josh dass radiation oncologist · bentzen et al rad onc 1989; 16:169 overgaard ijrobp 1986; 12:867...
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Josh Dass Radiation Oncologist
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Epidemiology
At diagnosis: Jemal et al: CA Cancer J Clin J ‘09
Localized disease 82 to 85%
Regional disease 10 to 13%
Non-regional metastases 2 to 5%
Prognosis: Homer: SEER Cancer Statistics R/V
Localised 98%
Regional 62%
Metastatic 15%
OS over the decades 1977 (82%) 2004 (92%)
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Myth: Radiation Effect
• Radiotherapy – Cook – Sizzle – Burn – Microwave – Electrocute – Nuclear holocaust
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Principles of Quantum Physics
Wave Theory Quantum
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Principles of Quantum Physics
Electromagnetic radiation Particles called photons
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Target: DNA
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The Principles
High Dose Low Dose
Cancer Normal Tissue
Delivery
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EBRT = Linear Accelerator
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Radical
• Definitive • Adjuvant
Palliative
• Definitive • Symptom
control
Stereotactic
• ?Radical
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Local control factors
Not clearly established
role
• Close/ positive margins • Early/multiple recurrences • Extensive satellitosis 12 to 14% recur • Desmoplasia 11 to 48% recur • Neurotropism
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Adjuvant = after surgery
Regional Nodal Involvement
Size > 3cm
Number 1 parotid
2 Head and neck/Axillae
3 Inguinal
ECE = extracapsular extension
ENE = extranodal extension
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Radiotherapy alone
Unresectable
Not suitable for systemic therapy
Patient preference
Co-morbidities
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Conspiracy Theory
• Irradiation alone by any technique should not be relied on for the cure of these lesions
• Based on orthovoltage radiotherapy and radium experience
MacKee 1946: Xrays & Radium in Rx of Skin
• Million et al 1984 Mx of HN Ca: A MDM approach • Jenrette 1996 MM: the role of RT revisited
• Seminars Oncology 1996 • Stevens et al: Dispelling the Myths of RT for MM
• Lancet Oncology 2006; 7:7:575 • Overgaard: important factors in treatment of MM
• RO 1986; 5:183 • Rofstad: Radiation biology of malignant melanoma
• Acta Radiol Oncol
Today questioned
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Barranco et al Cancer Res 1971; 31:830
Dewey Br J Radiol 1971; 44:816
Fertil et al IJROBP 1985; 11:1699
Doss et al IJROBP 1982; 8:1131
Cell Culture Studies
High repair capacity
Hypofractionation more effective •Rofstad Acta Radiol Oncol 1986; 25:1
Broad shoulder on surv curve
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Fraction Size makes no difference?
Bentzen et al Rad Onc 1989; 16:169
Overgaard IJROBP 1986; 12:867
Chang et al IJROBP 2006;66:1051
RTOG Phase III metastatic melanoma • Sause et al IJROBP 1991; 20:429 • 32Gy/4#/4wk @ 8gpf vs. 50Gy/25#/5wk @ 2.5gpf
• Complete response similar 24 vs 23% • Partial response similar 36% vs 34% • However increased toxicity in the hypo# arm
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Emerging paradigm shift
• head and neck
• High risk nodal disease
• uveal melanoma
• brain mets
Radiosurgery
Plaque brachytherapy
IMRT/VMAT
Adjuvant radiotherapy
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Hypofractionated
• Retrospective studies showing improved outcome Bentzen:
RO 1989; 16:169-182
• For fraction size > 5 Gy, 50% CR, vs 9% for < 5 Gy/fx. Local control @ 1 yr 25% vs 7%
Konefal: Radiology 1987; 164:607
• 2 yr LRC 95% in HN Melanoma node negative neck • 24 – 30Gy in 4 to 5# in 5 – 6 gpf
Ang & Peters: Arch Otol H N Surg 199;
116:169
• Increased progression free survival Burmeister:
RO 2006 TROG 96:06
• RT reduced the risk of Ly Node Field relapse by 52% Henderson:
JCO 2009 Josh Dass 18
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3D – CRT vs. IMRT
Equal Intensity Across Field Intensity is modulated across field
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3D – CRT vs. IMRT
Equal Intensity Across Field Intensity is modulated across field
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VMAT
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Single very high dose radiotherapy Pin point accuracy Almost total avoidance of normal tissue
Typically 2 to 8 high dose radiotherapy fractions Pin point accuracy Almost total avoidance of normal tissue
Ster
eota
ctic
radi
osur
gery
Stereotactic radiotherapy
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Radiosurgery
Brain Mets
contributes to 20 to 54% deaths
Skibber: Ann Surg Oncol 1996: Cranial Rt after Sx
Increased Risk a/w: (Sampson J Neuro 1998; 88: 11)
Male
Head and Neck mucosal melanoma
Nodal mets > 2 nodes Josh Dass 23
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Uveal Melanoma
• Choroid, Ciliary Body, Iris
Location
• Heterotrimeric G proteins upregulate MAPK
83% have mutation in GNA11 or GNAQ loci
• COMS – Collaborative Ocular Melanoma Study • 1317 pts enucleation vs. Plaque I-125 BT
• 5 yr survival 81% vs. 82% • 2.5 to 10mm in apical height • 5 to 16 mm largest basal diameter
Treatment
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Patient moves Organs move – lung, liver, etc…
Tight radiotherapy field = geographical miss • Make field larger = more
normal tissue damage
Need 4D capability • Hit a moving target
including changing shape
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OAR
Josh Dass, Sir Charles Gairdner Hospital, Perth
Planning
Day 1 Day 2 Day 3
Missed
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OAR = Organ at risk
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Original Plan Make the radiation field bigger to allow for movement
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Introducing CyberKnife M6
system
• Only one in Australia • Only 4 M6 systems in the world • Advantage
• 4D capability • Irregular shape targeting • Multiple targets in one
session
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• Tract detect and correct
Inter target motion tracking
Non co-planar = not single plane but any angle
• Orthogonal KV imaging systems • Fudicial Markers
• Gold seeds • Calypso
Fudicial Marker tracking
Stereotactic radiotherapy– shorter course with higher dose
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