From GTV to CTV: A Critical Step Towards Cure

Kenneth Hu, MD Associate Professor

New York University Langone Medical Center June 21, 2017

Head and Neck Cancer—Model for Understanding CTV Expansion

• Radiation therapy is key to successful definitive and adjuvant treatment

• Complex patterns of failure • Local tumor spread • Regional nodes • Perineural invasion • Distant Metastasis

• Multidisciplinary treatment options allow individualized treatment • Serious and life-threatening acute toxicities • Long-term impact on function/organ preservation and quality of life

Defining GTV

• Physical examination—Extent of local spread and relationship to adjacent organs

• Appropriate Anatomic and Functional Imaging—CT, PET, MRI • Multidisciplinary Evaluation

• Radiologist • Pathologist • Medical oncology plans • Surgical op notes/planned vs salvage

• Implications for simulation: IV contrast, Radiographic markers (wiring/bb’s)

Importance of Physical Exam to Define Primary GTV: Example 1 • 76yo Male non-smoker who presents with Base of Tongue carcinoma • PET/CT on 3/18/15 showed a FDG avid enhancing mass in the left

base of tongue measuring 2.8 x 2.2 cm in maximum area in the axial plane (SUV 7.4) and 2.9 cm in maximum craniocaudad dimension. Inferiorly, the mass extends into the left vallecula;

• Surgery agrees with imaging findings • Biopsy: squamous cell carcinoma

• Physical exam: • Inspection of oral cavity/oropharynx: Trismus, Tongue mobility, Tonsil/oral

tongue involvement • Palpation of primary site/neck nodes • Endoscopy: L bot lesion into larynx

Example 2: Importance of Physical Exam to Determine Unilateral vs Bilateral Treatment in Oropharynx • 69yo M with 35pk-yr Tob who presents with bulky left neck nodes II-

V. FNA showed p16+ SCC. • PET/CT showed:

• Stage T2N2b • Decision: Unilateral radiation concurrent with chemotherapy

Physical Exam showed L tonsil lesion lateralized away from midline

Unilateral treatment safe in lateralized T1-2 Tonsil cancer with N0-1

Defining CTV

• Clinical Target Volume defines areas of potential microscopic tumor spread—High Risk 66-70Gy, Intermediate Risk 60-63Gy, Low Risk (50-56Gy)

• Based on patterns of failure for a tumor • Tailored to histology, tumor location, stage • Impact on acute-and chronic toxicity to adjacent normal organs

Basics of Contouring CTV

• CTV High= GTV + 3-5mm—trim based on skin, air and bone along with compartments

• CTV Intermediate=Areas of potential spread locally and regional nodes • CTV Low=Areas at risk further away from GTV, second echelon nodes

Define CTV High & Intermediate

Draw Organs at Risk (OAR)

CTV Primary Site

Cover partial vs whole organ of tumor origin e.g. oral tongue/laryngopharynx Nasopharynx: Parapharyngeal space, paranasal sinus

Nodal Management

Nodal Management

• Lymph nodes involving in majority of cases • Predictable patterns of spread • Unilateral vs Bilateral • Selective nodal level coverage if clinically negative • Comprehensive nodal coverage if clinically positive

Incidence of Positive Lymph Nodes Unilateral versus Contralateral node positive

• Oral Cavity : 30% 5% • Oropharynx: 60-75% 20-30% • Larynx: 55% 20% • Hypopharynx: 75% 10% • Nasopharynx: 90% 50% • Nasal Cavity/PNS: 10% <5%

Percentage Incidence and Distribution of Pathologically Involved Nodes in a Clinical Node Negative Neck After

Elective Radical Neck Dissection

I II III IV V Oropharynx n=48 2 25 19 8 2

Hypopharynx n=24 0 13 13 0 0

Larynx n=79 5 19 20 9 2.5

Oral Cavity N=192 20 17 9 3 0.5

Shah, J.P et al. The patterns of cervical lymph node metastases from squamous carcinoma of the oral cavity. Cancer, 1990. 66(1): p. 109-13

Percentage Incidence and Distribution of Pathologically Involved Nodes in a Clinical Node Positive after Therapeutic

Radical Neck Dissection

I II III IV V Oropharynx n=165 14 71 42 28 9

Larynx n=183 7 57 59 29 4

Hypopharynx n=104 10 76 73 46 11

Oral Cavity n=324 46 43 33 15 3

Shah, J.P., Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract. Am J Surg, 1990. 160(4): p. 405-9.

