How This Answer is Structured (RGUHS 59-mark Pattern)

Key Exam Tips for RGUHS

1. Always draw Ohngren's line diagram - examiners expect it; shows supra vs infra-structure tumours and prognosis implication.
2. Draw Weber-Ferguson incision - a simple face diagram with the incision markings scores easy marks.
3. Quote the textbook directly: Scott-Brown's and Cummings are the prescribed texts for RGUHS MS ENT; quoting directly (as done above) gives you distinction-level marks.
4. Orbital exenteration vs preservation - a common 10-mark sub-question; the periorbita/fat invasion distinction from Cummings is the gold standard answer.
5. T4a vs T4b distinction is the most commonly tested point - memorize this cold.
6. EXTREME regimen and KEYNOTE-048 (pembrolizumab) are the contemporary additions examiners look for.
7. For a 59-mark question, write in headings + subheadings + tables/diagrams - never paragraph-only format.

MANAGEMENT OF STAGE IV CARCINOMA OF THE MAXILLARY SINUS

50-Mark RGUHS Pattern Answer

1. INTRODUCTION [2 marks]

2. STAGING - TNM Classification (AJCC 8th Edition) [6 marks]

Primary Tumour (T) - Maxillary Sinus

Nodal Staging (N)

• N0 - No nodes; N1 - Single ipsilateral ≤3 cm; N2a - Single ipsilateral >3-6 cm; N2b - Multiple ipsilateral ≤6 cm; N2c - Bilateral/contralateral ≤6 cm; N3 - Any node >6 cm

Stage IV Groups

3. OHNGREN'S LINE [2 marks]

Definition (Cummings, Chapter 94): "An imaginary line that extends from the medial canthus to the angle of the jaw, which gives a rough estimate of the dividing line between tumors that may be resected with a good prognosis (below the line - infrastructure) and those that have a poor prognosis (above the line - suprastructure)."

• Infrastructure tumours (below Ohngren's line): Better prognosis; involve hard palate, alveolus, anterior/lower sinus walls
• Suprastructure tumours (above Ohngren's line): Poorer prognosis; closer to orbit, pterygoid fossa, skull base

4. PRE-TREATMENT EVALUATION [5 marks]

A. Clinical Assessment

• Full ENT examination including rigid nasal endoscopy
• Orbital assessment: visual acuity, extraocular movements, Hertel exophthalmometry for proptosis
• Oral cavity: palate, alveolus, trismus (pterygoid involvement)
• Cranial nerve assessment (V2 sensory loss = infraorbital nerve; trismus = pterygoid = T4a)
• Neck palpation for lymphadenopathy

B. Imaging

• Demonstrates bony destruction, sinus walls, pterygoid plates
• Best for assessing extent of bone erosion

"Most tumors display low-to-intermediate signals on T1-weighted sequences and intermediate brightness on T2-weighted sequences... Encroachment into normally fat-rich areas is best defined with a precontrast T1-weighted MRI, allowing for delineation of the darker tumor in the periorbita, pterygopalatine fossa, and parapharyngeal space." - Cummings, Chapter 94

• Perineural invasion: nerve enhancement + enlargement on gadolinium MRI
• Dural invasion: irregular/nodular dural thickening and enhancement (smooth thickening <5 mm = reactive/equivocal)
• T2-bright secretions vs. intermediate-bright tumour helps delineate true tumour extent
• Fat-saturation sequences: critical for periorbital invasion assessment

C. Biopsy

• Rigid nasal endoscopic biopsy (preferred - avoids tumour seeding)
• Caldwell-Luc antrostomy if endoscopic access not possible
• Antral washings (cytology) - rarely adequate alone in T4
• FNAC of palpable cervical nodes

D. MDT Conference

5. MANAGEMENT

STAGE IVA (T4a) - RESECTABLE DISEASE [15 marks]

A. SURGICAL MANAGEMENT

Types of Maxillectomy

Weber-Ferguson Incision (Standard Approach)

Scott-Brown's (Figure 7.14): "An incision along the crest of the philtrum and stepped on the lip is more acceptable than a midline incision. The mucosal incision along the midline of the hard palate turns laterally at the junction with the soft palate passing behind the maxillary tuberosity and then round the alveolus anteriorly. The facial skin flap is raised in a submuscular plane."

