45:31 –5. 28. Johansson S, Svensson H, Denekamp J. Timescale of evolution of late radiation injury after postoperative radiotherapy of breast cancer patients. Int J Radiat Oncol Biol Phys 2000;48:745–50.
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
Radiation-induced Brachial Plexus Injury After Radiotherapy for Nasopharyngeal Carcinoma Beibei Gu1,†, Zhihua Yang2,†, Shixiong Huang3, Songhua Xiao1, Bei Zhang4, Lianhong Yang1, Jia Zhao1, Zhongyan Zhao3, Jun Shen1 and Jun Liu1,* 1
Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong, Guangzhou, Department of Neurology, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, 3Department of Neurology, Hainan Provincial People’s Hospital, Haikou and 4Department of Neurology, The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, China 2
Received February 12, 2014; accepted April 17, 2014
Objective: Radiation-induced brachial plexus injury is a devastating complication that occurs after radiotherapy in the vicinity of the brachial plexus. Nasopharyngeal carcinoma, the most common type of cancer in Guangdong Province, is primarily treated with radiotherapy with subsequent side effects. However, radiation-induced brachial plexus injury is rarely reported in nasopharyngeal carcinoma. To draw attention to this correlation, we analyzed the clinical characteristics including the imaging findings of 10 patients suffering from radiation-induced brachial plexus injury for nasopharyngeal carcinoma. Methods: We considered the patients’ medical histories, analyzed their clinical characteristics, and monitored the long-term efficacy of treatment. Results: The total irradiation dose of the nasopharynx ranged from 66.6 to 74 Gy, and that of the supraclavicular fossa ranged from 60 to 70 Gy. The mean latency was 8.2 + 5.5 years. Seven patients initially complained of bilateral weakness, and three patients complained of isolated pain. The injuries of eight patients reached Grade 3 or worse. Magnetic resonance imaging showed a low signal on T1-weighted images and a high signal on short tau inversion recovery sequences in all cases. Swollen nerve fibers were clearly displayed in magnetic resonance diffusion tensor imaging. Electromyography showed myokymia in three patients. With conservative therapy, only one patient was temporarily relieved of pain, while the conditions of others were not ameliorated. Conclusions: Radiation-induced brachial plexus injury is a late but catastrophic complication in patients with nasopharyngeal carcinoma. Clinicians should be aware of radiation-induced brachial plexus injury when deciding on treatment and should give them regular follow-up post radiotherapy. Key words: radiation-induced brachial plexus injury – nasopharyngeal carcinoma – neurological manifestations – MRI – electromyography
# The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
*For reprints and all correspondence: Jun Liu, Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong 510120, China. E-mail: [email protected] † These authors contributed equally to this work.
Jpn J Clin Oncol 2014;44(8)
INTRODUCTION
Table 1. Modified LENT/SOMA scale Grade Symptoms 1
Mild sensory deficits, no pain, no treatment required
2
Moderate sensory deficits, tolerable pain, mild arm weakness
3
Continuous paresthesia with incomplete paresis, pain medication required
4
Complete paresis, excruciating pain, muscle atrophy, regular pain medication required
LENT/SOMA, late effects of normal tissues conference/subjective, objective, management, and analytic.
DIAGNOSIS AND ASSESSMENT OF RIBP For patients with NPC who had previously received radiotherapy, RIBP was diagnosed based on the detailed history, as well as physical MRI and electrophysiological examination, on the condition that all other causes are excluded. The severity of RIBP was assessed based on a modified late effects of normal tissues conference/subjective, objective, management, and analytic (LENT/SOMA) score (6,7), the details of which are shown in Table 1.
RESULTS CLINICAL CHARACTERISTICS OF NPC
PATIENTS AND METHODS PARTICIPANTS From January 2007 to December 2012, 1209 patients at Sun Yat-sen Memorial Hospital of Sun Yat-sen University displayed various radiation-related complications after receiving radiotherapy for NPC. These patients were periodically evaluated at 6-month intervals after they were discharged from the hospital. Ten patients (0.83%) could not be contacted, so they were excluded from this study. Through this review, we found 10 patients (four males and six females) who suffered from RIBP, and obtained details from their clinical materials.
