13 Oropharynx

13 Oropharynx JJ Mazeron, E Van Limbergen

1 Introduction The oropharynx is essential in co-ordinating the complex acts of deglutition, phonation, and airway protection. Preservation of this function presents a difficult therapeutic challenge in the treatment of squamous cell carcinoma of this anatomical region. The available treatment modalities include surgery, external beam irradiation or chemoradiation, interstitial irradiation, and various combinations of the three. The wide range of results in the literature leaves considerable uncertainty as to the treatment of choice. Excision of structures important in swallowing leaves a functional impairment proportional to the extent of surgery. Simple excision of a limited tumour with adequate margins, with primary closure, is rarely possible, and is not generally considered sufficient treatment. More extensive resections often include a sub-total or a total laryngectomy and, despite reconstruction, leave considerable functional deficit. Furthermore, concern about adequate margins or lymph node involvement often results in the addition of postoperative irradiation, which further increases sequels. Considerable experience with the treatment of oropharyngeal tumours by irradiation has demonstrated the need for an elevated tumour dose to achieve local control. Unfortunately, with external beam irradiation alone, it is difficult to spare adjacent normal tissues, resulting in undesirable late effects on the salivary glands, mandible, and muscles of mastication. Interstitial implantation is ideally suited to deliver a boost dose limited to the volume of the primary tumour, thus minimising sequels. However, because of the complex anatomy and the rare incidence of the disease and its indications for using brachytherapy, these techniques should be reserved for centres with enough recruitment and experience. Anatomical Topography The oropharynx is a somewhat cubic cavity, which communicates anteriorly with the oral cavity, above with the nasopharynx, and below with the hypopharynx and the larynx. Its walls are anteriorly formed by the base of tongue, laterally by the two tonsillar regions, above by the soft palate, and posteriorly by the posterior pharyngeal wall. The base of tongue is limited anteriorly by a transverse plane passing through the lingual insertions of the palato-glossal folds, laterally by the glosso-tonsillar sulci, and posteriorly by the glosso- epiglottic sulcus or vallecula. The faucial arch is composed of the two tonsillar regions and the soft palate. The tonsil lies in a fossa formed by the anterior and posterior tonsillar pillars. This is separated from the tongue by the glossotonsillar sulcus. The two pillars merge and superiorly form the soft palate, which is anteriorly adherent to the hard palate and inferiorly supports the uvula. The tonsillar region continues anteriorly with the mucosa covering the ascending branch of the mandible, and posteriorly with the lateral wall of the oropharynx. Mucosa of the posterior pharyngeal wall is adherent to the cervical vertebrae and is usually poorly accessible to implantation. 2

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The oropharynx has a rich lymphatic plexus draining for the most part to the upper anterior cervical or subdigastric lymph nodes.

3 Pathology The vast majority of oropharyngeal cancers are well to poorly differentiated squamous cell carcinomas. Cancers of other types, as lymphomas and melanomas, are not suitable for interstitial irradiation. Lymphatic metastasis, whose frequency correlates with the size and degree of infiltration of the primary tumour, is noted at presentation in up to 80% of patients and is often bilateral. Work Up All patients undergoing irradiation for oropharyngeal cancer require a detailed examination of the head and neck region as well as a thorough general physical examination and the assessment of the clinical stage according to the UICC-TNM classification. In addition, routine blood examination is made and a chest radiograph and an electrocardiogram taken. An examination under general anaesthesia, preferably in combination with a panendoscopy of the higher respiratory and digestive tract, in order to rule out synchronous second primary tumours, is made. This includes bronchial and oesophageal examination with brushing cytological tests, a vital staining with toluidine blue and biopsies of any lesion. If brachytherapy is considered as a boost modality after initial external beam irradiation, it is useful to tattoo the limits of the gross disease during this endoscopy. MRI is the best imaging procedure for determination of tumour volume and extension. CT scan and cervical ultrasonography are both useful for diagnosis of metastatic cervical nodes. Indications, Contra-indications Iridium LDR, HDR or PDR interstitial implantation may be indicated in the treatment of squamous cell carcinoma of the base of tongue, the soft palate, the tonsillar fossa, and the vallecula. Tumours must be less than 50 mm in diameter. Implantation is contraindicated if the primary tumour extends to the retromolar trigone, the nasopharynx, the larynx, the hypopharynx, or if the lesion is fixed to the underlying structures or invades bone. Implantation is usually not performed when the primary tumour is associated with bulky cervical lymph nodes. Because of the high incidence of cervical lymph node metastases, which are present in more than one half of patients, brachytherapy is usually delivered as a boost after 45 - 50 Gy external beam radiation therapy to both primary tumour and cervical neck node areas. Brachytherapy alone may be used only for purely exophytic tumours, 10 mm or less in diameter, and in recurring cancers or new tumour arising in previously irradiated territory. Target Volume The clinical target volume for well-delineated squamous cell carcinoma is the palpable and visible tumour (including extensions visible on CT or MRI) before any treatment, with a safety margin of at 4 5 6

