A review of guidance on compensatory steps to take due to unscheduled interruptions in patient radiotherapy treatment, due to patient illness, staff illness or machine breakdown. Interruptions are quite often. Different centres in different literature have quoted from 6 up to 63% of patients experience interruption. To reduce the risk of cancer recurrence, the Medical Physicist needs to calculate and determine compensatory action in dose, number of fraction or other action required.

1. MIND THE GAP:
Dealing with Interruptions in Radiotherapy Treatment
Victor EKPO
Medical Physicist
ASI Ukpo Cancer Centre, Nigeria
May 2022

2. INTRODUCTION
Cancer cells can grow and repopulate between unscheduled gaps in
treatment.
Scheduled gaps in radiotherapy are mainly weekend breaks, which
are considered to compensate for normal tissues and tumour.
Unscheduled gaps in radiotherapy allow repopulation of cancer cells
to accelerate, increase risk of local recurrence, leading to potentially
lower cure rates. 2

3. GOOD CLINICAL PRACTICE
✘ Good clinical practice dictates that radical
courses of RT should not be interrupted.
✘ However, where interruptions are
unavoidable, compensatory treatment is
required.
3

4. MACKILLOP’S
ASARA PRINCIPLE
Interruptions should be kept
“as short as reasonably achievable”.
*

5. STATEMENT OF PURPOSE
✘ Identify categories of patients most at risk of loss of
tumour control due to unscheduled interruptions.
✘ Identify causes of interruptions.
✘ Identify how to prevent interruptions.
✘ Identify ways to manage unavoidable interruptions.
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6. DAY OF WEEK OF INTERRUPTION
✘ Interruption on a Monday or Friday, which lengthens the
weekend break by 33%, has a more serious adverse affect
than an interruption midweek. (R. Tarnawski, et al., 2002).
✘ The longer a gap, the more damaging the effect.
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7. DEFINITIONS
✘ Hypofractionation: The use of a lower number of fractions, with
dose fractions substantially larger than the conventional 2 Gy per
fraction.
✘ Hyperfractionation: The use of a high number of fractions, with dose
fractions smaller than the conventional 1.8–2 Gy per fraction, usually
delivered more than once a day.
✘ Twice-daily fractionation: 2 fractions of 1.8-2 Gy delivered same day,
with 6-hr gap, pref. with only 1 fraction given next and prev. days.
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8. “
Radiotherapy must eradicate
every tumour stem cell plus
any additional stem cell
generated during the course
of treatment, to achieve cure
of patient.
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GOAL OF RADIOTHERAPY

9. GUIDANCE DOCUMENTS
✘ The Royal College of Radiologists (RCR) UK produces guidelines for
management of treatment gaps.
✘ First, in 1996, then in 2001, 2008 and 2019.
✘ The 2008 document is key. In 2019, it is revised to include
specifications for breast, anal, lung cancers, Stereotactic Ablative
Radiotherapy (SABR), Proton Beam Therapy.
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10. PATIENT CATEGORIZATION
Category 1
Rapidly growing
tumours, such as
squamous carcinomas
of H&N and anus,
treated with radical
intent.
Interruption should
not exceed 2
treatment days.
Category 2
Slower growing
tumours, e.g.
adenocarcinomas,
treated with radical
intent. e.g. breast,
prostate, bladder.
Interruption should
not exceed 5
treatment days.
Category 3
Pt. treated with
palliative intent.
Interruption should
not exceed 7
treatment days.
10

11. 63%
of H & N patients*
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HOW OFTEN ARE INTERRUPTIONS?
*values from RCR UK, 2005

12. MANAGEMENT OF
INTERRUPTIONS
Machine breakdown, staff or patient illness
*

13. POSSIBLE MEASURES TO TAKE (1)
✘ Transfer all patients to another matched linear accelerator on
day of interruption, if possible.
✘ Institute facility that allow pt. who missed scheduled
weekday treatments can be treated on weekends.
✘ Patients can be treated twice daily, with minimum of six hours
between therapies. Only recommended for Frac. Dose < 2.2Gy.
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14. POSSIBLE MEASURES TO TAKE (2)
✘ Use of biologically equivalent dose (BED) calculations to
derive alternative schedule, with modified number of fractions,
in the planned overall time, but perhaps accepting higher BED
in normal tissues.
✘ Addition of extra treatment fractions where compensation
cannot be achieved within the original overall planned time.
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15. THE BED METHODS
15

