DETERMINATION for H&N tumors Primo Strojan Bucharest, November - - PowerPoint PPT Presentation

TARGET VOLUMES DETERMINATION

for H&N tumors

Primož Strojan Bucharest, November 2013

• ICRU REPORT 50 (1993, DEFINITION OF VOLUMES IN EBRT)
• ICRU REPORT 62 (1999, Suppl to No.50)
• ICRU REPORT 83 (2010, IMRT)

Specification of volumes & doses: for prescription for recording (documentation) for reporting

 to maintain a consistent treatment policy  to compare results of treatment

DEFINITION OF VOLUMENS

• GTV – Gross Tumor Volume
• CTV – Clinical Target Volume
• OAR - Organ at Risk
• 1. Defined prior to treatment planning
• 2. Based on purely

anatomic-topographic physiological considerations

Without technical factors taken into account

DEFINITION OF VOLUMENS

• PTV – Planning target volume
• PRV – Planning organ-at risk volume
• (ITV – Internal target volume)
• TV – Treated volume
• RVR – Remaining volume at risk

Defined during treatment planning Described as a result

• f treatment planning

GTV CTV PTV RVR TV

GTV – GROSS TUMOR VOLUME

= gross demonstrable extent and location of the malignant growth

• palpable or visible extent of the malignant tumor
• the part of the disease where the malignant tumor cell

concentration is at its maximum

“if it can be imaged and it is tumor  it is part of the GTV”

• Primary tumor (GTV-T)
• Lymph nodes (GTV-N)
• (Metastases (GTV-M))
• specific cases: a single GTV

for T&N

• after surgery: only CTV

TERMINOLOGY: GTV-T (CT, 0 Gy)

GTV-T+N (MRI T2 fat sat, 50 Gy)

GTV

Clinical examination

• inspection
• palpation
• endoscopy

Not specified in the ICRU definitions:

• mode of imaging or the imaging parameters.

Imaging techniques

• Anatomical

(X-ray, US, CT, MRI)

• Functional (PET, MRI)
• metabolic status
• hypoxia
• cellular proliferation

sub-GTVs

GTV

•  interobserver variability

training familiarity with delineation guidelines adding FDG-PET reduce (but not abolish!) interobserver variability

Geets X et al, RO 2005 Ashmalla H et al, IJROBP 2005 Ciernik IF et al, IJROBP 2003 Syes R et al, Br. J Cancer 2005

• Variations according to the diagnostic

modality

GTV

GTV-T (CT, 0 Gy): volume of 25.8 ml GTV-T (MRI T2, fat sat, 0 Gy): volume of 28.5 ml GTV-T (FDG-PET, 0 Gy): volume of 22.2 ml GTV-T (CT, 20 Gy): volume of 16.3 ml GTV-T (MRI T2, fat sat, 20 Gy): volume of 19.8 ml GTV-T (FDG-PET, 20 Gy): volume of 12.5 ml

ICRU Report 83

Daisne JF et al, Radiology 2004

GTV – Variations according to the diagnostic modality

GTV:

• 1. CT ≈ MRI

CT/MRI > FDG-PET (p≤0.01)

• 2. MRI > SURG specimen(p<0.01)

FDG-PET > SURG specimen (p=0.06) All: underestimation of mucosal infiltration!

Daisne JF et al, Radiology 2004

GTV – Variations according to the diagnostic modality

GTV – Variations according to the diagnostic modality MODALITY SENSITIVITY SPECIFICITY Palpation 74% 45% CT 82% 85% MRI 80% 70% US 88% 91% PET, all 79% 86%

PET, cN0

50% 87%

DETECTION OF LYMPH NODES METASTASES IN THE NECK

Kyzas PA et al, J Natl Cancer Inst 2008

GTV – Variations according to the diagnostic modality

PET: DIAGNOSTIC & TREATMENT CONSEQUENCES

N=233 TNM stage determination:

• Envelop 1: physical examination,

CT/MRIH&N, CT

chest

• Envelop 2: FDG-PETWB

Comparison (changes in TNM were recorded: when

TNM was found discordant „every reasonable effort were made to confirm the actual stage of the disease)

Standard: pathology, immaging, FUP RESULTS TNM (conventional vs. PET staging)

• Discordant: 43% (100/233)
• Standard available: 60/100 pts

PET accurate: 47 (20%)

PET  upstaging: 30/100 PET  downstaging: 17/100

PET inaccurate: 13 (5.6%)

• AccuracyPET = 78%
• AccuracyCONV = 22%
• Accuracy PET > CONV, P<0.0001)

TREATMENT PLAN (impact of PET):

• Significant: 13.7%

change in the N-stage, 5.2% change in the M stage 8.6%

Geets X et al. Radiother Oncol 2006;78:291-7.