1. Incision through upper lip along philtrum (stepped to improve cosmesis)
2. Along nasolabial fold to alar base
3. Up the nasal dorsum medially
4. Below medial canthus (can extend into lower lid crease for orbital access - Lynch extension)

• Bilateral sublabial incisions + bilateral intercartilaginous incisions through the nose
• Degloving the midface upward
• Avoids external facial scars; equivalent surgical exposure
• Preferred where cosmesis is important

Osteotomies in Total Maxillectomy

Scott-Brown's: "The body of the zygoma, midline of the palate and pterygoid plates need to be divided. The palatal osteotomy is placed in the floor of the nasal cavity... The pterygoid plates are best separated from the maxilla with a curved osteotome... Osteotomies are made medially through the ethmoid cells and then frontal process of the maxilla, the latter after dividing the lacrimal sac... Bleeding from the internal maxillary artery is controlled by packing."

1. Midline palatal osteotomy (power tools)
2. Frontal process of maxilla (after dividing lacrimal sac)
3. Through body of zygoma (or zygomatic arch if zygoma included)
4. Pterygoid plate separation with curved osteotome
5. Ethmoid cells osteotomy medially
6. Maxilla mobilized and soft tissue remnants divided with Mayo scissors

Orbital Exenteration - Decision Making

• Invasion of orbital fat (stranding, nodularity on MRI)
• Extraocular muscle enlargement and enhancement on MRI
• Clinical proptosis with imaging evidence of infiltration
• Intraoperative finding of periorbita invasion (peel test positive)

• Bone erosion alone (without periorbita/fat invasion)
• Periorbita is intact at surgery ("peeling" of periorbita off bone = negative)
• Planned postoperative radiotherapy to cover residual risk

Cummings Chapter 94: "Current endoscopic contraindications include... bilateral optic nerve or chiasm infiltration. Extension through the sphenoid sinus walls often suggests involvement of the carotid arteries... significant trismus is suggestive of gross invasion into the pterygoid musculature."

Craniofacial Resection (for T4a with skull base extension)

1. Type 1 (Endoscopic/microscopic): Operating microscope with endoscopic approach; for limited ethmoid roof/orbital periosteum disease; avoids craniotomy
2. Type 2 (Window craniotomy): Lateral rhinotomy (anterior) + bicoronal incision (posterior); small midline window craniotomy through frontal sinus; dura elevated from cribriform plate; allows en bloc resection of both ethmoid complexes; dura and olfactory bulbs resected and repaired with fascia lata and pericranium; bone flap replaced with miniplates
3. Type 3 (Full craniofacial resection): Combined transfacial + neurosurgical frontolateral craniotomy approach; for most extensive tumours; interdisciplinary approach (ENT + neurosurgeon)

Scott-Brown's: "In 1963, Alfred Ketcham first reported a series of patients who had undergone a combined craniofacial approach to anterior skull base malignancies."

• Pericranial flap (most reliable vascularized cover)
• Temporalis flap
• Free flap (rectus abdominis/radial forearm) for large defects

Neck Dissection

• N0 neck: Elective selective neck dissection (levels I-III) - occult nodal rate is 25% in sinonasal malignancies; ipsilateral level I-II most common drainage
• N+ neck: Modified radical neck dissection (MRND) levels I-V (preserve IJV and SCM if uninvolved)
• Bilateral neck: If N2c or midline tumour

B. RECONSTRUCTION [4 marks]

1. Obturator Prosthesis

• Immediate surgical obturator: Placed at time of surgery; maintains oral-nasal separation; allows oral feeding and speech; made from dental impressions taken preoperatively
• Interim obturator: During healing phase (weeks 2-6 post-surgery)
• Definitive obturator: Custom-fabricated 3-6 months post-surgery after wound stabilization
• Advantages: allows cavity inspection for recurrence, non-invasive
• Disadvantages: leakage, speech distortion, requires regular modifications

2. Free Flap Reconstruction

Scott-Brown's: "The use of the radial free-forearm flap or anterolateral thigh flap provides excellent reconstruction of larger soft-tissue defects... reconstruction following segmental resection should ideally be with free-tissue transfer such as the fibula, scapula or DCIA flaps. Since radiotherapy will almost certainly be indicated... the use of vascularized bone flaps results in more predictable healing with lower risk of non-union or resorption."

