Unresectable (T4b) When Medical Professionals Opt Not to Treat. What s Resectable? The Current State of Sino-nasal Tumors

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1 UC SF 2 What s Resectable? The Current State of Sino-nasal Tumors When Medical Professionals Opt Not to Treat Truly Unresectable? Incurable? Ivan El-Sayed MD, FACS Otolaryngology Minimally Invasive Skull Base Surgery Program Otolaryngology-Head and Neck Surgery University of California San Francisco Impact on Patient QL too great Unaware there is an option? AJCC Uncurable and Unresectablewho defines? Most Senior Surgeon Medical Oncologist? Radiation Therapist? Hospital Panels? Unresectable (T4b) Very advanced local disease Tumor invades Nasopharynx Orbital apex Dura Brain Clivus Middle cranial fossa Cranial nerves other than (V2) 3 4 1

2 Variability in Intracranial Invasion? 5 6 And Intracranial Invasion Indicators of Poor Outcome 7 8 2

Range of Tumors in Paranasal Sinuses Epithelial Salivary Osteo-Chondroid Lymphatic Vascular Neuroendocrine tumors Esthesioneuroblastoma Sinonasal neuroendocrine (SNEC)

3 Paranasal Sinus Cancer: What do we know? 3% of all Head and Neck Cancer 0.5% of all malignancies Few Centers with Large Experience Lack of uniform staging system in literature treatment protocols surgical technique employed. Range of Tumors in Paranasal Sinuses Epithelial Salivary Osteo-Chondroid Lymphatic Vascular Neuroendocrine tumors Esthesioneuroblastoma Sinonasal neuroendocrine (SNEC) Sinonasal Undiff Ca (SNUC) Small Cell Ca 9 10 Occur Adjacent Important Structures Carotid Artery Dura Brain Orbit and Optic Nerve Cranial Nerves Cavernous Sinus Presenting Symptoms Nasal Obstruction Epistaxis Mass Effect CN Defect Ocular disorders Anosmia Pain/Headache Silent

Routes of Tumor Spread Misconceptions in Paranasal Sinus Cancer Disparity in the care based on where patient treated Some patients deemed incorrectly inoperable and incurable Organ Preservation

4 Routes of Tumor Spread Misconceptions in Paranasal Sinus Cancer Disparity in the care based on where patient treated Some patients deemed incorrectly inoperable and incurable Organ Preservation Chemotherapy/Radiation is an equivalent treatment option. Usually offered when no OHNS input Trials needed The Morbidity of treatment is not worth it The tumor is worse Ed PD. Skull Base Surgery, Approach to Paranasal Sinus Ca Tumor Biology: What are Goals of Therapy? Role Radiation/Chemotherapy Improved Survival Rates? Advances in Surgical Techniques Move to endoscopic Tumor Biology and Presentation Local Aggressiveness Risk of Systemic Spread Initial Staging TNM Local Invasion Bone/Orbit Dural spread Brain Vascular 15 Complications of craniofacial resection for malignant tumors of the skull base: Report of an International Collaborative Study. Head Neck Jun;27(6):

Recognition of Spectrum of Sinonasal Neuroendocrine Tumors Esthesioneuroblastoma (ENB) Sinonasal Undifferentiated Ca (SNUC) Recurrence of ENB Late recurrence well documented Most neck metastases

5 Recognition of Spectrum of Sinonasal Neuroendocrine Tumors Esthesioneuroblastoma (ENB) Sinonasal Undifferentiated Ca (SNUC) Recurrence of ENB Late recurrence well documented Most neck metastases occur 1-2 years after treatment. Sinonasal Neuroendocrine Ca (SNEC) Small Cell Carcinoma (SmCC) Rosenthal et al, Cancer 2004 MD Anderson Series 39-50% occur > 5 years after treatment. Rinaldo Acta Otol 2002, McElroy et al, (Mayo) Neurosurg 1998 Simon et al, (Iowa) Laryngoscope 2001 UCSF 17 UCSF 18 What are the Options Treatment Options Surgery Radiation Systemic (chemotherapy, Immunotherapy?)

