Sino-nasal cancers are not uncommon. However, treatment is always challenging because of surrounding critical normal structures. Skilled surgical procedure and high end radiation therapy (IMRT, IGRT, SBRT) can definitely treat these difficult cancers.

1. Radiotherapy in Sinonasal
Cancer: Moving From
Adjuvant to Definitive
Treatment
Dr. Malhar Patel, DNB
Consultant Radiation Oncologist
CIMS Cancer Center
CIMS Hospital

2. Anatomy

3. Introduction
Very rare - < 3% of head and neck cancers (1 in lakh) [1]
Classified as undifferentiated neuroendocrine tumor
Originates from nasal cavity/paranasal sinus epithelium
Disease is typically locally advanced at presentation
Can involve orbit/skull/brain
10-30% present with clinically positive lymph nodes [2]
Distant metastasis unusual – Bone & Lungs (Recurrent Disease)
Treatment failure – Local and distant recurrence
1. Chambers KJ, Lehmann AE, Remenschneider A, et al. Incidence and survival patterns of sinonasal undifferentiated carcinoma in the United States. J Neurol Surg B Skull Base 2015;76:94–100.
2. Reiersen DA, Pahilan ME, Devaiah AK. Meta-analysis of treatment outcomes for sinonasal undifferentiated carcinoma. Otolaryngol Head Neck Surg 2012;147:7–14.

5. NCCN Staging

6. Stage Characteristics
A Confined to nasal cavity
B Confined to nasal cavity and paranasal sinus
C Beyond nasal cavity and paranasal sinus
KADISH Staging
*Originally described for esthesioneuroblastoma (ENB)

7. Facts
Exceedingly rare and aggressive tumor
Poor prognosis – Late diagnosis (>80% Stage IV) [1]
Early detection - chemotherapy, radiation, and/or surgery
The literature is sparse - no consensus for optimal treatment.
Surgical candidates - vast skill required – R0 – Reconstruct [2,3]
1. Lin EM, Sparano A, Spalding A, et al. Sinonasal undifferenti- ated carcinoma: a 13-year experience at a single institution. Skull Base 2010;20:61–7.
2. Righi PD, Francis F, Aron BS, et al. Sinonasal undifferentiated carcinoma: a 10 year experience. Am J Otolaryngol 1996;17:167–71.
3. Chen AM, Daly ME, El-sayed I, et al. Patterns of failure after combined-modality approaches incorporating radiotherapy for sinonasal undifferentiated carcinoma of the head and neck. Int J Radiat Oncol Biol
Phys 2008;70:338–43.

8. Carcinoma Maxilla

9. Primary treatment - Surgical resection.
Open surgery, and now endo- scopic resection
Silent disease – Late diagnosis
Anatomical Challenge!!
In-complete resection
Limiting oragan preservation
Radiotherapy – Definitive ot Adjuvant

10. Surgery or Radiation???
1. Jeng Y, Sung M, Fang C, et al. Sinonasal undifferentiated carcinoma and nasopharyngeal-type undifferentiated carcinoma: two clinically, biologically, and histopathologically distinct entities. Am J Surg Pathol 2002;26:371–6.
2. Musy PY, Reibel JF, Levine PA. Sinonasal undifferentiated carcinoma: the search for a better outcome. Laryngoscope 2002;112:1450–5.
Current literature focuses on comparing the survival probabilities
of patients who undergo surgery, radiation, chemotherapy, and a
multi-modal approach.
Single-modality - Surgery alone confers the highest survival rate
[1]
Musy et al report a 64% survival rate in patients who underwent
surgery compared with a 25% survival rate in those who received
definitive radiotherapy ± chemotherapy [2].

11. Surgery or Radiation???
Yoshida et al.
16 patients
Median survival
Surgery + Postoperative RT-CT: 30 months
Surgery alone: 7 months
Definitive RT-CT: 9 months
2 year Loco-Regional Control
Surgery + Postoperatie RT-CT: 78%
Surgery alone: 37%
Definitive RT-CT: 18%
2 year cumulative harard function: Risk
of local recurrence after 1 year less with
Surgery + RT-CT

12. Al-Mamgani et at (Less T4 cases)
5 year
overall survival: 74%
Disease Free Survival: 64%
Local failure risk is increased with bimodality treatment than trimodality
treatment
Surgery: Better Local Control (85% Vs 25%)
Surgery or Radiation???

13. Musy et al.
Residual tumour in 70% of surgical specimens
after primary chemoradiation.

14. Meta-analysis
Reiersen et al.
167 patients
Chance of survival
Surgery + radiation and/ or chemotherapy: 260%
(OR = 2.6; 95% CI, 0.82-7.87)
Presence of neck metastases was also a poor prognostic sign.

