## TDF Plan: Management of unscheduled treatment interruptions

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.

- Activate course #1.
- Enter a title for course #1 (e.g. BFCO_RCR examples).
- Set the IMR modality to EBRT.
- Set the # of fractions to 35.
- Lock the # of fractions.
- Set the Rx fraction to 200 cGy.
- Mark course #1 as included.
- Set
**Reactions:**to**Acute**. - Enable repopulation calculations by enabling the
**Repop: Include**and**Generic**checkboxes. - Open the repopulation parameters window by clicking the
**Set...**button found in the model control group next to the**Generic**checkbox. - Set the k parameter to 0.9.
- Enable the Tx-1 checkbox to indicate that repopulation calculations should be based on elapsed time (in days) between the first and last fraction rather than using the actual number of course days. This is how the examples in the reference were calculated.
- Alternatively select
**BFCO repop. (ab=10 k=0.9)**from the model group**Library**popup menu for acute effects.

- In the IMR Calendar window select course #1.
- Set Tx days/week to 5 and enable Tx days M to F.
- In this example the start date has been set to Monday, Feb. 2nd, 2015 by clicking on that day.

**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.

- In the IMR Calendar window select course #1.
- Set Tx days/week to 7 and enable Tx days S to S.
- Manually mark weekend dates as
**skip**days by shift-clicking on the dates to accomplish complete the prescription on the 47th treatment day, ie 46 days after the first fraction. Skipped days are designated by a red X.

**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.

- In the TDF Plan window uninclude course #1.
- In course #2 enter the treatment delivered before the gap, ie 50 Gy delivered in 25 fractions of 200 cGy.
- Mark course #2 as included.
- In course #3 enter the treatment to be delivered after the gap, ie 20 Gy delivered BID in 10 fractions of 200 cGy.
- Mark course #3 as included.
- Be sure to set course #3 as
**BID**.

- In the IMR Calendar window select course #2.
- Set course #2 to start on the same day as course #1.
- Set Tx days/week to 5 and enable Tx days M to F.
- In the IMR Calendar window select course #3.
- Set course #3 to start on the Monday following the gap.
- Set Tx days/week to 5 and enable Tx days M to F.

**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.

- In the TDF Plan window uninclude course #1.
- In course #2 enter the treatment delivered before the gap, ie 60 Gy delivered in 30 fractions of 200 cGy.
- Mark course #2 as included.
- In course #3 enter the treatment to be delivered after the gap, ie 10 Gy delivered in 5 fractions of 200 cGy.
- Mark course #3 as included.

- In the IMR Calendar window select course #2.
- Set course #2 to start on the same day as course #1.
- Set Tx days/week to 5 and enable Tx days M to F.
- In the IMR Calendar window select course #3.
- Set Tx days/week to 5 and enable Tx days M to F.
- Set course #3 to start on the Monday (e.g. Mar. 23rd) following the gap.

On completion, the overall time is seven days longer than originally scheduled. In course #2 of the IMR table we see that the BED_{3} delivered before the gap is 100 Gy_{3}. The BED_{10} (acute effects) delivered before the gap is 62.1 Gy_{10}. During the 9 day gap between the end of course #1 (Mar. 13) and the beginning of course #3 (Mar.23) repopulation continues. The BED_{10} (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 BED_{10} of -0.6. With a daily BED-equivalent of tumour repopulation of 0.9 Gy/day, the tumour BED_{10} will be lower than intended by an amount 7 × 0.9 = 6.3 Gy_{10}, ie it will be reduced to 67.8 – 6.3 = 61.5 Gy_{10}, a fall of over 9%. The late normal BED_{3} 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 BED_{10} is reduced by 5 × 0.9 = 4.5 Gy_{10} (6.6%). The tumor BED_{10} will be less than the reference BED_{10}, but by a smaller amount than the M-F schedule (63.3 vs 61.5) and the normal tissue BED_{3} will again be as prescribed.

- In the IMR Calendar window select course #3.
- Set the number of Tx days to 7 and enable the Saturday and Sunday checkboxes.
- Set course #3 to start on the Saturday (e.g. Mar. 21st) following the gap.

The dilemmas arise when attempts are made to increase the total dose to restore the tumour BED_{10} to that originally intended; in this case it is impossible to do so without increasing the normal tissue BED_{3} 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 BED_{10} 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 BED_{10} of 67.8 Gy_{10} is to be maintained. Therefore, for the whole schedule (pre-gap plus post-gap): BED_{10} (pre-gap) + BED_{10} (post-gap) – tumour repopulation factor = prescribed BED_{10}.

