Radiation Oncology/Head & Neck/Sinonasal/Overview

Nasal Cavity and Paranasal Sinuses


 * For now please see individual subpages

Epidemiology

 * Tumors of the nasal vestibule are frequently considered separately from nasal cavity and paranasal sinus tumors, because they are essentially skin cancers and as such have a different natural history
 * Primary tumors of the nasal cavity and paranasal sinuses are usually grouped together, because they are frequently advanced at presentation and it's not clear from which site they originated
 * Annual incidence ~1/100,000
 * Occur more often in men, and age >40 (except salivary gland tumors and esthesioneuroblastoma which are seen earlier)

Anatomy

 * Sites
 * Nasal vestibule
 * Nasal cavity
 * Maxillary sinuses
 * Frontal sinuses
 * Ethmoid sinuses
 * Sphenoid sinus
 * Lymphatic drainage
 * Nasal vestibule: submandibular LNs, usually ipsilateral but may be bilateral
 * Nasal cavity: olofactory group and respiratory group with different drainage patterns
 * Olofactory group drains to lateral retropharyngeal LNs, but can also communicate with subarachnoid space and CSF
 * Respiratory group drain lower, in lateral retropharyngeal LNs or in Level II LNs
 * Paranasal sinuses have minimal drainage

Pathology

 * Benign: inverting papilloma can be associated with carcinoma in 5-15% of cases
 * Squamous cell carcinoma most common
 * Minor salivary glands account for 10-15% cases
 * Lymphoma accounts for ~5%, and includes NK/T cell variant, which is locally very destructive
 * Esthesioneuroblastoma accounts for 3-4%
 * Mucosal melanoma accounts for ~1%

Treatment Overview

 * Combination of radical surgery and postop radiation is a frequently used approach
 * Surgical approaches depend on location, and include lateral rhinotomy, medial maxillectomy, total maxillectomy, or craniofacial resection
 * Extent of surgery correlates with DFS and OS, but not local control if RT is used
 * Higher radiation doses are associated with improved local control, but visual toxicity is common
 * Conversely, using conformal RT reduced toxicity while keeping survival comparable to conventional RT
 * Poor overall survival ~50% at 5 years

Outcomes

 * Ghent, Belgium
 * 2005 (1998-2003) PMID 15915466 -- "Postoperative intensity-modulated radiotherapy in sinonasal carcinoma: clinical results in 39 patients." (Duthoy W, Cancer. 2005 Jul 1;104(1):71-82.)
 * Retrospective. 39 patients, surgery + postop RT. AdenoCA 79%, SCC 21%. Cribriform plate invasion 28%, orbital invasion 36%. Median IMRT 70 Gy. Median F/U 2.6 years
 * Outcome: 4-year LC 68%, 4-year OS 59%
 * Toxicity: decreased vision 6%, no blindness
 * Conclusion: Postop IMRT good LC, with low acute toxicity
 * 2009 (1998-2006) PMID 18755554 -- "Intensity-modulated radiotherapy for sinonasal tumors: ghent university hospital update." (Madani I, Int J Radiat Oncol Biol Phys. 2009 Feb 1;73(2):424-32. Epub 2008 Aug 26.)
 * Retrospective. 84 patients. Postop IMRT in 89%, primary 11%. Median F/U 3.3 years
 * Outcome: 5-year LC 71%, DFS 60%, DMFS 82%, DSS 67%, OS 58%. Invasion of cribriform plate negative predictor
 * Toxicity: No radiation blindness, 1 patient radiation retinopathy, 1 patient lacrimal duct stenosis, 3 patients brain necrosis
 * Conclusion: IMRT low rate of toxicity, with high local control and survival


 * Turin, Italy; 2008 (2000-2005) PMID 18705398 -- "Stage III-IV sinonasal and nasal cavity carcinoma treated with three-dimensional conformal radiotherapy." (Gabriele AM, Tumori. 2008 May-Jun;94(3):320-6.)
 * Retrospective. 31 patients, locally advanced paranasal sinus and nasal cavity tumors. 3D-CRT. Postop (68%) dose 60 Gy or radical dose 68 Gy (32%). Some use of chemotherapy. Median F/U 3.5 years
 * Outcome: Postop: 5-year LC 74%, 5-year OS 72%. Radical RT 20% and 25%. Local recurrence most common site of failure
 * Toxicity: No radiation-induced blindness; 4 patients enucleation as part of radical surgery
 * Conclusion: Local control remains low; 3D-CRT reduces risk of optical pathways but doesn't modify survival