NPC: 29-89%

Tonsil 12-20%

BOT 0-13%

SP 0-56%

Post Pharynx 21-100%

HPX 0-50%

2D Allowed Comprehensive Nodal Coverage

CT-Based Neck Node Level Classification: Selective Nodal Radiation

Som et al, AJR, 2000

References for Lymph Node Delineation

• CT-Based Delineation of Lymph Node Levels and Related CTV in Node Negative Neck Dahanca, EORTC, GORTEC,NCIC,RTOG

• Gregoire, et al. Radiotherapy and Oncology, 65 2003, 227-236

• Proposal for the delineation of the nodal CTV in Node-positve and the post-operative neck

• Gregoire, et al. Radiotherapy and Oncology, 79 2006, 15-20

• 2013 update: Delineation of neck nodal levels: • Gregoire, et al, Radiotherapy and Oncology, 110 2014, 172-

81

Dose Constraints OAR

IMRT Improved Xerostomia: PASSPORT Trial • 94 pts with OP/HP cancer randomized to IMRT vs 3DRT • Whole contralateral parotid < 24Gy

Lent SOMA Score EORTC Dry Mouth Subscale

Nutting CM et al, Lancet Oncol 2011, 12:127

Submandibular Gland Sparing

• 36 pts OPX (n=28) NPX treated with RT • Case matched—18pts with SMG sparing and 18

without. • SMG spared had lower N stage (no N2b-3) vs SMG

non-spared group (59% N2b-3)

Saarilahti et al Radiotherapy and Oncology78 (2006) 270–75.

Pharyngeal Constrictors

Courtesy Dr. Eisbruch/Le Werbrouch J et al, IJROBP 2009, 73:1187

Superior

Mid

Inferior

0 .1

.2

.3

.4

.5

.6

0 10 20 30 40 50 60 70 80

Dose superior constrictor muscle (Gy)

Cyberknife (3x + 4x)

Brachytherapy implant

No BT / No Cyberknife

Probability Swallowing Problems

3x 4x

Levendag PC, et al. Radiother Oncol. 2007

Contouring in the Elective and Node Positive Neck

CTV of LN+ J foramen

Sparing of parotid in LN-

Sup constrictor spared on L

Upper Ib,II,Va

ICA, IJV

L Lat RP LN

C1 TVP

Ib,IIa/b

IIa/b

Submandib gl

Lx, SMG, mid constrictors

Ia LN spared

L III/Va LN, Lx, inf constrictors

L IV,Vb LN, Lx, cricopharyngeus

L IV,SCL LN, trachea, cervical esoph

Contouring in the Elective and Node Positive Neck—Implications for

Salivary and Swallowing Function

• Washington University • 748 pts opx/hpx/lx/unk primary • IMRT—3 generations of elective coverage (1997-

2010)in contralateral node neg neck • A) Bilateral RS/RP, 260pts B)Sparing CL RS 205 pts C)

Spared CL RS/RP 283 pts • Median Followup 37mo’s • MDADI Dysphagia QOL and POF

Swallowing Better in Group C vs A

MDADI at >30mo in group A vs group C Differences >18points are significant NO FAILURES IN SPARED RS/RP LN’S

Pathologic Factors Important for CTV Coverage

• Extracapsular /soft tissue extension—5-10mm margins • Post-operative-Treat scar/surgical bed • Perineural Invasion

Perineural Invasion: Radiation Most Effective Modality

Perineural Invasion—Pathologic and Clinical Definitions

• Pathologic • Focal—small nerve • Extensive—Multifocal, Intraneural, >0.1mm, named branch of nerve

• Clinical • Radiographic evidence of nerve involvement • Symptomatic

Recommended Elective Neural Coverage

• Focal PNI • Consider larger margin 2cm at tumor bed

• Extensive PNI • Involved nerve to skull base

• Clinical PNI • Involved nerve—peripheral to skull base and intracranial extension • Communicating nerve

• Histologies with PNI—Parotid (Salivary Duct, Adenoid Cystic Cancer) Recurrent skin cancers, Squamous cell carcinoma of nasopharynx, Lymphoma

Extensive PNI + RT

Extensive PNI - RT Extensive PNI- RT

Extensive PNI + RT

CN V & VII: Most Common Pathways at Risk

• Extracranial Path • Gross Disease: Extra- and Intracranial Pathways • Anastamotic Communication Between V and VII

PNI V1 SOF Cavernous Sinus Meckel’s Cave

Barker, Target Volume Delineation for Conformal and Intensity-Modulated Radiation Therapy, 129 Medical Radiology. Radiation Oncology, DOI: 10.1007/174_2014_975, © Springer International Publishing Switzerland 2014

Gluck, et al.

PNI: V2--> PPFForamen Rotundum Cav Sinus Meckel’s

Gluck, et al. Target Volume Delineation for Conformal and Intensity-Modulated Radiation Therapy, 167 Medical Radiology. Radiation Oncology,

PNI V3Parapharyngeal SpaceForamen Ovale Meckel’sPre-pontine Cistern

Target Volume Delineation for Conformal and Intensity-Modulated Radiation Therapy, 167 Medical Radiology. Radiation Oncology,

CN VIIStylomastoid Foramen MastoidTympanicIAC Pre-Pontine Cistern

Target Volume Delineation for Conformal and Intensity-Modulated Radiation Therapy, 167 Medical Radiology. Radiation Oncology,

Common Pathways of PNI spread between Auriculotemporal Nerve (V3 + VII)

Gluck, et al. Target Volume Delineation for Conformal and Intensity-Modulated Radiation Therapy, 167 Medical Radiology. Radiation Oncology,

Greater Superficial Petrosal Nerve (GSPN) Connects V2 + VII

Gluck, et al.

Conclusions

• Multidisciplinary evaluation of imaging, pathology, surgery, exam • CTV expansion based on radiation oncologist understanding of

patterns of failure • Importance of understanding CTV dosing impact on adjacent normal

organs—function and quality of life