- In the TDF Plan window select course #3.
- Lock the number of fractions at 5.
- Increase the dose per fraction until the acute BED for the combined courses 2 and 3 equals about 67.8. The solution is 262 cGy per fraction.

...that is, 5 × 2.62 Gy will restore the tumour BED_{10} to that initially prescribed. Again it should be noted that the required extra BED_{10} of (5 × 0.9) = 4.5 Gy_{10} cannot be added simply pro rata across the five 2 Gy fractions. The values of the biological Gy_{10} 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 BED_{3} to: BED_{3} (pre-gap) + BED_{3} (post-gap) = 124.5 Gy_{3}.

Thus the revised treatment delivers a 6.7% excess in normal tissue BED_{3}. 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 BED_{3} is approximately equivalent to just over 37 × 2 Gy fractions.

- In the TDF Plan window select
**late**reactions. - Open the
**Equivalent Single Course**window which provides alternative solutions for a constant target BED value. - In the ESC window, set the ESC target BED to 124.54 (or enable the
**Match IMR BED**checkbox). - In the ESC window, adjust the
**# Fractions**field or bumpers and observe the**Rx fraction**readout. For example, 37 fractions of 201.4 cGy/fraction is one possible solution.

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 BED_{3} (116.7 Gy_{3}), that is, the dose per fraction to use is d, where d is solved from: BED_{3} (pre-gap) + BED_{3} (post-gap) = Required BED_{3} ... for which d = 3.22 Gy
This same dose per fraction would produce a resultant tumour BED_{10} of:
BED_{10} (pre-gap) + BED_{10} (post-gap) – tumour repopulation factor ... = 58.8 Gy_{10}.

- In the TDF Plan window uninclude course #1.
- Set reactions to
**Late**. - In course #2 enter the treatment delivered before the gap, ie 50 Gy delivered in 25 fractions of 200 cGy.
- Mark course #2 as included.
- In course #3 set and lock the number fractions to 5. We will later adjust the Rx fraction cGy to deliver the desired result.
- Mark course #3 as included.

- In the IMR Calendar window select course #2.
- Set course #2 to start on the same day as course #1.
- Set Tx days/week to 5 and enable Tx days M to F.
- In the IMR Calendar window select course #3.
- Set Tx days/week to 5 and enable Tx days M to F.
- Set course #3 to start on the Monday (e.g. Mar. 23rd) following the gap.

- In the TDF Plan window select course #3
- Adjust the
**Rx fraction (cGy)**(e.g. using the bumper controls) for course #3 until the late BED_{3}for the combined courses 2 and 3 is approximately 116.7 Gy_{3}. A Rx fraction of 322 cGy yields 116.71 Gy_{3}and 58.78 Gy_{10}.

Thus, despite using a large dose per fraction for the last five fractions, the resultant tumour BED_{10} 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 BED_{10} of 60.1 Gy_{10}. 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 BED_{10} then being 61.9 Gy_{10}. This latter value is still 8.7% short of the prescribed tumour BED_{10} (67.8 Gy_{10}), 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 BED_{10} is obtained from: BED_{10} (pre-gap) + BED_{10} (post-gap) – tumour repopulation factor = 67.8Gy_{10} for which d = 2.85 Gy, leading to an associated BED_{3} of 138.9 Gy_{3}, 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 BED_{3}.

- In the TDF Plan window uninclude course #1.
- Set reactions to
**Acute**. - In course #2 enter the treatment delivered before the gap, ie 50 Gy delivered in 25 fractions of 200 cGy.
- Mark course #2 as included.
- In course #3 set and lock the number fractions to 10. We will later adjust the Rx fraction cGy to deliver the desired result.
- Mark course #3 as included.

- In the IMR Calendar window select course #2.
- Set course #2 to start on the same day as course #1.
- Set Tx days/week to 5 and enable Tx days M to F.
- In the IMR Calendar window select course #3.
- Set Tx days/week to 5 and enable Tx days M to F.
- Set course #3 to start on the Monday (e.g. Mar. 23rd) following the gap.

- In the TDF Plan window select course #3
- Adjust the
**Rx fraction (cGy)**(e.g. using the bumper controls) for course #3 until the acute BED_{10}for the combined courses 2 and 3 is approximately 67.8 Gy_{10}. A Rx fraction of 285 cGy yields 67.82 Gy_{10}and 138.91 Gy_{3}.

