Management overview in carcinoma of Nasal cavity

and Paranasal SinusesBy – Dr. Satyajeet Rath

Moderator – Prof. Kamal Sahni

Lymphatics

• Lymphatics of frontal, ethmoid and maxillary sinuses – sparse, connect with those of nasal cavity• Once tumour has extended beyond PNS – Increased nodal

incidence• Incidence of LN involvement -• 10-15% for maxillary & ethmoid sinus• 5-10% for nasal cavity

Histologic subtypes

• SCC (80-85%)• Adenoca (adenocystic ca)• Malignant melanoma• MFH• Sarcoma –Osteogenic sarcoma, RMS• Lymphoma, extramedullary plasmacytoma• Esthesioneuroblastoma• Metastatic• TCC

• Benign variants – angiofibroma, lethal midline granuloma

Treatment options

• Surgery• Radiotherapy• Surgery + adjuvant Radiotherapy• Concurrent chemo radiotherapy• Neo adjuvant chemotherapy

Surgical procedures• The goal of surgery for nasal cavity and paranasal sinus tumors

is to achieve en bloc resection of all involved bone and soft tissue with clear margins while maximizing the cosmetic and functional outcome.

• Limited nasal cavity lesions may be resected with medial maxillectomy.• Ethmoid lesions usually require medial maxillectomy and en

bloc ethmoidectomy.• combined craniofacial procedure for lesions involving the

inferior surface of the cribriform plate ,the roof of the ethmoid & frontal sinus.• Multidisciplinary skull base approach has improved the

outcome

SurgeryUnresectability:• extension to frontal lobes• invasion of prevertebral fascia• bilateral optic nerve involvement• cavernous sinus extension

Surgical approaches:• Endoscopic• Lateral rhinotomy• Transoral/transpalatal• Midfacial degloving• Combined craniofacial approach

Inferior medial maxillectomy

Medial maxillectomy Radical maxillectomy with exentration

Cranio-facial resection

Ethmoid sinus • Ethmoid sinus lesions are usually extensive when first diagnosed. • Localized lesions require resection of the ethmoids and the ipsilateral maxilla

and orbit.

Maxillary Sinus• Early infrastructure lesions may be excised and cured by surgery alone• Extension of cancer to the base of the skull, nasopharynx, or sphenoid sinus

contraindicates surgical excision. • If the floor of the orbit is free of disease, then the eye and the orbital rim may be

left undisturbed. • If there is involvement through the floor of the orbit, then a maxillectomy with

resection of the orbital floor with or without an orbital exenteration must be performed.

• If the posterior wall or the pterygoid plates are involved, they too must be included in the resection.

Surgery complication

• Complications of maxillectomy include failure of the split-thickness skin graft to heal, trismus, CSF leak, infection and hemorrhage.

• Complications of ethmoid sinus surgery include hemorrhage, meningitis, CSF leak, cellulitis and pansinusitis, brain abscess, and stroke.

• Complications of the craniofacial procedure include meningitis,

subdural abscess, CSF leak, diplopia, and hemorrhage

Radiotherapy• Addition of RT to surgery improves 5-years survival when compared to RT

alone or surgery alone.Indications:

• Adjuvant (standard of care).• Definitive: medically inoperable or who refuse radical surgery

• Pre- and postoperative radiation may result in similar control rates.

• But post-operative RT prefered:• Preoperative radiation increases the infection rate and the risk of post-

operative wound complications.• Preoperative radiation may obscure the initial extent of disease surgery

can not remove the microscopic extensions of the tumor.

• Postoperative radiation therapy is started 4 to 6 weeks after surgery.

Indications for postoperative radiation therapy include• Positive or close margins, • Extracapsular extension, • Perineural invasion, • Advanced T stage• Multiple cervical metastases

Post op radiotherapy dose• - ve margin – 60 Gy in 30 #• +ve/close margin - 66 Gy in 33 #• Gross residual disease – 70 Gy in 35 #

Bristol et al. (2007):

• 146 patients with maxillary sinus tumors• treated with post-op radiotherapy. • Group 1 included 90 patients treated before 1991.• Group 2 included 56 patients treated after 1991, when

radiotherapy technique incorporated coverage of the base of skull for patients with perineural invasion, elective neck RT in SCC or undifferentiated histology, and techniques to improve dose homogeneity to target.

