European Annals of Otorhinolaryngology Head and Neck diseases 131 20 - PDF document

1 European Annals of Otorhinolaryngology,
European Annals of Otorhinolaryngology, Head and Neck diseases 131 (2014) 223…226 Available online at ScienceDirectwww.sciencedirect.com for glomus jugulare paragangliomaP. Tran Ba Huy2, rue Saint-Petersbourg, 75010 Paris, France a r t i c l e i n f o Keywords:Glomus jugulare paragangliomaRadiotherapy complications a b s t r a c t Surgery has been long considered to be the treatment of choice for glomus jugulare paragangliomas, asit is the only modality able to totally eradicate the tumour. However, despite considerable progress ininterventional radiology and nerve monitoring, surgery is associated with an unacceptably high com-plication rate for a benign tumour, explaining the growing place of radiotherapy in the managementof these tumours. This review of the literature con“rms the ef“cacy of conformal radiotherapy with orwithout intensity modulation and stereotactic radiotherapy, which both achieve tumour control ratesranging from 90% to almost 100% of cases, but for different tumour volumes, almost constant stabilizationor even improvement of symptoms, and a considerably rate of adverse effects than with surgery.However, radiotherapy remains contraindicated in the presence of intracranial invasion or extensiveosteomyelitis. In the light of these results, together with the improved quality of life and a better knowl-edge of the natural history of this disease, many authors propose radiotherapy as “rst-line treatment forall glomus jugulare paragangliomas regardless of their size, particularly in patients with no preoperativede“cits.© 2014 Published by Elsevier Masson SAS. For a long time, radiotherapy was the only treatment optionavailable to otorhinolaryngologists to try to control glomus jugu-lare paragangliomas [1,2] The complex anatomy of the regionand the limited surgical techniques available discouraged a morehazardous approach, especially surgical resection of this highlyhaemorrhagic tumour [3,4] However, from the 1980s onwards, the development ofmicrosurgical techniques combined with progress in morpholog-ical interventional radiology and electrophysiological monitoringallowed surgical resection preceded by embolization to become thetreatment of choice [5] Nevertheless, the surgical iatrogenic effects frequentlyobserved, which are increasingly unacceptable for a benigntumour, the growing importance of quality of life, the betterknowledge of the natural history of the tumour and improve-ment of techniques and introduction of new irradiation modalitiesexplain why radiotherapy now, once again, constitutes an essentialtreatment option [6,7] This article presents a review of the literature concerning thecurrent place of radiotherapy in the management of glomus jugu-lare paraganglioma. E-mail address: patrice.tran-ba-huy@lrb.aphp.fr Various radiotherapy modalities 1.1. Conventional external beam radiotherapy Conventional external beam radiotherapy delivering photonsemitted by Cobalt 60 at doses of 45…55 Gy in 20…25 sessions con-stituted the reference modality for a long time. However, it isassociated with a risk of certain complications, such as temporalosteoradionecrosis, cranial nerve palsy, or even second tumour. Ithas now been replaced by two other techniques [8,9] 1.2. Conformal radiotherapy with or without intensitymodulation Initially two-dimensional irradiation (based on standard radio-graphy) has become three-dimensional or conformal. By basingirradiation “elds on CT and data, conformal radiotherapyallows the intensity of the irradiation delivered to be adapted tothe shape and size of the tumour.Intensity-modulated conformal radiotherapy (IMRT) wasintroduced in 1995, allowing intensity of irradiation to be adaptedto the shape and size of the tumour by means of mobile multi-leafcollimators. As a result of precise tumour delineation, irradiation ismodulated in terms of time and dose: high dose to the tumour (2to 2.2 Gy/session), lower doses to tumour margins (1.6 Gy/session),and theoretically very low doses to healthy tissues. 2014 Published by Elsevier Masson SAS. 224 P. Tran Ba Huy / European Annals of Otorhinolaryngology, Head and Neck diseases 131 (2014) 223…226 The conformation and homogeneity of the doses delivered byIMRT are further improved by tomotherapy: a medium-energyaccelerator is connected to the CT scan gantry and revolves aroundthe table, which is displaced longitudinally. Helical irradiation istherefore adapted to the target volume in real time.1.2.1. Recommended dosesThe dose necessary and suf“

