Using FDG-PET to define the GTV• How exactly should PET be used?• If the PET-based and CT-based GTVs differ, what is the “truth”?
Using PET-CT for GTV delineation CT-GTVsThe GTVs on CT and FDG-PET usually correlate well
FDG-PET may define the GTV better than CTLt BOT cancer. The GTV is blurred by CT artifact
FDG-PET may define the GTV better than CTLt tonsil cancer. CT: Retropharyngeal node was part of the CTV. PET: it should be a GTV.
FDG-PET may be false negative: failure to detect obvious gross diseasePrimary ca #1 Primary ca #1 #2 LN #2: extensive necrosis; not detected by PET
PET may be false positive: Benign lymphatic tissue in the BOT accumulates FDGConsult Nuc Med to verify that the signal intensity/SUV are right
Suspicious nodes on CT, PET (-): CTVs or GTVs?? + + ? Use clinical judgement
PET vs. other imaging modalities vs. LN pathology Adams et al, Eur J Nuc Med 1998
Larynx cancer: Matching the surgical specimen, CT, and PET Daisne, …Gregoire, Radiology 2004
Matching the surgical specimen, CT, MRI, and PET• The GTVs according to PET were usually slightly smaller than the CT/MRI volumes• No modality showed the extent of the primary with complete accuracy – evaluation of submucosal tumor extension was deficient by all modalities. Daisne, …Gregoire, Radiology 2004
Summary: Outlining the primary tumor GTV• Use the PET and CT/MRI information for composite GTV delineation• Add clinical examination results, especially for the mucosal extent of the gross disease
Summary: Outlining the nodal GTVs• Wherever a node is PET (+), include in the GTV• If CT is highly suspicious and PET is (-), include in the GTV.• In borderline cases of (+) CT and (-) PET, use clinical judgement to define as GTV or CTV.
Can FDG-PET be used to define the CTVs?• Sentinel node biopsy and neck dissection in the clinically (-) neck: nodes were examined by the pathologists at 2 mm slices• Occult metastases (size 1.2-1.5 mm): in 5/12 patients;• FDG PET correctly identified only one (sensitivity of 25%).• We cannot rely on PET for outlying the CTV. Stoeckli et al, Head Neck 2002
Outlining Lymph Node CTVs• Which LN groups at at risk for each tumor site and stage?• How should the LN be delineated on the planning CT?
Neck NodeLevels Som et al., Arch. Otolaryngol. Head Neck Surg.1999
Cranial-most extent of neck CTV• In the clinically (-) non-nasopharyngeal ca: – The bottom of the transverse process of C1 • Gregoire et alThis will ensure coverage of the JD (sub- digastric) nodes
…but significant ipsilateral level II nodal involvement
Parotidean metastases• Risk of retrograde lymphatic drainage when level II is heavily involved• Suggest: omit ipsilateral parotid sparing if ipsilateral level II is heavily involved.