C. POSTOPERATIVE RADIOTHERAPY (PORT) [4 marks]

Cummings, Chapter 94: "Most institutions today advocate complete surgical resection followed by radiation as offering the greatest chance of locoregional control and overall survival. Jansen et al. found that in comparing combined surgery and radiation with radiation alone, combined therapy gave significantly better 5-year disease-free (53% vs. 6%) and overall survival (60% vs. 9%)."

• T4a disease (by definition - all should receive)
• Positive/close surgical margins (<5 mm)
• Perineural invasion
• Lymphovascular invasion
• Nodal disease with extranodal extension (ENE)
• Multiple positive nodes

• IMRT (Intensity Modulated Radiation Therapy) - preferred over 3D-CRT
  • Reason: Spares optic chiasm, optic nerves, brain stem, parotid glands
  • Critical because: "The definitive postoperative radiation dose necessary to prevent relapse (60 to 70 Gy) exceeds the predicted radiation tolerance for the optic nerve (45-54 Gy) and spinal cord (50 Gy)" - Cummings
  • Conventional radiation: visual toxicity in ~35% of patients (retinopathy, glaucoma, keratitis, blindness) at median 2 years
• Dose: 60-66 Gy in 30-33 fractions to primary site
• Elective nodal dose: 44-50 Gy to at-risk levels
• Start PORT within 6 weeks of surgery (delay reduces benefit)
• Treat: ipsilateral neck + retropharyngeal nodes routinely

• Added when: positive margins OR extranodal extension (ENE)
• Cisplatin 100 mg/m² on Days 1, 22, 43 concurrent with radiotherapy
• Alternative (cisplatin-unfit): Carboplatin AUC 1.5 weekly, or Cetuximab weekly

STAGE IVB (T4b, N3) - UNRESECTABLE DISEASE [5 marks]

Cummings: "Such inoperable cases may be best treated with primary chemoradiation, potentially in a palliative setting."

• Cisplatin 100 mg/m² IV on Days 1, 22, 43
• Radiation: 70 Gy in 35 fractions (2 Gy/fraction, 7 weeks)
• OR Weekly Cisplatin 40 mg/m² with 70 Gy (better tolerability, similar efficacy)
• Cetuximab (EGFR antibody) + Radiation (Bonner protocol): if Cisplatin contraindicated (CrCl <50, SNHL, poor PS)

• Used to downstage massive unresectable tumours prior to CRT
• Docetaxel 75 mg/m² + Cisplatin 75 mg/m² + 5-FU 750 mg/m²/day × 5 days
• 3 cycles every 21 days, then definitive CRT
• TAX 324 trial: TPF superior to PF regimen in locally advanced HNSCC

STAGE IVC - METASTATIC DISEASE (Palliative) [3 marks]

• EXTREME regimen (First-line):
  • Cisplatin 100 mg/m² D1 + 5-FU 1000 mg/m²/day D1-4 + Cetuximab (400 mg/m² loading, then 250 mg/m² weekly)
  • Continued for 6 cycles, then Cetuximab maintenance
  • EXTREME trial (Vermorken et al., 2008): Median OS 10.1 vs 7.4 months
• Pembrolizumab (PD-1 inhibitor): KEYNOTE-048 trial - pembrolizumab ± chemotherapy is now standard first-line in recurrent/metastatic HNSCC (CPS ≥1)
• Nivolumab: Second-line post-platinum failure (CheckMate 141 trial)

• Bone metastasis pain: 30 Gy/10 fractions
• Brain metastasis: Whole brain RT 30 Gy/10 fractions or stereotactic radiosurgery (SRS)

