plan evaluation for lung cancer radiotherapy

1. Plan evaluation: Lung Cancers
Dr. Ashutosh Mukherji
Additional Professor,
Department of Radiotherapy,
Regional Cancer Centre,
and Associate Dean (Research), JIPMER

2. Target Volumes
• Radiotherapy alone affords intrathoracic control in
up to 50% of NSCLC cases, provided a total dose > 60
Gy is employed
• For many years, standard RT practice was:
– 40 to 50 Gy to the electively irradiated regional-nodal
areas
– Additional 10-20 Gy delivered to the primary tumor
through reduced fields.

3. Lung cancer radiotherapy
• RT for lung cancer getting increasingly sophisticated
• Usually addition of concurrent chemotherapy in
radical treatment of locally advanced tumours
• Side effects tend to increase with poor lung function
patients and addition of chemotherapy.
• Need to identify parameters to preempt / reduce
toxicity
• V 20 and V 5 are two such parameters

4. RT-Planning – Definition of Target Volumes
ICRU 50 + 62
Gross Tumour Volume
Clinical Target Volume
Planning Target Volume
CT: standard imaging modality
Complementary information by MRI and PET scanning
Limiting factors of CT imaging for lung cancer:
-planning-CT without intravenous contrast so as not to
disturb
the electron density information
interpretation always in conjunction with diagnostic CT
-not routinely possible to distinguish T3 – T4
(MRI some advantages)
-MRI used for imaging apical primary tumours
(Pancoast)
-Sensitivity / specificity only 60 / 77% for LN
knowledge of normal anatomy (LN levels, hilar anatomy) !
knowledge of patterns of lymphatic drainage

5. RT-Planning – Defining the GTV
Integrating PET
Value of PET for PT:
Atelectasis – reduction of
irradiated volume
Value of PET for LN staging:
Sensitivity 79%
Specificity 91%
Negative predictive value 95%
Positive predictive value 80%
(hot spots still require
verification)
Value of PET for Metastases:
metastases detected in10-15%
of surgical candidates
Impact of PET on RT planning
PTV increased in 64% (detected
nodes)
decreased in 36% (exclusion of
atelectasis)
(Erdi 2002)
Average reduction of PTV by 29%
Average reduction of V20 by 27%
(Vanuytsel 2000)
Interobserver variability reduced:
mean ratio of GTV without PET:
2.31
mean ratio of GTV with PET:
1.56
(Caldwell 2001)

6. RT-Planning –
Defining the GTV
Impact of PET: PTV

7. RT-Planning – Defining the GTV
Limiting factors of PET
-Resolution 4-8mm (depending on scanner and institution)
-Registration errors (esp. with software based fusion)
-Threshold value (SUV) individually to be determined
Summary:
PET is a promising complementary tool in RT planning of NSCLC.
Its value for staging has been established and preliminary
reports suggest that it may lead to more consistent definition of
GTV in RT planning. However, it is still not clear, whether this will
translate into better survival.

8. RT-Planning – Defining the CTV
1. Margin around primary tumour (microscopic spread)
Histopathologic quantification of subclinical cancer around the grossly visible primary
(Giraud 2000):
Microscopic extension Adeno Squamos
mean value 2.69mm 1.48mm
5mm margin covers: 80% 91%
margin to cover 95% 8mm 6mm
This data could also be used for IMRT planning:
-define constraint for GTV (dose escalation to primary)
-define constraint for subclinical disease (less dose)
-increase therapeutic index

9. RT-Planning – Defining the CTV
2. Subclinical lymph nodes (ENI)
-high risk of nodal spread in lung cancer
-but value of ENI is not proven
Reasons against ENI:
-less than 20% locally controlled 1y after RT with conventional
dose (Arriagada 1991)
-need for more intense treatment to gross tumour
-large volumes prevent dose escalation (normal tissue tolerance)
-small primary tumor and small total tumor volume predictive
(Basaki 2006, RTOG 93-11 2008)
-modern chemotherapy regimens may lead to better control of
microscopic disease

10. ?? Elective Nodal Irradiation ??
• The rationale against elective nodal irradiation
is the high local recurrence rates and the high
chance of distant metastasis.
• A series of 171 patients treated definitively
with 3DCRT to only involved field volumes.
• 6.4% of patients suffered elective nodal
failures

11. Why the less than expected nodal
recurrence?
• Incidental doses to the ipsilateral hilum,
paratracheal, and subcarinal nodes approach
40 to 50 Gy
• Patients may die of local failure, distant
failure, or intercurrent illness without
detection of elective nodal failures.

