Carcinoma Nasopharynx


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  • The nasopharynx is a roughly cuboidal space, opening into the nasal cavity through the posterior choane anteriorly, and the oropharynx, inferiorly. The lateral and the posterior wall are bounded by the pharyngobasilar fascia, descending from the base of the skull. The roof contains abundant lymphomatous tissue special in children and the aggregate of lymphomatous tissue forms the pharyngeal tonsil in this age group. The Eustachian tube opens into the lateral wall of the nasopharynx, and the posterior cartilaginous edge of the same makes the bulge, which is known as the torus tubaris. Just posterior to this torus lies the fossa of Rosenmuller which is considered as the most common site for origin of nasopharyngeal carcinomas. This is the place where the nasopharynx is at it’s widest.
  • This diagram shows the base of the skull from below, and the close relationship of the foramen lacerum to the nasopharynx is immediately apparent. Since the foramen lacerum opens directly into the middle cranial fossa, It forms an important route by which nasopharyngeal cancers can spread into this area. In addition to this important foramen, other foramina in close relationship, include the foramen rotundum, which transmits the maxillary division of the trigeminal nerve, foramen ovale which transmits the mandible division of the trigeminal nerve, foramen spinosum, which transmits the middle meningeal vessels and the recurrent branch of the mandibular nerve. In addition to this the hypoglossal canal and jugular foramen are in close relationship posteriorly and serve as potential pathways of spread to the cranial nerves, particularly 9 th, 10 th , 11 th and 12 th .
  • Superiorly bound by the base of the skull and overlies the carotid canal, jugular foramen, and hypoglossal foramen. The inferior border is the junction of the posterior belly of the digastric muscle and the greater cornu of the hyoid bone.  Medially, the boundary is made up of the buccopharyngeal or visceral fascia overlying the superior pharyngeal constrictors.  The lateral boundary is made up of the fascia over the medial pterygoid muscle, the ramus of the mandible, the posterior belly of the digastric muscle, and the fascia over the retromandibular deep portion of the parotid gland.  Anteriorly the limit is the pterygomandibular raphe.  The posterior limit is the dorsal layer of fascia making up the carotid sheath.  Fascia which extends from the styloid process to the tensor veli palantini muscle , called the tensor-vascular-styloid fascia, because it also contains the ascending palatine artery and vein, divides the parapharyngeal space into an anterolateral or prestyloid, and  a posteromedial, or retrostyloid compartments .  The prestyloid compartment contains fat, a portion of the retromandibular parotid gland, and some lymph nodes.  The retrostyloid compartment contains the internal carotid artery, internal jugular vein, cranial nerves IX-XII, sympathetic chain, and lymph nodes.  The parapharyngeal nodes superiorly are connected to the node of Rouviere in the lateral most retropharyngeal space.
  • The exact incidence of cranial nerve involvement varies from series to series being higher in Asian series and those using CT scans. 12% patients have clinically detected cranial nerve palsy while 29% have radiologically detected cranial nerve involvement.
  • Lymph nodes are involved at presentation in 89%. There is unilateral involvement in 39% and bilateral involvement in 51%. Low-grade squamous cell carcinomas produce fewer metastases (73%) than high-grade carcinomas (92%). Metastases to submental and occipital nodes may appear when there is blockage of the common lymphatic pathways either by massive neck disease or by an untimely neck dissection.
  • Inactivation of the tumor suppressor genes namely the Chromosomes 14, 15 and 16 are considered central steps in the pathogenesis of high grade dysplasia.
  • SO line is the line connecting the styloid process to the posterior edge of the foramen magnum.
  • Ho’s System was a better predictor of prognosis than the 1988 AJCC system but it failed to include the prognostic importance of parapharyngeal extension. Further 5 stages were given which was not same as the western standard. The new AJCC system includes the nodal staging of the Ho’s system which is of prognostic significance
  • Midline nodes are considered unilateral. Supraclavicular zone or fossa is relevant to the staging of nasopharyngeal carcinoma and is the triangular region originally described by Ho. It is defined by 3 points: (1) the superior margin of the sternal end of the clavicle, (2) the superior margin of the lateral end of the clavicle, and (3) the point where the neck meets the shoulder. Note that this would include caudal portions of Levels IV and V. All cases with lymph nodes (whole or part) in the fossa are considered N3b.
  • Stage IIa includes patients with T2a disease without neck nodes Stage IIb includes patients with N1 disease with T 1 – T 2a disease and also includes T2b disease without neck nodes. Stage III includes patients with T 1 –T2b disease with bilateral neck nodes or patients with T3 disease no, unilateral or bilateral neck nodes. Stage IVA includes patients with T4 disease while IVB includes patients with N3 disease Stage IVC stands for distant mets.
  • The Lymphoepitheliomas subtype consists of undifferentiated cells forming syncitial mass is along with which large number of small lymphocytes are interspersed. Some authors believe that this histology confers a higher local control rate, as well as better prognosis than squamous cell carcinoma. Overall, it has been found that patients with undifferentiated histology have a higher proportion of advanced stage at presentation.
  • The biological markers include IgA , IgE , anti-VCA often are predictors of relapse. Similiarly high ADCC levels are correlated with a better prognsis.
  • Fletcher at all in their textbook recommended that parallel opposing fields should not be used in the entire treatment course, unless photos of energy 20 MeV or higher are available.
  • Most commonly used technique and easiest to use. Also set up is a lot easier. As per Perez et al the superior border extends along a line joining the lateral canthus of the eye to the helix of the ear.
  • Shielding is done for the external auditory meatus and the oral cavity upto the third molar tooth to avoid hearing problems and oral mucositis.
  • Advantage is more homogenous dose distribution and coverage in the posterior cervical and lower supraclavicular nodes.
  • As the lower and superior fields are abutted so an area of high dose created on the deeper structures e.g. spinal cord.
  • Advantages of the posterior tilt: Reduced dose to the opposite eye Direct irradiation of ipsilateral and middle ear avoided ( when posterior border is situated in front of the external auditory canal only). In addition it enhances the posterior coverage at the basi-occiput Fletcher writes – “ In case posterior margin of the portal is located behind the external auditory canal no posterior tilt is necessary”
  • Electrons are simple to use but have the disadvantages viz.: Skin sparing advantage is absent. Hot spot develop in the region of the photon field abutting the electron field Small cold spot develops under the electron field edge abutting the photon field Dose to the posterior surface of the neck is increased.
  • This technique is best when high energy beams are not available and cannot be used when there is posterior extension into the base of skull as well as inferior extension into the oropharynx.
  • This technique is used for boosting the nasopharynx in the early disease T1 and T2 disease preferably. A oral stent is usually used to pust the tongue away from the palate and reduce the oral mucosal dose.
  • In effect the hyperextension of the head allows the orbital floor and the base of the skull to become parallel to the beam edge.
  • As this dose distribution shows using the 4 field approach allows us to spare the TM joint and the parotid while at the same time allows us to increase the dose to nasopharynx and para nasopharyngeal tissues. Anterior facial fields are used for boosting the nasopharynx – preventing excess dose to the TM joints S/C tissues and the ear.
  • The CTV included the anterior table of clivus, 5mm of normal oropharynx below the GTV, the entire sphenoid sinus floor, the parapharyngeal space including both medial and lateral pterygoid muscles, the pterygoid plates, the pterygomaxillary fissures, and the posterior part of nasal cavities, 5 mm anterior to the GTV.