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least 10 mm. In tumours of the base of tongue, a larger safety margin may be taken because delineation of the gross disease may be problematic, leading in most cases to the need to cover the whole organ.

7

Technique

7.1 Base of tongue The classical plastic loop technique is described. Under general anaesthesia with nasal intubation, the patients lying in supine position with the neck in hyperextension, three or four sagitally oriented parallel loops, spaced 15 - 20 mm, are implanted to irradiate all or most of the base of tongue (Fig 12.1). Following skin antisepsis, a projection of the tumour is outlined on the skin of the anterior neck. The posterior branch of the central loop is first implanted. A guide needle is inserted perpendicularly to the skin above the hyoid bone. The needle is guided into the pharynx, in most cases into the vallecula, with the index fingertip. A nylon filament is introduced into the needle. Then the needle is removed. A 40 cm long nylon tube is advanced along the nylon filament, and the two are clamped together. Then the tube is pulled into oropharyngeal cavity. The filament is removed. A second needle is implanted anteriorly into the base of tongue, and a filament is advanced into the needle. The needle is removed and the filament inserted into the first plastic tube. The two are clamped together and pulled through tongue and skin, so completing the loop. The filament is removed. The two or three other sagittal loops are implanted with the same method, paying great attention to keeping them parallel. The loops are secured with plastic spacers and buttons.

Fig 12.1: Plastic tube technique for implantation of base of tongue (by courtesy of M. Pernot).

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When large tumours are implanted, the separation between the branches of the loops may exceed 20 mm in order to encompass the entire lesion. To prevent underdosage in the central area of the PTV, a frontal loop may be added, with its branches equidistant of those of the sagittal loops. The bridge of the frontal loop is not loaded to avoid high spot resulting from overlapping of sagittal and frontal loop (Fig 12.2).

Fig 12.2: Base of tongue implant. A: Anterior-Posterior view: the tubes are loaded with Ir 192 wires. B: Lateral view.

Fig 12.3: Base of tongue: modification of the implant technique for the vallecular region.

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As for tumours of the mobile tongue, the above described classical plastic loop technique may be unsuitable for stepping source afterloaders because the stepping source cannot take very bended loops. In that case, straight-blinded plastic tubes are implanted with a 15 - 20 mm interneedle spacing in a square pattern. Six to nine tubes are usually required for covering the target. The nylon filament, which is connected to the implantation tube, is inserted into the needle through its intra- oropharyngeal end. Then, the needle is withdrawn, and the tube is gently pulled through the tongue and the skin. It is advised to prepare nylon tube spacers, which will hold the blind ends of the tubes in a correct position, before inserting the nylon filaments into the guide needles. Vallecular region The loop technique can be modified for implanting vallecular tumours. The posterior inferior branches of the loops are implanted between the hyoid bone and the thyroid cartilage through the epiglottis, and the superior branches into the base of tongue. When the loops are formed, the free portion of the epiglottis is pulled forward and held against the base of tongue (Fig 12.3). Straight, blind-ended plastic tubes may replace loops if a stepping source afterloader is used. 7.2

7.3 Soft Palate 7.3.1 Classical Pernot technique

The procedure is carried out under general anaesthesia with nasal intubation or neurolept analgesia combined with local anaesthesia, with the patient sitting in a dental chair. Two parallel frontal loops 15 -20 mm apart are implanted to cover the whole or two thirds of the faucial arch (Fig 12.4). Fig 12.4: Pernot technique for implanting the faucial arch.

