Trans-Oral Robotic Surgery What is the Benefit?

Transcription

1 Trans-Oral Robotic Surgery What is the Benefit? Radiation Rules Mihir R. Patel Director Trans-Oral Robotic Surgery Department of Otolaryngology / Head & Neck Surgery 27 July

2 Outline Benefit of TORS Early Treatment Paradigms DE-Revolution Impact of ENE TORS for Unknown Primary TORS at EMORY Summary 2

3 HPV-Related OPSCC Demographic Marur S, et al. Curr Opin Oncol. 2014;26(3):

4 HPV-Related OPSCC: Cancer Cured Cured of cancer at age years of post-rt related morbidities 2nd primary Carotid vascular disease? immune system lymphopenia > 60 mos. T-cells CD4+ / CD8+ B-cells 56 Gy leads to fibrosis of pharyngeal constrictor Dysphagia Xerostomia 4

5 Early Data: What is the trade off? CRT TORS Standard treatment for OPSCC RT 70 Gy OP & Bilateral Cervical Nodes Early/ Late Complications Mucositis, Xerostomia, Dysphagia, Tissue Fibrosis High dose Cisplatin added to RT regimen 70 Gy 29% PEG 2yrs > 30% constrictor 70 Gy > 50% = stricture / aspiration late toxicity in OP 56% = CRT 30% = RT Morbidity 0% Orocutaneous fistula 2% Tongue swelling/ numbness 8% Bleeding 3% (5 cases to OR) 1% MI Swallow Function 9% Dysphagia 7% PEG 5% excluding 3 salvage cases Margins 4% positive Machtay M, et al. J Clin Oncol. 2008;26(21): Weinstein GS, et al. Laryngoscope. 2012;122(8):

6 Optima: A phase II dose and volume de-escalation trial for high- and low-risk HPV+ oropharynx cancers Patient Selection: HPV+ OPC low-risk ( T3, N2B, 10 PYH) OR high-risk (T4 or N2C or > 10 PYH) 3 cycles induction carboplatin + nab-paclitaxel 1) Low-risk 50% - low-dose RT 50Gy 2) Low-risk 30-50% - low-dose CRT 45Gy 3) High-risk poor response - CRT 75Gy CRT = paclitaxel, 5-FU, hydroxyurea, + 1.5Gy BID RT Primary site biopsy + neck dissection post de-escalated treatment (RT50, CRT45) Primary endpoint - 2-year PFS Secondary endpoints - pathologic complete response (pcr) rate and toxicity Results: 62 patients enrolled: 28 low-risk Low-Risk: 71.4% RT % CRT45 2-year PFS and OS were both 100% for low-risk Grade 3 mucositis 15.8% - RT % - CRT % - CRT75 (p =.033) Grade 3 dermatitis 0% - RT % - CRT % - CRT75 (p =.056) PEG-tube dependency post-treatment 3 months 0% - RT % - CRT % - CRT75 (p <.001) 6 months 0% - RT50 3.7% - CRT % - CRT75 (p =.066) pcr rate: 94.4% RT % CRT45 Melotek J, et al. J Clin Oncol. 2017;35(suppl): Abstract

7 TORS De-Intensification 7

8 A personalized approach using hypoxia resolution to guide curative-intent radiation dose-reduction to 30 Gy: a novel de-escalation paradigm for HPV-associated oropharynx cancers (OPC) Patient Selection: HPV+ OPC low-risk: T3, N2B, 10 PYH Primary tumors were excised and analyzed for DNA repair foci ex-vivo pre-rt dynamic 18 F-FMISO (fluoromisonidazole) PET to assess tumor hypoxia (defined as > 1.2 tumor to muscle SUV ratio) in cervical lymph nodes No hypoxia after initiation of CRT 30Gy over 3 weeks - tumor bed + neck 2 cycles of concurrent high-dose cisplatin or carboplatin/ 5-FU If persistent hypoxia Standard dose of 70Gy over 7 weeks with chemo Neck dissection (ND) was done 4-months post CRT Weekly DWI MRI, ctdna, whole exome & RNA sequencing were performed Results: 19 patients 3 T0, 11 T1, 5 T2; 5 N1, 3 N2a, 11 N2b pre-rt 18 F-FMISO scans 6 No hypoxia 30Gy 13 + hypoxia 12 intra-treatment 18 F-FMISO scans 3 were + hypoxia - 70Gy CRT 15 patients de-escalated to 30Gy complete pathologic response in 8 of 9 patients To date, 18 of 19 patients (95%-6 pending ND) remain disease free Riaz N, et al. J Clin Oncol. 2017;35(suppl): Abstract