  • Lee AWM, Poon YF, Foo W, et al. Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976±1985. Overall survival and patterns of failure. Int J Radiat Oncol Biol Phys 1992;31:261±270. Lee AWM, Law SCK, Foo W, et al. Retrospective analysis of patients with nasopharyngeal carcinoma treated during 1976±1985: survival after local recurrence. Int J Radiat Oncol Biol Phys 1993;26:773±782.
  • BED = 41.25 Gy for late reaction ( α / β = 3 Gy) for the boost phase. For the initial phase the dose is 66.67 Gy for late reactions. The total BED is 107.52. For 66 Gy in 33# for late reactions BED ~ 110
  • With 2DRT alone, the 5-year local relapse-free survival was in the range of 75–95% for UICC T1-T2 stages and 45–80% for UICC T3-T4 stages, and the overall survival was in the order of 50–70% for all stages
  • However a trial conducted by Lee et al found that a 6 day course of radiotherapy did indeed confer an advantage in terms of local control. Thus it can be concluded that the SLD repair times of at least > 6 hrs are necessary and any BID RT course should be avoided as a high chance of neurological sequelae exist.
  • At the same time, several other alternative, brachytherapy techniques were also developed by other authors, notably Cade who had used, a linear array of radium tubes inside catheters and for paris where radium needles packed in gauze was used for brachytherapy. However the bulky size of the applicators, inconstant dosimetry and discomfort associated with prolonged application made this form of brachytherapy unpopular.
  • The Forzhou catheters are made from rubber and obviate the need for requiring expensive catheters. Their design mimics the Levendag applicator.
  • This technique by Pierquin as early as 1963.
  • A pair of feeding tubes, is inserted through the nasal cavity and brought out through the oral cavity. To this is fixed a dummy applicator, which contains the silicone gel. This silicone gel is quick setting and takes the shape of the nasopharynx quickly. One this has been done. The silicone gel mould is brought out and a negative plaster of Paris cast in made from this. Using acrylic, a fresh mould is prepared from this negative plaster of Paris, which is usually 3-5 mm thick. The surface is smoothened and the edges are whittled away. Grooves are ground in this mould, in which catheters are placed. A careful note is made of the catheter length, and the end towards the oral site remains blind. Two rubber strips are inserted towards the nasal end of acrylic applicator in order to fix the applicator to the nasal cavity. Again the feeding tubes are brought out through the oral cavity, and the applicator is placed upside down and fixed to these feeding tubes by the means of the catheters and the rubber strips. Using a detractor the palate is retracted upwards, and traction is placed upon the lateral students. In order to drag the applicator into position, snugly in the nasopharynx. The rubber bands are tied in front of the nasal septum, while buttons are threaded through the plastic tubes which are brought out through the nasal cavity.
  • In addition to the design of the applicator Prof Levendag also defined several dose points which corresponded to the normal tissue doses. This was necessary as he was using ICBT after delivering doses in the range of 60 Gy in absence of parapharyngeal extension to 70 Gy in the presence of the same
  • The divergence of the tubes is due to the fact that the separation between the two tubes at the base is 22.5 mm and at the nose it is 14 mm. So the plane of the two tubes are converging at the sagittal plane. The procedure of insertion is straightforward and consists of a pull and push technique – usually performed under local anesthesia.
  • While taking the simulation films 2 lead markers are placed – one at the tragus of the ear and the other at the lateral canthus of the contralateral eye. A Line (Line 1) is drawn joining these two points. A second reference line joins the anterior clinoid process and the ventral part of the body of the C1 vertebrae ( Line 2). Orthogonal isocentric fields are taken and the points are marked on the lateral film and projected on the AP film using the TPS. The tumor points are marked as follows: Point R corresponds to the ventral part of the body of the C1 vertebra. The point of intersection of line 1 and line 2 on the lateral radiograph gives the BOS point. The intersection of the line which joins the BOS point to the end of the hard palate on the with the bony skull base is taken as the Na point. Dose is prescribed at the Na point and the dotted line represents the 3 Gy isodose line. Usually this point is situated at a distance of 0.75 cm from the sources. On the AP film both the Na and BOS points are situated 1.5 cm to the midline on the AP view. The Normal Tissue points are defined as follows: Re – The retinal points are situated 1 cm posterior to the point on the outer canthus along line 1 and situated 2.5 cm on either side of midline. C point – Situated along the posterior border of the C1 vertebrae behind the R point Pa point – Situated at the posterior edge of the hard palate and situated 1 cm from the midline. P point – Situated 0.5 cm below the anterior clinoid process along the line 2. OC point – Situated 1.5 cm in front of the anterior clinoid process. No point – Situated on a line drawn perpendicular to the source from the retinal point 0.75 cm below the source.
  • Advantages : Shrinks nodal volume in time to initiation of therapy Potential to assess tumor sensitivity Some treatment given during waiting period Disadvantages : Delays initiation of radiotherapy Temporal profile of side effects altered – impaired dose delivery May allow selection of resistant clones – triggering accelerated repopulation.
  • The incidence of severe complications was related to the total cumulative dose of external beam irradiation; 4% for patients receiving doses less than or equal to 100 Gy compared with 39% for those patients who received doses greater than 100 Gy ( p =0.066). The recommendation is an additional salvage 20–30 Gy in 10–15 fractions to the nasopharynx, to limit the total dose of external irradiation to less than 100 Gy. Intracavitary brachytherapy is then used to deliver an additional 40–50 Gy to the surface of the recurrent cancer. Serious CNS sequelae may be seen in as high as 12% Most common complications: Soft tissue necrosis in nasopharynx, osteonecrosis of sphenoid sinus.
  • Wei et al reported on the use of gold grains.
  • The importance of neurological Sequelae in determining the overall long-term morbidity in patients with none of nasopharyngeal cancer is demonstrated by the findings Lee and associates, who treated over 4000 patients with radiation therapy, delivering 65 GY to nasopharynx and 53 GY to the cervical lymph nodes. 10% of the patients had developed neurological Sequelae, and these accounted for 59 of 62 (95%) treatment-related deaths in their population.