B: X-Ray control: lateral view with dummy sources

A: Soft palate plastic tubes implant: diagram C: Tomography, lateral view

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Fig. 4D (continued): AP view with Iridium wires

After palpation of the position of the hyoid bone and the carotid artery, the entrance points of the needles are marked on the skin. The anterior loop will enter 10 mm above the hyoid and will pass through the anterior faucial pillar. The entrance point of the posterior loop is marked 10 mm beneath the hyoid and will pass through the posterior pillar (Fig 12.5).

Fig 12.5 : Pernot technique for implanting the faucial arch: skin entrance points of posterior pillar and palatal free border. Anterior pillar and border soft or hard palate.

The posterior tube is positioned first. A 10 cm guide needle is introduced under the hyoid bone perpendicularly to the skin and is then advanced posteriorly about 25 mm into the neck, towards the pharyngeal mucosa, guided by a palpating finger in the oropharynx. Then the needle is turned cranially, and it is gently manoeuvred through the tissues and along the posterior faucial pillar to emerge in the oropharyngeal cavity at the junction of the inferior border of the soft palate and the posterior faucial pillar. A strong nylon thread is pushed through the lumen of the needle, the needle is removed, and a 30 - 40 cm plastic tube is threaded along the nylon guide. The both are clamped together and pulled into position by gentle traction on the oropharyngeal end of the nylon thread. A Reverdin hook is inserted at the junction of the inferior border of the soft palate and the left posterior faucial pillar, and it is manoeuvred along the free border until it penetrates the oropharyngeal cavity at the same point as the plastic tube. The nylon thread is grasped with the Reverdin and pulled through the free border of soft palate. The plastic tube, still coupled to the nylon thread, is then pulled into position. The two are unclamped and the nylon thread is withdrawn from the lumen of the tube. Curved hollow needles, fixed to a Boomerang device as used for bladder implantation (see that chapter) may also be used.

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A 10 cm guide needle is introduced on the left side along the posterior faucial pillar, as described in point 2, to emerge in the oropharygal cavity at the same point as the plastic tube. Another 30 - 40 cm nylon thread is introduced into the oropharygal cavity through the needle and pushed through the lumen of the plastic tube until it emerges at the initial entry point on the right side of the neck. The nylon thread and the plastic tube are coupled by clamping them together at this external extremity. Traction on the left hand end of the nylon thread brings the plastic tube into its final position, spanning the oropharynx from the right side to the left, without penetrating the oropharyngeal cavity. A second plastic tube is then introduced, parallel and anterior to the first. The tube enters and exits at the right and left sides of the neck, at the marked points above the hyoid bone. The needles are introduced into the skin at these points, advanced about 5 mm posteriorly, are turned cranially to follow the anterior faucial pillars, and exit in the soft palate, close to the border with the hard palate. A Reverdin needle is again necessary to traverse the soft palate along the border with the hard palate, as described on point 3. When the uvula takes part of the clinical target volume, it may be underdosed using the described technique. In that case, the extremity of the uvula may be either stitched to the soft palate or threaded with the posterior plastic tube or removed. 7.3.2 Poseidon Technique (developed by Van Limbergen) This technique permits to treat lesions of the uvula and small central tumours of the soft palate (Fig 12.6).