16. THE BED METHODS (contd.)
16

17. THE BED METHODS (contd.2)
17

18. CALCULATION PROCESS
OPTIONS 3A
1. Twice-daily fractionation
2. Hyperfractionation
3. Increased fraction size
(Hypofractionation)
4. Weekend Treatment
STEPS (A)
1. Calculate prescribed tumour control
BED10 and normal tissue BED3
2. Determine remaining treatment
time and remaining fractions.
3. Determine if there are ways of
delivering treatment fractions which
will allow the original prescribed
treatment time to be maintained,
e.g. by treating weekends or twice
daily..
If Step 3A is possible, then radiobiological compensation should not be necessary.
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19. CALCULATION PROCESS
19
RADIOBIOLOGICAL COMPENSATION
1. Calculate Normal Tissue BED3
Makes use of dose actually received
by critical normal tissue, if different
from prescribed tumour dose.
2. Determine respective pre-gap
normal tissue BED, using Eq. A
3. Difference between (1) and (2)
determines post-gap BED (late-
normal BED) yet to be given.
N = number of well-spaced fractions given
d = fractional dose
α/β = 3 Gy (except spinal cord = 2 Gy)

20. CALCULATION PROCESS
20
RADIOBIOLOGICAL COMPENSATION
4. Review options in 3A
5. Calculate associated tumour BED10
in Eq. B
6. Review final tumour and normal
tissue BEDs for preferred
compensation technique.
7. If tumour BED is significantly less
than originally prescribed, clinical
judgment will be necessary.
N = total number of fractions prescribed
d = fractional dose
T = overall treatment time in calendar days
Tdelay = time elapsed from onset before the onset of
repopulation, usually 28 days
K = daily BED equivalent of repopulation, usually 0.9
α/β = 10 Gy for tumours

21. 21

22. EXAMPLE 1 – 5 MISSED DAYS IN 3RD WEEK
Head and Neck Cancer with 70 Gy delivered in 35 fractions over 46 days (? should be 47)
Patient missed entire 3rd week of treatment (5 fractions).
10 fractions have been delivered. 25 fractions remains to be given. 5 fractions missed.
If patient is to finish on prescribed finishing date, the number of calendar days remaining is 26.
SOLUTIONS
1. To finish on end date, patient can take 20 fractions weekdays, and 5 fractions in some weekends in between.
2. If weekend treatments are not possible, on 5 days, patient can take two fractions.
Days should NOT be consecutive days, but spaced throughout. Fridays are good days for some.
Not recommended for patients with big fractional dose (>> 2 Gy).
22

23. EXAMPLE 2 – 5 MISSED DAYS IN 6TH WEEK
Head and Neck Cancer with 70 Gy delivered in 35 fractions over 46 days (? should be 47)
Patient missed entire 6th week of treatment (5 fractions).
25 fractions have been delivered. 10 fractions remains to be given. 5 fractions missed.
If patient is to finish on prescribed finishing date, the number of calendar days remaining is 7.
SOLUTIONS
1. To finish on end date, patient can take twice-daily fractions (min. 6hrs apart) on each of the
remaining 5 days.
2. Use weekend before final week (making 7/10 fractions). 3 remaining days can have twice-daily
fractions (preferably spaced days – e.g. Monday, Wednesday, Friday).
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24. EXAMPLE 3 – 5 MISSED DAYS IN 7TH WEEK
Head and Neck Cancer with 70 Gy delivered in 35 fractions over 46 days (? should be 47)
Patient missed entire 7th week of treatment (5 fractions).
30 fractions have been delivered. 5 fractions remains to be given.
If patient is to finish on prescribed finishing date, the number of calendar days remaining is 0.
SOLUTIONS
Patient’s treatment has been extended inevitably. Calculate BEDs.
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25. EXAMPLE 3 – 5 MISSED DAYS IN 7TH WEEK
25
The allowable BED left to give = 116.7 – 100 = 16.7 Gy3

26. EXAMPLE 3 – 5 MISSED DAYS IN 7TH WEEK
26
Assuming only 5 calendar days are missed, not 7 (incl. weekends), then T = 46+5 = 51. Therefore:
d = 2.62 Gy over 5 fractions, Saturday to Wednesday
This is 6.7% excess in normal BED3.