  • Carcinoma Nasopharynx

    1. 1. Carcinoma Nasopharynx Moderator: Dr Sushmita Ghoshal
    2. 2. Anatomy
    3. 3. Anatomy Foramen lacerum Foramen spinosum Foramen ovale Foramen rotundum
    4. 4. Parapharyngeal Space <ul><li>The parapharyngeal space is located deep within the neck lateral to the pharynx and medial to the ramus of the mandible. </li></ul><ul><li>Shape of an inverted pyramid with the floor at the skull base and it’s tip at the greater cornu of the hyoid bone </li></ul><ul><li>Two compartments : </li></ul><ul><ul><li>Prestyloid </li></ul></ul><ul><ul><li>Retrostyloid </li></ul></ul>Retrostyloid Space Prestyloid Space
    5. 5. Lymphatic Drainage <ul><li>Richest lymphatic plexus in the head and neck region. </li></ul><ul><li>Submucosal lymphatics congregate at the pretubal region – “pretubal plexus”. </li></ul><ul><li>These then pass on to the retropharyngeal nodes as 8 -12 trunks which decussate in the midline. </li></ul><ul><li>Lymphatic trunks pierce the level of the base of the skull and run between the pharyngobasilar fascia and the longus capitis. </li></ul><ul><li>The lymphatic trunks drain in three directions: </li></ul><ul><ul><li>To the retropharyngeal nodes. </li></ul></ul><ul><ul><li>To do the posterior cervical nodal and the confluence of the 11 th , cranial nerve and the jugular lymph node chains, situated at the tip of the mastoid. </li></ul></ul><ul><ul><li>To the Jugulo-digastric nodes (Lederman ) </li></ul></ul>
    6. 6. Anatomy: RPLN <ul><li>The retropharyngeal nodes are present in two groups. </li></ul><ul><ul><li>Median group. </li></ul></ul><ul><ul><li>Lateral group. </li></ul></ul><ul><li>The median group consists of 1 - 2 nodes interconnected in the midline. </li></ul><ul><li>The lateral group consists of 1- 3 nodes located between the lateral aspect of the posterior pharyngeal wall and the carotid artery. </li></ul><ul><li>These nodes are present from the vertebral levels C1- C3. </li></ul><ul><li>The superior-most lymph node of the latter group is also known as the node of Rouviere. </li></ul><ul><li>This node lies in front of the arch of the Atlas being separated from it by the longus colli muscle. </li></ul>
    7. 7. CT anatomy
    8. 8. Incidence
    9. 9. Incidence: Sex
    10. 10. Clinical Features <ul><li>Most common: Asymptomatic cervical lymphadenopathy (87%) </li></ul><ul><li>MC node involved is the posterior deep cervical (direct drainage from the lateral pharyngeal) </li></ul><ul><li>Other presenting symptoms: </li></ul><ul><ul><li>Nasal twang to speech </li></ul></ul><ul><ul><li>Unilateral serous otitis media ( in adults) </li></ul></ul><ul><ul><li>Cranial nerve palsy : </li></ul></ul><ul><ul><ul><li>U/L Cr nv. II to VI (petrosphenoidal syndrome of Jacod) </li></ul></ul></ul><ul><ul><ul><li>U/L Cr nv. XI to XII ( Retroparotid syndrome of Villaret.) </li></ul></ul></ul><ul><ul><ul><li>Cr nv V and VI most commonly involved. </li></ul></ul></ul><ul><ul><ul><li>Cr nv I, VII and VIII rarely involved. </li></ul></ul></ul><ul><ul><li>Sore throat : Oropharyngeal extension </li></ul></ul><ul><ul><li>Pain : Compression of Vth cranial nerve ( facial pain) </li></ul></ul><ul><ul><li>Trismus : Mandibular nerve involvement or pterygoid muscle invasion. </li></ul></ul>
    11. 11. Cranial Nerve involvement
    12. 12. Local Spread Nasal cavity & PNS Orbital invasion Base of Skull, Clivus Sphenoid sinus Cavernous Sinus Lateral Parapharyngeal space Middle ear cavity Oropharynx (tonsillar pillars) C1 vertebrae
    13. 13. Nodal Spread
    14. 14. Etiology Normal Epithelium Low Grade Dysplasia High Grade Dysplasia Invasive Carcinoma Metastatic Carcinoma P53 Mutation Gain Chromosome 12 Deletion 11 and 13 Deletion of Chromosomes 3p and 9p Inactivation of Chromosome p14, 15 and 16 EBV infection
    15. 15. Investigations <ul><li>Staging: </li></ul><ul><ul><li>CT </li></ul></ul><ul><ul><li>MRI </li></ul></ul><ul><ul><li>Endoscopy </li></ul></ul><ul><ul><li>PET scan </li></ul></ul><ul><ul><li>Chest Xray </li></ul></ul><ul><ul><li>USG Abdomen </li></ul></ul><ul><ul><li>Bone Scans </li></ul></ul><ul><li>Other Investigations </li></ul><ul><ul><li>EBV Serology </li></ul></ul>
    16. 16. Staging <ul><li>Several staging systems are in use: </li></ul><ul><ul><li>Complex anatomy and spread patterns </li></ul></ul><ul><ul><li>Lack of international consensus: </li></ul></ul><ul><ul><ul><li>Separate Chinese, Hong Kong and American staging systems </li></ul></ul></ul><ul><li>Systems available: </li></ul><ul><ul><li>Fletcher (1967) </li></ul></ul><ul><ul><li>Ho’s staging (1978) </li></ul></ul><ul><ul><li>IUAC (1988) </li></ul></ul><ul><ul><li>Huaqing staging (1994) </li></ul></ul><ul><ul><li>AJCC (2002) </li></ul></ul>
    17. 17. Comparison Infratemporal fossa / cavernous sinus / PNS / direct invasion of C2 or C1 / anterior cranial nerves Pterygoid process / posterior cranial nerve / posterior cervical vertebrae / BOS / PPS beyond SO line Involving the nasal cavity, oropharynx, anterior cervical vertebrae, PPS before SO line Limited to nasopharynx Huaqing (1994) Bony destruction including eustachian tube No bony destruction Extending to two sites in nasopharynx Limited to one site in nasopharynx IUAC (1988) NA Bone/ Cranial nerve/ orbital / hypopharyngeal / infratemporal fossa involvement Extending to nasal fossa or oropharynx Confined to nasopharynx Ho (1978) Involving skull base or cranial nerves Beyond nasopharynx > 1 cm but confined to nasopharynx < 1 cm diameter Fletcher (1967) T4 T3 T2 T1 Staging System
    18. 18. Ho’s vs AJCC
    19. 19. AJCC system: T staging <ul><li>T1 : </li></ul><ul><ul><li>Tumor confined to the nasopharynx </li></ul></ul><ul><li>T2 : </li></ul><ul><ul><li>Tumor extends to soft tissues </li></ul></ul><ul><ul><ul><li>T2a : Extends to the oropharynx or the nasal fossa </li></ul></ul></ul><ul><ul><ul><li>T2b : With parapharyngeal extension </li></ul></ul></ul><ul><li>T3 : </li></ul><ul><ul><li>Tumor invades bony structures and/or paranasal sinuses </li></ul></ul><ul><li>T4 : </li></ul><ul><ul><li>Tumor with intracranial extension and/or involvement of cranial nerves, infratemporal fossa, hypopharynx, orbit, or masticator space </li></ul></ul>