12. RT-Planning – Defining the CTV
2. Subclinical lymph nodes (ENI)
From large ....
“Old“ Standard … (Perez 1997)

13. RT-Planning – Defining the CTV
2. Subclinical lymph nodes (ENI)
.... to small !
…“New“ Trend (IMRT 2007)

14. RT-Planning – Defining the PTV
ICRU recommendations
CTV ...
+ Internal Margin (Internal Target Volume)
variations in position, size and shape of CTV
(internal reference system
attached to the patient)
+ Set-up Margin
variations in relation patient - beam
(external reference system
attached to machine)

15. RT-Planning – Defining the PTV
Reducing set-up uncertainty:
-Daily EPID: -matching DRR - EPI
-distinguish between systematic (needs correction)
and random error (no correction needed)

16. RT-Planning – Defining the PTV
Reducing respiration induced
errors:
Size of movement dependent on:
- tumour location in the lung
- fixation to adjacent structures
- lung capacity and oxygenation
- patient fixation and anxiety
Steppenwoolde 2004
Reducing respiration induced errors:
-Breath - hold
-Voluntary (Deep Inspiration Breath Hold)
-Forced (Active Breathing Control)
-CT scanning
-Slow scanning
-Respiration correlated CT
-Gating
Average movement in normal breathing:
- Upper lobe 0 - 0.5cm
- Lower lobe 1.5 - 4.0cm
- Middle lobe 0.5 - 2.5cm
- Hilum 1.0 - 1.5cm

17. RT-Planning – Defining the PTV
Reducing respiration induced errors:
Gated CT normally
reduces the margin
PTV - CTV
(compared to using
published data):

18. RT-Planning – Defining the PTV
Drawing PTV in gated planning CT:
-Define GTV/CTV for inspiration and expiration phase
-Give a margin of 0.5 - 1cm in all directions (setup uncertainty)
DON’T use dose escalation and highly conformal techniques
such as IMRT for lung cancer until tumour motion can be taken
into account !
In the meantime ...
-Outline GTV as best as possible
-Construct CTV based on the literature
-Construct PTV based on measured tumour motion and known
setup uncertainty.

19. ERS 2009
19
The risk of developing radiation pneumonitis-induced
lung toxicity can be estimated by calculating the dose–
volume histogram of the lungs, including V20 and mean
lung dose (MLD)

20. V 20
“V20”
Percentage of the lung volume which receives
radiation doses of 20 Gy or more.
(with subtraction of the vol involved by lung cancer
- PTV)
The risk for radiation pneumonitis depends on V20
V20 = 22% risk for radiation pneumonitis is nearly zero.
V 20 = 33% radiation induced pneumonitis is 10 -15%
V20 of 35%, 40% - radiation pneumonitis nearly 50%.

21. PhaseI/II
Stage 1-3
unresectable
3DCRT, 2.15Gy fr
Group1
V20Gy<25%:
70.9Gy/33frs to
90.3Gy/42frs
Group2
V20Gy – 25-36%:
70.9Gy/33frs to
77.4Gy/36frs
Group 3:
V20>37%
Closed early
RTOG 9311: Trial Schema
179 pts

22. RTOG 9311 : Conclusions
• RT dose was safely escalated using the 3D CRT
• 83.8 Gy for pts with V20 values of <25% Grp I,
• 77.4 Gy for pts with V20 values 25% - 36% Grp 2,
• The 90.3 Gy dose was too toxic (deaths 2 pts)
• Using fraction size of 2.15 Gy.
• Elective nodal failure occurred in <10 pts
Jafrey Badley IJRBP vol 61, No 2, 318-328, 2005

23. Volumes while contouring lung as
OAR
• Need to select the optimal CT window settings
(Lung window)
• W = 1600 and C=-600 for parenchyma
• Contour each lung separately
• Contour GTV, CTV and PTV
• Using Boolean function , generate lung OAR
• Lung OAR= (Left lung + Right Lung) - PTV

24. Dose/Volume constraints
Kong et al, IJROBP, 2010

25. Basic Definitions
• V 20 = Volume of (B/L lung – PTV) receiving 20 Gray OR MORE
Total volume of B/L Lung – PTV
(represents intermediate dose area)
• V 5 = Volume of (B/L lung – PTV) receiving 5 Gray OR MORE
Total volume of B/L Lung – PTV
(represents low dose area)
Normal tissue constraints for Lung
V 20 <35%
V 5 < 60%

26. V 5
• Represents area of lung receiving low /very low dose
RT
• Gained in importance in IMRT era
• Especially important in techniques such as VMAT and
Tomotherapy which give rotational therapies
• Another way to emphasising that low dose areas
with IMRT are as equally important.

27. 27
V5

28. 28
V5 opposite lung
V5 treated lung

29. Seminal Publication – V 20
Graham MV, Purdy JA, Emami B, et al. Clinical dose-
volume histogram analysis for pneumonitis after 3D
treatment for non-smallcell lung cancer (NSCLC).
Int J Radiat Oncol Biol Phys 1999;45:323-329.