27. EXAMPLE 4 – 10 MISSED TREATMENTS IN
6TH AND 7TH WEEK
27
35 fractions of 2 Gy each were prescribed.
25 fractions of 2Gy each were given. Last 10 fractions interrupted / yet to be given
Prescribed no. of fractions = 35
Prescribed dose per fraction in Gy = 2
α/β = 3 for normal tissue
α/β = 10 for tumour
Total number of prescribed treatment calendar days = 46
Number of fractions delivered before gap = 25
Total number of treatment calendar days due to gap = 60
Solution
Total being 60 assumes the remaining 10 fractions are given once a day Monday - Friday

28. EXAMPLE 4 – 10 MISSED TREATMENTS IN 6TH & 7TH WEEK
28
BED10 (pre-gap) + BED10 (post-gap) – tumour repopulation factor = prescribed BED10
Solution 1 – Maintaining tumour BED10
To maintain prescribed tumour BED10,
25 x 2 x (1 + 2/10) + 10 x d x (1 + d/10) – (60-28) x 0.9 = 67.8 Gy10
50 x 1.2 + 10d (1 + d/10) – 28.8 = 67.8
60 + 10d + d2 – 28.8 = 67.8
d2 + 10d + 60 – 28.8 – 67.8 = 0
d2 + 10d - 36.6 = 0
d = 2.85 Gy
Solving as a quadratic equation
a = 1, b = 10 , c = -36.6
𝑥 =
−𝑏± 𝑏2−4𝑎𝑐
2𝑎
x = 2.85 or -12.84

29. EXAMPLE 4 – 10 MISSED TREATMENTS IN 6TH & 7TH WEEK
29
New BED3 = BED3 (pre-gap) + BED3 (post-gap)
To confirm if new calculated dose (2.85 Gy) to maintain tumour BED10 is okay for normal tissue BED3,
New BED3 = 25 x 2 x (1 + 2/3) + 10 x 2.85 ( 1 + 2.85/3)
= 83.5 + 55.58
= 139.08 Gy3
% diff in BED3 = Diff in BED3 / Prescribed BED3
= (139.08 – 116.75) / 116.75
= 19%
This 19% increase in normal tissue BED is higher than the recomm. 3%
2.85 Gy maintains the tumour BED but increases
toxicity/BED3 to normal tissues by 19%

30. EXAMPLE 4 – 10 MISSED TREATMENTS IN 6TH & 7TH WEEK
30
Prescribed BED3 = BED3 (pre-gap) + BED3 (post-gap)
Solution 2 – Maintaining normal tissue BED3
To maintain prescribed late-normal tissue BED3,
116.7 Gy3 = 25 x 2 x (1 + 2/3) + 10 x d (1 + d/3)
116.7 = 83.5 + 10 d (1 + d /3)
116.7 = 83.5 + 10d + 3.33 d2
3.33d2 + 10d – 33.2 = 0
d2 + 3d - 10 = 0
d = 2 Gy
Solved as a quadratic equation
a = 1, b = 3 , c = -10
𝑥 =
−𝑏± 𝑏2−4𝑎𝑐
2𝑎
x = 2 or -5

31. EXAMPLE 4 – 10 MISSED TREATMENTS IN 6TH & 7TH WEEK
31
New BED10 = BED10 (pre-gap) + BED10 (post-gap) – repopulation factor
To confirm effect of new calculated dose (2 Gy) to tumour BED10,
New BED10 = 25 x 2 x (1 + 2/10) + 10 x 2 x ( 1 + 2/10) – (60 – 28) x 0.9
= 60 + 24 – 28.8
= 55.2 Gy10
% diff in BED10 = Diff in BED10 / Prescribed BED10
= (55.2 – 67.8) / 67.8
= -18.58%
This 18.58 % decrease in tumour BED10 is lower than the recomm. +/-3%,
2 Gy maintains the late-normal tissue BED but compromises tumour control / BED10 by 18.58%
2.85 Gy maintains the tumour BED but compromises late-normal tissue tissue /BED3 by 19%