    20. 20. AJCC system: N staging <ul><li>N0 : </li></ul><ul><ul><li>No regional lymph node metastasis </li></ul></ul><ul><li>N1 : </li></ul><ul><ul><li>Unilateral metastasis in lymph node(s), < 6 cm in greatest dimension, above the supraclavicular fossa </li></ul></ul><ul><li>N2 : </li></ul><ul><ul><li>Bilateral metastasis in lymph node(s), < 6 cm in greatest dimension, above the supraclavicular fossa </li></ul></ul><ul><li>N3 : </li></ul><ul><ul><li>N3a: Metastasis in a lymph node(s) >6 cm </li></ul></ul><ul><ul><li>N3b: Extension to the supraclavicular fossa </li></ul></ul>Ho’s Triangle
    21. 21. Staging: AJCC 2002 Stage I Stage IIA Stage IIB Stage III Stage IVA Stage IVB
    22. 22. Pathology <ul><li>Some authors consider carcinomas to be of two types: </li></ul><ul><ul><li>Keratinizing </li></ul></ul><ul><ul><li>Non keratinizing </li></ul></ul><ul><li>Others consider carcinomas to be of 4 types: </li></ul><ul><ul><li>Keratinizing Squamous </li></ul></ul><ul><ul><li>Non Keratinizing Squamous </li></ul></ul><ul><ul><li>Lymphoepithelioma </li></ul></ul><ul><ul><li>Undifferentiated carcinomas </li></ul></ul><ul><li>WHO 3 types: </li></ul><ul><ul><li>Type I : SCC </li></ul></ul><ul><ul><li>Type II : Non Keratinizing carcinoma </li></ul></ul><ul><ul><li>Type III : Undifferentiated carcinoma </li></ul></ul>
    23. 23. Endemic NPC <ul><li>Known to occur in China, Hong Kong, South Eastern Asia, Greenland </li></ul><ul><li>Associated with EBV virus infection </li></ul><ul><li>In India similar pathology seen in Kashmiris. </li></ul><ul><li>Present a decade younger. </li></ul><ul><li>Not associated with smoking or alcohol consumption </li></ul><ul><li>Associated with undifferentiated carcinoma ( WHO II and III) </li></ul><ul><li>Associated with more advanced disease at presentation </li></ul><ul><li>Nodal stage also more advanced and more frequently involved. </li></ul><ul><li>Both chemo and radio sensitive </li></ul><ul><ul><li>Histologically more vascularized (Better Rx response) </li></ul></ul><ul><ul><li>Greater % of cell in the growth fraction. </li></ul></ul><ul><li>Better loco regional control and survival than sporadic variants. </li></ul><ul><li>Several markers for predicting biological behavior </li></ul>
    24. 24. Prognostic factors <ul><li>Most important stage. </li></ul><ul><li>Parapharyngeal extension is associated with a poorer prognosis. </li></ul><ul><li>A Chinese series found that 4 th cranial nerve involvement – poor prognosis. </li></ul><ul><li>Nodal disease status: </li></ul><ul><ul><li>Bilateral cervical lymphadenopathy </li></ul></ul><ul><ul><li>Supraclavicular lymphadenopathy </li></ul></ul><ul><ul><li>Lymph node fixity </li></ul></ul><ul><li>Lymphoepithelioma histology: better prognosis </li></ul><ul><li>Undifferentiated histology: better prognosis </li></ul><ul><li>Molecular markers: </li></ul><ul><ul><li>Ki -67 over expression </li></ul></ul><ul><ul><li>P 53 </li></ul></ul><ul><ul><li>E – cadherin expression </li></ul></ul>
    25. 25. Treatment strategy Stage Early stage Late stage External Radiation EBRT + ICBT KPS > 70 KPS < 70 Concurrent Chemoradiation Palliative Radiotherapy
    26. 26. Dose response <ul><li>Significant dose response relationship exists. </li></ul><ul><li>Several series demonstrate that an increased-dose leads to better survival </li></ul><ul><ul><li>Doses of 90 Gy delivered by boost increase the local control and the distant metastasis free rate significantly over doses > 70 Gy </li></ul></ul><ul><ul><li>Price however paid in increased morbidity </li></ul></ul><ul><li>Local recurrence rate reduced with the use of larger fields (Field size more than 250 cm 2 associated with a doubling of local control as compared to field size of 100 cm 2 ) </li></ul>
    27. 27. Dose-response
    28. 28. Doses used <ul><li>Radical radiotherapy: </li></ul><ul><ul><li>60 – 66 Gy in 2 Gy per fraction over 6 – 6 ½ weeks </li></ul></ul><ul><ul><li>Higher dose can be given with more conformal techniques: </li></ul></ul><ul><ul><ul><li>ICBT </li></ul></ul></ul><ul><ul><ul><li>IMRT </li></ul></ul></ul><ul><ul><ul><li>3 DCRT </li></ul></ul></ul><ul><ul><li>In our patients with poor nutrition, advanced disease and absence of individualized care split course radiotherapy is an alternative </li></ul></ul><ul><ul><ul><li>35 Gy in 15 # </li></ul></ul></ul><ul><ul><ul><li>25 – 30 Gy in 10 – 15 # after 2-3 weeks </li></ul></ul></ul><ul><li>Palliative radiotherapy: </li></ul><ul><ul><li>30 Gy / 10# </li></ul></ul><ul><ul><li>20 Gy / 5# </li></ul></ul><ul><ul><li>800 -1000 cGy single fraction </li></ul></ul>
    29. 29. Treatment volume <ul><li>The nasopharynx. </li></ul><ul><li>Posterior 2 cm of nasal cavity. </li></ul><ul><li>Posterior ethmoid sinuses. </li></ul><ul><li>Entire sphenoid sinus and the basiocciput </li></ul><ul><li>Cavernous sinus. </li></ul><ul><li>Base of skull, including the foramen ovale, carotid canal and foramen spinosum. </li></ul><ul><li>Pterygoid fossae </li></ul><ul><li>Posterior 1/3 rd of maxillary sinus. </li></ul><ul><li>Lateral and posterior oropharyngeal wall to the level of mid-tonsillar fossa </li></ul><ul><li>Posterior 1/4 th of orbit ( Fletcher – YES, Perez - NO ) </li></ul>
    30. 30. Nodal volumes <ul><li>The entire neck is at high risk for microscopic spread of disease. </li></ul><ul><li>The neck nodes that should be treated are: </li></ul><ul><ul><li>Upper deep jugular </li></ul></ul><ul><ul><li>Submandibular </li></ul></ul><ul><ul><li>Jugulodigastric </li></ul></ul><ul><ul><li>Midjugular </li></ul></ul><ul><ul><li>Posterior cervical </li></ul></ul><ul><ul><li>Retropharyngeal </li></ul></ul>
    31. 31. Treatment planning <ul><li>Positioning: </li></ul><ul><ul><li>Supine position. </li></ul></ul><ul><ul><li>Head should be extended </li></ul></ul><ul><li>Immobilization </li></ul><ul><ul><li>To ensure accuracy in setup patient should be immobilized with a custom-made thermoplastic cast. </li></ul></ul><ul><li>Localization: </li></ul><ul><ul><li>All nodes are delineated with the use of radio – opaque lead wires. </li></ul></ul><ul><ul><li>The outer canthus the eye opposite to which simulation film is taken is marked with a lead wire. </li></ul></ul><ul><ul><li>Tumor localization performed with the help of CT and clinical details. </li></ul></ul>