Can we improve outcome by GTV dose escalation?• Escalate doses to the whole GTV• Escalate the doses to the parts of the GTV judged to be at highest risk
Escalate/accelerate doses to the whole GTV• Baylor: “SMART”: 60 Gy/2.4 Gy/fraction – BED2Gy 70 Gy, over 5 weeks – Concurrent with chemotherapy: not tolerable due to acute mucositis • Amosson, ASTRO 2003
Escalate/accelerate doses to the whole GTV• Nasopharynx ca: 64.8/2.4/fr. Over 5.5 weeks conc. with cisplatin – “modest increase in toxicities” • WS Koom, Head Neck 2008• Larynx/hypopharynx ca: 67.2 Gy/2.4 conc. with cisplatin – “acceptable acute toxicity”. • Guerrero-Urbano , Radiother Oncol 2007
High fraction doses: Oropharyngeal ca• RTOG 00-22: 66 Gy/30 fractions, no chemo – Few long-term complications • 6% ORN • Eisbruch et al, IJROBP 2009• Stanford: 66 Gy/30 fractions, conc. chemo – Few long-term complications • Orocutaneous fistula, tracheal stenosis, ORN • Daly ME et al, IJROBP 2009
Moderately high fraction doses: laryngeal/hypopharyngeal ca• MSKCC: 70 Gy/32-33 fractions (2.12 Gy/fraction) conc with chemo – Late complications: • 20% PEG dependency at 2 years • Laryngeal necrosis, necrotizing skin fascitis • Lee NY, IJROBP 2007
Escalate the dose to part of the GTV• The FDG-PET avid part of the GTV tumor• Hypoxic regions within the GTV
CTV• Outlining the CTV – Anatomically: taking into account the compartments at risk – Uniformly, arbitrary margins: 1-2.5 cm
CTV Doses and their BED(2 Gy) (assuming alpha/beta 10 Gy and loss of 0.7 Gy/day of extending treatment)Total dose (Gy) Dose /fraction (Gy) BED2 (Gy)63 1.8 6059 1.7 5456 1.6 4952 1.5 42
Considerations• Conc chemo: – Adds 12 Gy/ 2 Gy fractions (Kasibhatla et al, IJROBP 2007) – Adds 7 Gy/2 (Fowler JF, IJROBP• Very good prognosis patients, such as HPV- related oropharyngeal ca, may require quite low doses
Laryngeal shield: do not extend caudallybecause jugular vein and nodes become more medial Mendenhall, Amdur, Million, 1992
Extend the midline blockto shield also inferior constrictor and esophagus Caudell JJ IJROBP 2009
Whole neck IMRT or upper neck IMRT + abutted AP low neck field• Abutting AP low neck field: 30% of the recurrences were in the low neck – Chao et al IJROBP 2003
Whole-neck IMRT in cases of low neck involvement or high risk
Higher weight to targets or organs• PTV doses: 99%-107% presc. doses• Larynx/constr./esophagus: reduce mean dose as much as possible (<20 Gy) – Targets weigh higer than organs – Organs weigh higher than targets
PTVs (yellow/purple) weigh lower than larynx/inf. constrictor
The low neck• Split-field technique is simpler, faster, less monitor units, likely less skin toxicity• Whole-field IMRT allows better certainty in target coverage – may be preferable in cases of gross low neck involvement or when the low neck is at high risk
After 23 fractions (GTV dose 46 Gy) concurrent with carboplatin+taxolEstimated lip mucositis site dose 30 Gy/1.3 Gy/fraction
Mucosal point doses vs. length of time of mucositis Narayan et al, IJROBP 2008;72:756
Lt tonsillar ca, chemo-RT: oral cavity outside the PTVs spared
Induction chemotherapy for HN cancer Response to induction chemo: CR 17%, PR 55% CR 9%, PR 59%Patients proceed to chemo-RT after most tumors shrink by induction. GTVs: the pre-chemo or the post-chemo volumes?
Neoadjuvant chemo: Its tumor effect may be trivial even if clinical CR is achieved. Ian Tannock
After induction chemotherapy• Use the pre-chemo targets• It is essential to examine the patient, have adequate imaging studies, and preferably simulate the patient before chemo starts.• Re-simulate after induction chemo and register the pre-chemo GTVs to the new planning CT.• Same principle: do not reduce the GTV as tumor shrinks during RT. Salama et al, IJROBP 2009
Acknowledgements• UM Rad-Onc residents, • Speech pathology students & fellows – Teresa Lyden – Felix Feng – Marc Haxer – Mary Feng • Dentistry – Alex Lin – Carol-Anne Murdoch-Kinch – Siavash Jabbari – Jonathan Ship – Laura Dawson • Rad-Onc Physics – Aron Popovtzer – Randall Ten Haken – Iris Gluck – Karen Vineberg• Otolaryngol-HN Surgery – Dick Fraas – Doug Chepeha • NKI, Amsterdam – Ted Teknos – Marco Schwartz – Carol Bradford – Coen Rasch – Gregory WolfSupported by NCI grants PO1 59827 and HN SPORE P50 CA/DE97248