AUXILIARY EXAMINATION In this retrospective study, all the patients were assessed by certified neurologists. The latency of RIBP was evaluated from the end of radiotherapy to the onset of the symptoms. MRI, including conventional T1-weighted enhanced images and short tau inversion recovery sequences (STIR) using 3T magnets, was performed to confirm the diagnosis and to distinguish RIBP from tumor metastases. Diffusion tensor imaging (DTI) and maximum intensity projection (MIP) were used to show edema of the brachial plexus more clearly. Electromyography (EMG) was also performed to confirm the brachial plexus injury.
All 10 patients were definitely diagnosed with NPC according to their pathological manifestations. Tumor staging was performed according to the 2002 tumor, node, and metastasis classification system of the American Joint Committee on Cancer (AJCC). They all suffered from regionally (Nþ: 100%) advanced tumors. Three of them had stage T1, two had stage T2, four had stage T3 and one had stage T4. Nodal involvement was N1 in three patients, N2 in six patients and N3 in one patient, and there were no distant metastases. The pathological subtypes included seven keratinizing squamous cell carcinomas (KSCC), two undifferentiated nonkeratinizing carcinomas (UD-NKC), and one differentiated non-keratinizing carcinoma (D-NKC). The detailed information is listed in Table 2. All patients underwent conventional external beam radiotherapy comprised of a three-field facial technique encompassing the nasopharynx and immediate risk areas, and a single matched anterior split neck field. Two large bilateral opposed fields were used to treat the nasopharynx and the upper neck, and an anterior port was applied to the rest of the neck and the supraclavicular fossa (8,9). Conventional radiotherapy was given in 2 –3 different phases. The target dose to the nasopharynx and upper neck ranged from 66.6 to 74 Gy (70.5 + 1.9). The lower neck and supraclavicular fossa received a dose of 60 to 70 Gy (64.2 + 3.3). Treatment was completed in 1.8–2.0 Gy fractions daily five times per week. In addition, seven patients with advanced stage T3–T4 or N2–N3 NPC were treated with five or more cycles of neoadjuvant chemotherapy.
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
Nasopharyngeal carcinoma (NPC) is the most common type of cancer in the Guangdong province of China. The incidence of NPC in Guangdong Province is the highest in the world, which is .30 per 100 000 people among males (1). Due to its special pathological features, radiotherapy is the primary treatment for NPC. However, radiation exposure may cause serious side effects in normal tissues. Radiation-induced brachial plexus injury (RIBP) is a rare but severe complication in patients who have received radiation in the vicinity of the brachial plexus (2,3). RIBP usually begins months to years after the end of radiotherapy (4). Symptoms of RIBP including motor and sensory disorders in the bilateral upper extremities, may largely affect the quality of life for each patient. RIBP is most commonly observed in breast and lung cancers, yet it is seldom reported in patients with NPC (5). Recent improvements in radiation techniques have resulted in longer survival time; thus, patients with NPC have more opportunities to develop RIBP, which means that more attention should be given to RIBP, despite the rarity of reports. In the present study, we report on 10 patients who suffered from RIBP after receiving radiotherapy for NPC. Studying the clinical characteristics of RIBP may increase awareness of RIBP and offer an opportunity to explore strategies to prevent or ameliorate this side effect.
737
738
RIBP for NPC
Table 2. Characteristics of nasopharyngeal carcinoma patients with radiation-induced brachial plexus injury Patient number
Pathological classification
Tumor stage
Dose of irradiation (nasopharynx)
Dose of irradiation (supraclavicular fossa)
Adjuvant treatments
Latency period (years)
1
34/F
D-NKC
T1N2M0/III
66.6 Gy/37F
61.2 Gy/34F
Yes
2
58/F
UD-NKC
T3N2M0/III
70 Gy/35F
64 Gy/32F
Yes
17
Pain
Bilateral
III
3
59/F
KSCC
T2N1M0/II
70 Gy/35F
60 Gy/30F
No
7
Pain
Bilateral
III
4
52/M
KSCC
T4N1M0/IV
74 Gy/37F
66 Gy/33F
Yes
12
Weakness
Bilateral
III
5
43/M
UD-NKC
T3N2M0/III
72 Gy/36F
64 Gy/32F
Yes
1
Weakness
Unilateral
III
6
60/M
KSCC
T1N2M0/III
70 Gy/35F
63 Gy/35F
No
9
Weakness and numbness
Bilateral
II
7
54/F
KSCC
T1N2M0/III
70 Gy/35F
60 Gy/33F
Yes
12
Pain and weakness
Bilateral
III
8
60/F
KSCC
T3N2M0/III
70 Gy/35F
70 Gy/35F
Yes
14
Pain
Bilateral
IV
9
48/F
KSCC
T2N1M0/II
70 Gy/35F
66 Gy/33F
No
5
Weakness and paresthesia
Bilateral
III
10
46/M
KSCC
T3N3M0/IV
72 Gy/36F
68 Gy/34F
Yes
3
Weakness
Bilateral
IV
1.8
First symptoms
Involvement
Scales of clinical manifestation
Weakness and hypesthesia
Bilateral
II
NKC, non-keratinizing carcinoma; D-NKC, differentiated NKC; UD-NKC, undifferentiated NKC; KSCC, keratinizing squamous cell carcinoma.
