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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