Fig 12.6A: Poseidon Technique for palatal implant Fig 12.6B: Radiograph of palatal Poseidon

It also permits to cover tumour extensions to the mucosa of the oral cavity (hard palate). Three curved needles (see bladder needle technique) are implanted in a sagittal direction into the soft palate. They are inserted into the mucosa at the junction of the hard and soft palate and sort at the free border laterally and through the uvula for the central line. Then a loop is made joining the two lateral lines. Before making the loop, a larger piece of plastic tube is shoved over the implantation tubes, to fix the loop to the central tube, which will perforate the piece of plastic. Loading of the sources may be extended to the hard palate region. In that case it is advised to make a customised apparatus, covering the hard palate and with predrilled holes in it, to contain the sources close against the hard palate mucosa (Fig 12.7). The nylon tubes sort through the mouth

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Fig 12.7: Mould containing plastic tubes to treat a cancer of the hard palate. The same mould can be used in combina- tion with the Poseidon technique of the soft palate to treat extensions to the hard palate.

7.4 Tonsillar region: For tumours of the tonsillar region, the implant covers only the homolateral tonsillar region and a part of the soft palate. The two pillars and the soft palate are implanted as described above in the Pernot technique, but the tubes exit in the oropharyngeal cavity at the opposite side of the soft palate (Fig 12.5). A plastic spacer secures spacing between the oropharyngeal extremities of the tubes. These extremities are fixed with buttons. For tumours limited to the lower half of the tonsillar region, the two tubes can be replaced by a loop covering only the tonsillar region (Baillet technique) (Fig 12.8).

Fig 12.8: Baillet technique for implanting tumours of the lower tonsillar region. Fig 12.9: Pernot technique for implanting tumours of the tonsillar region invading the adjacent tongue,AP view. For tumours involving the tonsillar region as well as the adjacent tongue, an additional loop may be implanted into the tongue, in order to irradiate the glosso-tonsilar sulcus and the adjacent tongue (Fig 12.8). However, it is advised to use this technique only when there is limited (< 1 cm) invasion in

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the adjacent tongue. Parallelism between this loop and the tubes implanted into the faucial arch can be optimised using fluoroscopy.

8 Dosimetry Dosimetry is based on a 3-D reconstruction of the catheters of the applicator (source positions). At least two projection images (radiographs) are needed for such a reconstruction of the implant loaded with dummy sources. CT images and/or MR images may also be used. The rules of the Paris system of dosimetry are often followed and the resulting distribution is calculated. The dose is prescribed on an isodose representing 85% of the mean basal dose rate (mean central dose rate), calculated in the central plane. For the base of tongue, the central plane passes through the middles of the parallel branches of the loops For tumours of the faucial arch, the central plane passes through the midpoints of the two wires and the centre of the quadrilateral basis formed by their extremities. It may be useful to calculate the dose delivered at points of interest marked with metallic seeds during implantation. With the stepping source technology, some optimisation facility can often improve dose distribution, i.e. reduce the inhomogeneity inside the implant and decrease the dose outside the implant to some extend (see physics chapter). Dose, Dose Rate, Fractionation In almost all cases, the implantation is performed following 45 - 50 Gy external beam irradiation of the primary tumour and cervical lymph nodes. The implant delivers then an additional dose of 25 - 30 Gy LDR-PDR to the tumour bed in tonsillar region tumours, and 30 - 35 Gy in base of tongue tumours. For tumours of the base of tongue it may sometimes be useful to fuse the base of the tongue by boosting the whole base to 65 - 70 Gy and the macroscopic tumour site to 75 - 80 Gy. When the implant is carried out in a previously irradiated area for a recurrent tumour or a new tumour, a dose of 60 Gy is required. It is advisable to deliver the dose at 0.3 to 0.6 Gy.h -1 or by hourly 0.5 Gy pulses. For high dose-rate brachytherapy, fraction sizes of less than 6 Gy and an interval between fractions of 6 hours or more are recommended. Typical treatment protocols combine 50 Gy external beam radiation therapy and a high dose rate interstitial brachytherarapy delivered in 4 - 6 fractions of 4 Gy. 10 Monitoring Patients should receive adequate analgesics. Steroids, antibiotics and a feeding tube may be indicated. The implantation site is inspected at least twice daily. Removal of the plastic tubes should always be carried out in an operating room equipped with adequate illumination and suction facilities and means of dealing with extensive bleeding. Arterial 9