    32. 32. Techniques <ul><li>Techniques </li></ul><ul><ul><li>Conventional technique </li></ul></ul><ul><ul><li>Three-dimensional conformal radiation therapy. </li></ul></ul><ul><ul><li>Intensity-modulated radiotherapy. </li></ul></ul><ul><ul><li>Image-guided radiotherapy. </li></ul></ul><ul><li>Energy selection: </li></ul><ul><ul><li>Co 60 : 1.25 MeV </li></ul></ul><ul><ul><li>LINAC : 4 – 6 MV </li></ul></ul><ul><ul><li>Higher-energies used in certain Western centers during the boost phase to: </li></ul></ul><ul><ul><ul><li>Reduce dose to the mandible, temporomandibular joints, ears and subcutaneous tissue (lateral edge effect) </li></ul></ul></ul><ul><ul><li>Kutcher and associates however warn that use of these high energy beams may be associated with underdosage near the surface and near the paranasal sinus cavities. </li></ul></ul>
    33. 33. Portal selection <ul><li>For Initial Phase: </li></ul><ul><ul><li>Two parallel opposing fields </li></ul></ul><ul><ul><li>Three field approach </li></ul></ul><ul><li>For the boost phase: </li></ul><ul><ul><li>Fletcher’s Technique ( 4 fields – antral boost) </li></ul></ul><ul><ul><li>Anterolateral wedge pair technique </li></ul></ul><ul><ul><li>Ho’s technique ( with separate parapharyngeal boost) </li></ul></ul>
    34. 34. Two field technique <ul><li>Clinical field markings: </li></ul><ul><ul><li>Superior border: </li></ul></ul><ul><ul><ul><li>2.5 cm above the zygomatic arch </li></ul></ul></ul><ul><ul><ul><li>5 cm above the zygomatic arch in case of intracranial extension </li></ul></ul></ul><ul><ul><li>Anterior border: </li></ul></ul><ul><ul><ul><li>2 cm beyond the anterior most extent of the disease (usually placed just along the lateral canthus of the eye) </li></ul></ul></ul><ul><ul><li>Posterior border: </li></ul></ul><ul><ul><ul><li>Along the tip of the mastoid or behind the posterior most extent of cervical lymphadenopathy </li></ul></ul></ul><ul><ul><li>Inferior border: </li></ul></ul><ul><ul><ul><li>Along the superior border of the clavicle </li></ul></ul></ul>
    35. 35. Two Field technique <ul><li>Radiological boundaries: </li></ul><ul><ul><li>Superior border: </li></ul></ul><ul><ul><ul><li>Splitting the pituitary fossa and extending along the superior surface of the sphenoid sinus </li></ul></ul></ul><ul><ul><ul><li>In case of IC extension to include at least 1 cm above the pituitary fossa. </li></ul></ul></ul><ul><ul><li>Anterior border: </li></ul></ul><ul><ul><ul><li>At least 2 cm of the nasal cavity and maxillary antrum. </li></ul></ul></ul><ul><ul><ul><li>At least 2 cm margin to the gross tumor extent </li></ul></ul></ul><ul><ul><li>Posterior border: </li></ul></ul><ul><ul><ul><li>Kept open if gross cervical LAD </li></ul></ul></ul><ul><ul><ul><li>Else match with tips of spinous processes of the cervical vertebrae. </li></ul></ul></ul>
    36. 36. Technique
    37. 37. Three field technique <ul><li>The superior, anterior and posterior boundaries are kept as same. </li></ul><ul><li>Inferior boundary restricted to the level of the thyroid notch unless cervical LAD is present </li></ul><ul><li>In latter case matching done more inferiorly. </li></ul><ul><li>Dose prescription done usually at 3 cm depth. </li></ul><ul><li>Several measures need to be taken to circumvent the problem of field matching </li></ul>
    38. 38. Field Matching <ul><li>Without asymmetrical jaws : </li></ul><ul><ul><li>Using laryngeal block : </li></ul></ul><ul><ul><ul><li>A laryngeal block is placed at the level of the larynx. </li></ul></ul></ul><ul><ul><ul><li>The block has a thickness such that it is located 1cm medial to the lateral border of thyroid cartilage </li></ul></ul></ul><ul><ul><ul><li>The block extends from the superior border of the lower field to 2 cm below the level of the cricoid cartilages. </li></ul></ul></ul><ul><ul><li>Using collimator tilt : </li></ul></ul><ul><ul><ul><li>A collimator rotation may be given for the lateral fields to counteract the divergence of the lower anterior field – 5 ° for Co 60. </li></ul></ul></ul><ul><ul><ul><li>May increase the dose to the supero-anterior portion of the field where the eyes are located </li></ul></ul></ul><ul><li>With asymmetrical jaws : </li></ul><ul><ul><li>Using an isocentric technique with half beam block for 3 fields overdosage at the field junction can be avoided. </li></ul></ul><ul><ul><li>Alternative is to use half beam block in the lower anterior field only and use a small shield of 1 – 2 cm in midline to shield the spinal cord. </li></ul></ul>
    39. 39. Additional modifications <ul><li>In both 3 field and 2 field techniques a higher dose can be given to the eye due to the beam divergence. </li></ul><ul><li>Lateral fields need to angled – a “posterior” tilt needs to be given </li></ul><ul><li>Magnitude by which the field edge shifts at the midline ( for Co 60 ) </li></ul><ul><ul><li>5 ° – 0.5 cm </li></ul></ul><ul><ul><li>10 ° – 1.2 cm </li></ul></ul>5° 10° 1.2 0.5 1.1 2.5
    40. 40. Actual Implementation 270 ° 5 ° 275 ° Lateral Canthus
    41. 41. Doses Prescribed <ul><li>40 – 44 Gy in 2 Gy per fraction over 20 – 22 fractions ( 4 – 4½ weeks) for the entire field. </li></ul><ul><li>Rest of the dose ( 20 – 26 Gy) to delivered with spine shielding: </li></ul><ul><ul><li>Lateral fields : </li></ul></ul><ul><ul><ul><li>Posterior border drawn along the junction of the posterior 1/3 rd and the anterior 2/3 rd of the vertebral bodies ( Co 60 ). </li></ul></ul></ul><ul><ul><ul><li>In LINACs the posterior edge of the vertebrae may be choosen. </li></ul></ul></ul><ul><ul><ul><li>Clinically marked straight along the lobule of ear. </li></ul></ul></ul><ul><ul><li>Anterior fields : </li></ul></ul><ul><ul><ul><li>2 cm wide midline shield is adequate. </li></ul></ul></ul>
    42. 42. Boosting neck nodes <ul><li>Photons only : </li></ul><ul><ul><li>Antero-posterior glancing fields ( ± wedges) – Medial border is 2 cm from midline. </li></ul></ul><ul><ul><li>Additional boost radiation may be delivered by posterior fields to increase the dose to the posterior cervical nodes after the course of RT is completed. </li></ul></ul><ul><li>Electrons : </li></ul><ul><ul><li>Direct abutting lateral fields used. </li></ul></ul><ul><ul><li>Energy selected 9 MeV </li></ul></ul><ul><ul><li>Prescribed at 85% isodose ( Usually 3 cm depth) </li></ul></ul><ul><ul><li>6 x 6 cm usually adequate </li></ul></ul><ul><ul><li>Treated at extended SSD of 110 cm </li></ul></ul>