PET: DOSIMETRIC CONSEQUENCES

GTV – Variations according to the diagnostic modality

• Quantification of changes occurring during

treatment  definition of modified GTV

(to adjust absorbed dose distribution)

GTV

pre-TH at 46 Gy

Geets X et al. Radiother Oncol 2006;78:291-7

GTV – Definition of modified GTV due to changes during treatment

Wang ZH et al. Laryngoscpe 2009 Gregoire V et al. Lancet Oncol 2012

GTV – Definition of modified GTV due to changes during treatment

Mayer JL. Karger: Basel, 2007. p.8.

WEIGHT LOSS

Before RT At 46 Gy After re-planning

GTV

• Lesson_1:

physical examination (palpation, fiberoptic endoscopy): mucosal tumor extent is better assessed than by imaging

• base of tongue
• locally advanced tonsillar cancer (involvement of the

palate, glossotonsillar sulcus)…

Daisne JF et al, Radiology 2004

GTV

• Lesson_2:

integrate the FDG-PET into diagnostic work-up

• staging  treatment decision
• target volume determination (reduce interobserver

variability, FDG-PET vs. surgical specimen  ~13% mismatch)

dosimetric consequences interobsever variability

GTV after induction ChT

• TAX 323, 324  ~15% CR, 70% responders

BUT: 1) 10 g TU = 1010 cells  3 x ChT (each kills 50 – 90% of Tu cells)  after 3 cycles: 108 viable cells (<0.1 g)  CR

(Tannock IF, Radiother Oncol 1989)

2) TU stem cells (the most important targets):  resistant to RT compared to non-stem cells

(Baumann M et al, Nat Rev Cancer 2008)

Delineation of the

PRE_CHEMOTHERAPY target!

GTV after tumor shrinkage during RT

• Substantial shrinkage of TU observed after

delivery of 30 – 50 Gy

anatomically, on functional/metabolic evaluation reduction in GTV  improved organ sparing

• Poor correlation:

radiologic/metabolic shrinkage during RT vs. existence of TU cells in the surgical specimen

(Klug C et al, Head Neck 2003; Murphy JD et al, Radiother Oncol 2011)

The same considerations apply

as for TU cell kill after induction ChT!

GTV CTV PTV TV RVR

CTV – CLINICAL TARGET VOLUME

= tissue volume that contains a demonstrable GTV and/or subclinical malignant disease* (with a certain probability, 5-15%)

• volume of tumor-bearing cells  must be irradiated to

an appropriate dose to control the tumor

CTV = GTV + subclinical disease

• r AFTER SURGERY:

CTV = subclinical disease

*structures with clinically suspected but unproved involvement

CTV

• Multiple CTVs:
• Different dose levels  based on an estimate
• f variations in tumor cell densities
• Based on general oncological principle

(independent of any therapeutic approach)

• Terminology

CTV-T (0 Gy) , CTV-T+N (30 Gy)

• Primary tumor (CTV-I)
• Lymph nodes (CTV-II)
• Metastases (CTV-III)

• How the GTV(T) should be expanded to generate

the CTV? ANATOMIC PRINCIPLE (Eisbruch A et al. Semin Radiat Oncol 2002, 2009)

• microscopic spread of tumor cells follows anatomical

compartments (e.g. para-laryngeal, para-pharyngeal, pre-epiglottic space)

• bounded by anatomical barriers (e.g. bone cortex, ligaments,

muscular fascia)  exception: anterior boundary of base of tongue cancer

• r Uniform expansion of the GTV?