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haemorrhage is exceptional but has to be anticipated, and presence of two persons is recommended. It is also prudent to put an intravenous access before removing the implant. In case of bleeding eight to 10 min bimanual compression usually effectively stops arterial bleeding. Mucositis develops 1 - 2 weeks after brachytherapy. The reaction is maximal after 3 - 4 weeks, and heals progressively in 5 - 8 weeks. Mouth washes, analgesics, and adapted alimentation should be given. 11 Results T1 - 3 squamous cell carcinomas of the base of tongue can be treated by surgery followed by radiation therapy, by external radiation followed by interstitial implant or by external beam irradiation alone. In a retrospective analysis of results obtained with these three modalities in 110 T1 - 2 squamous cell carcinoma of the base of tongue at the same institution (Necker Hospital, Paris), local failure occurred twice as often in patients treated by external beam alone (43%) compared to the other two modalities (20.5% for external beam radiation followed by brachytherapy and 18.5% for surgery plus irradiation) (8). The 5-year survival rate for N0-1 patients was 30.5% for patients treated by external beam irradiation alone and 50% with the other two methods. Similar conclusions were drawn from another retrospective single-institution comparison of these three modalities in 131 T1 - 4N0 - 3 squamous cell carcinoma of the base of tongue (Centre Alexis-Vautrin) (9). Five-year local control rates were 39%, 32%, and 19%, and five-year overall survival rate, 45%, 44%, and 19%, respectively. Reguiero et al reviewed 65 patients with T1 - 3 squamous cell carcinomas of the base of tongue (1). Thirty-five patients were treated with external irradiation alone, and 30 with external irradiation plus brachytherapy boost. The 3-year relapse-free survival rates were 67% and 42% (p < 0.05), respectively. By contrast, others, including Foote et al in the University of Florida, concluded, reviewing the results achieved with external beam irradiation alone in 84 patients with T1 - 4 squamous cell carcinomas of the base of tongue, that interstitial implantation is not essential for the successful radiotherapeutic treatment of base of tongue (4). Table 12.1 summarizes local control and complication rates obtained with combined external beam radiotherapy and brachytherapy boost according to TNM classification. At Memorial Sloan-Kettering Cancer Centre, New York, a retrospective analysis compared results of external beam irradiation followed by interstitial implant (30 patients) and primary surgery followed by external beam irradiation (10 patients) for T1 - 4 squamous cell carcinoma of base of tongue. Similar local control rates (80-90%) were observed, but consistently better performance status score and quality of life, as seen with primary radiation therapy (5). A dose response relationship was observed in T1 - 2 squamous cell carcinoma of the base of tongue at the Henri Mondor hospital (Créteil, France), with local control rate of 79% (26/33) obtained with a combined dose > 75 Gy, but only 50% (4/8) with < 70 Gy (1). It was then recommended that T1 - 2 (and some limited T3) tumours of the base of tongue should be treated with 45 - 50 Gy radiation or chemoradiation followed as soon as possible by a 30 - 35 Gy interstitial boost. For node positive patients, a 20 - 30 Gy electron boost is added to the involved nodes or a neck dissection is performed. With such strategy, a local control rate of 80 - 90% can be expected in T1 - 2 tumour patients with a 5-year overall survival rate of about 50%, and with the occurrence of a temporary late necrosis of the mucosa in about 25% of cases (1, 5, 6,16). The largest experience with exclusive irradiation including an interstitial implant for T1 - 3 squamous cell carcinoma of the velotonsillar area was accumulated in Nancy, France (15). Patients were treated with brachytherapy alone (18) or with a combination of external beam irradiation (343 patients) and using an afterloading interstitial technique with plastic tubes. Five-year and 10-year local control rates were 80% and 74%, and overall survival rates 53% and 27%, respectively.The

