This page of the TDFPlan user guide includes illustrations of how to use TDFPlan version 1.7.2 and later to work the example problems in The Royal College of Radiologists. The timely delivery of radical radiotherapy: standards and guidelines for the management of unscheduled treatment interruptions, Third edition, 2008. London: The Royal College of Radiologists, 2008. Appendix B from that publication is reproduced on the right to summarize their approach.
Illustrations in this guide were captured from the MacOSX 10.9 version of TDFPlan 1.7.2. The appearance of the Windows version of the program will be similar.
Worked Examples 1–3 each consider ways of handling five-day gaps. In practice, the majority of unscheduled interruptions will probably involve interruptions of less than five days and are correspondingly easier to deal with. Examples 1–5 involve a reference schedule of 70 Gy delivered in 35 fractions over 46 days, typically used for Category 1 head and neck tumours. The overall time of 46 days corresponds to a treatment beginning on a Monday, continues with daily fractionation for seven weeks with no treatment at weekends and finishes on a Friday. These examples assume a generic repopulation rate parameter k = 0.9 Gy/day and repopulation kick-in delay of Tk = 28 days.
Example #1. Loss of all of the third week (five fractions) of a treatment schedule of 70 Gy in 35 fractions over 47 total days.
Assuming the treatment began on a Monday, the intended elapsed time between the first and last fraction is 46 days. After the gap, treatment resumes on the Monday of the fourth week of the schedule. Ten fractions have been delivered; 25 remain to be given. If treatment is to be completed on the prescribed finishing date the available number of days (including weekends) is 26. Thus the missed dose in the gap can be compensated for by delivering the remainder of the treatment on weekdays (20 fractions) and on five of the six remaining weekend days. This does not involve changing the fraction size and, as the treatment is not extended, constitutes a ‘good’ compensation.
Example #2. Loss of all of the sixth week (five fractions) of a treatment schedule of 70 Gy/35 fractions/46 days.
After the gap, treatment resumes on the Monday of the seventh week of the schedule. Twenty-five fractions have been delivered and ten remain to be given. Ideally these ten fractions should be delivered over the five remaining treatment days so as not to extend the treatment. The missed dose can therefore be compensated for by delivering the remainder of the treatment as twice-daily fractions (minimum of 6 hours apart) in each weekday of the final week. This does not involve changing the fraction size and, as the treatment is not extended, constitutes a good compensation.
Example #3. Loss of all of the seventh week (five fractions) of a treatment schedule of 70 Gy/35 fractions/46 days.
In this example, the unscheduled gap extends to the time when treatment should have finished and any form of compensation will therefore extend the treatment time beyond the scheduled time. It is, therefore, necessary to use calculations to first determine how much normal tissue BED there is still ‘to give’ after the gap.
We begin by assuming that the missing dose is replaced by treating with five 2 Gy fractions over a full extra (8th) week, beginning on a Monday.
On completion, the overall time is seven days longer than originally scheduled. In course #2 of the IMR table we see that the BED3 delivered before the gap is 100 Gy3. The BED10 (acute effects) delivered before the gap is 62.1 Gy10. During the 9 day gap between the end of course #1 (Mar. 13) and the beginning of course #3 (Mar.23) repopulation continues. The BED10 (acute effects) delivered after the gap by makeup course #3 (5 fractions of 2 Gy beginning Mar. 23rd) is insufficient to compensate for repopulation during the gap, resulting in an effective BED10 of -0.6. With a daily BED-equivalent of tumour repopulation of 0.9 Gy/day, the tumour BED10 will be lower than intended by an amount 7 × 0.9 = 6.3 Gy10, ie it will be reduced to 67.8 – 6.3 = 61.5 Gy10, a fall of over 9%. The late normal BED3 will be as originally prescribed.
If instead, the outstanding daily treatments are given in the period Saturday–Wednesday, the net treatment extension is five days; that is, the tumour BED10 is reduced by 5 × 0.9 = 4.5 Gy10 (6.6%). The tumor BED10 will be less than the reference BED10, but by a smaller amount than the M-F schedule (63.3 vs 61.5) and the normal tissue BED3 will again be as prescribed.
The dilemmas arise when attempts are made to increase the total dose to restore the tumour BED10 to that originally intended; in this case it is impossible to do so without increasing the normal tissue BED3 beyond that originally prescribed. Delivering extra doses by treating with extra fractions has the effect of further extending the treatment time, which may compound the original problem. Increasing the dose per fraction helps offset the deleterious influence of the treatment extension but, because of the greater sensitivity of the late-responding critical tissue to changes in dose per fractions, will increase the normal tissue BED proportionately more than that for the tumour.
We next consider an instance where it is felt essential to restore the tumour BED10 to what it should be, initially without regard for the effect on the normal tissue. We assume the option of treating additionally over the weekend is to be adopted, taking the overall time to 46 + 5 = 51 days. The tumour BED10 of 67.8 Gy10 is to be maintained. Therefore, for the whole schedule (pre-gap plus post-gap): BED10 (pre-gap) + BED10 (post-gap) – tumour repopulation factor = prescribed BED10.
...that is, 5 × 2.62 Gy will restore the tumour BED10 to that initially prescribed. Again it should be noted that the required extra BED10 of (5 × 0.9) = 4.5 Gy10 cannot be added simply pro rata across the five 2 Gy fractions. The values of the biological Gy10 and the physical Gy units are different and they cannot be added; to do so would lead to an even higher fraction dose of 2.9 Gy. For the normal tissue, the compensated treatment increases the BED3 to: BED3 (pre-gap) + BED3 (post-gap) = 124.5 Gy3.