• No difference in 5 years OS (51 vs. 62%), RFS, LRC, DM between the two groups

• Advanced age, need for enucleation, and positive margins were independent predictors of worse OS.

Bristol IJ, IJROBP;68:719-730.

Role of chemotherapy

• Neoadjuvant chemotherapy is sometimes offered in order to reduce tumor volume, which may permit removal of tumor with a less morbid resection or facilitate radiotherapy planning if shrinkage pulls away tumor from critical structures.

• Chemotherapy may be given concurrent with radiotherapy in the management of inoperable tumors on the basis of improved results in more frequent head and neck carcinomas.

• Some recent studies give encouraging results for NACT for Ca PNS

Radiotherapy

Treatment Planning

OBJECTIVE : • To attain adequate tumor coverage• Deliver uniform dose distribution throughout target volume• Minimize doses to normal tissue

Simulation • Position: supine, straight , head extended

• Head Immobilisation: with thermoplastic mask fixed to the couch

• Shoulders :positioned as caudally as possible

• Eyes open, straight ahead to keep posterior pole away from high dose region.• Tongue blade/cork to depress tongue out of fields.• Fill surgical defects with tissue equivalents• Preferably CT based RTP scan with 3mm cuts to accurately define GTV • Image should be taken from above the calvarium to the carina• IV contrast should be used to help delineation• For Post Operative Patients: all surgical scar, drain sites, and stoma should be

wired on skin

Nasal Vestibule• Radiation therapy is usually the preferred treatment because of the deformity

produced by excision.

• Nasal cavities are filled with bolus during simulation and treatment to reduce dose heterogeneity

• Target Volumes for small, well-differentiated lesions measuring < 1.5-2 cm, small fields with a 1- to 2-cm margin are appropriate.

• The initial target volume for all poorly differentiated tumors and well-differentiated primaries of >1.5 -2 cm without palpable lymphadenopathy includes both nasal vestibules with at least 2- to 3-cm margins around the primary tumor (wider margins for infiltrative tumor) as well as bilateral facial, submandibular, and subdigastric nodes.

Borders- Anterior Portals

• Superior- bridge of the nose or higher in large tumor• Inferior- depends on extent of

upper lip invasion( from mid upper lip to vermillion border)• Lateral portals- about 1 cm

lateral to ala nasi

Lateral Portals• Used when tumor size is > 1.5-2 cm

• Anterior right and

left appositional electron fields

(usually with an approx.

15-20 degree) are used to

treat facial lymphatics.

• Medial-lateral border of anterior field• Anterior-oral commissure to middle of horizontal

ramus of mandible• Posterior-upper edge of anterior field to just above

angle of mandible• Inferior- split horizontal ramus of mandible and

adjoins the upper neck field

The combination of all three fields is known as moustache field

Upper neck field portal

• Used for tumor > 1.5 -2 cm in size

• Upper neck node are treated by parallel opposed photon field.

• Anterior border- 1 cm fall off• Posterior- just behind mastoid process• Superior- matched to moustache field• Inferior- just above arytenoid

Dose

• Small lesions- (<1.5-2 cm)- 50 Gy in 25 # f/b 10-16 Gy boost by EBRT• Larger lesions- 50 Gy in 25 # f/b 10-16 Gy boost by EBRT +

elective treatment to facial ( moustache area) and upper node ( 50 Gy)• Palpable neck node receive a total dose of 66-70 Gy

Nasal septum tumor may be treated using a customized bee wax and lead skin collimation.

Mixed electron and photon beams being used in 3-5:1 ratio.