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five-year local control rate was better for T1-2 tumours than for T3 tumours (87% versus 67%, p = 0.00004). The prognosis of tumours extending to the mobile tongue or base of tongue was worst ( p < 0.002). For maximising local control, the authors recommended that the total duration of the treatment should be less than 55 days. The number of days between external beam irradiation and brachytherapy should be less than 20, and the security margin around the gross disease more than 5 mm large. Similar results were achieved at the Henri Mondor Hospital where 165 T1 - 2 squamous cell carcinomas of the faucial arch were treated with irradiation with external beam irradiation, interstitial implantation, or external beam irradiation followed by an interstitial implantation (13). Five- year local control rates were 58%, 100%, and 91%, and five-year overall survival rates 21%, 50.5%, and 60%, respectively. The best local control rate was achieved with a combination of external beam irradiation and brachytherapy using the plastic tube technique described above (94% at 5 years); the probability of minor or moderate necrosis was 20%. A local control rate of 92% was obtained in the Gustave Roussy institute in a population of 53 patients treated with a combination of 50 Gy external beam irradiation and of 20 - 35 Gy interstitial brachytherapy for a limited carcinoma of the soft palate and uvula (3). We recommend that T1 - 2 (and some limited T3) tumours of the faucial arch should be treated with 45 - 50 Gy radiation or chemoradiation followed as soon as possible by a 20 - 25 Gy interstitial boost. For node positive patients, a 20 - 30 Gy electron boost should be added to the involved nodes or a neck dissection performed. We can expect in T1 - 2 tumour patients, a local control rate of about 90%, a 5-year overall survival rate of about 60%, with the occurrence of a temporary late necrosis of the mucosa in about 20% of cases (3,13,15). The above-cited results were achieved using low dose rate technique. Results obtained with a combined external beam and fractionated high dose rate or pulse dose rate brachytherapy boost are preliminary. Some results are now available with high dose-rate brachytherapy, and look comparable to those achieved with low dose-rate brachytherapy (Table 12.2). Results obtained at 3 years in a population 38 T1 - 4 squamous cell carcinomas of the tonsillar region and soft palate with fractionated high dose rate or pulsed dose rate regimens by Levendag et al. also look similar to those obtained with low dose rate techniques (10). Interstitial implantations may also play a special role for salvage treatment. It can be successfully carried out for treating tumours arising or recurring in previously irradiated areas (7,12,14). The five- year local control rate was 57 - 69%, five-year overall survival rate 14 - 30%, and necrosis rate 11 - 27%.

Table 12.1: Local control and complication rates obtained with combined external beam irradiation and brachytherapy boost in carcinomas of base of tongue.

Authors

Local control rate

Complication rate

T1

T2

T3

T4

Crook et al. (1) Hoffsteitter et al. (6) Horwitz et al. (7) Housset et al. (8) Lusinchi et al. (11) Puthawala et al. (16)

85% 71% 86% 69%

12/48 14/72 4/20 3/29 29/108 10/70

64%

10/11

8/9

6/6

74%

83% 51%

69%

2/2

88%

75% 67%

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Table 12.2: Results of high dose-rate brachytherapy for Cancer of the oropharynx :

Authors

Pts 11 19 15

T

Site B, S

EBRT

HDR Local control rate

Dixit et al. (2) Senan et al. (18) Yu et al. (19)