(VOLUMETRIC PINCIPLE)

• CLINICAL EXPERIENCES
• PATHOLOGY STUDIES

CTV_tumor

CTV – Definition of CTV-T

Int J Radiat Oncol Biol Phys 2010;76: 164-8

P>0.05

N=14 N=71

• Unexplored area
• 2 CTVs:

 LOW-DOSE CTV (50 Gy) = up to 2 cm margin around GTV

(to eradicate microscopic tumor extensions)

 HIGH-DOSE CTV (70 Gy) = 0.5-1 cm margin around GTV

(to compensate  in imaging modalities, imperfect visualisation TU/NT border)

CTV – Definition of CTV-T

Postop_CTV

• presurgical extent of the primary TU (physical

examination, imaging)

• description of tumor extent by surgeon &

pathologist = surgical bed (identified by inflammation, edema, fibrosis…) preoperative CT:

• to facilitate the definition of preop_GTV
• co-registration with postoperative planning_CT

CTV_neck nodes

• What to delineate (neck regions / pattern of spread)
• How to delineate (contouring guidelines)

CTV – Definition of CTV-N

Lymph nodes levels and sublevels of the neck (Robbins KT, 1991) Radiother Oncol 2000;56:135-50.

 Surgical series  Analysis of recurrences (topography)  Autopsy series

CTV – Definition of CTV-N

ICRU Report 83

Unilateral irradiation?

Primary tumor originating in the:

• tonsillar region
• retromolar trigonum
• lateral tongue
• cheek
• floor of the mouth
• gingiva

+ contralateral neck pN0/cN0 + ipsilateral neck:

• cN0/pN0
• cN+ (only for N1)
• pN+ (contralateral neck pN0)

CTV – Definition of CTV-N

QUALITY of:

• imaging
• surgery

(m)RND – 20 (10 – 30) SND – 15 (10 – 20)

+ no extention across the midline

CTV – Definition of CTV-N

Radiother Oncol 2003;69:227-36

Gregoire V et al. Radiother Oncol 2003

CTV – Definition of CTV-pN

Radiother Oncol 2006;79:15-20

N+ in level II:

• inclusion of retrostyloid

space cranially

N+ in levels IV or Vb:

• inclusion of the supra-

clavicular fossa

N+, pharyngeal tumors:

• inclusion of retropharyngeal

space

Epub ahead of print: October 31, 2013

Gregoire V et al. Radiol Oncol 2006

ECE+:

• inclusion of adjacent

muscles (≥invaded level) N+ located at the boundary between contiguous levels:

• inclusion of both levels

GTV CTV PTV TV RVR

VARIATION & UNCERTAINTIES

In:

• Positions
• Sizes
• Shapes
• Machine parameters

Tumor/patient

IN RELATAION TO COMMON

COORDIANTE SYSTEM

• 1. During a given treatment fraction (INTRA-fractionally)
• 2. Between successive fractions (INTER-fractionally)
• 3. Between planning and treatment

PTV – PLANNING TARGET VOLUME

= a geometrical concept used for treatment planning:

• it is tool to shape absorbed-dose distributions

(with selection of appropriate beam size, arrangements & intensities)

to assure that prescribed dose is actually delivered to the CTV

PTV = CTV + margin

• each CTV has a corresponding PTV
• size = depends on the irradiation technique

stuff skills

PTV

• similar to the CTV or much larger

(clinical situation, treatment technique)

• the size of uncertainties may be different for different

parts of a CTV & at different times

• purely geometrical concept  may extend beyond

normal anatomical borders

• when PTV encroaches/overlaps

another PTV, OAR or PRV:  primary PTV margin should not be compromised!  dose reporting should be done for the whole PTV

• priority rules in optimizer planning systems
• PTV-subvolumes

ICRU Report 83

PTV margin:

• 3-dimensional
• take into account the net effect of all geometrical errors

For adequate treatment of CTV:

• 100% confidence (by adding margins)  unreasonably large margins
• margin calculation on the basis of uncertainties

(systematic, random)

H&N: CTVPTV margin = between 3 to 5 mm

(skills, equipment)

• thermoplastic mask & vacuum bag  3 mm (Cox & Ang, 2010)
• H&N_shoulder fixation device  5 mm (Gilbeau L et al. Radiother Oncol 2001)
• intensified & advanced position verification procedures
• off-line set-up correction protocol: - min 1/wk
• daily on-line set-up verification

PTV

ICRU Report 83

PTV

The risk of complications The risk of missing parts of the CTV PTV = too large PTV = too small