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 Defined during • PRV – Planning organ-at risk volume treatment planning • (ITV – Internal target volume ) • TV – Treated volume Described as a result • RVR – Remaining volume at risk of treatment planning

RVR TV PTV CTV GTV

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”  specific cases: a single GTV • Primary tumor (GTV-T) for T&N • Lymph nodes (GTV-N)  after surgery: only CTV • (Metastases (GTV-M)) TERMINOLOGY: GTV-T (CT, 0 Gy) GTV-T+N (MRI T2 fat sat, 50 Gy)

GTV Not specified in the ICRU definitions:  mode of imaging or the imaging parameters. Clinical examination Imaging techniques • Anatomical • inspection (X-ray, US, CT, MRI) • palpation • Functional (PET, MRI) • endoscopy  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

GTV • Variations according to the diagnostic modality GTV-T (CT, 0 Gy): GTV-T (MRI T2, fat sat, 0 Gy): GTV-T (FDG-PET, 0 Gy): volume of 25.8 ml volume of 22.2 ml volume of 28.5 ml GTV-T (MRI T2, fat sat, 20 Gy): GTV-T (CT, 20 Gy): GTV-T (FDG-PET, 20 Gy): volume of 19.8 ml volume of 16.3 ml volume of 12.5 ml ICRU Report 83

GTV – Variations according to the diagnostic modality 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 DETECTION OF LYMPH NODES METASTASES IN THE NECK MODALITY SENSITIVITY SPECIFICITY Palpation 74% 45% CT 82% 85% MRI 80% 70% US 88% 91% PET, all 79% 86% PET, cN0 50% 87% Kyzas PA et al, J Natl Cancer Inst 2008

GTV – Variations according to the diagnostic modality PET: DIAGNOSTIC & TREATMENT CONSEQUENCES RESULTS TNM (conventional vs. PET staging) - Discordant: 43% (100/233) - Standard available: 60/100 pts PET accurate: 47 (20%) PET  upstaging: 30/100 N=233 PET  downstaging: 17/100 PET inaccurate: 13 (5.6%) TNM stage determination: - Envelop 1: physical examination, - Accuracy PET = 78% CT/MRI H&N , CT - Accuracy CONV = 22% chest - Envelop 2: FDG-PET WB - Accuracy PET > CONV, P<0.0001) Comparison (changes in TNM were recorded: when TREATMENT PLAN (impact of PET): TNM was found discordant „every reasonable effort - Significant: 13.7% were made to confirm the actual stage of the disease) change in the N-stage, 5.2% Standard: pathology, immaging, FUP change in the M stage 8.6%

GTV – Variations according to the diagnostic modality PET: DOSIMETRIC CONSEQUENCES Geets X et al. Radiother Oncol 2006;78:291-7.

GTV • Quantification of changes occurring during treatment  definition of modified GTV (to adjust absorbed dose distribution) 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 WEIGHT LOSS Before RT At 46 Gy After re-planning Mayer JL. Karger: Basel, 2007. p.8.

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 = 10 10 cells  3 x ChT (each kills 50 – 90% of Tu cells)  after 3 cycles: 10 8 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!

RVR TV PTV CTV GTV

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 or AFTER SURGERY : CTV = subclinical disease *structures with clinically suspected but unproved involvement

CTV • Multiple CTVs: • Primary tumor (CTV-I) • Lymph nodes (CTV-II) • Metastases (CTV-III) • Different dose levels  based on an estimate of 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)

CTV_tumor • How the GTV(T) should be expanded to generate the CTV? • CLINICAL EXPERIENCES • PATHOLOGY STUDIES 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 or Uniform expansion of the GTV? (VOLUMETRIC PINCIPLE)

CTV – Definition of CTV-T N=71 N=14 P>0.05 Int J Radiat Oncol Biol Phys 2010;76: 164-8

CTV – Definition of CTV-T • 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)

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  Surgical series  Analysis of recurrences (topography) Radiother Oncol 2000;56:135-50 .  Autopsy series Lymph nodes levels and sublevels of the neck (Robbins KT, 1991)

CTV – Definition of CTV-N ICRU Report 83

CTV – Definition of CTV-N Unilateral irradiation? Primary tumor originating in the: - tonsillar region - retromolar trigonum - lateral tongue + no extention across the midline - cheek - floor of the mouth - gingiva + contralateral neck pN0/cN0 QUALITY of: • imaging + ipsilateral neck : • surgery (m)RND – 20 (10 – 30) - cN0/pN0 SND – 15 (10 – 20) - cN+ (only for N1) - pN+ (contralateral neck pN0)

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: N+ in levels IV or Vb: N+, pharyngeal tumors:    inclusion of retrostyloid inclusion of the supra- inclusion of retropharyngeal space cranially clavicular fossa space

Epub ahead of print: October 31, 2013

ECE+: N+ located at the boundary between contiguous levels:  inclusion of adjacent muscles (≥invaded level )  inclusion of both levels Gregoire V et al. Radiol Oncol 2006