    43. 43. Nasopharynx Boost <ul><li>A 4 field approach can be used to boost the nasopharynx to additional 10 – 15 Gy. </li></ul><ul><li>Volume treated is roughly cuboidal and has the dimensions of 7 cm x 6 cm. </li></ul><ul><li>The anterior fields are tilted “medially” by 20 ° – 30 ° in order to </li></ul><ul><ul><li>Increase the dose to the Posterior nasopharynx </li></ul></ul><ul><ul><li>Spare the anterior nasal cavity and the deeper brain-stem </li></ul></ul><ul><li>Opposing lateral fields also used with lower border at the level of angle of mandible. </li></ul>
    44. 44. Field marking <ul><li>The boundaries for the anterior facial fields are: </li></ul><ul><ul><li>Superiorly – below the eyeball </li></ul></ul><ul><ul><li>Medially – 1 cm in either side of midline </li></ul></ul><ul><ul><li>Inferiorly – upto the commissure of lips </li></ul></ul><ul><ul><li>Laterally – Usually a distance of 6 cm – allow beam fall-off. </li></ul></ul><ul><li>In order to ensure that the superior border of the anterior field matches the lateral fields the head position is adjusted (hyperextended) based upon the collimator lights. </li></ul><ul><li>Beam weights are adjusted to ensure that the brain doesn't receive excess dose. </li></ul><ul><ul><li>Anterior : Lateral = 33% : 66% </li></ul></ul>
    45. 45. 4 field technique
    46. 46. Dose distribution
    47. 47. Nasopharynx Boost <ul><li>In case of gross anterior extension : </li></ul><ul><ul><li>Three field, lateral wedge pair arrangement is preferred </li></ul></ul><ul><ul><li>Anterior border of the lateral fields are extended to cover the anterior disease adequately </li></ul></ul><ul><ul><li>Alternative technique is to use differential beam weights </li></ul></ul><ul><ul><li>Electrons may be used to supplement the doses to the anterior diseases with lateral photon fields. </li></ul></ul><ul><li>In lateralized anterior extension : </li></ul><ul><ul><li>Anterior field may be “wedged” with thin end towards side where disease is present. </li></ul></ul><ul><li>In inferior extension : </li></ul><ul><ul><li>Boost fields are by necessity parallel opposing. </li></ul></ul>
    48. 48. Ho’s Technique <ul><li>Proponent: Prof John H C Ho </li></ul><ul><li>Developed: late 1960s </li></ul><ul><li>Extensive experience : 3 decades </li></ul><ul><li>Special features: </li></ul><ul><ul><li>Different CTV specification </li></ul></ul><ul><ul><li>Field arrangements and patient position are different. </li></ul></ul><ul><ul><li>Arrangement of different shields specified based upon bony anatomy – customized shields not necessary. </li></ul></ul><ul><ul><li>Reproducible treatment plan. </li></ul></ul><ul><ul><li>Lack of CT planning facilities circumvented. </li></ul></ul><ul><ul><li>Ease of use in a busy radiotherapy department Cost saving additional factor. </li></ul></ul><ul><li>Over 10,000 patients have been treated in Hong Kong – excellent long term results in early disease T1, T2 and T3. </li></ul>
    49. 49. Ho’s technique: Planning <ul><li>Patient is immobilized in FLEXED head position in the initial phase. </li></ul><ul><li>Similar to the planning technique for pituitary. </li></ul><ul><li>Allows easier shielding of the brainstem and the oral cavity and reduces the field size requirements. </li></ul><ul><li>Dose: 40 Gy in 20 # </li></ul>
    50. 50. Ho’s technique: Planning <ul><li>Three field arrangement: </li></ul><ul><ul><li>Opposed lateral fields irradiate the upper cervical lymphatics ( upto level III) en bloc. </li></ul></ul><ul><ul><li>An anterior field irradiates the lower field. </li></ul></ul><ul><ul><li>Shielding of the lateral fields is done to adjust for the beam overlap with the anterior field. </li></ul></ul><ul><ul><li>In the lower anterior field a midline shield is placed throughout the treatment. </li></ul></ul>Below vocal cords C6 0.5 cm above the anterior clinoid process Bisecting the maxillary antrum
    51. 51. Ho’s technique: Planning <ul><li>Specialized arrangement of shielding is done for all patients. </li></ul><ul><ul><li>Brain Stem : Shielded with 5 HVL block placed in a manner such that it is 0.5 cm behind the upper edge of the clivus and 1 cm below the lower edge. </li></ul></ul><ul><ul><li>Eye : 5 HVL shield placed 1.5 cm behind the lateral canthus. </li></ul></ul><ul><ul><li>Posterior tongue also shielded with standard block. </li></ul></ul><ul><ul><li>Pituitary and temporal lobes : upper half of the pituitary fossa shielded. </li></ul></ul>
    52. 52. Ho’s technique: Planning <ul><li>In the boost phase a 3 field arrangement was used. </li></ul><ul><li>Patient was replanned in the EXTENDED head position with oral stent. </li></ul><ul><li>Anterior cervico-facial field was used in all patients </li></ul><ul><li>Lower border of the later fields reduced down to level of angle of mandible. </li></ul><ul><li>Allowed dose reduction to: TM joints, ear, parotids & pinnae. </li></ul><ul><li>Dose prescribed: 22.5 Gy in 9 # </li></ul><ul><li>Total tumor dose was 62.5 Gy in 29# </li></ul><ul><li>Biologically equivalent to 66 Gy in 33# </li></ul>
    53. 53. Ho’s technique: Planning <ul><li>In patients with parapharyngeal disease a posterior oblique boost was given after the 2 nd phase. </li></ul><ul><li>Dose prescribed was 20 Gy /10# </li></ul><ul><li>This field was usually 5.5 cm x 8 cm in size. </li></ul><ul><li>Ascending ramus of the mandible was shielded in this phase. </li></ul>
    54. 54. Ho’s vs 3D CRT and IMRT T1 NO MO T4 N2 MO Kam et al: IJROBP 2003
    55. 55. Results by Ho’s Technique
    56. 56. Conventional Radiation
    57. 57. Conventional Radiation
    58. 58. Altered fractionation <ul><li>Concomitant boost technique has been evaluated in a large series by Teo et al (IJROBP 2000). </li></ul><ul><li>Study prematurely terminated as: </li></ul><ul><ul><li>40% incidence of temporal lobe neuropathy </li></ul></ul><ul><ul><li>17% incidence of cranial nerve palsies </li></ul></ul><ul><ul><li>50% patients had one or other form of neurological complication </li></ul></ul><ul><ul><li>2.6% treatment related mortality </li></ul></ul><ul><ul><li>Neural complications were more severe and occurred earlier than conventional techniques. </li></ul></ul><ul><ul><li>No difference in outcome </li></ul></ul>
    59. 59. Conformal Radiation <ul><li>Includes 3 D CRT , IMRT and IGRT </li></ul><ul><li>Potential: </li></ul><ul><ul><li>Dose escalation </li></ul></ul><ul><ul><li>Conformal avoidance </li></ul></ul><ul><li>Results are immature for IMRT </li></ul><ul><li>Largest series of IMRT by Kam et al: </li></ul><ul><ul><li>63 patients </li></ul></ul><ul><ul><li>Median F/U 30 months </li></ul></ul><ul><ul><li>Only 4 had local failure ( None marginal miss) </li></ul></ul><ul><ul><li>OS was 90% </li></ul></ul><ul><ul><li>Distant metastasis primary cause of failure </li></ul></ul><ul><ul><li>Grade III mucositis: 41% patients </li></ul></ul><ul><ul><li>Late toxicity till 2 yrs : Xerostomia (21%) </li></ul></ul>