Brachytherapy

Criteria –1. lesions of nasal cavity and external nares2. lesions on the septum or the mucosa medial to ala nasi –

distal 1/3 of nasal cavity3. Preferable for relatively smaller lesion.

Role of Brachytherapy

• For small lesions of nasal vestibule.

• Using Ir 192 wire implant or intracavitary mold.

• The recommended doses for low-dose-rate brachytherapy range from 60 to 65 Gy delivered during 5 to 7 days.

• In patients with T1 or T2 a boost of 20 to 25 Gy (LDR) over 2 days or 18 Gy (HDR; 3 Gy twice daily), following EBRT after 50 Gy, if there is good reduction of tumor volume.

• This technique has been reported as yielding a 2-year local control of 86%.

Mazeron JJ et al the Groupe Europeen de Curietherapie. Radiother Oncol 1988;13:165-173.

• Either brachytherapy or external-beam radiotherapy cures up to 95% to 100% of small (up to 2 cm) tumors.

• When adequate doses of radiation are used, 70% to 80% of lesions >2 cm can be controlled.

• As many as 40% of patients with larger lesions who do not receive elective nodal irradiation will fail in the neck, most can be salvaged and ultimate regional control is excellent.

Nasal Cavity

• EBRT 1.8–2 Gy/fx.

• Definitive RT or chemo-RT: CTV1 to 66–70 Gy, CTV2 to 60–63 Gy, CTV3 to 54–57 Gy.

• Post-op RT: CTV1 to 60 Gy with optional boost to 66 Gy to high-risk areas (close/+ margins, ECE, PNI). CTV2 to 50–54 Gy

• If combined treatment is planned operation first followed by irradiation is started 4 to 6 weeks afterward.

• The dose is usually 60 to 66 Gy for clear margins; patients with positive margins or for gross residual tumor after operation receive 70 Gy.

• In altered fractionation dose upto 74.4 may be given(twice daily at 1.2 Gy per fraction)

Ethmoid Sinus Ca Radiotherapy

• Radiotherapy is indicated in medically inoperable disease or in post op setting With/Without chemotherapy

• Radiation treatment is entirely by external beam, emphasizing treatment through an anterior field combined with one or two lateral fields.

• EBRT 1.8–2 Gy/fx.

• Definitive RT or chemo-RT: CTV1 to 66–70 Gy, CTV2 to 60–63 Gy, CTV3 to 54–57 Gy.

• Post-op RT: CTV1 to 60 Gy with optional boost to 66 Gy to high-risk areas (close/+ margins, ECE, PNI). CTV2 to 50–54 Gy

• IMRT should be considered if a more conformal dose distribution can be achieved with this technique.

Maxillary Sinus Carcinoma

Patterns of tumour spread

Anteriorly: cheek, skin

Posteriorly: pterygopalatine fossa, infra temporal

fossa, temporal bone middle cranial fossa

Medially: nasal cavity,NLD

Laterally: cheek, skin

Superiorly: orbit, ethmoid sinuses

Inferiorly: palate, buccal sulcus

Maxillary sinus Tumors

• Surgery is preferred treatment in T1 and T2 tumors with post op RT indicated if margin is close or positive.

• Surgery f/b post op RT is preferred in T3 and T4 lesions

• Medically inoperable or where there is contraindication for surgery upfront RT can be given .

Maxillary sinus tumorTumor of infrastructure • Anterior and I/L wedge pair photon fields are usually

used• Borders- Anterior portals• superior– just above floor of orbit below the cornea• Lateral– 1 cm beyond the lateral wall of maxillary sinus• Medial – 1-2 cm across midline• Inferior– 1 cm below floor of maxillary sinus or below surgical bed

Infrastructure Maxillary sinus tumor

• Latreral portals border:• Superior and inferior same as anterior Portal• Anterior – in front of anterior wall• Posterior- behind the pterygoid plates or more posteriorly

depending on the extent of tumor spread

Use of half beam block with isocenter at the level of orbital floor and shielding upper half of field prevent exposure to C/L eye by beam divergence.

