Fractionation Schedules

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Dividing a dose into a number of fractions can spare normal tissues while destroying tumor tissues.


• Normal tissues are able to repair sublethal XRT damage between dose fractions and cellular repopulation.


• Fractionation increases tumor damage because of reoxygenation and reassortment.


• Most radiation oncologists today consider 1.8 to 2.0 Gy per day, delivered once daily five days a week as “standard fractionation” for curative intent radiotherapy.  


• This has developed over many years as a result of both radiobiological experiments and clinical experience.



STANDARD FRACTIONATION BROAD GENERALIZATIONS:


For many common malignancies, especially epithelial based tumors (breast cancer, head and neck squamous cell cancer), clinicians often use these general dosing guidelines when implementing 


Standard fractionation:


• Gross disease = 70 Gy


• Microscopic disease (ex:  positive margin):  60-66 Gy


• Elective coverage (ex:  uninvolved but at-risk lymph nodes):  45-54 Gy.



ALTERATIONS TO STANDARD FRACTIONATION:


There are many variations outside of 1.8 Gy – 2.0 Gyonce daily prescriptions (some will be covered later in this presentation)

• Side effects and implications of changing prescriptions from standard fractionation can vary greatly based up treatment site, but often times these principles can apply:


• Lowering the per-fraction dose (ie 1.2 Gy per fraction) can decrease the late effects (ie:  soft tissue fibrosis)


• Increasing the number of fractions per day or per week(ie using BID treatments)  can increase the acute effects (ie skin erythema, mucositis) and acute effects may present earlier than those seen for standard fractionation


• Increasing the dose per fraction (ie 2.5 Gy per fraction) can increase late effects


• At more extreme high-dose per fraction courses (and especially for short courses), patient acute side effects may present a number of days AFTER radiotherapy is complete – patients and staff need to be educated about this phenomenon


“Hyperfractionation” – keeping a similar (or sometimes higher) total dose in the same total time, but delivering it in more fractions with lower doses per fraction as compared to standard fractionation


• Example:  RTOG 90-03 showed improved outcomes for head and neck cancer patients treated with radiotherapy alone using this hyperfractionated regimen versus a standard fractionation regimen:


• 81.6 Gy at 1.2 Gy BID (68 treatments total) 


• Advantage:  improved outcomes in head and neck cancer if no chemotherapy is utilized, reduced late effects due to low per-treatment dose


• Disadvantage:  can be inconvenient, may see more acute effects (skin, mucus membrane) as compared to once daily conventional fractionation.


“Accelerated Treatment” - similar total dose delivered in a shorter amount of time using similar dose per fraction as compared to standard fractionation


• Example:  The Dutch Head and Neck Cancer group (DAHANCA) showed improved outcomes for patients treated with 6 fractions a week versus 5 fractions a week of 2 Gy per fraction to 66-68 Gy total with radiotherapy alone.


• Accelerated Treatment patients were either treated BID once a week (ex:  Friday AM and PM treatment) or had a Saturday treatment.


• Advantages:  improved outcomes for some sites, morconvenient than hyperfractionation/BID treatments.


• Disadvantages:  possibly more acute effects, slightly more inconvenient than standard fractionation.


“Hypofractionation” - most often involves increasing the dose per fraction and decreasing total treatment time


• Example:  A Phase III randomized trail 1 of prostate cancer patients receiving standard 2 Gy/fraction vs. 2.7 Gy/fraction XRT showed no differences in PSA control rate and late effects.  Slightly higher early GU and GI effects noted.


• Advantages:  shorter treatment times, possibly improved outcomes for some sites


• Disadvantages:  slightly worse acute toxicity, potential for worse late toxicity if careful treatment planning/delivery is not accomplished

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