NEUROLOGICAL MANIFESTATIONS The first onset of clinical manifestations ranged between 34 and 60 (51.4 + 8.6) years of age. The latency of RIBP encompassed a large time span, which was from 1 to 17 (8.2 + 5.5) years. There were nine bilateral and one unilateral RIBP patients in our report. Seven patients complained of weakness, including disorders in shoulder abduction, arm raising, elbow bending and forearm rotation, yet their wrist and finger movements remained normal. The other three patients simply presented with isolated but intense pain in the upper limbs throughout the entire course. Among the former seven patients, only one suffered single motor symptoms, two combined with hyposthesia, one with numbness, and the remaining three with persistent but tolerable pain localized in the proximal arm. In addition, one of the 10 patients experienced significant atrophy in the deltoid muscle, biceps, and interosseous muscle 17 years after radiation. The symptoms of eight patients reached Grade 3 or 4 of the LENT/SOMA score.
and median nerve were exhibited in all patients. As an indication of neurogenic damage, broadened and increased motor unit action potentials (MUAPs) in the deltoid, biceps brachii and first dorsal interosseous muscles, were observed in each patient, supporting the injury of C5 – C7 nerve plexus (Fig. 2). Myokymia, an important symbol of radiation plexopathy, was observed in three patients. TREATMENT AND PROGNOSIS All 10 patients were medicated with drugs including glucocorticoids, mannitol, gangliosides, nerve growth factors and anticoagulants. Furthermore, pregabalin and/or neurotropin were used to alleviate neuropathic pain. Unfortunately, through all these active treatments, only one patient experienced temporary relief of pain, while symptoms of other patients increased continuously.
MRI EXAMINATION
DISCUSSION
Obvious swelling of bilateral nerve plexus from cervical 5 to thoracic 1 (C5 – T1), especially C5 – C7, was observed in all patients, which showed a low signal on T1-weighted MRI and a high signal on STIR (Fig. 1A). Peripheral enhancement of the nerve plexus was observed on T1-weighted enhanced images (Fig. 1B). Edema of brachial plexus fibers was clearly and completely displayed on MIP (Fig. 1C) and DTI (Fig. 1D).