9 Tumor Board Discussion Straight Forward advanced lesions surgically contraindicated (ie T3 / 4) advanced nodal disease (ie N2c / N3) lesions with high chance of avoiding adjuvant therapy (ie T1 / T2N1) In Between p16+/- smokers amenable to TORS p16+ non-smokers requiring postoperative radiation (ie N2a / b) Difficult p16+ Low-Risk T1/2 N2a/b non-smokers with high likelihood of needing postoperative CRT (ie suspicion of extracapsular (ENE) spread on scan / or > 4 nodes) SELECTION RELIES ON IMAGING 9

10 HPV OPSCC Pre-Op CT ENE Characteristics Lymph node characteristics: Necrosis (small versus > 75% cystic ) Lobular contours Perinodal stranding (subtle vs gross) Gross invasion of adjacent structures Matted/conglomerate appearance Size subtle Overall impression of rene: yes/ no any stranding yes gross 10

11 HPV OPSCC Pre-Op CT versus Pathology 1. High inter-observer agreement (k <.001) except subtle stranding 2. Size > 3 cm significant correlation with macro pene but not predictive 3. Subtle stranding was not a predictor of macro pene rene Radiologist 1 13/24 Radiologist 2 12/24 All pecs Macro pene Pathology 8/24 5/24 Sensitivity All pene Specificity All pene Specificity Macro pene Radiologist 1 100% 69% 58% Radiologist 2 100% 75% 63% 11

12 HPV Pre-OP CT Results: False Positives High sensitivity (100%) for detecting pene in OP SCC than previously reported Low specificity, especially for macroscopic pene (53%-64%) FP rate is unacceptably high to base treatment decisions when compared to previously published criteria for rene in non-hpv SCC 12

13 PET in HPV-Related OPSCC 95% PPV of predicting N+ disease 13

14 Gold Standard for ENE: Gross Pathology

15 HPV-Related Nodal Pathology Stage 1: Level I IV < 10 % Occult Met n = 181 cn1 = 56 (31%) pn1 = 28 (15%) cn2a = 42 (23%) pn2a = 48 (27%) cn2b < 5 nodes = 83 (46%) pn2b < 5 nodes = 105 (58%) 4.1 cm Hazard Ratio ENE (30%) = 1.17 Adjuvant RT = or > nodes = % LRC vs. 92% with CRT alone Zenga J, et al. Laryngoscope.2017;127(3):

16 Gross Pathology: TORS Radical Tonsillectomy 16

17 HPV-Related Recurrences 4.1 cm Zenga J, et al. Laryngoscope.2017;127(3):

18 To TORS or Not to TORS 61yF T1N0M0 Tonsil former smoker > 10 pk year Radiation Treatment Summary 2015 GTV70 involved tonsil, right soft palate, right base of tongue, right retromolar trigone, and glossotonsillar sulcus to create a CTV 70. CTV54 bilateral neck nodes levels II-IV retropharyngeal nodes The CTVs were expanded 3 mm to create PTVs PTV70 treated to 70 Gy 35 fractions PTV54 treated to 53.9 Gy 35 fractions 18

19 Morbidity of CRT Failures 19

20 TORS HPV+ HNCUP Identification Rate 100% 75% TORS Endoscopy 50% PET / CT + Panendoscopy 25% 0% UPENN (60) UPMC (51) OSU (11) Emory (7) Multi (21) Identified Unknown Unknown 20 2

21 2005: HNCUP Linked to HPV 1Neck mass PE = No Primary 2+ Neck FNA SCCa p16 El-Naggar & Westra P16 Surrogate Marker for HPV+ in the setting of HNCUP 3 PET/CT 4 MicroDL w/ biopsies OP HNCUP HPV Surrogate Marker for OP Primary in HNCUP El-Mofty et al Vent et al El-Naggar AK, et al. Head Neck. 2012;34(4): El-Mofty SK, et al. Head Neck Pathol. 2008;2(3): Vent J, et al. Head Neck. 2013;35(11):

22 Is it necessary to identify HPV+ HNCUP? HPV patients have favorable OS Projected HNCUP 2 5 % est. / year Emory 93% p16+ OPSCC 7 HPV+ HNCUP 5 identified (71%) No unified treatment strategy RT Neck + Surgery RT Neck + Surgery + Tongue Base C + RT Neck + Tongue Base + Tonsil + RPN C + RT to Neck + Pharynx (all sites) Chaturvedi AK, et al. J Clin Oncol. 2011;29(32):