15. The combination of radiotherapy with surgery is superior, compared to radiation alone [1].
Complete surgical resection with post-operative radiation therapy is considered the
mainstay of sinonasal cancer treatment [2].
1.Jansen EP, Keus RB, Hilgers FJ, Haas RL, Tan IB, Bartelink H. Does the combination of radiotherapy and debulking surgery favor survival in paranasal sinus carcinoma? Int J Radiat Oncol Biol Phys. 2000;48(1):27–35.
2.Llorente JL, Lopez F, Suarez C, Hermsen MA. Sinonasal carcinoma: clinical, pathological, genetic and therapeutic advances. Nat Rev Clin Oncol. 2014; 11(8):460–72.

16. Radiation
• Sx + Conventional RT
Local Control 59%
Overall survival 40% at 5 years [1]
• Conventional radiation
Loss of vision in 1/3rd patients [2,3]
1.Dulguerov P, Jacobsen MS, Allal AS, Lehmann W, Calcaterra T: Nasal and paranasal sinus carcinoma: are we making progress? A series of 220 patients and a systematic review. Cancer 2001, 92:3012-3029.
2.Parsons JT, Mendenhall WM, Mancuso AA, Cassisi NJ, Million RR: Malignant tumors of the nasal cavity and ethmoid and sphenoid sinuses. Int J Radiat Oncol Biol Phys 1988, 14:11-22.
3.Shukovsky LJ, Fletcher GH: Retinal and optic nerve complications in a high dose irradiation technique of ethmoid sinus and nasal cavity. Radiology 1972, 104:629-634.

17. Various planning studies were already
able to demonstrate that
patients with sinunasal tumours highly
profit from modern RT-techniques

19. 1987 – 2005 : 85 patients
Post operative radiation
50% T4 lesion
Median Radiation Dose: 63 Gy
Median follow up: 60 months
5 year eatimate
Local PFS: 62%
Regional PFS: 87%
Distant Metastasis FS: 82%
Disease Free Survival: 55%
Overall Survival: 67%
IMRT
Grade 3-4 late complication NONE

20. 1998-2004: 36 patients
89%: Adjuvant radiation
Median Follow Up: 51 months
Local Control
2 year: 62%
5 year estimates: 58%
5 year
DFS: 55%
OS: 45%
No decreased vision recorded
Minimal late toxicity

21. 32 patients
Median follow up 15 months
No corneal injury
Dry eye symdrome: mild
No grade 3 or 4 toxicity

22. Role Of Radiation
Radiation Neo-Adjuvant
(Musy et al)
Adjuvant
(Tanzler et al)
Definitive
(Tanzler et al)
Median Dose 50 Gy 64.8 Gy 70.8 Gy
Range 50-54 Gy 62.4-74.4 Gy 70-74.8 Gy

23. Evolution of Radiation Oncology
Intensity Modulated Radiotherapy (IMRT)
Volumetric Modulates Arc Therapy (VMAT)
Image Guided Radiotherapy (IGRT)
Image Fusion

24. MRI Fusion

25. PET CT Scan Fusion

26. Non-Operated
GTV – MRI
CTV
Flanked by intact bone or cranial nerve – No margin
Invades compartment – Whole compartment
Invades radiologically defined space (Parapharyngeal, masticator) – Entire space or 0.5 to 1.0
cm margin
Orbit – Whole or Medial part (including rectus medialis muscle)
Intra cranial – Incude meningeal structures or cranial fossa
PTV – 3 to 5 mm margin to CTV
No elective nodal irradiation
(Except T3 T4 Maxilla and Undifferentiated)
Target Delineation

28. Complete Surgery
GTV – Edge of resection margin
CTV – Resection cavity + Variable Margin
COMPARTMENTAL CTV
Target Delineation

29. Planned Risk Volume (PRV)
Optic chiasm, optic nerve, retina, lactimal glands, pitutary, brainstem, brain, mandible, parotid gland
MRI – Posterior part of optic nerves, optic chiasm, pitutary gland
Optic Pathway – 2mm isotropic expansion
Brainstem – 3mm isotropic expansion

30. Dose Contraint
PTV
70 Gy in 35 fractions (Definitive)
60 Gy in 30 fractions (Adjuvant)
Acceptable minimum (Dmin) – 5% of precribed dose
>5% underdosage – Overlaping with critical structures
Dose Maximum – Must be under PTV
Overdosage – 7% - ICRU guideline

31. PRV
60 Gy to D-95
95% of the Volume of the structures has to receive 60 Gy or less
Very HARD to achieve
Dry Eye Syndrome
30 Gy to major lacrimal gland
Pitutary Gland
Hormonal substitution not required below 50 Gy
Dose Contraint

32. Brain
Maximum dose constraint of 70Gy to a 2cm rind of brain tissue flanking the PTV.
Complemented by 50 Gy dose maximum constraint for brain tissue outside the rind.
Mandible
70 Gy dose maximum constraint is proposed after good dental care
Parotid glands
26 Gy maximum of the mean dose is consistent with preservation of function
Dose Contraint

33. Case

34. Adaptive Radiation
T4 lesions

35. Recent Advances

37. Take Home Message