2 cient to control this slowly g
cient to control this slowly growing,benign tumour appears between 40 and 50 Gy [10,11] adminis-tered in 25 fractions, 5 days a week, for an average of 35 days. Thisdose avoids toxic effects, especially temporal necrosis and osteora-dionecrosis, while ensuring satisfactory local control (see below).This dose schedule therefore constitutes an ef“cacy-safety com-promise: relapses are observed at doses less than 40 Gy [12] whileat doses higher than 50 Gy, the relapse rate is not lower than thatobserved at radiation doses between 40 and 50 Gy. 1.3. Stereotactic radiotherapy 1.3.1. PrincipleStereotactic radiotherapy consists of delivering radiation byusing mini-beams converging onto the tumour target. In practice,photons are delivered to the tumour precisely delineated by CTand image fusion [13] Stereotactic radiotherapy therefore onlyirradiates the tumour volume and stops its biological activity. Thedose delivered, initially about 50 Gy, has now been decreased to12…14 Gy to avoid damage to adjacent tissues. This dose is deliveredin a single session. However, recent studies suggest the advantagesof dose fractionation [14] Precision at the target is about 0.25 this modality appears to be very effective on the tumour bloodsupply.1.3.2. Types of equipmentThree types of equipment can be used:€ Unit or Knife uses radiation of photonsemitted from the nucleus of the Cobalt 60 atom and projectedby a comb-line arrangement of 201 sources distributed in 5crowns around a steel hemisphere inside a primary collimatorthat directs the radiation to the centre. A rigid metallic frame is“xed to the patients head under local anaesthesia to prevent anyhead movements. Treatment lasts 30 to 90 minutes;€the LINAC is a linear particle accelerator producing X photonsused according to kinetic radiotherapy. This conformal radio-therapy adapts the irradiated volume to the tumour volume bymodulating the direction of the beams and by means of a multi-leaf collimator that modulates the dose rate delivered by eachbeam;€the CyberKnife®is a miniaturized version of the LINAC attachedto an industrial robot with 6 axes of mobility. Combining highly”exible targeting and beam orientation, it can be used to detect,track and correct real time displacements of the tumour andthe patients movements during treatment with an accuracy ofless than one millimetre. In contrast with the Knife, theCyberKnife system does not use a stereotactic frame but two X-ray cameras.The radiation source can therefore be either single (LINACor Cyberknife) or multiple knife), with either single knife or LINAC) or fractionated dose delivery (LINAC andCyberknife).1.3.3. Advantages and limitationsThe advantages of stereotactic radiotherapy are: €sparing of healthy tissues by means of perfect conformation ofthe radiation onto a well de“ned target, stabilized by a speci“ccontention system;€it can be used after failure of normofractionated radiotherapy;€the patient is immobilized for only one session and therefore only1- to 2-day hospitalisation is required.The patient can therefore rapidly return home and can return towork the following week. In terms of economic impact (duration ofimmobilization, hospital expenses, sick leave, etc.), this techniqueis also 25 to 30% less expensive than a neurosurgical procedure [15] Its limitations are:€it can only be used to irradiate a small tumour volume and istherefore reserved for small paragangliomas;€it can only be applied to intracranial paragangliomas, i.e. arisingin a region that can be easily repositioned from one session tothe next and which can be immobilized, although the Cyberknifeovercomes this limitation. 2. Tumour control The ef“cacy of radiotherapy is de“ned not by disappearance ofthe tumour, but by tumour control, i.e. stabilization and absenceof recurrence of symptoms and absence of tumour growth andradiological signs of progression [16] This de“nition is now widelyaccepted and the published results all appear to be concordant,regardless of the technique used. 2.1. Conventional radiotherapy All studies published since the 1970s have reported tumour con-trol rates close to 90% [12,16…25] In his doctorate thesis, Dupinreported a 5-year local control rate of 97% and a 10-year localcontrol rate of 94%, i.e. better results than those obtained withsurgery [24] He also suggested that advanced age and large tumourvolume appeared to constitute risk factors for fail

3 ure of radio-therapy, in which
