SAM I Lecture 58

Uncommon tumors; adenocarcinoma most common histology; AdCA>SCC>Sarcoma; sx + chemo have no survival impact

Mucositis, moist desquamation, erythema; total radiation dose is typically limited by late not acute tissue injury

Side effects are delayed by weeks-months-years; seen in slowly responding tissues; examples: bone, lung tumors

Combining tx overcomes limitations for large tumors; cost of therapy

Radiation is further focused on tumor by dividing radiation dosage into multiple fields

Focused electrons can be used to directly treat tumors; modern linear accel. able to generate photons + electrons

Sensitive normal tissues: may limit dosage + lower success rate; general condition of patient (tolerate ax/sedation)

Breaking up total dosage into multiple smaller fractions allows for __ within tumor population

Rapid cycling cells more sensitive (mucosa, skin); higher % of cells in G2/M phase

By modifying type of ionizing particle and its energy you can optimize dosage to tumor and minimal normal tissue dosing

Large tumors hard to kill - outcome improved if gross tumor removed first - radiation effective for microscopic dz

Therapeutic radiation typically admin. in fractionated (divided) protocols to improve outcome

Radiation alone is only modality w/ documented survival benefit; MST ~8-18 months

Size + location of primary; inverse relationship of size + outcome; proximity of sensitive normal tissues

Tumor shrinkage decreases hypoxic areas; breaking up total dosage allows for previously hypoxic regions to reperfuse

Rapidly proliferating tumors regenerate faster; impact of __ depends on tumor's repair capacity and effects of redistr.

Large tumors often have hypoxic regions; areas will be relatively resistant to radiation - hard to kill large tumors

Amt per dose + total dosage determine severity of side effects (normal + tumor tissue); palliative

Cellular lethality of radiation determined by repair of cell dmg, reoxygenation of tumor, redistr. w/in cell cycle

Chemotherapy only indicated for high grade or metastatic tumors, non-resectable tumors

Most common skin/SQ tumor; viral etiology; variety of growth patterns; sensitive to surgery, chemo, + radiation

Fraction size described using "Gray" Gy to refer to amt of radiation delivered to target per dose; conventional

Disease free interval 6 months

Higher dose per fraction is worse

Generate different energies; photons vs electrons have dramatically diff. depth-dose distributions

Xerostomia, KCS, fibrosis, soft-tissue necrosis, nerve tissue dmg; related to both cumulative dose + dose per fraction

Tumor tissue lacks ability to repair or does slowly; breaking up total radiation dosage allows repair of normal tissue

Most common SQ tumor in dog/cat; high local recurrence rate for cats, low to moderate for dogs; large tumors resistant

Cellular lethality of radiation determined by repopulation of cells

~5% of all cutaneous tumors; more common in unpigmented regions - solar induced, ~30% multifocal

Excessive delays allow tumor tissue to recover/repair

Oxygen stabilizes free radicals + increases cell kill - hypoxic cells require more radiation to kill

Most common skin tumor; locally invasive (<30% metastatic rate); marginal resection curative in ~60-70%

Injury typically reversible; rapidly dividing tissue most affected; happen during or immediately after radiation

Electronic machines: electron gun, water coolant, tungsten target; electron gun generates electrons

Resistant tumors: low growth fraction, long doubling time, hypoxia; control w/ radiation; 70-80% @ 3y low grade dog

Radiation -> free radicals -> DNA damage -> cell death

Use of ionizing energy to kill cancer cells; energy is provided by photons, electrons, + other particles

Happen right away; rapidly dividing tissue; examples include skin, hair, mucosa, and TUMOR TISSUE

Control probability variables; effect of 4 R's can be est. from tumor size, radiation dose (cum. + indiv.), histo type

Cell cycle position determines sensitivity of cells (G2/M phase most sensitive); slower cyclers (CT, brain) spared

After selecting appropriate energy + particle type, radiation is further focused on tumor by collimators

Small, well-vascularized tumors; homogenous tumors

Palliative: 4-8 Gy given daily-weekly; lower total dose; effort to min. short-term effects, lower control rates

Radiation -> DNA dmg -> cell death

Injury tends to be permanent; cells w/ low turnover (fibroblasts, neurons, muscle, bone); develop w/in months-years

Electrons are accel. + focused using magnets; they impact tungsten target to create high energy (>1 Mv) photons

Higher doses per tx result in ^ side effects: lower doses/tx allow for reduced side effects + ^ cumulative dosages

Dosage of radiation is limited such that incidence of "unacceptable" side effects is ~5% (ex: non-healing skin wounds)

What is being shown?

Negative predictors include tumor size and viral load

Conventional: 2-3 Gy given 5x/wk; total of 4-6 wk; effort to minimize long term side effects

Radiation therapy useful for extremities, head + neck, urogenital - >90% curative for low-grade

Energetic ionizing radiation interacts w/ tissues + directly dmg tissues or creates 2nd charged particles (e-) that dmg

Side effects of radiation therapy can be divided into two distinct groups: acute + late tissue reactions

50-60% @ 3y high grade dog; 50% @ 1y for a cat

Exception - palliative therapy

Ionized particles + free radicals lead to cell death via break chemical bonds, dmg lipid membranes, -> DNA strand breaks

Depends on % cells in G2/M; may also be easier to kill if deficit in cellular repair/by redist. to sensitive cycle phase

Distribution of cellular dmg is random; resultant cellular death also random

Large, bulky tumors (hypoxia); heterogenous, variable cell numbers

Prognostic factors include histology + tumor stage; AdCa>Sarcoma>SCC, T1>T2>T3

Radiation reserved for peri-ocular +/or large tumors - typically brachytherapy; control rate 80-90% long-term

Cells that are exposed to sparse ionization fields can be repaired; most normal tissues repair in 3-24 hours

Low metastatic potential; bulky tumor poorly responsive; DFI ~3-9m for T3 tumors, DFI ~5y for T1 tumors