• Three field technique with Rt and Lt lateral portals and anterior portal are preferred in these cases

Three field technique -Tumor of suprastructure

Borders - anterior portals• Superior – Above crista galli to cover ethmoids In the absence of orbital invasion at lower edge of cornea• Inferior –1 cm below the floor of the maxillary sinus or below surgical bed• Medial– 1 to 2 cm across midline to cover C/L ethmoid extension• Lateral – Depend on tumor extent 1 cm beyond lateral orbital wall when the structure is intact

Lateral portals

• Superior – Follows the contour of floor of ant. Cranial fossa• Inferior – same as anterior portals• Anterior - Behind lateral bony canthus parallel to slope of face• Posterior– Behind the Pterygoid plates or more posteriorly depending on extent of spread or surgeyFor boost The portal size is reduced to encompass the tumor bed and to exclude as much of optic pathway as possible.

Neck node • I/L upper neck irradiation given to patient with

squamous cell carcinoma or undifferentiated stage T3 to T4

Borders- lateral portal• Superior- sloping up from the horizontal ramus of the

mandible to the inferior border of primary portals posteriorly• Anterior- just behind oral commissures• Posterior- At the mastoid process • Inferior– Thyroid notch

• B/L neck node treatment indicated with palpable nodes

DoseUpfront radiotherapy• 50 Gy in 25 # to initial target volume • 16 to 20 Gy in 8-10 # to the boost volume

Post op Radiotherapy• Dose 60 Gy in 30 # for -ve margin• 66 Gy in 33 # for +ve margin• Gross residual disease- 70 Gy

Ethmoid sinus and Nasal cavity

• Most patient are treated with surgery and post operative radiotherapy• Post op radiotherapy techniques are same for ethmoid sinus

and suprastructure of maxillary sinus.• It includes 3 field technique with 1 anterior and 2 lateral

fields

Anterior Portals• The anterior portal extends 1.5 to 2.0 cm across the midline to encompass the

entire nasal cavity and ethmoid-sphenoid complex and medial contralateral orbit.

• The superior margin encompasses the cribriform plate and includes all or part of the frontal sinus.

• The inferior margin (usually the lip commissure) includes the floor of the nose, maxillary antrum, and alveolar ridge

• The mandible and tongue are displaced out of the treatment portal by a tongue blade and cork

Lateral portals

• Superior – Follows the contour of floor of ant. Cranial fossa• Inferior – same as anterior portals• Anterior - Behind lateral bony canthus

parallel to slope of face• Posterior– Behind the Pterygoid plates or

more posteriorly depending on extent of spread or surgey

For boost The portal size is reduced to encompass the tumor bed and to exclude as much of optic pathway as possible.

• If the ethmoid sinuses are extensively involved but there is no clinical or radiographic evidence of orbital involvement, a portion of the orbit (one-half to three-fourths) is usually irradiated to approximately 45 Gy for possible microscopic disease extension.

• Portals are then reduced to transect the ipsilateral eye medial to the limbus. This technique usually prevents severe lacrimal or retinal injury, but does produce a cataract.

• During treatment, the patient is instructed to gaze straight ahead with eyes wide open. The lateral-gaze or upward-gaze eye positions were discontinued because they rotate the posterior pole of the eye and retina into the treatment portal.

• Advanced orbital invasion requires irradiation of the entire orbital contents and ethmoid sinus lesions.

• The inferior border must be shaped to cover the lowest extent of disease.

• If the temporal fossa is grossly invaded, the lateral border of the anterior portal is usually allowed to fall off for all or part of the treatment.

• The lateral portals for nasal cavity, ethmoid, and maxillary sinus lesions are all similar.

• The anterior border of the lateral portals is at the lateral bony canthus, which means that a portion of the posterior pole of the ipsilateral eyeball is included in the lateral fields; the contralateral globe is missed because of the posterior angulation of the lateral portals.