ure of radio-therapy, in which case the tumour could be treated by salvagesurgery. 2.2. Stereotactic radiotherapy Most recent data of the literature show that Knife, LINACand/or Cyberknife achieve very good tumour and symptom controlrates, ranging from 71% to 100% and 88% to 100%, respectively, withmuch lower morbidity than with surgery [26…33] Several tran-sient adverse effects have been reported, such as facial paralysisand headache. In contrast, pulsatile tinnitus and deafness generallyremain unchanged. However, this stereotactic irradiation modalityonly concerns residual paragangliomas less than 3 cm in diame-ter or that have relapsed after surgery. Fractionated irradiationdelivering low doses in 30 sessions equivalent to a single dose of15…16 Gy also appears to be an interesting option for inoperablegiant paraganglioma [14] 3. Functional results Functional results are dif“cult to assess in view of the wide rangeof symptoms and the heterogeneous methodologies of the stud-ies evaluating these results. However, regression of signs of nerveparalysis (dysphonia, swallowing disorders or even facial paralysis)are observed in about 20% of cases. P. Tran Ba Huy / European Annals of Otorhinolaryngology, Head and Neck diseases 131 (2014) 223…226 225 4. Adverse effects The introduction of intensity-modulated conformal radiothe-rapy (IMRT) that adapts the intensity delivered to the shape and sizeof the tumour has markedly decreased iatrogenic effects [22,26] affecting tumour control rates in practically all series pub-lished to date.Acute toxicity symptoms are frequently observed, such as nau-sea, weight loss or mucositis, which require interruption oftreatment or even hospitalisation [24] Long-term adverse effects are dominated by xerostomia withdysphagia, ear problems such as serous otitis media or exter-nal otitis and stenosis of the external auditory canal, and morerarely neurological disorders such as headache, ageusia or transientglossopharyngeal, vagus, and accessory nerve paralysis with swal-lowing disorders, aspiration or dysphonia. Other complications arevery rare: temporal osteoradionecrosis, cerebral radiation necrosisor vascular disorders such as labile blood pressure or, more serious,carotid artery stenosis with resolving or permanent hemiplegia.Paradoxically, stereotactic radiotherapy is responsible for moresevere neurological toxicity than conventional normofractionatedradiotherapy, as delivery of stereotactic radiotherapy as a singledose results in a dose equivalent to 15 Gy, or even 35 Gy on the50% isodose [16] versus about 2 Gy per session for conventionalnormofractionated radiotherapy.The risk of radiation-induced cancer, either malignant transfor-mation of the residual tumour occurring years later or malignanttransformation of irradiated healthy tissues, appears to be very low,ranging from 0.28% [34] to 1/2000 [35] Several cases of “brosar-coma [35] malignant astrocytoma or glioma [36] and meningioma have been reported in the literature. This risk must be weighedup against the much higher risk of neurological lesions and com-plications secondary to tumour progression. 5. Implications for the indications of radiotherapy This review of the literature therefore appears to demonstratethat “rst-line radiotherapy provides better results than those ofsurgery, regardless of the tumour volume:€all published series report tumour control rates of up to 95 to100% for follow-ups that are now up to ten years;€in terms of functional results, radiotherapy appears to stabilizeor even improve neurological lesions and induces few iatrogeniceffects, and certainly far fewer iatrogenic effects than surgery Hearing and facial nerve functions are usually preserved aftertreatment, especially since reduction of the doses are delivered.These “ndings suggest the need to rede“ne the place of radio-therapy, which is classically indicated in three main situations:€exclusive radiotherapy for inoperable tumours due to tumoursize, internal carotid artery invasion with poorly tolerated clam-ping test or exclusively ipsilateral venous return or de“cientcontralateral venous return … various types of surgical contraindi-cations … or bilateral tumours;€as an adjunct to incomplete surgery;€salvage therapy after failure of surgery or relapse.The published results together with the improved quality of lifeand a better knowledge of the natural history of the disease suggestthat radiotherapy can be proposed as “rst-line treatment for all

4 glo- jugulare paragangliomas regar