6 Historical Data and Confounding Factors Majority of Sinonasal Tumors Present as T3-T4 lesions Many lesions in ancient literature are misclassified Studies are retrospective and subject to selection bias Radiotherapy with Surgery Meta analysis of 5 year survival by decade conclude surgery +RT is best outcome Surgery + RT 61% Primary Radiotherapy/Chemotherapy 51% Surgery alone 48% Radiation alone 47% Dulgeurov et al Lancet Oncol Role of Surgery Guntinas-Lichius reported 229pts (2007) from Overall survival 41% 51% DSS, 64% Local Control Recommended Surgery for stage I/II and multimodaolity Stage III/IV 25 patients had radiation alone with worse outcome Mendenhall 2009 Radiation + Surgery 109 treated Pts 5yr Local Control RT alone 43% vs 84% Surg+ RT (p<.0010) Surgery + post op RT: 81% for T1-T3 (? Role of selection bias?) T4 50% local control Concluded cause-specific survival is better after surgery + RT

7 Primary RT-30% Ipsilateral blindness 14% Bilateral blindness 1 patient Maxillary ORN 1 pt Fatal post op meningits 1 pt after salvage CRF Complications Surgery Post op RT 26% Ipsilateral blindness 1pt Bilateral blindness 1pt Infection with hospitalization 1pt Post op sepsis 1 pt Graft failure 1 pt Frontal lobe necrosis, intracrainal bleed, CSF leak, nasal bone necrosis, fatal infected bone flap History of Craniofacial Resections 1963 Ketcham Classic Craniotomy with total maxillectomy 1976: Dr. Janes and Fitz-Hugh introduced Craniofacial Resection for ENB at University of Virginia Documented 5 year survival increase from 37% to 82% 1990 s Endoscopic Resections Mendenhall Surgery for Paranasal Sinus Tumors Goals of Surgery Remove tumor for Local Control Separate cranial cavity from paranasal sinus with adequate reconstructin Protect contralateral side from progressive tumor? Surgical Outcomes Craniofacial Resection Multi-institutional review 334 patients CRF for Malignant cancer (mostly SCCA or adeno) 188 had prior single modality or combined Tx (surg, RT, chemo) 4.5% mortality post op, 32% complication 5yr overall survival 45%, DSS 48%, Recurrence free survival 53% UCSF 7

Surgical Margins Have Clear Effect (non neuroendocrine) Degree of Invasion N= 234 N=138 N=74 N=89 N=31 N= 52 Head Neck. 2005 Jun;27(6):445-51. 29 Head Neck.

30 Role of Endoscopic Surgery MD Anderson experience 120 pts 93 purely endoscopic 50% T1-T2, T3 22%, T4 29% 50% Surg alone, 37% surgery/rt, Remainder had surg/rt/chemo

8 Surgical Margins Have Clear Effect (non neuroendocrine) Degree of Invasion N= 234 N=138 N=74 N=89 N=31 N= 52 Head Neck Jun;27(6): Head Neck Jun;27(6): Role of Endoscopic Surgery MD Anderson experience 120 pts 93 purely endoscopic 50% T1-T2, T3 22%, T4 29% 50% Surg alone, 37% surgery/rt, Remainder had surg/rt/chemo 5 and 10 yr survival 87% and 80% Appears acceptable outcomes Has Improved Radiation Increased Survival? The UCSF experience No survival improvement in 50 years for ASB lesions. Reduced side effects of IMRT. Disease Free Survival by RT modality. Chen et al UCSF Experience Int J Rad Onc 2007 Hanna Archives UCSF 32 8