U/L Ethmoid /nasal cavity invovement

Ethmoid /nasal cavity tumor with I/L maxillary sinus invasion

Ethmoidal carcinomaI – 45 degree wedge filtered portal at rt angle

III- parallel opposed field with an anterior field with wedge filters for tumors of ethmoid, nasal cavity, sphenoid or antrum

Sphenoid and Frontal sinuses

• Cancers of this region is very rare • Radiation is often offered as an adjunct to surgery.• Frontline therapy in patients with inoperable tumor or with

tumor type thought to be chemo &/or radiosensitive.• IMRT is preferred due to proximity to optic structures.

3D - CRT

• For three-dimensional (3D) conformal radiotherapy, the initial target volume is either Gross Tumor Volume or for postoperative radiotherapy consists of the surgical bed with 1- or 2-cm margins• It depends on the surgical pathology findings and the

proximity of critical structures. • The boost volume consists of areas at greatest risk for

recurrence, such as• close or positive resection margins • regions of perineural invasion• with 1- to 2-cm margins.

Delineation• Gross tumor volumes (GTV) – Includes all known primary and

cervical lymph node tumor extension based on clinical, endoscopic and imaging findings.

• Clinical target volume (CTV) –• HRCTV: GTV is expanded to include a margin for microscopic

extension forming high dose CTV.• IRCTV: optional. Includes area adjacent to GTV at high risk of

having occult microscopic spread• LRCTV: nodal regions at low risk for occult microscopic spread

included in a low-risk CTV

• Planning target volume (PTV)-CTV is expanded with 3-7 mm margin to account for organ motion & setup error

Gross tumor target delineation

Target volume delineation : Nancy Y Lee

GTV and CTV for various maxillary sinus tumor

Nodal GTV delineation

T2 N0M0 ethmoid sinus tumor delineation

Maxillary sinus tumor extending to nasal cavity

• The external-beam radiation schedule is typically 50 Gy in 25 fractions followed by a boost of 10 to 16 Gy in 5 to 8 fractions .

• Larger lesions to be treated by external-beam radiation alone receive 50 Gy in 25 fractions plus a boost of 16 to 20 Gy in 8 to 10 fractions.

• The schedule for elective nodal irradiation is 50 Gy in 25 fractions.

• Palpable nodes are given a boost to a total dose of 66 to 70 Gy in 33 to 35 fractions, depending on the size

IMRT• Intensity-modulated radiotherapy (IMRT) is preferred for tumors of the nasal

cavity in which the target volume extends >5 cm depth or for tumors of the ethmoid sinus .

• This technique delivers the desired dose to the target volume while minimizing the dose to critical organs such as cornea, lens, lacrimal glands, retina, optic nerve, optic chiasm, brain, and brainstem.

• For postoperative radiotherapy, the CTV1 consists of the primary tumor bed with a 1.0- to 1.5-cm margin.

• A boost subvolume consisting of high-risk regions (sites of positive margins, gross macroscopic residual tumor) to be treated to higher dose may be outlined.

• The CTV2 includes the entire operative bed. For ethmoid sinus tumors, this might include the frontal sinus, maxillary sinus, and sphenoid sinus.

• The bony orbit is part of the operative bed when orbital exenteration is performed because of tumor invasion.

• For lesions involving the ethmoid sinuses or olfactory region, the CTV should also include the cribriform plate.

• A third CTV may be delineated to encompass the tract of cranial nerve V2 to the foramen rotundum if there is perineural invasion.

• For primary radiotherapy using IMRT, the CTV1, consisting of the gross tumor volume plus a margin of 1 to 2 cm, receives the full dose of 66 to 70 Gy.

• In patients receiving neoadjuvant chemotherapy, target volume definition is based on the extent of disease before chemotherapy.

CTV or Maxillary Ca

Practical essentials of IMRT –K.S. Clifford Chao

Organ at risk delineation

Dose limitations• Lens <10 Gy (cataracts).• Retina <45 Gy (vision). May go higher if treating bid or partial volume.• Optic chiasm and nerves <54 Gy at standard fractionation.• Brain <60 Gy (necrosis).• Mandible <60 Gy (osteoradionecrosis).• Parotid mean dose <26 Gy .• Lacrimal gland <30–40 Gy.• Pituitary and hypothalamus mean dose <40 Gy.