T3

46-48 Gy

7x3 Gy 7x3 Gy 10x3 Gy

82% 87% 94%

T2-3 T, S T2-3 B, T

45 Gy 50 Gy

B = Base of tongue S = Soft palate T = Tonsil

12 References 1. Crook J, Mazeron JJ, Marinello G, et al. Combined external and interstitial implantation for T1 and T2 epidermoid carcinoma of base of tongue: the Créteil experience. Int J Radiat Oncol Biol Phys 1988; 15 : 105-14. 2. Dixit S, Babbo HA, Rakesh V, Bhavsar. Interstitial high dose rate brachytherapy in head and neck cancers: preliminary results. J Brachyther Int 1997; 13 : 363-10. 3. Esche BA, Haie C, Gerbaulet AP, et al. Interstitial and external beam radiotherapy in carcinoma of the soft palate and uvula. Int J Radiat Oncol Biol Phys 1988; 15 : 619-25. 4. Foote RL, Parsons JT, Mendenhall WM, et al. Is interstitial implantation essential for successful treatment of base of tongue carcinoma? Int J Radiat Oncol Biol Phys 1990; 18 : 1293-8. 5. Harrison LB, Zelefsky MJ, Armstrong JG, et al. Performance status after treatment for squamous cell cancer of base of tongue – A comparison of primary radiation therapy versus primary surgery. Int J Radiat Oncol Biol Phys 1994; 30 : 953-7. 6. Hoffstetter S, Malissard L, Pernot M, et al. Retrospective study of a series of 136 carcinomas of the base of tongue treated in Centre Alexis Vautrin. Bull Cancer Radiother 1996; 83 : 90-6. 7. Horwitz EM, Frazier AJ, Martinez AA, et al. Excellent functional outcome in patients with squamous cell carcinoma of the base of tongue treated with external irradiation and interstitial iodine 125 boost. Cancer 1996; 78 : 948-57. 8. Housset M, Baillet F, Dessard-Diana B, et al. A retrospective analysis of three treatment techniques for T1-2 base of tongue lesions: surgery plus postoperative irradiation, external irradiation plus interstitial implantation and external irradiation alone. Int J Radiat Oncol Biol Phys 1987; 13 : 511-6. 9. Langlois D, Hoffsteitter S, Malissard L, et al. Salvage irradiation of oropharynx and mobile tongue about iridium brachytherapy in Centre Alexis Vautrin. Int J Radiat Oncol Biol Phys 1988; 14 : 849-53. 10. Levendag PC, Schmitz PI, Jansen PP, et al. Fractionated high-dose-rate and pulsed-dose-rate brachytherapy: first clinical experience in squamous cell carcinoma of the tonsillar fossa and soft palate. Int J Radiat Oncol Biol Phys 1997; 38 : 497-506. 11. Lusinchi A, Elkandari Json Y, Gerbaulet A, et al. External irradiation plus curietherapy boost in 108 base of tongue carcinomas. Int J Radiat Oncol Biol Phys 1989; 17 : 1191-7. 12. Mazeron JJ, Langlois D, Glaubiger D, et al. Salvage irradiation of oropharyngeal cancers using Iridium 192 wire implants: 5-year results of 70 cases. Int J Radiat Oncol Biol Phys 1987; 13 : 957-62.

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13. Mazeron JJ, Belcacemi Y, Simon JM, et al. Place of faucial arch implantation in definitive irradiation of faucila arch squamous cell carcinomas. Int J Radiat Oncol Biol Phys 1993; 27 : 251- 7. 14. Peiffert D, Pernot M, Malissard L, et al. Salvage irradiation by brachytherapy of velotonsillar squamous cell carcinoma in a previously irradiated field: results in 73 cases. Int J Radiat Oncol Biol Phys 1994; 29 : 681-6. 15. Pernot M, Malissard L, Hoffstetter S, et al. Influence of tumoral, radiobiological, and general factors on local control and survival in a series of 361 tumors of the velotonsillar area treated by exclusive irradiation (external beam irradiation + brachytherapy or brachytherapy alone). Int J Radiat Oncol Biol Phys 1994; 30 : 1051-7. 16. Puthawala AA, Syed AMN, Eads DL, Gillin L, Gates TC. Limited external beam interstitial 192 Iridium irradiation in the treatment of carcinoma of the base of tongue: a ten year experience. Int J Radiat Oncol Biol Phys 1988; 14 : 839-48. 17. Regueiro CA, Milan I, de la Torre A, et al. Influence of boost technique (external beam radiotherapy or brachytherapy) on the outcome of patients with carcinoma of the base of the tongue. Acta Oncol 1995; 34 : 225-33. 18. Senan S, Levendag PC. Brachytherapy for recurrent head and neck cancer. Hematol Oncol Clin N Amer 1999; 13 : 531-42. 19. Yu L, Vikram B, Chadha M, et al. High dose rate brachytherapy in patients with cancer of the head and neck. Endocur hyperthermia Oncology 1996; 12 : 1-6.