RIBP, first recognized in 1966 by Stoll and Andrews, was considered a disastrous complication after radiotherapy for breast and lung cancer (10). NPC is the most common type of cancer in the Guangdong province, which has the highest incidence in the world (11,12). The treatment strategy for NPC has always been a challenge to radiation oncologists because of its unique histological features, strategic location, and high radiosensitivity, which distinguishes it from other head and neck cancers. With improvements in radiotherapy techniques, the 5-year survival rate of patients with NPC is up to 80% or more (13). Along this prolonged lifetime, the complications of radiotherapy have begun to garner the attention of specialists
ELECTROMYOGRAPHY Reduced sensory and motor nerve conduction velocity, prolonged latency, and decreased amplitude in the radial nerve
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
Age/ sex
Jpn J Clin Oncol 2014;44(8)
739
and scholars. Even so, there have been almost no reports on RIBP in patients with NPC until now, likely due to various aspects. First, the radiation field of NPC is further from the brachial plexus than in breast and lung cancer, so the brachial plexus is not often involved, which makes it a neglected area of research. Second, the long interval between irradiation and the onset of RIBP renders clinical follow-up more difficult. Finally, clinicians often have no awareness of RIBP, and patients with symptoms in the upper extremities are often misdiagnosed with tumor metastasis or other diseases. The mechanism of RIBP remains elusive. Brian C. Bowen divided RIBP into acute plexopathy and classic delayed injury (14). Acute injury develops several days to 6 months after the completion of radiotherapy. The main pathological of acute injury is inflammatory edema due to the direct neurotoxicity of radiation. Abnormal radiosensitivity of a genetic origin is the possible cause of acute onset. However, all the cases here suffered delayed injury. Delayed injury occurs 6 months or later, it may be caused by the late toxicity of accumulated rays within neighboring tissues. The vascular lesions and fibrosis of connective tissues surrounding the brachial plexus may ultimately result in ischemia as well as nerve demyelination. Some degree of recovery following the 3-month use of anticoagulant agents was reported in radiation injuries of peripheral nerves, which may be a support of blood vessel injury (15,16). In addition, our previous experiment demonstrated
that basic fibroblast growth factor (bFGF) could protect neurons from late radiation injury in vitro via the ERK1/2 signal transduction pathway, which may identify a new direction in neural regeneration for future research on the mechanism of RIBP (17,18). As the pathogenesis of neuroinjury after irradiation is a slow, gradual process, the incidence of RIBP is likely to increase over time. Typical RIBP occurs in patients with the following risk factors: high dose per fraction and total irradiation dose, overlapping fields, increased dose in axilla, as well as concurrent chemotherapy (19). High-dose radiation could bring damage to nuclear chromosomes and mitochondria, then leads to declination of cellular regeneration and aggravation of hypoxia. Historical data gathered mostly on breast cancer patients suggested that the 5% RIBP risk at 5 years was .60 Gy and that the 50% risk at 5 years was nearly 75 Gy, respectively (4). The incidence of brachial plexus injury significantly increased with doses .2 Gy per fraction (20). In our study, the total radiation dose of the nasopharynx ranged from 66.6 to 74 Gy, that of the supraclavicular fossa ranged from 60 to 70 Gy, and the per fraction dose of most patients reached 2.0 Gy. On the basis of the literature, they were all within the range of risk exposure that could result in RIBI. Cytotoxic chemotherapy is likely to bind to tubulin in the axoplasm and reduce the anterograde axoplasmic transport. It may be neurotoxic due to treatment-related immunosuppression and
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
Figure 1. Coronal magnetic resonance (MR) image of one patient. Female, 48 years old, 9 years after radiotherapy of NPC, the bilateral damage of C5 – T1 nerve plexus. (A) Swelling of nerve plexus, high signal on short tau inversion recovery sequences; (B) significantly strengthen of nerve plexus on T1-weighted magnetic resonance imaging enhanced images; (C and D) maximum intensity projection and diffusion tensor imaging showed injuries of brachial plexus fibers clearly and completely.
740
RIBP for NPC
subsequent impaired cellular response to damaged tissue (21). High-dose irradiation and concomitant chemotherapy were also shown to contribute to the severity of neurological injury. In this study, the total dose of eight patients whose symptoms reached Grade 3 or 4 received irradiation dose of .70 Gy, and six patients who received chemotherapy suffered injuries reaching Grade 3 or 4. The symptoms of our patients were predominantly distributed in the bilateral upper brachial plexus, mainly involving the C5 – C7 nerve plexus. This is quite different from the plexopathy caused by tumor infiltration, in which muscle weakness could begin unilaterally and is always limited in a C8 to T1 (lower plexus) distribution (3,19). As for the lower risk for lower trunk of brachial plexus injury, we speculate it may be
explained by the following reasons: Firstly, the supraclavicular region, where the lower trunk distributes, receives a lower radiation dose (64.2 + 3.3 Gy) than the upper neck region (70.5 + 1.9 Gy) when the neck was treated, therefore, the lower trunk may be at lower risk of RIBP than the upper trunk. Secondly, the ray could be attenuated when it passes through the high-density clavicle, then it may be less invasive to the lower trunk of brachial plexus (19,22). While the upper trunk traces a longer course through the radiation field and has less protection due to a smaller amount of tissue within the occipital triangle (19). MRI is a momentous application for the diagnosis of RIBP. Bilbey et al. (23) reported that delayed radiation injury or fibrosis were usually isointense or hypointense relative to
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
Figure 2. Electromyography examination of one patient. Male, 46-years-old, 3 years after radiotherapy of NPC, the injury of right brachial plexus. (A) The first dorsal interosseous, 15 MUAPs were analyzed and 1(6.67%) of them was polyphasic; (B) The deltoid, 12 MUAPs were analyzed and 6(50.00%) of them was polyphasic.