Thus the revised treatment delivers a 6.7% excess in normal tissue BED3. To evaluate what this compensated scheme would mean in terms of the equivalent dose in a schedule delivered with 2 Gy fractions we note that ... the total dose in 2 Gy fractions would be 74.7 Gy. Thus, the given normal tissue BED3 is approximately equivalent to just over 37 × 2 Gy fractions.
Unscheduled interruptions of longer than five days are generally more difficult to deal with as there is less chance of completing treatment without incurring a significant extension of the treatment time. The following examples highlight such cases.
Example #4. Loss of all of the sixth and seventh weeks (ten fractions) of a treatment schedule of 70 Gy/35 fractions/46 days .
As in Example 3, the unscheduled gap runs right up to the time when treatment should have finished. In this case however, a very significant part of the treatment has yet to be delivered. In order to minimise the consequent extension to treatment time it is inevitable that an increased dose per fraction will need to be considered if treatment is to be delivered in once-daily fractions.
We initially attempt to complete treatment in five fractions delivered during the eighth week – the treatment time is extended by seven days to 53 days. We first aim to match the prescribed late-normal tissue BED3 (116.7 Gy3), that is, the dose per fraction to use is d, where d is solved from: BED3 (pre-gap) + BED3 (post-gap) = Required BED3 ... for which d = 3.22 Gy
This same dose per fraction would produce a resultant tumour BED10 of:
BED10 (pre-gap) + BED10 (post-gap) – tumour repopulation factor ... = 58.8 Gy10.
Thus, despite using a large dose per fraction for the last five fractions, the resultant tumour BED10 is still 13.2% less than prescribed. If the weekend prior to the eighth treatment week is used for treatment, then seven fractions may be delivered, leading to a fractional dose of 2.57 Gy and a tumour BED10 of 60.1 Gy10. If 11 fractions are distributed over the seven available treatment days (by treating bi-daily on four of them) the required fractional dose drops to 1.87 Gy, the tumour BED10 then being 61.9 Gy10. This latter value is still 8.7% short of the prescribed tumour BED10 (67.8 Gy10), thus some degree of compromise, achieved by increasing dose per fraction as illustrated in the previous example, might be considered. In extreme cases, three times-daily fractionation could be considered, but only after careful consideration of the potential for detriment from incomplete repair.
If weekend or twice-daily fractionation cannot be accommodated, then it might be considered necessary to carry out the remaining treatment over two full working weeks – extend treatment into an eighth and ninth week – making the overall treatment time 46 + 14 = 60 days. For this, the dose per fraction (d) ideally required to maintain the tumour BED10 is obtained from: BED10 (pre-gap) + BED10 (post-gap) – tumour repopulation factor = 67.8Gy10 for which d = 2.85 Gy, leading to an associated BED3 of 138.9 Gy3, which is 19% higher than prescribed. This result demonstrates the alternative dilemma associated with further extending the treatment to avoid weekend and twice-daily treatments: the total dose to be delivered is again increased by the extension into the ninth week, with a consequent penalty to BED3.
Example #5. Loss of the final 13 fractions of a treatment schedule of 70 Gy/35 fractions/46 days.
This represents a very difficult case. As a compromise between minimising the extension while at the same time ensuring that a reasonable number of fractions are used, we assume that ten post-gap fractions will be given, twice daily from Saturday to Wednesday, extending the treatment to 46 + 5 = 51 days. We first assume that the effect of incomplete repair is negligible, ie that Eq(A) remains valid. The relevant equation to determine the dose per fraction (d) to maintain the prescribed normal tissue BED3 (116.7 Gy3) is: BED3 (pre-gap) + BED3 (post-gap) = Required BED3 = 116.7 Gy3 for which d = 2.41 Gy. The resultant tumour BED10 would then be: BED10 (pre-gap) + BED10 (post-gap) – tumour repopulation factor = 62.0 Gy10.
Example #6. A nominal four-week head and neck schedule beginning on a Wednesday is prescribed as 54 Gy/20 fractions/27 days. The patient is too unwell to be treated for the last seven scheduled fractions and their deferment extends eventual completion of treatment to 38 days.
The prescribed normal tissue BED3 = 102.6 Gy3. Because the overall time is extended from 27 to 38 days we assume for calculation purposes that K is zero in the time up to 28 days and 0.9 Gy/day thereafter. The prescribed tumour BED10 is therefore = 68.6 Gy10.
The interruption extends the overall time to 38 days. If the seven outstanding fractions were treated at the original fraction size (2.8 Gy) the late-reaction normal tissue BED3 would be unaltered. However, the tumour BED10 will be compromised because the treatment has extended beyond the 28 days at which time faster tumour repopulation is assumed to begin. The tumour BED10 would then be calculated from: BED10 (pre-gap) + BED10 (post-gap) – tumour repopulation factor = 59.6 Gy10 a reduction of 13.1%.
In short-duration treatments of this type, the dose per fraction is already relatively large and any further increase (as may be required to strike a balance between normal tissue and tumour BEDs) should be considered with caution. As an example, to achieve a tumour BED10 with an intermediate value 65.0 Gy10 requires a dose per fraction (d) which is obtained from: BED10 (pre-gap) + BED10 (post-gap) – tumour repopulation factor = required BED10 of 65.0 Gy10, ie: d = 3.19 Gy per fraction. Use of this fraction size for the deferred seven treatments would increase the normal tissue BED3 to: BED3 (pre-gap) + BED3 (post-gap) = 112.8Gy3. This is still 10% more than that prescribed, even though the tumour BED10 has been deliberately compromised.