Workshop on Advanced Technologies in Radiation Oncology

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Workshop on Advanced Technologies in Radiation
Oncology
Kian Ang
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Specific Assignment
Regimen A 3-D CRT, B SRT, C IMRT, D
IGRT/Proton, E Other particles
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Specific Assignment
Regimen A 3-D CRT, B SRT, C IMRT, D
IGRT/Proton, E Other particles
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Topic Analogy
Important to differentiate between Drug X vs
Drug Y? or Regimen A vs B of Drug X? (cisplatin
for HNSCC Firm evidence is for 100 mg/m2, q3W
but common prescription is 30 mg/m2, qW or 75
mg/m2, q3W or even carboplatin, qW q3W)
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Principal Dose-Limiting ToxicityHead and Neck
Carcinoma
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Spinal Cord Tolerance Survey
Fowler et al., Radiot Oncol, 2000
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Generating Evidence for IMRT
In general, randomized trial is considered the
gold standard for changing practice standard

• Does dose escalation improve outcome?
• Experience with HFX in HNSCC (15 ? dose) Yes,
  but the benefit is lt RT cisplatin
• Challenge competing with RT novel agents
• Does better tumor coverage improve outcome?
• Difficult or impossible to conduct phase III
  trial
• Does NT sparing decrease late toxicity?
• May not need to conduct phase III trial

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Generating Evidence

• In some clinical settings, phase III trial is
• not rational (potential harm)
• not necessary (longitudinal control)
• not feasible (variability in toxicity reporting
  need large N to show a difference)

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Nasopharyngeal Carcinoma T3N2c
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Phase III Trial 3-D vs IMRT (A vs C)Not
Rational e.g., T3-4 NPC
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Ipsilateral RT for Tonsil Carcinoma
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Alternative to Randomized Trial?
Reproduce (validate) single institutions data
preferably in multi-institutional setting
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IMRT for Oropharynx Cancer

• 2000-June 2003 133 patients
• Age 30-75 (53) years 85 male
• Site tonsil-52 tongue base-40
• T1-2(x) 114 T3-4 19
• Chemotherapy 28 (T3-4 or N2-3)
• 3-Y local control 95
• 3-Y overall survival 93

Garden et al., 2005
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IMRT for Oropharyngeal SCCRTOG Protocol H-0022
(Eisbruch Chao)
Stage T1-2 N-1 Site Tonsil, BOT, Soft Palate

R E G I S T E R
Gross disease PTV 66 Gy/30 FX Subclinical
disease PTV 54-60 Gy/30 FX Boost of 4-6 Gy/2-3
FX to the tumor PTV allowed
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RTOG 0022 ASTRO 2006

• Study population 67 patients (14 centers)
• Tumor tongue base-20 (39), tonsil-33 (49),
  soft palate 8 (12)
• Stage T1-25, T2-75 N0-57, N1-43
• Median follow-up 1.6 (0.2-3.8) years
• LR progression 3 patients (4.9)
• No metastatic disease observed

A Eisbruch, J Harris, A Garden, C Chao, W
Straube, C Schultz, G Sanguineti, C Jones, W
Bosch, K Ang
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IMRT Chemo for NPC (Single Institutions)
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IMRT for NPCRTOG Protocol H-0225 (Lee Garden)
IMRT 2.12 Gy/F/d X 33 F to ? 95 of GTV 1.8
Gy/F/d X 33 F to ? 95 of CTV
R E G I S T E R
Stage I-IVb Histology WHO I-III
Chemotherapy (?T2b or N) Concurrent Cisplatin x
3 Adjuvant Cisplatin 5-FU
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Generating Evidence

• In some clinical settings, phase III trial is
• not rational (potential harm)
• not necessary (longitudinal control)
• not feasible (variability in toxicity reporting
  need large N to show a difference)

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Recovery of Salivary Flow (A vs C)
Mean Flow
Chao et al., Sem Radiat Oncol, 2002
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Recovery of Saliva Flow (A vs C)
Kam et al., ASCO 2005 (NPC)
Impact on QOL parameters was less obvious
IMRT
Non-IMRT
p lt 0.0001 0.0001
0.0001
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Patient with Tongue Base Carcinoma 19 CT Scans
over 47 Days
Elapsed Days
Patient Immobilized with Acquaplast MaskCTs
Aligned Using BBs on Mask
Barker et al. IJROBP 59960, 2004 Lei Dong et
al. (MDACC)
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Changes in Anatomy during Therapy Course
Three Weeks into RT
Planning CT
Barker et al. IJROBP 59960, 2004 Lei Dong et
al. (MDACC)
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Changes in Anatomy during Therapy Course
Mid Course CT
Planning CT
Target Before RT Course
Lei Dong et al. (MDACC)
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Dosimetric Impact of Anatomic Changes
Barker et al. IJROBP 59960, 2004 Lei Dong et
al. (MDACC)
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Right Parotid Dose Planned vs Delivered
CTV1
Cord
CTV2
CTV3
R Parotid
L Parotid
Lei Dong et al. (MDACC)
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Generating Evidence

• In some clinical settings, phase III trial is
• not rational (potential harm)
• not necessary (longitudinal control)
• not feasible (variability in toxicity reporting
  need large N to show a difference)

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Toxicity Recording Reporting
JCO 22 19, 2004
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Principal Dose-Limiting ToxicityHead and Neck
Carcinoma
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Value of IGRT or Protons (D)
Other Toxicity Tumor Control Assess in defined
patient subsets (phase III for NPC)
Parotid dose 3-D CRT gt50 Gy IMRT 26 Gy
Clear ? in salivary flow
Need to show clin benefit !
Will improve D-R data
Proton ?? Gy
IGRT ?? Gy
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Value of Other Particle Therapies (D)
Exploiting potential advantages in ? RBE ?
Dose Distribution
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Resources for Clinical Research
Training Quality Control
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Training QC HN Atlas
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Training QC IMRT Credentialing

• Primary PTV
• 4 cm diameter
• 4 TLD
• Secondary PTV
• 2 cm diameter
• 2 TLD
• Organ at risk
• 1 cm diameter
• 2 TLD
• Axial and sagittal radiochromic films

1º PTV treated to 6.6 Gy 2º PTV treated to 5.4
Gy OAR limited to lt 4.5 Gy
Courtesy G. Ibbott
Designed in collaboration with RTOG Molineu et
al, IJROBP, October 2005
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Phantom Results
34 of institutions failed on the first attempt
Courtesy G. Ibbott
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Training QC
Online Review
CTV56
CTV63
Protocol
ATC Advanced Technology Consortium
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Summary

• IMRT (Regimen C)
• It is an important progress for treatment of
  patients with HN cancer
• Requires training QC to do it well
• Firm data exist on xerostomia reduction
• Need more multi-institutional trials to validate
  strong single institutional data on tumor control
• IGRT, proton beam, other particle therapies
  (Regimens D E)
• Need well designed studies to test document
  their values in tumor control and toxicity
  reduction