9 Chemotherapy? May be improving with multimodality chemo/rt and Surgery U Chicago 11/12 pts disease free with induction Chemo, Surg/RT (55mo med f/u) 67% 10yr DFS in 19 pts Stage III/IV chemo (cis/5fu) followed by surgery Molecular Therapy? Not Proven Yet Maybe role to target Epithelial growth factor overexpression- cetuximab CD117 mutations -Imatinib 1) Robbins et al Head and Neck )Lee,MM, et al. Cancer Journal From Scientific American. 1999;5: Robbins et al. Head and Neck Management of Neck Failure Rate in Neck is Only 3% Subgroups have higher rates neck disease SCCA SNUC ENB Maxillary Sinus Elective RT to neck for SCCA and SNUC dropped metastatic rate from 36% to 7% (MD Anderson) Surgical Approaches to Paranasal Sinus

37 38 Frontal Craniotomy UCSF OHNS Facial Incision Traditional Approaches Denker s Maxillotomy Remove and replace Anterior

10 Craniofacial Resection Currently Entire Skull Base Accessible to Open Approaches Multiple Approaches Skull Base Region Anterior Central Antero-Lateral Posterior 1963 Ketcham presents first series of craniofacial resection Approaches Overlap Frontal Craniotomy UCSF OHNS Facial Incision Traditional Approaches Denker s Maxillotomy Remove and replace Anterior wall Provides Access to lesions in maxilla and ITF PJ Donald: Skull Base Surgery Image PJ Donald. Skull Base Surgery 40 10

11 Sublabial Facial Degloving Cosmetic Incisions A Paradigm Shift??? Endoscopic Technology revolutionizing paranasal sinus and skull base surgery Image PJ Donald. Skull Base Surgery Piecemeal Resection Is the concept of En Bloc Resection Dead? UCSF Skull Base Advantages of Endoscope Principles of Endoscopic Tumor Resection Less Morbidity Cosmesis Less Brain Retraction Better View than Microscope? Light is divergent at the tip Magnified Maintain View No scope holder Stay in Control Wide Working Corridor Two Surgeon Technique (four hands) Tumor Dissection Debulking often necessary Extracapsular dissection Final Surgical Margin is Equal to Open Approach

Create a wide working corridor Within nasal cavity Corridor Surgery To Neurologic structures Allow two surgeons Maintain endoscope view The Central Corridor Is Still Created for Lateral Lesions Total

12 Create a wide working corridor Within nasal cavity Corridor Surgery To Neurologic structures Allow two surgeons Maintain endoscope view The Central Corridor Is Still Created for Lateral Lesions Total Ethmoidectomy ASB = Bilateral CSB= Unilateral Middle Turbinate Resection Open up maxillary sinus Define orbit to orbit in sphenoid. Posterior septectomy or septal incision Kassam, Snyderman et al. Univ Pittsburgh Corridors: Trans-sellar Corridors: Trans-Planum

Corridors: Trans-cribiform Corridors: Trans-clival 49 50 Cranio Cervical Junction Endo-Nasal Endo-Oral Lateral Corridor Endoscopic Anterior Maxillotomy Transnasal

13 Corridors: Trans-cribiform Corridors: Trans-clival Cranio Cervical Junction Endo-Nasal Endo-Oral Lateral Corridor Endoscopic Anterior Maxillotomy Transnasal Endoscopic Anterior Maxillotomy Remove nasofrontal bar at piriform aperture Anterior maxillary wall as needed UCSF Entire medial maxillary wall. 51 El-Sayed, Laryngoscope

(not shown) El-Sayed et al, Laryngoscope 2011 53 54 If Further Access Needed Endoscopic

14 What is Resected for EAM Some Danger Points IJ/Carotid Lingual, maxillary Carotid canal behind eustachian tube Middle Meningeal Artery! (not shown) El-Sayed et al, Laryngoscope If Further Access Needed Endoscopic Assisted Closure of Defects with Vascularized Septal Flap Convert to Open 55 El-Sayed et al, Nasal Septal Flap. Skull Base Journal,