Jpn J Clin Oncol 2014;44(8)
CONCLUSIONS RIBP is a scarce but devastating complication of radiotherapy that may lead to upper limb disability in patients with NPC. To date, the mechanism of RIBP has been unclear. Medical providers should be aware of this side effect when developing a radiotherapeutic plan for patients with NPC and should maintain regular clinical follow-up with these patients after radiotherapy.
Funding This study was supported by grants to Jun Liu from the National Natural Science Foundation of China (no.81372919) and the Guangdong Natural Science Foundation (no. S2013010013964).
Conflict of interest statement None declared.
References 1. Zhao Z, Lan Y, Bai S, et al. Late-onset radiation-induced optic neuropathy after radiotherapy for nasopharyngeal carcinoma. J Clin Neurosci 2013;20:702– 6. 2. Ferrante MA. Brachial plexopathies: classification, causes, and consequences. Muscle Nerve 2004;30:547– 68. 3. Jaeckle KA. Neurological manifestations of neoplastic and radiationinduced plexopathies. Semin Neurol 2004;24:385– 93. 4. Fathers E, Thrush D, Huson SM, Norman A. Radiation-induced brachial plexopathy in women treated for carcinoma of the breast. Clin Rehabil 2002;16:160–5. 5. Bajrovic A, Rades D, Fehlauer F, et al. Is there a life-long risk of brachial plexopathy after radiotherapy of supraclavicular lymph nodes in breast cancer patients? Radiother Oncol 2004;71:297– 301. 6. Johansson S, Svensson H, Larsson LG, Denekamp J. Brachial plexopathy after postoperative radiotherapy of breast cancer patients—a long-term follow-up. Acta Oncol 2000;39:373–82. 7. Fehlauer F, Tribius S, Holler U, et al. Long-term radiation sequelae after breast-conserving therapy in women with early-stage breast cancer: an observational study using the LENT-SOMA scoring system. Int J Radiat Oncol Biol Phys 2003;55:651–8. 8. Tuan JK, Ha TC, Ong WS, et al. Late toxicities after conventional radiation therapy alone for nasopharyngeal carcinoma. Radiother Oncol 2012;104:305 –11. 9. Jen YM, Shih R, Lin YS, et al. Parotid gland-sparing 3-dimensional conformal radiotherapy results in less severe dry mouth in nasopharyngeal cancer patients: a dosimetric and clinical comparison with conventional radiotherapy. Radiother Oncol 2005;75:204– 9. 10. Wouter VEH, Engelen AM, Witkamp TD, Ramos LM, Feldberg MA. Radiation-induced brachial plexopathy: MR imaging. Skeletal Radiol 1997;26:284– 8. 11. Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev 2006;15:1765– 77. 12. Chen J, Dassarath M, Yin Z, Liu H, Yang K, Wu G. Radiation induced temporal lobe necrosis in patients with nasopharyngeal carcinoma: a review of new avenues in its management. Radiat Oncol 2011;6:128. 13. Lee AW, Sze WM, Au JS, et al. Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys 2005;61:1107– 16. 14. Bowen BC, Verma A, Brandon AH, Fiedler JA. Radiation-induced brachial plexopathy: MR and clinical findings. AJNR Am J Neuroradiol 1996;17:1932 –6. 15. Soto O. Radiation-induced conduction block: resolution following anticoagulant therapy. Muscle Nerve 2005;31:642– 5. 16. Tung TH, Liu DZ, Mackinnon SE. Nerve transfer for elbow flexion in radiation-induced brachial plexopathy: a case report. Hand (N Y) 2009;4:123– 8. 17. Luan P, Zhou HH, Zhang B, et al. Basic fibroblast growth factor protects C17.2 cells from radiation-induced injury through ERK1/2. CNS Neurosci Ther 2012;18:767– 72. 18. Zhao ZY, Luan P, Huang SX, et al. Edaravone protects HT22 neurons from H2O2-induced apoptosis by inhibiting the MAPK signaling pathway. CNS Neurosci Ther 2013;19:163– 9. 19. Gosk J, Rutowski R, Reichert P, Rabczynski J. Radiation-induced brachial plexus neuropathy—aetiopathogenesis, risk factors, differential
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
