Principles of Radiation Oncology

Principles of Radiation Oncology
by
Michael Underbrink, MD
Anna Pou, MD

Introduction

* Increasing use for head and neck cancer
* Combined or as single modality
* Outline basic principles, radiobiology
* General treatment approach
* Common complications

Radiation Physics

* Basis – ionizing particles interact with cellular molecules
* Relies on transfer of energy created by secondary charged particles (usually electrons)
* Break chemical bonds
* External beam vs. Brachytherapy
* Radiant energy is discrete yet random

External Beam Irradiation

* Dual-energy linear accelerators generate:
o Low energy megavoltage x-rays (4-6 MeV)
o High energy x-rays (15-20 MeV)
o Photon energy
* Particle Radiation (electrons, protons, neutrons)
* Photon therapy advantages
o Skin sparing, penetration, beam uniformity
* Head and Neck sites – 4-6 MeV x-ray or Co60 gamma ray radiation

External Beam Irradiation
Brachytherapy

* Radioactive source in direct contact with tumor
o Interstitial implants, intracavitary implants or surface molds
* Greater deliverable dose
* Continuous low dose rate
* Advantage for hypoxic or slow proliferators
* Shorter treatment times

Brachytherapy

* Limitations
o Tumor must be accessible
o Well-demarcated
o Cannot be only modality for tumors with high risk of regional lymph node metastasis


Radiobiology

* Ionizing radiation ejects an electron from a target molecule
* Distributed randomly within cell
* Double-strand DNA breaks – lethal
* Cell death: no longer able to undergo unlimited cell division
* Direct vs. Indirect injury (free radicals – O2)
* Inadequate cellular repair mechanisms implied

Radiobiology

* Random cell death
o Deposition of energy & injury is random event
o Same proportion of cells is damaged per dose
o 100 to 10 cell reduction = 106 to 105 cell reduction
o Larger tumors require more radiation
o 105 cells = nonpalpable
o Applies to normal tissue also
* Therapeutic advantage – 4 R’s of radiobiology

4 R’s of radiation biology

* Repair of cellular damage
* Reoxygenation of the tumor
* Redistribution within the cell cycle
* Repopulation of cells

Repair of sublethal injury

* Sublethal injury – cells exposed to sparse ionization fields, can be repaired
* Killing requires greater total dose when given in several fractions
* Most tissue repair in 3 hours, up to 24 hours
* Allows repair of injured normal tissue, potential therapeutic advantage over tumor cells
* Radioresistance – melanoma?

Reoxygenation

* Oxygen stabilizes free radicals
* Hypoxic cells require more radiation to kill
* Hypoxic tumor areas
o Temporary vessel constriction from mass
o Outgrow blood supply, capillary collapse
* Tumor shrinkage decreases hypoxic areas
* Reinforces fractionated dosing
* Hypoxic cell radiosensitizers, selective chemo


Redistribution

* Cell cycle position sensitive cells
* S phase – radioresistant
* G2 phase delay = increased radioresistance
* RAD9 gene mutation – radiosensitive yeast
* H-ras and c-myc oncogenes - G2 delay
* Fractionated XRT redistributes cells
* Rapid cycling cells more sensitive (mucosa, skin)
* Slow cyclers (connective tissue, brain) spared

Repopulation

* Increased regeneration of surviving fraction
* Rapidly proliferating tumors regenerate faster
* Determines length and timing of therapy course
* Regeneration (tumor) vs. Recuperation (normal)
* Reason for accelerated treatment schedules
* Reason against:
o Treatment delay
o Protracted XRT, split course XRT (designed delay)

Dose-Response Relations

* Control probability variables
o Tumor size
o XRT dose
* Favorable response curves
o Small, well-vascularized tumors
o Homogeneous tumors
* Unfavorable response curves
o Large, bulky tumors (hypoxia)
o Heterogeneous, variable cell numbers
* Normal tissue injury risk increases with XRT dose (size of tumor)

Fractionation Schedules

* Conventional
o 1.8 to 2.0 Gy given 5 times/week
o Total of 6 to 8 weeks
o Effort to minimize late complications
* Accelerated fractionation
o 1.8 to 2.0 Gy given bid/tid
o Similar total dose (less treatment time)
o Minimize tumor repopulation (increase local control)
o Tolerable acute complications (increased)
* Hyperfractionation
o 1.0 to 1.2 Gy bid/tid, 5 times/week
o Similar total treatment time (increased total dose)
o Increases total dose
o Potentially increases local control
o Same rates of late complications
o Increased acute reactions

Treatment Principles

* Size and location of primary
* Presence/absence and extent/incidence of regional or distant metastasis
* General condition of patient
* Early stage cancers
o Surgery alone = XRT alone
o Treatment choice depends on functional deficits
* Late stage – usually combination of treatments
* Surgical salvage of primary radiation failures is better than radiation salvage of surgical failure
* Explains rationale behind organ preservation strategies
* XRT tumor cell killing is exponential function
o Dose required for tumor control is proportional to the logarithm of the number of viable cells in the tumor

Shrinking field technique

* Initial dose = 45 to 50 Gy (4.5 to 5.0 weeks)
o Given through large portals
o Covers areas of possible regional metastasis and primary
* Second dose = 15 to 25 Gy (1.5 to 2.5 weeks)
o Boost field (gross tumor and small margin)
o Total dose of 60 to 75 Gy in 6 to 7.5 weeks
* Boost dose = 10 to 15 Gy
o Massive tumors
o Second field reduction at 60 to 65 Gy
o Total of 7 to 8 weeks

Combined Modalities

* Surgery and XRT complement each other
* Surgery – removes gross tumor (bulky tumors are more difficult to control with XRT)
* XRT – effective for microscopic disease, better with exophytic tumors than ulcerative ones (Surgical failures may leave subclinical disease)
* Combining treatments counteracts limitations
* Pre or Post-operative XRT

Preoperative XRT

* Advantages
o Unresectable lesions may become resectable
o Extent of surgical resection diminished
o Smaller treatment portals
o Microscopic disease more radiosensitive (blood supply)
o Decreased risk of distant metastasis from surgical manipulation?
* Disadvantages
o Decreased wound healing
o Decreased safe dose (45 Gy in 4.5 weeks eradicates subclinical disease in 85% to 90% of patients)
* Advantages
o Better surgical staging
o Greater dose can be given safely (60 to 65 Gy in 6 to 7 weeks)
o Total dose can be based on residual tumor burden
o Surgical resection is easier
o Tissue heals better
* Disadvantages
o Distant metastasis by manipulation?
o Delay in postoperative treatment if healing problems (poorer results if delayed more than 6 weeks)

Complications

* Acute Tissue Reactions
* Late Tissue Reactions

Acute Toxicity

* Time onset depends on cell cycling time
* Mucosal reactions – 2nd week of XRT
* Skin reactions – 5th week
* Generally subside several weeks after completion of treatment

* RTOG – acute toxicity <90>PRINCIPLES OF RADIATION ONCOLOGY