 * UCSF
 * IMRT; 2007 (1998-2004) PMID 17189068 -- "Intensity-modulated radiation therapy for malignancies of the nasal cavity and paranasal sinuses." (Daly ME, Int J Radiat Oncol Biol Phys. 2007 Jan 1;67(1):151-7.)
 * Retrospective. 36 patients with PNS cancers, 32 after gross total resection. Sites: 13 ethmoid, 10 maxillary, 7 nasal cavity, 6 other. IMRT 70 Gy to GTV, and 60 Gy to CTV. Median F/U 51 months
 * 5-year outcomes: LC 58%; DFS 55%; OS 45%
 * Toxicity: minimal, no decreased vision, 1 xerophalmia, 1 lacrimal stenosis, 1 cataract
 * Conclusion: IMRT no benefit on disease control, but low incidence of complications
 * Historical; 2007 (1960-2005) PMID 17459609 -- "Carcinomas of the paranasal sinuses and nasal cavity treated with radiotherapy at a single institution over five decades: are we making improvement?" (Chen AM, Int J Radiat Oncol Biol Phys. 2007 Sep 1;69(1):141-7. Epub 2007 Apr 24.)
 * Retrospective. 127 patients, sinonasal carcinoma. Conventional 46%, 3D-CRT 39%, IMRT 18%
 * Outcome: 5-year OS: 1960's 46%, 1970's 56%, 1980's 51%, 1990's 53%, 2000's 49%
 * Toxicity: Grade 3-4 late: 53%, 45%, 39%, 28%, 16% (SS)
 * Conclusion: No improvement in disease control or survival, but decreased incidence of complications


 * MSKCC; 2006 (1987-2005) PMID 17161557 -- "Treatment of nasal cavity and paranasal sinus cancer with modern radiotherapy techniques in the postoperative setting-the MSKCC experience." (Hoppe BS, Int J Radiat Oncol Biol Phys. 2006 Dec 7)
 * Retrospective. 85 patients with PNS, treated with post-op RT. Median RT 63 Gy. 62% treated with IMRT or 3D-CRT, rest with 2D. Median F/U 60 months
 * 5-year outcomes: LC 62%, DM-free 82%, DFS 55%, OS 67%. Bad prognosis: squamous cell and cribriform plate involvement
 * Toxicity: 1 blindness (but no Grade 3-4 among patients treated with IMRT/3D-CRT)
 * Conclusion: Local recurrence main problem. Modern RT safe.

Treatment Technique

 * Utah; 1991 PMID 1764170 -- "Graduated block technique for the treatment of paranasal sinus tumors." (Tobler M, Med Dosim. 1991 Dec;16(4):199-204.)
 * 5-field graduated wedge technique. AP beam heavily weighted, prescribed just beyond lens. Lateral wedge fields posteriorly fill-in dose as anterior contribution decreases