muscle on T 2-weighted images (T2 WI). Wouter et al. (10), however, noted that swelling and diffuse infiltration of the brachial plexus showed slight hyperintensity or hyperintensity on T 2WI. Radiation is known to cause a connective tissue response ranging from edema and acute inflammation to chronic inflammation, progressive fibrosis and neovascularization. These diverse pathological changes could account for the different signal abnormalities. All our patients suffered delayed injury and showed obvious hyperintensity on T2WI or STIR sequences. In particular, as an advanced MRI technique, DTI is performed to clearly visualize the injured nerve fibers and detect radiation injury earlier. EMG is another valid means to diagnose RIBP. Myokymia may be a significant distinction between radiation-induced and neoplastic brachial plexopathy (24,25). As for a differential diagnosis, not only tumor infiltration but also chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) should be considered. Patients with neuropathy of otherwise unknown etiology are more likely to have CIDP. The following clinical factors are suggestive of CIDP: classical symmetrical distal weakness in upper and lower extremities, sensory disturbance at nerve roots distributing areas, cranial nerve involvement and a favorable response to therapy (26). When the classical clinical features are present, the distinguished diagnosis between RIBP and CIDP can be straightforward. With active medications, almost no patients in our study obtained significant relief of their symptoms. It is not difficult to explain with respect to the mechanisms mentioned above. All patients here suffered delayed injury, which was considered caused by the compression of surrounding tissues. This nerve compression could not be removed via pharmacotherapy, so necrosis would eventually occur, and finally, the neurological function would be lost inevitably. Therefore, some surgical procedures, including neurolysis and omentoplasty, have been attempted for patients whose injuries reached Grades 3 or 4 on the modified LENT/SOMA scale (19,27). Pathogenesis of radiation injury is a chronic process. Recent publications have shown the progressively increasing morbidity of RIBP over the entire 34-year follow-up after aggressive telecobalt therapy (28). From our data, the latency of RIBP in NPC patients encompassed a long time span from 1 to 17 years, which indicates the importance of regular follow-up after radiotherapy for NPC.
741
742
20. 21. 22. 23.
RIBP for NPC
diagnostics, symptoms and treatment. Folia Neuropathol 2007;45: 26 – 30. Wittenberg KH, Adkins MC. MR imaging of nontraumatic brachial plexopathies: frequency and spectrum of findings. Radiographics 2000;20:1023–32. Chambless LB, Angel FB, Abel TW, Xia F, Weaver KD. Delayed cerebral radiation necrosis following treatment for a plasmacytoma of the skull. Surg Neurol Int 2010;1:65. Brennan MJ. Breast cancer recurrence in a patient with a previous history of radiation injury of the brachial plexus: a case report. Arch Phys Med Rehabil 1995;76:974–6. Bilbey JH, Lamond RG, Mattrey RF. MR imaging of disorders of the brachial plexus. J Magn Reson Imaging 1994;4:13– 8.
24. Shimazaki H, Nakano I. Radiation myelopathy and plexopathy. Brain Nerve 2008;60:115– 21. 25. Ko K, Sung DH, Kang MJ, et al. Clinical, electrophysiological findings in adult patients with non-traumatic plexopathies. Ann Rehabil Med 2011;35:807–15. 26. Brannagan TR. Current diagnosis of CIDP: the need for biomarkers. J Peripher Nerv Syst 2011;16(Suppl 1):3 –13. 27. Gosk J, Rutowski R, Urban M, Wiecek R, Rabczynski J. Brachial plexus injuries after radiotherapy—analysis of 6 cases. Folia Neuropathol 2007;45:31 –5. 28. Johansson S, Svensson H, Denekamp J. Timescale of evolution of late radiation injury after postoperative radiotherapy of breast cancer patients. Int J Radiat Oncol Biol Phys 2000;48:745–50.
Downloaded from http://jjco.oxfordjournals.org/ at University of Cambridge on October 21, 2014