30. 30
V20

31. 31
V20 opposite lung
V20 treated lung

32. Elevated V 20 and V 5
• Truly elevated V 20 and V 5
– Large PTV
– Poor planning
• Spurious elevation of V 20 and V 5
– Lung not contoured properly (portions left out)
– Incorrect window used
– PTV not subtracted out from bilateral lungs

33. Means to reduce V 20 (3D CRT)
– Need to have a good measure of tumour location and
likely volumes
– Lower lobe tumours likely to have worse dosimetric
parameters
– Need to place appropriate beams(beam angles, number)
– Special arrangements in specific tumour positions

34. Means to reduce V 20
• Use IMRT instead of 3 DCRT in appropriate cases
• Use of advanced strategies like gating/tracking/breath
hold (it shall decrease the PTV and thereby decrease the
zone that get 20 Gray)
• Use of ABC device
– PTV smaller
– Simulation and treatment in inspiratory position
– Lungs inflated
– Lung volume increases and hence denominator more, V 20
falls

36. • 41 patients of NSCLC
• 3 D CRT and IMRT plans(9 F, equidistant, coplanar, generated)
• Target, isocentre and prescription same as 3 D CRT
Murshed, IJROBP, 2003V 10 and V20 reduced by 7% and 10% respectively

37. IGRT- 4 D aspects
• Further ensuring the Planned dose and the treatment dose similarity
• Removal of motion encompassing margins may reduce normal tissue dose
• Reduction in normal tissue dose may facilitate tumour dose escalation
• Higher doses delivered to the tumour could result in an improved cure
rate
Individualised
Motion Margin
Setup &
Equipment Margins
Clinical Target
Volume
Planning Target Volume
Residual Error
Margins
Clinical Target
Volume
Target tracking Treatments

38. Conventional With gated imaging
Effect of Gated/4 D imaging
Tumor
Keall et al Aust Phys Eng Sci Med 2002

39. ABC
• Device holds the patients breath in a
particular phase of respiration
• Usually the mDIBH level chosen – 70%to
80% of maximum inspiratory capacity
• Suitable breath hold duration chosen –
commonly 20 to 25 seconds

40. ABC
• CT scan acquired (approx two breath
holds required to scan the thorax/breast
area)
• Treatment planning and
execution(4-6 breath holds per
treatment)

41. ABC outcomes
• 18 NSCLC patients from RMH , UK
• Mean reduction in GTV 25% (p= 0.003).
• Compared with free-breathing, ABC reduced
• V(20) by 13% (p=0.0001)
• V(13) by 12% (p=0.001)
• MLD by 13% (p<0.001)
Brada et al IJROBP 2010

42. Outcomes of Respiratory Gating
• Twenty patients with CT under assisted breath
hold at normal inspiration, at full expiration
and under free breathing
• 13 of 20 patients had GTVs of <100 cm3
• Benefit of V20 reduction only with small
tumours (volume of GTV < 100 cm3) and
significant tumour motion
Starkschall IJROBP 2004

43. Caution!
• V20 and V5 could vary from one planning workstation to
another
• Different algorithms may yield variable V 20 and V 5
(Batho, Monte Carlo algorithm)
• Algorithms can be especially important as there is
variation in lung density.
• Algorithms derived directly from Monte Carlo, such as
superposition-convolution and collapsed cone far
superior to algorithms of the past (e.g. the one used in
seminal publication)

44. Drawbacks of V 20/ V 5
• DVH represents anatomic pulmonary volume, which
does not reflect a variety of confounding factors.
• Not a functional parameter (does not take into
account lung function)
• Several other factors important in radiation
pneumonitis and need to be accounted
(PS,concurrent chemo, smoking, age, ….)

45. 45
V30 opposite lung
V30 treated lung

46. 46
Global Dmax location
Target volume Dmax
location
Vdmax

47. QA…… Fluence analyses showed
most planned cases treatable
with ≥ 95% fidelity
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48. Summary / Conclusions
• V 5 and V 20 are important parameters to see and
evaluate during radical radiotherapy of lung cancer
• V30 and VDmax also need to be seen.
• For IMRT plans PTV cover and contouring should take
into account tumour movement
• Be cognizant of the pitfalls of these parameters as
well
• See totality of patient / tumour / dosimetric
parameters and not one or two factors in isolation

49. Summary planning Recommendations - EORTC
• 3-D radiotherapy planning is essential for ensuring optimal both
target coverage and the sparing of normal tissues.
• 3D margins for the PTV based on institutional random and
systematic errors and tumour movement
• Margins required for microscopic tumour extension in
radiotherapy planning of NSCLC are approximately 5-6 mm.
• Risk of radiation pneumonitis can be estimated from the V20
(volume of both lungs minus the PTV which receives a dose of 20
Gy), and by the mean lung dose.
• Incorporating FDG-PET findings into CT-based planning scan
results in changes to radiotherapy plans in a significant proportion
of patients.
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51. THANK YOU
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