32. EXAMPLE 4 – 10 MISSED TREATMENTS IN 6TH & 7TH WEEK
32
New BED10 = BED10 (pre-gap) + BED10 (post-gap) – tumour repopulation factor
Solution 3 – Finding an intermediate dose
Choose fractional dose 2.4 Gy for remaining 10 fractions once a day
New BED3 = BED3 (pre-gap) + BED3 (post-gap)
New BED3 = 25 x 2 x (1 + 2/3) + 10 x 2.4 (1 + 2.4/3)
New BED3 = 83.5 + 43.2 = 126.7 Gy3. (A 8.57% increase on prescribed BED3 of 116.7 Gy3 )
New BED10 = 25 x 2 x (1 + 2/10) + 10 x 2.4 (1 + 2.4/10) – (60-28) x 0.9
New BED3 = 60 + 29.76 - 28.8 = 60.96 Gy3. (A 10% decrease on prescribed BED10 of 67.8 Gy3 )

33. COMPARING DIFFERENT DOSES
Fractional Dose
(Gy)
Normal Tissue
(BED3)
BED3
(+/-)
Tumour Control
(BED10)
BED10 (+/-)
Prescription (without
interruptions)
2.0 Gy 116.7 - 67.8 -
Maintaining Tumour
Control
2.85 Gy 139.08 +19% 67.8 0%
Maintaining Late Normal
Tissue BED
2.0 Gy 116.7 0% 55.2 -19%
Finding a Middle Ground 2.4 Gy 126.7 +9% 60.96 -10%
Reducing no. of calendar
days (10 fractions in 7
treatment days)
2.67 Gy
(calculated from
BED10)
133.96 +15% 67.8 0%
Twice-daily fractionation
(T = 53 days, 10 fractions,
5 treatment days)
2.2 Gy
(chosen/max
allowed for b.d.f.)
121.63 +4% 64.34 -5%
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34. An online engine for
BED calculation and
treatment gap
compensation.
www.radiobiology.org/bed1c.asp

35. RECOMMENDATIONS
✘ If gaps occur, first consider post gap acceleration using twice-daily
fractionation (frac. Dose ≤ 2.2 Gy) to reduce treatment time.
✘ Try different intermediate values of fractional dose, and compare
normal tissue BED3 and total tumour BED10 to get as close to +/- 3%.
✘ Use of hypofractionating treatment after the gap is not necessarily
the best option.
✘ Restrict use of excessive fraction size.
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36. OTHER NOTES
✘ Accelerated repopulation starts at 28 days. If a treatment + gap does
not exceed 28 calendar days, no radiobiology corrections may be
required.
✘ If there had been tumour shrinkage, the oncologist should consider
reducing field size during gap compensation.
✘ Cure is always achieved at some cost in terms of normal tissue
damage. The risk of not giving adequate dose to the PTV may be
greater than the risk of normal tissue damage.
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37. REFERENCES
The Royal College of Radiologists. Ref No BFCO (19) 1. The timely delivery of radical radiotherapy:
guidelines for the management of the unscheduled interruption, fourth edition. London: The Royal
College of Radiologists, 2019.
Dale RG, Hendry JH, Jones B et al. Practical methods for compensating for missed treatment days in
radiotherapy, with particular reference to head and neck schedules. Clin Oncol (R Coll Radiol) 2002;
14(5): 382-393.
Fenwick JD, Faivre-Finn C, Franks KN, et al. Managing treatment gaps in radiotherapy of lung cancer
during the COVID-19 pandemic. London: The Royal College of Radiologists, 2020.
Barrett A, Dobbs J, Morris S, et al. Practical Radiotherapy Planning. 4th ed. London: Hodder Arnold.
2009.
Radiobiology Treatment Gap Compensation. http://www.radiobiology.org/bed1c.asp. Last accessed:
May 27, 2022
Hall EJ, Giaccia AJ. (2012) Radiobiology for the Radiologist. 7th ed. Philadelphia: LWW.
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38. THANKS!
Any questions?
You can find me at:
⬢ about.me/overjoy
⬢ ekpovictortoday@gmail.com
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