Trans-Oral Robotic Surgery What is the Benefit? Radiation Rules - - PowerPoint PPT Presentation

▶
trans oral robotic surgery what is the benefit
SMART_READER_LITE
LIVE PREVIEW

Trans-Oral Robotic Surgery What is the Benefit? Radiation Rules - - PowerPoint PPT Presentation

Dec 13, 2023 117 likes •457 views

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 2017 1 Outline Benefit of TORS Early Treatment Paradigms

slide-1
SLIDE 1

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 2017

slide-2
SLIDE 2

2 Winship Cancer Institute | Emory University

Early Treatment Paradigms DE-Revolution Impact of ENE TORS for Unknown Primary

TORS at EMORY Summary

Outline – Benefit of TORS

slide-3
SLIDE 3

3 Winship Cancer Institute | Emory University

HPV-Related OPSCC Demographic

Marur S, et al. Curr Opin Oncol. 2014;26(3):252-258.

slide-4
SLIDE 4

4 Winship Cancer Institute | Emory University

HPV-Related OPSCC: Cancer Cured

  • Cured of cancer at age 55
  • 20 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
slide-5
SLIDE 5

5 Winship Cancer Institute | Emory University

CRT

  • 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 dependency @ 2yrs
  • > 30% constrictor 70 Gy
  • > 50% = stricture / aspiration
  • late toxicity in OP
  • 56% = CRT
  • 30% = RT

TORS

  • 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

Early Data: What is the trade off?

Machtay M, et al. J Clin Oncol. 2008;26(21):3582-3589. Weinstein GS, et al. Laryngoscope. 2012;122(8):1701-1707.

slide-6
SLIDE 6

6 Winship Cancer Institute | Emory University

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% RT50 21.4% CRT45
  • 2-year PFS and OS were both 100% for low-risk
  • Grade ≥3 mucositis 15.8% - RT50 46.4% - CRT45 60.0% - CRT75 (p = .033)
  • Grade ≥3 dermatitis 0% - RT50 21.4% - CRT45 30.0% - CRT75 (p = .056)
  • PEG-tube dependency post-treatment
  • 3 months 0% - RT50 14.8% - CRT45 70.0% - CRT75 (p < .001)
  • 6 months 0% - RT50 3.7% - CRT45 20.0% - CRT75 (p = .066)
  • pCR rate: 94.4% RT50 92.3% CRT45

Melotek J, et al. J Clin Oncol. 2017;35(suppl): Abstract 6066.

slide-7
SLIDE 7

7 Winship Cancer Institute | Emory University

TORS De-Intensification

slide-8
SLIDE 8

8 Winship Cancer Institute | Emory University

A personalized approach using hypoxia resolution to guide curative-intent radiation dose-reduction to 30 Gy: a novel de-escalation paradigm for HPV-associated

  • ropharynx 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 18F-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 18F-FMISO scans
  • 6 No hypoxia – 30Gy
  • 13 + hypoxia
  • 12 intra-treatment 18F-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 6076.

slide-9
SLIDE 9

9 Winship Cancer Institute | Emory University

  • 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

Tumor Board Discussion

slide-10
SLIDE 10

10 Winship Cancer Institute | Emory University

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

Overall impression of rENE: yes/ no

  • any stranding  “yes”

subtle

gross

slide-11
SLIDE 11

11 Winship Cancer Institute | Emory University

HPV OPSCC Pre-Op CT versus Pathology

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%

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

slide-12
SLIDE 12

12 Winship Cancer Institute | Emory University

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

slide-13
SLIDE 13

13 Winship Cancer Institute | Emory University

PET in HPV-Related OPSCC

95% PPV of predicting N+ disease

slide-14
SLIDE 14

Gold Standard for ENE: Gross Pathology

slide-15
SLIDE 15

15 Winship Cancer Institute | Emory University

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%)
  • Hazard Ratio
  • ENE (30%) = 1.17
  • Adjuvant RT = 0.59
  • 5 or > nodes = 3.08
  • 96% LRC vs. 92% with CRT

alone

4.1 cm

Zenga J, et al. Laryngoscope.2017;127(3):597-604.

slide-16
SLIDE 16

16 Winship Cancer Institute | Emory University

Gross Pathology: TORS Radical Tonsillectomy

slide-17
SLIDE 17

17 Winship Cancer Institute | Emory University

4.1 cm

HPV-Related Recurrences

Zenga J, et al. Laryngoscope.2017;127(3):597-604.

slide-18
SLIDE 18

18 Winship Cancer Institute | Emory University

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

slide-19
SLIDE 19

19 Winship Cancer Institute | Emory University

Morbidity of CRT Failures

slide-20
SLIDE 20

20 Winship Cancer Institute | Emory University

2

0% 25% 50% 75% 100% UPENN (60) UPMC (51) OSU (11) Emory (7) Multi (21) Identified Unknown Unknown

PET / CT + Panendoscopy TORS Endoscopy

TORS HPV+ HNCUP Identification Rate

slide-21
SLIDE 21

21 Winship Cancer Institute | Emory University

①Neck mass – PE = No Primary ②+ Neck FNA – SCCa p16

  • El-Naggar & Westra. 2011
  • 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. 2008
  • Vent et al. 2013

2005: HNCUP Linked to HPV

El-Naggar AK, et al. Head Neck. 2012;34(4):459-461. El-Mofty SK, et al. Head Neck Pathol. 2008;2(3):163-168. Vent J, et al. Head Neck. 2013;35(11):1521-1526.

slide-22
SLIDE 22

22 Winship Cancer Institute | Emory University

Is it necessary to identify HPV+ HNCUP?

  • HPV patients have favorable OS
  • Projected HNCUP
  • 2 – 5 %
  • 200 – 500 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):4294-4301.

slide-23
SLIDE 23

23 Winship Cancer Institute | Emory University

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

2

7.3 cm

slide-24
SLIDE 24

24 Winship Cancer Institute | Emory University

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

2

1. 1.3 3 mm

slide-25
SLIDE 25

25 Winship Cancer Institute | Emory University

Pre-TORS ERA Treatment (2013-2014)

slide-26
SLIDE 26

26 Winship Cancer Institute | Emory University

TORS ERA Treatment (2015-2016)

slide-27
SLIDE 27

27 Winship Cancer Institute | Emory University

Pre-TORS vs. TORS Treatment

slide-28
SLIDE 28

28 Winship Cancer Institute | Emory University

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

Emory Experience (2015-2016)

slide-29
SLIDE 29

 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)

Early FEES post-TORS

slide-30
SLIDE 30

30 Winship Cancer Institute | Emory University

1 2 3 4 5 6 7 Pre-Op MBSS 3-5 Days Post-Op FEES 3 Week Post-Op MBSS Intervention Control

Sw allow Function after TORS

  • 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

slide-31
SLIDE 31

31 Winship Cancer Institute | Emory University

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

HHPV OPSCC Re-Defining the Standard

slide-32
SLIDE 32

32 Winship Cancer Institute | Emory University

Summary – Still looking for answ ers

  • 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
slide-33
SLIDE 33

33 Winship Cancer Institute | Emory University

Acknow ledgement

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