Clinical Outcomes

 * Harvard
 * 2008 (1991-2002) PMID 17902164 -- "Extent of surgery in the management of locally advanced sinonasal malignancies." (Resto VA, Head Neck. 2008 Feb;30(2):222-9.)
 * Retrospective. 102 patients, locally advanced, treated with proton therapy with or without surgery (R0 20%, R1 49%, R2/biopsy 31%). Squamous cell 32%, neuroendocrine 29%, adenoid cystic 20%, sarcoma 13%, adenocarcinoma 6%. Median RT dose if R0 resection 67.6 Gy, if R1/R2 resection 75.6 Gy usually given BID. Median proton contribution 57%. Concurrent chemo 33% (typically for neuroendocrine). Median F/U 3.6 years, alive 5.1 years
 * Outcome: 5-year LC R0 95% vs R1 82% vs R2 87% (NS, no difference by histology); 5-year DFMS 95% vs. 69% vs 52% (no difference by histology). 5-year OS 90% vs 49% vs 39% (worst for squamous cell). Regional failure rate 12%
 * Conclusion: High dose proton RT excellent local control regardless of extent of surgery. However, DFS and DMFS depended on extent of surgery. Can consider observation for regional neck
 * 2006 (1991-2001) PMID 17050017 -- "Visual outcome of accelerated fractionated radiation for advanced sinonasal malignancies employing photons/protons." (Weber DC, Radiother Oncol. 2006 Dec;81(3):243-9. Epub 2006 Oct 16.)
 * Retrospective. 36 patients, advanced stage nasal or paranasal malignant tumors. Treated with aggressive surgery and post-op RT (78%) or radical RT (22%). Median dose 69.6 CGE, usually BID or concomitant boost. Proton contribution 20-85% depending on beam availability. No concurrent chemo. Median F/U 4.4 years
 * Outcome: 3-year OS 90%, 5-year OS 81%. 3-year DFS 77%, 5-year DFS 73%
 * Toxicity: late visual/ocular toxicity Grade 2+ (retinopathy, optic neuropathy, cataract, dry-eye syndroma, or nasolacrimal duct blockage) 22% in median 2.6 years after RT)
 * Conclusion: AFRT enables delivery of 70 CGE with acceptable ophthalmologic complications
 * 2002 (1992-1998) PMID 12173330 -- "Neuroendocrine tumors of the sinonasal tract. Results of a prospective study incorporating chemotherapy, surgery, and combined proton-photon radiotherapy." (Fitzek MM, Cancer. 2002 May 15;94(10):2623-34.)
 * Prospective. 19 patients with olofactory neuroblastoma or neuroendocrine carcinoma. Kadish Stage B 4/19, Kadish Stage C 15/19. Induction cisplatin/etoposide x2 cycles, then proton/photon RT to 69.2 CGE concomitant boost. If response, further 2 cycles of chemo. Median F/U 3.7 years
 * Outcome: 5-year OS 74%; 5-year LC 88%
 * Toxicity: 1 patient unilateral vision loss after induction chemo. 4 patients frontal/temporal lobe damage by MRI. 2 patients soft tissue/bone necrosis. No radiation-induced visual loss
 * Conclusion: This approach is successful, with radical surgery reserved for nonresponders


 * Chiba; 2007 (1999-2005) PMID 17398027 -- "Proton-beam therapy for olfactory neuroblastoma." (Nishimura H, Int J Radiat Oncol Biol Phys. 2007 Jul 1;68(3):758-62. Epub 2007 Mar 29.)
 * Retrospective. 14 patients (Kadish A 2/14, Kadish B 5/14, Kadish C 7/14). Dose 65 GyE in 2.5 Gy/fx. Median F/U 3.3 years
 * Outcome: 5-year LC 84%, 5-year RFS 71%, 5-year OS 93%
 * Toxicity: Liquorrhea 1 patient, no other Grade 3+
 * Conclusion: Excellent local control and survival outcome, without serious side effects

Treatment Planning

 * PSI
 * Paranasal; 2003 PMID 12559516 -- "Intensity modulation in radiotherapy: photons versus protons in the paranasal sinus." (Lomax AJ, Radiother Oncol. 2003 Jan;66(1):11-8.)
 * Treatment planning. Paranasal case, three dose levels 76 Gy, 66 Gy, and 54 Gy. IMRT vs IMPT comparison
 * Outcome: Comparable target conformality and sparing of critical structures; low dose regions or target homogeneity trade-off in IMRT plan
 * Conclusion: Comparable target conformality and sparing of critical structures, low dose regions better with IMPT
 * Paraorbital; 2000 PMID 10863085 -- "Optimizing radiotherapy of orbital and paraorbital tumors: intensity-modulated X-ray beams vs. intensity-modulated proton beams." (Miralbell R, Int J Radiat Oncol Biol Phys. 2000 Jul 1;47(4):1111-9.)
 * Treatment planning. 4 orbital/paraorbital tumors. IMRT vs IMPT.
 * Outcome: PTV coverage comparable. DVHs for OAR better with IMPT, though predicted severe NTCP equally low
 * Conclusion: Both IMRT and IMPT optimally treated PTV and reduced severe late toxicity; IMPT better at low/mid dose regions