glo- jugulare paragangliomas regardless of their size, particularlyin patients with no preoperative de“cit. Surgery remains indicated in certain situations: young patients;preoperative facial nerve or glossopharyngeal, vagus, and acces-sory nerve paralysis; low probability of surgical complications;intracranial extension; recurrence after irradiation; major petro-clival extension with internal carotid artery invasion and welltolerated clamping test. An emerging concept, which used to be sac-rilegious but which is now recommended by many authors, is thatof subtotal or almost-total resection leaving residual tumour in con-tact with critical nerves or blood vessels and systematic adjuvantradiotherapy or when radiological follow-up suggests growth ofthe residual tumour. Another argument justifying “rst-line surgerycan be that resection of surrounding bone reduces the risk of lateosteoradionecrosis in the event of subsequent radiotherapy. 6. Special indications: malignant and/or secreting forms The place of radiotherapy is not clearly de“ned in this particularsetting.Surgical resection is theoretically the only curative treatment forprimary and secondary malignant paragangliomas. However, thetreatment options for these tumours depend on their site and theiroperability. Surgery is obviously indicated in the case of isolated ormultiple cervical, thoracic or abdominal lymph node metastases,especially as it allows histological con“rmation of malignancy.Similarly, a solitary liver metastasis be amenable to surgicalresection. Complete surgical resection allows long-term survival However, two-thirds of metastases are situated in bone, usu-ally the vertebrae, and are therefore unresectable. Decompressionlaminectomy followed by vertebroplasty can be proposed in thepresence of signs of spinal cord compression. Combined medi-cal and surgical treatment can also be proposed: analgesics andanti-in”ammatory drugs to control pain and nerve compressionphenomena, as well as biphosphonates and localized radiotherapyor sometimes embolization and radiofrequency ablation.Surgery of secreting tumours is always very delicate and mustbe preceded and accompanied by very careful medical prepara-tion [44…46] Surgical dissection must comprise control of feedingarteries and every effort must be taken to avoid capsular effraction.Many authors consider radiotherapy to be a particularly valuablealternative. 7. Conclusions and perspectives This review of the literature appears to demonstrate that radio-therapy now constitutes an effective treatment for glomus jugulareparagangliomas with an equivalent if not better tumour controlrate and considerably fewer iatrogenic effects than surgery. Themanagement of glomus jugulare paraganglioma therefore closelyfollows the changing approach to the management of acoustic neu-roma.However, the potential late toxicity of radiotherapy suggeststhat treatment will inevitably evolve towards chemotherapy.Tenenbaum et al. [47] using cold (non-radioactive) octreotide,demonstrated a 50% reduction of the size of a parotid metastasisof paraganglioma, and Kau and Arnold [48] reported 22% and 47%reductions of tumour size, respectively, after 6 months of treat-ment in 2 patients. Metabolic scintigraphy or chemotherapy canraise objections related to their cost, the low tumour growth rateand their adverse effects [49] The future will therefore proba-bly consist of targeted molecular treatments designed to inhibitgenes targeted by hypoxia-induced factors. Ongoing trials in thetreatment of malignant paraganglioma provide a positiveresponse to the hopes for purely medical management of this dis-ease [50] 226 P. Tran Ba Huy / European Annals of Otorhinolaryngology, Head and Neck diseases 131 (2014) 223…226 Disclosure of interest The author declares that he has no con”icts of interest concern-ing this article.References[1] lareto perspective. tumors. Otolaryngol surgery jugularSkull treatmentstill de ther tomas Int control andtiveness therapyOncol laremanagement ganglioma. therapy1989;17:1303…7. Mayo of tympanicum agementHead ganglioma2010;22:382…9. 82Médecine. trolreview Neurosurg progress. surgery2010;8:76. with of radiation2010;97:395…8. meta-analysis. and tomaNeck therapy radiation aPhys 47nerve systematic2013;35:1195…204. of2007;14:569…85. risk ing Mediouni A, Ammari S, Wassef et al. Malignant head/neck paragan-gliomas. Comparative study. Eur Ann Otorhinolaryngol Head Neck Dis2013;S1879…7296(13):00127, http://dx.doi.org/10.1016/j.anorl.2013.05.003 [44] gliomas. byFr ganglioma: in neuroendocrine1996;116:345…9. alternativescope treatmentMet