UCSF Center Experience in 2008 with Endoscopic Skull

Base Volume 12 Month Expose Anterior Skull Base Dura

10 0 52 43 15 16 19 Anterior/Midline Lateral

Lateral Skull Base Maxillary Sinus Lateral Corridor

15 UCSF Center Experience in 2008 with Endoscopic Skull Base Surgery (excludes single surgeon pituitary) Skull Base Volume 12 Month Expose Anterior Skull Base Dura Resect Cribiform Resect Dura Patients Anterior/Midline Lateral Craniocervical Junction Pituitary CSF Leak The Lateral Skull Base Maxillary Sinus Lateral Corridor Infratemporal Fossa Pterygoid Fossa Deep Infratemporal Fossa

Anterior Incision Anterior Maxillotomy Incise Anterior to the

Turbinate Drill out nasal frontal bar Remove medial maxillary

canine fossa 61 62 Address Posterior Maxillary Sinus Lesion

plane of normal tissue Drill posterior maxillary wall Resect

Precoagulate tissue Bony landmarks Identify soft tissue planes

16 Anterior Incision Anterior Maxillotomy Incise Anterior to the Inferior Turbinate Incise Superior and Inferior to the Inferior Turbinate Drill out nasal frontal bar Remove medial maxillary wall back to Sphenopalatine Art Remove anterior wall up to canine fossa Address Posterior Maxillary Sinus Lesion Dissection Eggshell Intact Bone Soft Bone Due to JNA Locate plane of normal tissue Drill posterior maxillary wall Resect with cloward ronguer Access ptergyoid contents Dissect Precoagulate tissue Bony landmarks Identify soft tissue planes Control Vessels Internal maxillary artery Mid Meningeal art. Pterygoid plexus veins

Control of Internal Maxillary Specific Examples: Melanoma Post Operative

0-20% 5 yr survival However death will be due to systemic failure Local

ITF adjacent carotid Artery Endoscopic Assisted Maxillectomy with

unresectable) Kadish C ENB Neuroendocrine: ENB Endoscopic Resection of

17 Control of Internal Maxillary Specific Examples: Melanoma Post Operative Photo: Photo Consent Obtained Malignant melanoma of the nasal cavity 0-20% 5 yr survival However death will be due to systemic failure Local Control NO Scar Melanoma SCCA Maxillary Sinus 90yo F SCCA Invading ITF adjacent carotid Artery Endoscopic Assisted Maxillectomy with Sublabial Incision + RT NED 4 years (by prior guidelines this was unresectable) Kadish C ENB Neuroendocrine: ENB Endoscopic Resection of Dura and Tumor to clean margins Brain is peeled off whether open or endoscopic

18 Squamous Cell Maxillary Sinus Discussion-Surgical Approach Aggressive Need margins where possible Invading through anterior wall Max Sinus and palate En Block modified Weber Ferguson transfacial approach Step Ladder Approach to Nasal Cavity and Lateral Lesions Trans-nasal/Trans-septal Endo Anterior Maxillotomy Sublabial Incision Transfacial Factors Lesion Location Skin? Orbit Relation to vital structures Vascularity Histopathology Conclusion Aggressive tumors may be curable Improvements in chemo, RT, and surgery may be leading to improved outcomes Attaining local control may provide improved QOL for patients who may ultimately succumb to disease Different protocols exist, but for solid tumors treatment generally consist of combination of surgery and radiation +/- chemotherapy 71 18

Skull Base Volume 12 Month. Patients. Anterior/Midline. Pituitary CSF Leak. Lateral. Craniocervical Junction

Skull Base Volume 12 Month. Patients. Anterior/Midline. Pituitary CSF Leak. Lateral. Craniocervical Junction UC SF 2 11/7/2009 Skull Base Surgery in 2009 Ivan El-Sayed MD, FACS Director- Otolaryngology Minimally Invasive Skull Base Surgery Program Department Otolaryngology-Head and Neck Surgery University of