6. SPECIAL HISTOLOGY-SPECIFIC CONSIDERATIONS [2 marks]

7. COMPLICATIONS [3 marks]

Surgical Complications

• Haemorrhage (internal maxillary artery - packing first-line, then ligation)
• CSF leak (craniofacial resection) - meningitis risk
• Orbital/optic nerve injury
• Trismus (postoperative fibrosis of pterygoid muscles)
• Palatal fistula
• Facial deformity/enophthalmos

Radiotherapy Complications

• Acute: Mucositis, xerostomia, skin reaction, fatigue, loss of taste
• Late: Osteoradionecrosis of maxilla/mandible, radiation cataract, retinopathy, optic neuropathy (critical with high-dose RT near orbit), temporal lobe necrosis, chronic rhinosinusitis, trismus from fibrosis

Chemotherapy

• Cisplatin: Nephrotoxicity, ototoxicity, peripheral neuropathy
• Cetuximab: Acneiform rash (paradoxically good prognostic sign), hypomagnesaemia

8. PROGNOSIS AND FOLLOW-UP [3 marks]

Scott-Brown's (Table 7.6): 5-year survival: nasal cavity 77%, maxillary sinus 62%, ethmoid sinus 48%. Above Ohngren's line = worse prognosis.

• T4b disease, N3 nodes, extranodal extension (ENE)
• Positive surgical margins, perineural/vascular invasion
• Above Ohngren's line, dural involvement
• Delay in diagnosis (silent expansion)
• ACC: late distant metastasis despite local control

• Years 1-2: Every 1-2 months (peak recurrence period; >90% of recurrences occur within 2 years - Scott-Brown's)
• Years 3-5: Every 3-6 months
• After 5 years: Annual review
• At each visit: Nasal endoscopy, oral cavity/neck examination, obturator assessment
• Baseline MRI/CT at 3 months post-treatment
• PET-CT at 12 weeks post-CRT to assess nodal response
• Annual thyroid function (post-neck irradiation)
• Audiometry (post-cisplatin)
• Dental review: extractions before RT; fluoride trays thereafter

9. SUMMARY ALGORITHM

STAGE IV MAXILLARY CARCINOMA
          |
   _______|________
  |                 |
IVA (T4a)        IVB / IVC
Resectable     Unresectable / Metastatic
  |                 |
SURGERY           IVB: Definitive CRT
  |                 (70 Gy + Cisplatin)
  |                 OR Induction TPF → CRT
  |                 
  +--Total Maxillectomy        IVC: Palliative
  +--± Orbital Exenteration         EXTREME / Pembrolizumab
  +--± Craniofacial Resection        ± Palliative RT
  +--± Neck Dissection
  |
  +--Reconstruction
      (Obturator / Free Flap)
  |
  PORT (60-66 Gy IMRT)
  ± Cisplatin (if +ve margins / ENE)

10. KEY EXAMINATION POINTS (RGUHS Distinction Level) [1 mark]

1. Ohngren's line = medial canthus to angle of mandible; above = suprastructure = poor prognosis
2. T4a (resectable): skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid/frontal sinus, anterior orbital contents
3. T4b (unresectable): orbital apex, dura, brain, CN other than V2, nasopharynx, clivus
4. Trismus = pterygoid plate/muscle involvement = T4a (minimum)
5. Exenteration required only when orbital FAT invaded, not bone erosion alone
6. Weber-Ferguson = standard open incision (philtrum + nasolabial fold + medial canthus)
7. Midfacial degloving = scar-free alternative
8. Craniofacial resection (Ketcham 1963) = for skull base involvement
9. PORT dose = 60-66 Gy; 70 Gy if definitive (unresectable)
10. Combined surgery + RT = 5-year DFS 53% vs RT alone 6% (Jansen et al. - Cummings)
11. EXTREME regimen = cisplatin + 5-FU + cetuximab (metastatic)
12. Pembrolizumab = first-line recurrent/metastatic (KEYNOTE-048)
13. 5-year survival maxillary sinus = 62% overall; Stage IVA = 25-35% (Scott-Brown's)