    60. 60. Brachytherapy <ul><li>The following requirements should be fulfilled prior to taking up a patient for brachytherapy: </li></ul><ul><ul><li>Tumor thickness less than 10 mm. </li></ul></ul><ul><ul><li>Absence of intracranial, paranasal sinus and oropharyngeal involvement. </li></ul></ul><ul><ul><li>Absence of involvement of underlying bone or infratemporal fossa. </li></ul></ul><ul><ul><li>Absence of metastatic disease. </li></ul></ul><ul><ul><li>Expertise in nasopharyngeal intracavitary brachytherapy. </li></ul></ul><ul><li>“ In effect, nasopharyngeal brachytherapy is ineffective in tumors extending beyond the nasopharynx” -Xiao-Kang Zheng </li></ul>
    61. 61. Techniques <ul><li>Techniques: </li></ul><ul><ul><li>Temporary intracavitary application </li></ul></ul><ul><ul><li>Temporary interstitial implantation </li></ul></ul><ul><ul><li>Permanent interstitial implantation </li></ul></ul><ul><li>Dose-rates used: </li></ul><ul><ul><li>Low dose rate (LDR). </li></ul></ul><ul><ul><li>High dose rate (HDR). </li></ul></ul><ul><li>Situations used: </li></ul><ul><ul><li>Routine use as a boost after XRT ( Hong Kong, China and Netherlands) </li></ul></ul><ul><ul><li>Use with documented residual disease ( USA) </li></ul></ul><ul><ul><li>Recurrence ( Hong Kong, USA - Syed and Chinese Series) </li></ul></ul>
    62. 62. History of brachytherapy <ul><li>In 1920s, Pierquin and Richard were the first persons is to employ brachytherapy in the treatment of nasopharyngeal carcinomas. </li></ul><ul><li>In the Christie hospital at Manchester, Peterson used a 15 mg radium tube inserted in a cork with a diameter of 15 to 20 mm. </li></ul><ul><li>The dose prescribed was 80 rads in seven days to a depth of 0.5 cm. </li></ul><ul><li>Peterson described this technique as a useful alternative to small field X-ray technique but not superior to the use of X-rays </li></ul>Cork Ra 226 tube String at either end of the cork
    63. 63. Applicator Design <ul><li>Several applicator designs available: </li></ul><ul><ul><li>Mould technique </li></ul></ul><ul><ul><li>Levendag’s </li></ul></ul><ul><ul><li>Forzhou (Chinese district) </li></ul></ul><ul><ul><li>Simple catheter based </li></ul></ul>
    64. 64. Mould Technique <ul><li>Customized mould prepared for each patient </li></ul><ul><li>Uses a special quick setting silicone jel to take the nasopharyngeal impression. </li></ul><ul><li>The source placement for an average nasopharynx are: </li></ul><ul><ul><li>2 sources for 1 wall </li></ul></ul><ul><ul><li>3 sources for two adjoining wall </li></ul></ul><ul><ul><li>4 sources for 3 walls </li></ul></ul><ul><li>Intersource separation kept at 1 – 1.5 cm. </li></ul>
    65. 65. Technique of Insertion
    66. 66. Rotterdam Applicator <ul><li>Designed by Levendag. </li></ul><ul><li>Designed so that the applicator could be worn by the patient comfortably continuously throughout the fractionated course of treatment given. </li></ul><ul><li>Made up of silicone which is flexible and closely conforms to the curvature of the nasopharynx. </li></ul><ul><li>Applicator design based upon a 3 D model of the nasopharynx ( based on CT of two patients) </li></ul><ul><li>Allows closer fit to the base of the skull and situated at a fixed distance from the soft palate. </li></ul><ul><li>A silicone bridge and flange used to fix the applicator against the posterior nasal septum and the anterior one respectively. </li></ul>
    67. 67. Rotterdam Applicator <ul><li>Tube diameter </li></ul><ul><ul><li>Outer diameter 15 F (5.5 mm) </li></ul></ul><ul><ul><li>Inner diameter 9 F ( 3.5 mm) </li></ul></ul><ul><li>Can accommodate the 6 F HDR source easily. </li></ul><ul><li>Two tubes ensure catheter stability. </li></ul><ul><li>The tubes are diverging at the base </li></ul>
    68. 68. Prescription and points <ul><li>Several anatomical points defined by Levendag to calculated dose to the tumor as well as critical normal tissues. </li></ul><ul><li>Tumor points : </li></ul><ul><ul><li>Na (Nasopharynx) – 2 </li></ul></ul><ul><ul><li>BOS (Base of Skull) - 2 </li></ul></ul><ul><ul><li>R (Node of Rouviere) - 1 </li></ul></ul><ul><li>Normal Tissue points : </li></ul><ul><ul><li>OC ( Optic Chiasm) - 1 </li></ul></ul><ul><ul><li>P (Pituitary gland) - 1 </li></ul></ul><ul><ul><li>C (Cord) – 1 </li></ul></ul><ul><ul><li>Pa (Soft Palate) – 2 </li></ul></ul><ul><ul><li>Re (Retina) - 2 </li></ul></ul><ul><ul><li>No ( Nose) - 2 </li></ul></ul>
    69. 69. Prescription points BOS Pa R Na Re P OC C Pa Pa C R OC Re Re BOS BOS Na Na P No No No Line 1 Line 2
    70. 70. Dose prescribed <ul><li>In case EBRT given in dose of 60 Gy: </li></ul><ul><ul><li>3 Gy x 2 fractions per day for 6 fractions by HDR </li></ul></ul><ul><ul><li>Total dose ~ 78 Gy </li></ul></ul><ul><ul><li>Minimum interfraction gap of 6 hrs. </li></ul></ul><ul><li>In case of EBRT given in dose of 70 Gy: </li></ul><ul><ul><li>3 Gy x 2 fractions for 4 fractions by HDR </li></ul></ul><ul><ul><li>Total dose ~ 82 Gy </li></ul></ul><ul><ul><li>Minimum interfraction gap of 6 hrs. </li></ul></ul>
    71. 71. Advantages <ul><li>Comfortable applicator – can be kept between fractions </li></ul><ul><li>Optimization possible – Na, BOS and the R points. </li></ul><ul><li>Can be reused after steam sterilization. </li></ul><ul><li>Reduced normal tissue dose – to the retina, palate and the nasal cavity </li></ul><ul><li>In earlier work Levendag used to use two other points: </li></ul><ul><ul><li>FL point : </li></ul></ul><ul><ul><ul><li>corresponding to the BOS point </li></ul></ul></ul><ul><ul><ul><li>Approximates the position of the foramen lacerum </li></ul></ul></ul><ul><ul><li>FO point: </li></ul></ul><ul><ul><ul><li>Situated at the foramen ovale </li></ul></ul></ul><ul><ul><ul><li>Taken 2 cm lateral to the midline in then same plane as the BOS point. </li></ul></ul></ul>
    72. 72. Disadvantages <ul><li>Nasal synechia have been observed in few patients. </li></ul><ul><ul><li>Corresponds to the hyperdose sleeve of 200% isodose around the applicator. </li></ul></ul><ul><ul><li>Approximately occurs in a radius of 6 mm around the source axis after standard prescription </li></ul></ul><ul><ul><li>Reduced by use of nasal pack for 7 days after ICBT </li></ul></ul><ul><li>Optimization can result in increased dose to some points (especially the spinal point). </li></ul>
