Transoral Robotic Surgery (TORS) for Oropharyngeal Cancer

Transcription

1 Transoral Robotic Surgery (TORS) for Oropharyngeal Cancer Ellie Maghami, MD, FACS Professor of Otolaryngology / Head and Neck Surgery Chief, Division of Head and Neck Surgery Norman and Sadie Lee Professor of Head and Neck Cancer emaghami@coh.org Multidisciplinary Approaches to Cancer Symposium September 23, 2018, Coronado, CA

2 Disclosure No financial conflicts of interest I am a surgeon I am the institution PI for ECOG 3311 trial

3 Changing trends of HNSCC Gray s anatomy 2008

4 25% of US cases are not related to tobacco and alcohol 70% of OPC cases in the United States are caused by an infectious carcinogen-hpv JNCI J Natl Cancer Inst (2000) 92 (9):

5 Human Papillomavirus (HPV) Sexually transmitted Small ds DNA virus >120 sub-types Low risk = 6 and 11 High risk = 16, 18, 31, 33, 35 Greater than 90% of OPCs are due to HPV 16 E6 & E7 oncogenes

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8 H and E Basaloid SCC p16 IHC High sensitivity HPV-16 ISH High specificity Forastiere et al, Lancet Oncology Aug 2010 Lewis and Maghami, Oncology 2015

9 Overall survival for HPV+ OPC patients and HPV OPC patients according to AJCC staging (7th edition), NCDB Stage I Stage II M1 disease Stage III Stage IV Horne ZD et al, Cancer Jul 1;122(13):

10 RTOG 0129 and 0522: P16 maintains positive prognostication even in the recurrent setting LRF DF Salvage surgery No salvage surgery Fakhry C. J Clin Oncol. 2014

11 HPV positive OPSCC is unique: younger and healthier high cancer cure rates live longer Functional outcomes are important considerations There is no profit in curing the body if in the process we destroy the soul Golter Gate at City of Hope

12 Current treatment for advanced stage oropharyngeal cancer Surgery + adjuvant radiation +/- chemotherapy (margins, ENE) Concurrent chemoradiation (cisplatin preferred) No RCT comparing the two head on Comparable oncologic efficacy had favored nonsurgical management over open trans-cervicofacial surgery historically Growing and favorable experience with minimally invasive transoral surgery has now revived surgery in the discussion of upfront treatment choices for this disease

13 Morbidity of Open Surgery Scars and disfigurement Mandibulotomy Free flaps Tracheostomy Feeding tube Prolonged surgery Prolonged recovery

14 Parsons JT et al. Cancer 2002;94: Base of Tongue LC 79% vs 76% (P=0.087) LRC 60% vs 69% (P=0.009) 5 yr OS 49% vs 52% (P=0.2) 5 yr CSS 62% and 63% (P=0.4) Complications: Severe 32% vs 3.8% (P<0.001) Fatal 3.5% vs 0.4% (P<0.001) 51 studies (United States and Canada) 6400 patients (tonsil and tongue base) Surgery with or without RT RT with or without neck dissection Tonsil LC 70% vs 68% (P=0.2) LRC 65% vs 69% (P=0.1) 5 yr OS 47% vs 43% (P=0.2) 5 yr CSS 57% vs 59% (p=0.3) Complications: Severe 23% vs 6% (P<0.001) Fatal 4.3% vs 0.8% (P<0.001) Comparable oncologic but worse functional data suggested the superiority of RT +/- ND. The authors concluded that RT +/-ND is preferable for the majority of patients.

15 Pignon JP et al. Radiotherapy and Oncology 92 (2009) 4 14

16 Advanced Oropharyngeal Cancer Treatment Trends, National Cancer Database ,983 patients Amy Chen et al. Laryngoscope 124: January 2014

17 RTOG 91-11, 97-03, and chronic grade 3 to 4 pharyngeal/laryngeal toxicity requirement for a feeding tube >or= 2 years potential treatment-related death within 3 years 43% severe late toxicity 20% feeding tube dependence >2yrs 10% death rate Machtay M et al. J Clin Oncol Jul 20;26(21):3582-9

18 Intensity-modulated radiation therapy as primary treatment for oropharyngeal squamous cell carcinoma Lee Moffitt Cancer Center, Tampa Florida May JT et al. Head Neck Dec;35(12):

19 MDACC case series of late dysphagia patients referred for MBSS 5 or greater years since finishing definitive treatment Holsinger FC et al. Cancer December 1; 118(23):

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21 Cautionary equipoise: How can we titrate our treatments more appropriately? De-intensification of current standard of care of concurrent chemoradiation (cisplatin) is a research question; any modifications medical or surgical should be done only on clinical trial. Patients with HPV positive disease still die of this disease and we need to identify prognosticators of relevance for these patients. Distant metastasis still a major concern regardless of HPV (10% vs 14%) DC rate was lower in N2c subset managed by RT alone (73% v 92% for CRT; P.02). O Sullivan B et al. J Clin Oncol 31: by American Society of Clinical Oncology

22 RTOG 0129 Risk stratification for OS in OPC stratified by p16 Recursive partitioning revealed 3 risk categories: 64/178 (36%) of HPV+ pts were Intermediate Risk Ang et al. N Engl J Med. 2010

23 De-escalation Trials: Radiation Use Dose Volume CRT Selective use Cetuximab Instead of cisplatin RTOG 1016 With lower RT dose ECOG1308 Trans Oral Surgery (TOS) Lewis and Maghami. Oncology, 2015.