Toxicity

• Acute = mucositis, skin erythema, nasal dryness, xerostomia• Late = xerostomia, chronic keratitis and iritis optic pathway injury soft tissue or osteoradionecrosis cataracts radiation induced hypopituitarism

Toxicity• The formation of nasal cavity synechiae (fibrous mucosal bands causing

airway stenosis)is common.

• It can be prevented by intermittent dilation of the nasal passages with a petroleum based jelly-coated cotton swab until mucositis has resolved.

• Dry mucous membranes can be managed symptomatically with saline nasal spray.

• Soft-tissue or cartilage necrosis is uncommon after therapy with an

estimated incidence of 5% to 10%

Eyes and Optic Pathway Toxicity

• Chronic keratitis and iritis (dry-eye syndrome ) If tumor extension to the orbital cavity mandates irradiation of the lacrimal gland to doses of more than 30 to 40 Gy .

• Without lacrimal irradiation, fewer than 20% of patients treated with up to 55 Gy to

the cornea develop chronic corneal injury .

• There is an approximately 5% risk (at 5 years) of cataract formation after doses of up to 10 Gy to the lenses using conventional fractionation; this risk increases to 50% at 5 years after 18 Gy.

• Radiation retinopathy is rare after doses of less than 45 Gy, but the incidence increases to about 50% after doses of 45 to 55 Gy .

• The reported incidence of optic neuropathy is <5% after 50 to 60 Gy but increases to around 30% for doses of 61 to 78 Gy.

Madani et al. (2009):• 84 sinonasal tumors definitively treated by IMRT. • Median dose of 70 Gy in 35 fractions• Sixty-four percent patients had adenocarcinoma histology• squamous cell carcinoma in 17, esthesioneuroblastoma in 9, and

adenoid cystic carcinoma in 4. • Postoperative IMRT was performed in 75 patients and 9 patients

received primary IMRT• No chemotherapy was given• Median follow-up 40 m• with 5-year LRC, OS, DFS were 71, 58, and 59%, respectively• No difference was found in local control and survival between patients

with primary or recurrent tumors• Toxicity rates were low

Madani I et al IJROBP 2009 73:424-432

Maxillary sinus tumor

Esthesioneuroblastoma

Esthesioneuroblastoma

• A single modality treatment, either surgery or radiotherapy, yields >90% ultimate locoregional control for early ENBs (Kadish stage A) .

• The optimal therapy for stage B disease is unclear, partly because this

group is heterogeneous; a combination of surgery and radiotherapy may have a slight advantage.

• For patients with stage C lesions, evidence suggests better results with the combination of surgery and radiotherapy.

• The available data do not justify routine elective nodal treatment because the incidence of isolated nodal relapse is <15%.

Elkon D et al Cancer 1979;44:1087-1094

• Chemotherapy is not routinely used for patients with ENB.• Although responses to chemotherapy have been reported, they

are usually of limited duration . • Overall, local therapy with surgery and postoperative

radiotherapy yield excellent results at 5 years with regard to both overall survival (93.1%) and local control (96.2%).

• Concurrent Cisplatin chemotherapy during radiation may be considered in inoperable cases

• NACT - Vincristine/Doxorubicin based or Cis/Etoposide

Esthesioneuroblastoma

Rosenthal DI et al Cancer 2004;101:2567-2573

• Juvenile Nasopharngeal Angioibroma• Highly vascular tumour• Young males – 12-14 yrs• Posterolateral part of nasal cavity• Angioembolisation + Sx + RT• 30-35 Gy(3-3.5 wks) / 45 Gy

• Lethal Midline Granuloma• Diagnosis of exclusion• Requires Sx + RT• 40-45 G (5-5.5 wks)• 30-70% Local control for 2 mnths-10 yrs• Also requires constant antibiotics, dressing

Thank You