IMRT planning for HN cancr: Some clinical issues: IMRT planning for HN cancr : Some clinical issues Avraham Eisbruch University of Michigan
Defining the targets : Defining the targets The GTV: 1. Clinical information: palpation, mirror/fiberoptic exam, direct endoscopy report 2. Imaging: Planning CT (contrast-enhanced) Register with MRI / PET
PowerPoint Presentation: Nasopharynx ca CT
PowerPoint Presentation: Nasopharynx ca MRI
Using FDG-PET to define the GTV: 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: Using PET-CT for GTV delineation CT-GTVs The GTVs on CT and FDG-PET usually correlate well
FDG-PET may define the GTV better than CT: FDG-PET may define the GTV better than CT Lt BOT cancer. The GTV is blurred by CT artifact
FDG-PET may define the GTV better than CT: FDG-PET may define the GTV better than CT Lt 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 disease: FDG-PET may be false negative: failure to detect obvious gross disease #1 #2 #1 LN #2: extensive necrosis; not detected by PET Primary ca Primary ca
PET may be false positive: Benign lymphatic tissue in the BOT accumulates FDG: PET may be false positive: Benign lymphatic tissue in the BOT accumulates FDG Consult Nuc Med to verify that the signal intensity/SUV are right
Suspicious nodes on CT, PET (-): CTVs or GTVs?: Suspicious nodes on CT, PET (-): CTVs or GTVs? ? ? + + Use clinical judgement
PET vs. other imaging modalities vs. LN pathology: PET vs. other imaging modalities vs. LN pathology Adams et al, Eur J Nuc Med 1998
PowerPoint Presentation: Larynx cancer: Matching the surgical specimen, CT, and PET Daisne, …Gregoire, Radiology 2004
Matching the surgical specimen, CT, MRI, and PET: 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 : 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: 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?: 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: 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?
PowerPoint Presentation: Som et al., Arch. Otolaryngol. Head Neck Surg.1999 Neck Node Levels
PowerPoint Presentation: www.rtog.org/hnatlas/main.htm Gregoire, Levendag, et al. WWW.RTOG.ORG Researchers HN Atlas
Cranial-most extent of neck CTV: Cranial-most extent of neck CTV In the clinically (-) non-nasopharyngeal ca: The bottom of the transverse process of C1 Gregoire et al This will ensure coverage of the JD (sub- digastric ) nodes
PowerPoint Presentation: Rouviere, 1938 Oral cavity lymphatics
PowerPoint Presentation: Rouviere, 1938 Pharyngeal lymphatics
PowerPoint Presentation: What about nasopharyngeal cancer? Lateral retroph. n Junctional n.
PowerPoint Presentation: Level II Level V Nasopharynx ca
PowerPoint Presentation: Should we biopsy all non-specific parotid nodules? IJROBP 2007
PowerPoint Presentation: Parotidean LN metastases in NPC
Eustachian Tube: Lymphatic Drainage: Eustachian Tube: Lymphatic Drainage In addition to sub-digastric and RPN: Lymphatics to parotidean nodes H. Rouviere, 1932
PowerPoint Presentation: Parotidean LN metastases in NPC Due to retrograde flow when level II is heavily involved?
PowerPoint Presentation: Tonsil ca, T3N2c Parotidean LN metas Primary Tu
PowerPoint Presentation: No nasopharyngeal involvement…
PowerPoint Presentation: …but significant ipsilateral level II nodal involvement
Parotidean metastases : 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?: 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: Escalate/accelerate doses to the whole GTV Baylor: “SMART”: 60 Gy/2.4 Gy/fraction BED 2Gy 70 Gy, over 5 weeks Concurrent with chemotherapy: not tolerable due to acute mucositis Amosson, ASTRO 2003
Escalate/accelerate doses to the whole GTV: 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: 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: 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: Escalate the dose to part of the GTV The FDG-PET avid part of the GTV tumor Hypoxic regions within the GTV
CTV : 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): 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 60 59 1.7 54 56 1.6 49 52 1.5 42
Considerations: 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
How should we treat the low neck?: How should we treat the low neck?
PowerPoint Presentation: NTCP: Glottic edema grade 2+ Rancati T, IJROBP 2009 Extensive neck RT for non-laryngeal cancer, mostly no conc. chemo
PowerPoint Presentation: No effort to spare the larynx/esophagus: High rates of dysphagia after whole-neck IMRT compared with split-field. Fua et al, 2007
split field vs whole neck IMRT: split field vs whole neck IMRT Head Neck 2004
PowerPoint Presentation: Amdur et al, Head Neck 2004
PowerPoint Presentation: Laryngeal shield: do not extend caudally because jugular vein and nodes become more medial Mendenhall, Amdur, Million, 1992
PowerPoint Presentation: Extend the midline block to shield also inferior constrictor and esophagus Caudell JJ IJROBP 2009
Whole neck IMRT or upper neck IMRT + abutted AP low neck field : 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
PowerPoint Presentation: Whole-neck IMRT in cases of low neck involvement or high risk
Higher weight to targets or organs: 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
PowerPoint Presentation: PTVs (yellow/purple) weigh lower than larynx/inf. constrictor
PowerPoint Presentation: PTVs (yellow) weigh higher than esophagus
The low neck: 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
PowerPoint Presentation: Rosenthal et al, IJROBP 2008
PowerPoint Presentation: Rosenthal et al, IJROBP 2008
Oral cavity: Oral cavity Not included in the cost function
Oral cavity: Oral cavity Included
PowerPoint Presentation: Lt tonsillar cancer
PowerPoint Presentation: After 23 fractions (GTV dose 46 Gy) concurrent with carboplatin+taxol Estimated lip mucositis site dose 30 Gy/1.3 Gy/fraction
PowerPoint Presentation: Mucosal point doses vs. length of time of mucositis Narayan et al, IJROBP 2008;72:756
PowerPoint Presentation: Lt tonsillar ca, chemo-RT: oral cavity outside the PTVs spared
PowerPoint Presentation: Induction chemotherapy for HN cancer Response to induction chemo: CR 9%, PR 59% CR 17%, PR 55% 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. : Neoadjuvant chemo: Its tumor effect may be trivial even if clinical CR is achieved. Ian Tannock
After induction chemotherapy: 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: Acknowledgements UM Rad-Onc residents, students & fellows Felix Feng Mary Feng Alex Lin Siavash Jabbari Laura Dawson Aron Popovtzer Iris Gluck Otolaryngol-HN Surgery Doug Chepeha Ted Teknos Carol Bradford Gregory Wolf Speech pathology Teresa Lyden Marc Haxer Dentistry Carol-Anne Murdoch-Kinch Jonathan Ship Rad-Onc Physics Randall Ten Haken Karen Vineberg Dick Fraas NKI, Amsterdam Marco Schwartz Coen Rasch Supported by NCI grants PO1 59827 and HN SPORE P50 CA/DE97248