24 ECOG3311

25 Transoral Surgery (TOS) TORS: Transoral Robotic Surgery TLM: Transoral Laser Microsurgery

26 TLM TORS Line of site restrictions Negotiates tighter anatomy Negotiates distant anatomy Less thermal injury with laser Tumor-Normal interface Tactile feedback Steep learning curve Line of sight improvement 3D visualization Wristed instrumentation Motion scaling Tremor filtration 4 handed surgery Easier learning curve

27 TORS Invented at U.Penn Da Vinci Surgical System; Intuitive Surgical Inc., Sunnyvale, CA Preclinical testing Clinical trials FDA approval 2009, T1-T2 OPC First COH case 2010 Laryngoscope, 116: , 2006

28 Implementation Reverse anatomical learning Mannequin modeling Cadaver Lab Animal surgery Mentored simulation Live surgery observation Build a Team Proctored cases Be highly selective

29 Inside out anatomy: Courtesy of Michael Hinni MD

30 TOS Contradictions Comorbidities Aberrant vasculature Poor Access Uncertainly of complete resections Mandible invasion Tumor fixation Unresectable neck disease Midline tumors Functional loss with larger defects

31 Surgeon experience and complications with Transoral Robotic Surgery (TORS). Electronic survey of 300 US surgeons sent out 3 times over a month 45 responded; 2015 procedures Chia SH et al. Otolaryngology Head and Neck Surgery 149(6)

32 Postoperative bleeding in 5.4% of patients (49 of 906) with 2/3 requiring operative intervention Greater risk with T3-T4 Severe bleeding very rare (1.1%) larger tumors prior treatment Greatest bleeding risk postoperative day 7-14 TORS=TLM Ligation of external carotid branches did not reduce number of bleeding events but there was a trend towards less severe bleeding Pollei et al. JAMA Otolaryngology Head & Neck Surgery 2013, Mayo Clinic Mandal R et al. Head and Neck University of Pittsburgh Greg Weinstein---Univ Penn

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34 TOS Best Targeted therapy CR within a couple hours Personalized Minimally invasive Cost effective

35 Transoral Surgery versus Open Surgery Avoidance of mandibulotomy Avoidance of tracheostomy Quicker return to normal speech and swallowing Less pain Less Blood loss Less risk of wound infection Shorter hospital stay Shorter recovery time Minimal scarring Less cost Ford SE et al. Otolaryngology Head and Neck Surgery 2014, Vol. 151(4) UAB Williams CE et al. Eur Arch Otorhinolaryngol (2014) 271:

36 TORS outcomes: 410 patients/11 centers 88.8% OP 83.5% T1-2 Fatal hemorrhage 1/410 (0.2%) vs 2% chemoradiation mortality in recent literature. 9.9% had positive margin, <1mm Adjuvant Rx 47.3% none 31.4% adj radiation 21.3% adj chemoradiation 8.0% LRR, 2.4% DM Mean f/u 20 mos De Almeida J et al. JAMA Otolaryngol Head Neck Surg. 2015;141(12):

37 Moore and Hinni. Intl J Rad Onc 2012.

38 Gastrostomy Tube Prevalence Over Time---University of Washington & University of Minnesota Patients with OPSCC are matched by T stage and compared by treatment group (88 patients in the nonsurgical treatment group and 39 in the TORS group). RR indicates relative risk 3% 11% Sharma A et al. JAMA Otolaryngol Head Neck Surg. 2016

39 Comparison of functional outcomes and quality of life between transoral surgery and definitive chemoradiotherapy for oropharyngeal cancer---uc Davis Normal Swallowing at 1 year : 74% vs 32% Chen A et al. Head Neck 37(3):

40 OHSU TORS, N=64 Majority Tonsil SCC advanced stage Health related quality of life (HRQOL) outcomes of advanced HNC cases at 12 months Compared with matched patients with advanced head and neck cancer in the study by El-Deiry et al.(2005). Within the eating domain the TORS group had statistically significant higher outcomes (p=0.003) Otolaryngol Head Neck Surg. 2012;146(1): OHSU

41 FOSS scores worse with CRT Haughey BH. Head Neck Dec;33(12):

42 CRT costs money. Triple therapy costs money. Moore EJ et al. Otolaryngol Head Neck Surg Jun;146(6):946-51

43 New treatments lead to new problems: STN in 12/51 oropharyngeal cancer cases (23.5%): Risk factors: Greater depth of invasion >1.2 cm, p=0.005 CTVpmax/fx >2.3Gy/fx, p=0.021 Tonsil, 39% vs 9% (BOT) Depth of resection Total radiation dose Grade 3 mucositis Rec 2 Gy/fx; reduced rate to 8% Medicine Volume 95, Number 9, March 2016 Int J Radiation Oncol Biol Phys, 2014

44 TORS experience Most publications are from a few high volume centers Excellent cancer outcomes Most patients got radiation therapy Close to half the patients also received chemotherapy TORS compares favorably in QOL studies Favorable profile is weakened by the addition of adjuvant therapy Cost advantage also weakened by the addition of adjuvant therapy Research Question for Clinical Trials: Which modality is being overused? What risk factors are important in TOS series?

45 Cancer Jul 15;118(14):

46 Sinha and Haughey. Oral Oncol May;51(5):514-20

47 Summary TOS may help personalize therapy for OP cancer Still unclear how best to triage patients Clinical trials are necessary and underway. NCCN does not endorse any treatment modification outside of carefully designed clinical trials. A new staging system for p16 positive OPC in AJCC 8 th ed.

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