    73. 73. Chemoradiation <ul><li>Sequence: </li></ul><ul><ul><li>Induction </li></ul></ul><ul><ul><li>Concurrent </li></ul></ul><ul><ul><li>Adjuvant </li></ul></ul><ul><li>Concurrent regimen is best. </li></ul><ul><li>Principle: </li></ul><ul><ul><li>Local cooperation </li></ul></ul><ul><ul><li>Spatial cooperation </li></ul></ul><ul><li>We use Concurrent Cisplatin in doses of 50 mg/m 2 D 1 and D 22 . </li></ul>
    74. 74. Results: NACT
    75. 75. Results: Adjuvant CT <ul><li>Adjuvant Chemotherapy: </li></ul><ul><ul><li>Of no benefit even if CDDP based. </li></ul></ul><ul><ul><li>Chi et al reported results of a phase III randomized trial (2002) N = 157 </li></ul></ul><ul><ul><li>Adjuvant chemotherapy with 24 hr infusional Cisplatin 20 mg/m 2 , 5-fluorouracil 2,200 mg/m 2 , and leucovorin 120 mg/m 2 x 9 cycles after 70 Gy XRT </li></ul></ul><ul><ul><ul><li>5-year overall survival 60.5% vs. 54.5% (p = 0.5) </li></ul></ul></ul><ul><ul><ul><li>5 yr relapse-free survival rates 49.5% vs. 54.4% (p = 0.38) </li></ul></ul></ul>
    76. 76. Results: Concurrent CT <ul><li>Huncharek et al performed a meta-analysis in 2002. </li></ul><ul><li>6 RCTs included </li></ul><ul><li>Statistically significant increase in the disease free survival by approximately 20% to 40% </li></ul><ul><li>OS improved by ~ 20% (Statistically NS) </li></ul><ul><li>Better results with Cisplatin + 5 FU based regimen ( Al Sarraf) </li></ul>
    77. 77. Results : Metastatic disease
    78. 78. NPC in Children <ul><li>Problem of long term toxicity: </li></ul><ul><ul><li>Skull deformities </li></ul></ul><ul><ul><li>Neurological deficits </li></ul></ul><ul><ul><li>Pituitary dysfunction </li></ul></ul><ul><ul><li>Hearing impairment </li></ul></ul><ul><ul><li>TM joint ankylosis </li></ul></ul><ul><ul><li>Visual defects </li></ul></ul><ul><li>RT is the treatment modality of choice: </li></ul><ul><ul><li>Dose 50 -60 Gy </li></ul></ul><ul><ul><li>Boost only after skull growth is complete (15yrs) </li></ul></ul><ul><ul><li>Lower neck usually not treated if clinically –ve. </li></ul></ul><ul><li>Outcome: </li></ul><ul><ul><li>DFS is 70 – 80% in T1 and T2 tumors </li></ul></ul><ul><ul><li>DFS is 40 – 50% in T3 – T 4 tumors </li></ul></ul>
    79. 79. Recurrence <ul><li>2 types described (Wang et al) </li></ul><ul><ul><li>Persistent disease </li></ul></ul><ul><ul><li>Relapse: Appearing 1 yr after treatment. </li></ul></ul><ul><li>Detecting recurrence: </li></ul><ul><ul><li>Tc 99m SPECT </li></ul></ul><ul><ul><li>MRI – High signal intensity on T1 weighted spin echo images </li></ul></ul><ul><li>Options: </li></ul><ul><ul><li>Palliative treatment </li></ul></ul><ul><ul><li>Radiation therapy </li></ul></ul><ul><ul><li>Surgery </li></ul></ul>
    80. 80. Surgery <ul><li>Usually indicated in situations like isolated nodal recurrence </li></ul><ul><li>Local recurrences have been salvaged by extensive craniofacial surgery </li></ul>
    81. 81. Radiotherapy <ul><li>EBRT </li></ul><ul><li>Brachytherapy </li></ul><ul><ul><li>Both temporary and permanent implants used. </li></ul></ul><ul><ul><li>Best results from Gold grain implantation. </li></ul></ul><ul><li>IMRT and 3 DCRT </li></ul><ul><ul><li>Investigational </li></ul></ul><ul><li>Sterotactic Radiosurgery </li></ul><ul><li>Chemotherapy </li></ul><ul><ul><li>Cisplatin or taxane based </li></ul></ul><ul><ul><li>Mainstay in: </li></ul></ul><ul><ul><ul><li>Distant spread </li></ul></ul></ul><ul><ul><ul><li>Early recurrence </li></ul></ul></ul><ul><ul><ul><li>Extensive disease </li></ul></ul></ul>
    82. 82. Radiotherapy <ul><li>External radiotherapy: </li></ul><ul><ul><li>High energy beams are better choosen </li></ul></ul><ul><ul><li>Small 6 x 6 field used to treat site of local recurrence </li></ul></ul><ul><ul><li>Doses in range of 20 – 30 Gy. </li></ul></ul><ul><ul><li>Indications: </li></ul></ul><ul><ul><ul><li>Limited tumour size, </li></ul></ul></ul><ul><ul><ul><li>a relatively long period since previous irradiation (minimal time period ~ 1 year) </li></ul></ul></ul><ul><ul><ul><li>Good performance status and </li></ul></ul></ul><ul><ul><ul><li>Lack of evidence of skin or soft tissue damage (skin fibrosis, atrophy or telangiectasis) from the previous irradiation course </li></ul></ul></ul>
    83. 83. Results of RT
    84. 84. Results
    85. 85. Neurological Sequelae <ul><li>Hypothalamo-Pituitary dysfunction </li></ul><ul><ul><li>Median incidence of clinical dysfunction is 3%. </li></ul></ul><ul><ul><li>Cumulative incidence of endocrine dysfunction higher at 67% at 2 yrs . </li></ul></ul><ul><ul><li>Most common disturbance seen in GH secretion . </li></ul></ul><ul><ul><li>Thyroid hormone production affected the least. </li></ul></ul><ul><li>Hearing defects : </li></ul><ul><ul><li>Almost 7% patients become deaf with standard therapy. </li></ul></ul><ul><ul><li>Otitis media seen in 14% patients </li></ul></ul><ul><ul><li>Prolonged tinnitus may be seen in 30% patients </li></ul></ul><ul><li>Temporal lobe injury : </li></ul><ul><ul><li>Incidence as high as 3% after 2 yrs. </li></ul></ul><ul><ul><li>Toxicity more in altered fractionation regimens </li></ul></ul><ul><li>Cranial nerve injury : </li></ul><ul><ul><li>The incidence is as high as 6%. </li></ul></ul>
    86. 86. Other Sequelae <ul><li>Significant xerostomia can be seen in as high as 80 % </li></ul><ul><li>Some degree of xerostomia is seen all patients. </li></ul><ul><li>Fibrosis of the subcutaneous tissue is seen when doses exceeding 50 Gy are used in almost 16% patients. </li></ul><ul><li>Significant trismus, can occur in 5 to 10% patients. </li></ul><ul><li>This particular complication can be reduced by using a three-field approach for boosting the nasopharynx. </li></ul>
    87. 87. Conclusions <ul><li>Nasopharyngeal malignancies make up a different population of head and neck malignancies. </li></ul><ul><li>These are eminently radio sensitive and curable. </li></ul><ul><li>Treatment planning is by necessity complicated and time consuming. </li></ul><ul><li>Brachytherapy can be used for boosting the local activities. </li></ul><ul><li>Chemoradiation is standard treatment in locally advanced tumors </li></ul>
    88. 88. Thank You