**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 BED_{3} (116.7 Gy3) is: BED_{3} (pre-gap) + BED3 (post-gap) = Required BED_{3} = 116.7 Gy_{3} for which d = 2.41 Gy. The resultant tumour BED_{10} would then be: BED_{10} (pre-gap) + BED_{10} (post-gap) – tumour repopulation factor = 62.0 Gy_{10}.

- In the TDF Plan window uninclude course #1.
- Set reactions to
**Late**. - In course #2 enter the treatment delivered before the gap, ie 44 Gy delivered in 22 fractions of 200 cGy.
- Mark course #2 as included.
- In course #3 set and lock the number fractions to 10. We will later adjust the Rx fraction cGy to deliver the desired result.
- Set course #3 as
**BID**. - Mark course #3 as included.

- In the IMR Calendar window select course #2.
- Set course #2 to start on the same day as course #1.
- Set Tx days/week to 5 and enable Tx days M to F.
- In the IMR Calendar window select course #3.
- Set Tx days/week to 7 and enable Tx days S to S.
- Set course #3 to start on the Saturday (e.g. Mar. 21rd) following the gap.

- In the TDF Plan window select course #3
- Adjust the
**Rx fraction (cGy)**(e.g. using the bumper controls) for course #3 until the late BED_{3}for the combined courses 2 and 3 is approximately 116.7 Gy_{3}. A Rx fraction of 241 cGy yields 116.79 Gy_{3}and 62.01 Gy_{10}.

**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 BED_{3} = 102.6 Gy_{3}. 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 BED_{10} is therefore = 68.6 Gy_{10}.

- In the TDF Plan window select and include course #1.
- Title course #1 as the reference schedule.
- Set reactions to
**Acute**. - Select BFCO repopulation (ab=10, k=0.9) from the acute effects library.
- Set reactions to
**Late**. - Set and lock the number of fractions to 20.
- Set the Rx fraction to 270 (ie for a total dose of 5400 cGy).

- In the IMR Calendar window select course #1.
- Set course #1 to start on a Wednesday (e.g. Feb. 4th, 2015) by clicking on the calendar.
- Set Tx days/week to 5 and enable Tx days M to F.

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 BED_{3} would be unaltered. However, the tumour BED_{10} will be compromised because the treatment has extended beyond the 28 days at which time faster tumour repopulation is assumed to begin. The tumour BED_{10} would then be calculated from: BED_{10} (pre-gap) + BED_{10} (post-gap) – tumour repopulation factor = 59.6 Gy_{10} a reduction of 13.1%.

- In the TDF Plan window uninclude course #1.
- Set reactions to
**Acute**. - In course #2 enter the treatment delivered before the gap, ie 35.1 Gy delivered in 13 fractions of 270 cGy.
- Mark course #2 as included.
- In course #3 enter the treatment delivered after the gap, ie 18.9 Gy delivered in 7 fractions of 270 cGy.
- Mark course #3 as included.

- In the IMR Calendar window select course #2.
- Set course #2 to start on the same day as course #1.
- Set Tx days/week for course #2 to 5 and enable Tx days M to F.
- In the IMR Calendar window select course #3.
- Set Tx days/week for course #3 to 6 and enable Tx days M to S.
- Set course #3 to start on the Wednesday (e.g. Mar. 4th) following the gap.
- Mark 3 days as skipped (shift-click) such that the last fraction is delivered on the 38th day after the first fraction (e.g. Saturday Mar. 14th) for a total of 39 treatment days (the total days are shown in the # days column of the IMR table in the main plan window).

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 BED_{10} with an intermediate value 65.0 Gy_{10} requires a dose per fraction (d) which is obtained from: BED_{10} (pre-gap) + BED_{10} (post-gap) – tumour repopulation factor = required BED_{10} of 65.0 Gy_{10}, ie: d = 3.19 Gy per fraction. Use of this fraction size for the deferred seven treatments would increase the normal tissue BED_{3} to: BED_{3} (pre-gap) + BED_{3} (post-gap) = 112.8Gy_{3}. This is still 10% more than that prescribed, even though the tumour BED_{10} has been deliberately compromised.

- In the TDF Plan window select course #3.
- Set reactions to
**Acute**. - Adjust the
**Rx fraction**of course #3 to achieve and acute BED for the combined courses 2 and 3 of about 65 Gy_{10}. An approximate solution is 319 cGy.