23 TORS Approach to HPV+ OPSCC HNCUP PET / CT No Definitive Primary Telescopic Panendoscopy Directed Biopsies Ipsilateral to Neck Mass Nasopoharynx 7.3 cm Robotic-assisted Panendoscopy (TORS) Palatine Tonsillectomy Effective method for identifying unknown tonsil primary Ipsilateral to adenopathy Lingual Tonsillectomy 23 2

24 TORS Approach to HPV+ OPSCC HNCUP PET / CT No Definitive Primary Telescopic Panendoscopy Directed Biopsies Ipsilateral to Neck Mass Nasopoharynx Robotic-assisted Panendoscopy (TORS) Palatine Tonsillectomy Effective method for identifying unknown tonsil primary Ipsilateral to adenopathy Lingual Tonsillectomy 1.3 mm 24 2

25 Pre-TORS ERA Treatment ( ) 25

26 TORS ERA Treatment ( ) 26

27 Pre-TORS vs. TORS Treatment 27

28 Emory Experience ( ) TORS Tumor Characteristics (n = 51) Tonsil = 26 (51 %) BOT = 25 (49 %) T1 = 23 (45 %) T2 = 25 (49 %) T3 = 2 ( 4 %) T4a = 1 ( 2 %) Neck N0 = 7 (14 %) N1 = 6 (12 %) N2a = 21 (41 %) N2b = 15 (29 %) N2c = 1 ( 2 %) N3 = 1 ( 2 %) Pre-Operative Imaging 5 of 51 (10 %) Unknown 13 of 51 (25 %) + Nodes on PET 3 cases PET noted rn+ but pn- 10 cases N2b vs. N2a on Path ENE 22 of 51 (43 %) 9 micro (< 1.0 mm) Margins 1 of 51 (2 %) positive 28

29 Early FEES post-tors Control (n = 14) DHT 3 weeks post TORS + SND Ib - IV MBSS Fiberoptic Endoscopic Evaluation of Swallow (FEES) (n = 8) 3-5 days post-tors + SND Ib IV Personalized therapeutic program Decline on MBSimp base of tongue retraction pharyngeal residue anterior hyoid excursion Penetration-Aspiration Score Control = 4 (p = 0.001) FEES = 2.5 (p = 0.086)

30 Swallow Function after TORS 7 FOIS (Functional Oral Intake Score) 7 = PO diet, no restriction 6 = PO diet, specific food limits 5 = PO diet, multiple consistency & special preparation / compensation 4 = PO diet, one consistency 3 = tube dependent, consistent PO 2 = tube dependent, min PO 1 = NPO Pre-Op MBSS 3-5 Days Post-Op FEES 3 Week Post-Op MBSS Intervention Control 30

31 HHPV OPSCC Re-Defining the Standard CRT NRG - HN002 ARM 1 60 Gy in 6 wks + cisplatin ARM 2 60 Gy in 5 wks TORS ECOG 3311 Phase II ARM 1 T1/T2 N0 /1 observation ARM 2 T1/T2; N2a / 2b; < 2 mm ENE 50 Gy adjuvant RT 60 Gy adjuvant RT ARM 3 > 2 mm ENE; > 4 nodes; + margin 66 Gy + weekly cisplatin Quality of Life & Swallow Outcomes 31

32 Summary Still looking for answers Low-Risk Disease Are we still treating to 70 Gy + cisplatin? How much more can we de-escalate Recommend patients for clinical trials cure quality of life ECOG-ACRIN 1308 Phase 2 selecting for low risk IC w/ cis / paclitaxel/ cetuximab followed by 54 Gy significantly improved swallow outcomes TORS may aid de-escalation TORS + 36Gy 20 fractions BID 1-12 days + docetaxel Intermediate / High Risk Does ENE matter patients amenable to TORS where path data is needed based on newer markers Facilitate development of new drugs 32

33 Acknowledgement Kelly Summers, PA Martha Ryan, NP Traci Switzer, NP Nabil Saba, MD Dong Shin, MD Conor Steuer, MD Mark El-Deiry, MD Amy Chen, MD Arturo Solares, MD Kelly Magliocca, DDS H. Michael Baddour, MD Danielle Gainor, MD Jonathan Beitler, MD Kristen Higgins, MD Mark McDonald, MD Pat Hudgins, MD Ashley Aiken, MD Kristen Baugnon, MD Christopher Griffith, MD Georgia Chen, PhD Rafi Ahmed, PhD Meryl Kaufman, SLP Beth Seelinger, SLP Lauren Ottenstein, SLP 33