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Dosimetric Analysis of 3DCRT or IMRT with Vaginal-cuff Brachytherapy (VCB) for Gynaecological Cancer

Tan Chek Wee15 06 2016National University Cancer Institute, Singapore

Singapore

• Located at the southern tip of Peninsular Malaysia

• Population of 5.4 millions

• Total land area of 704 square km (278 square miles)

• Temperature ranges from 28C to 32C (82.5- 86 F)

• Multi-racial and culture country

• Consisting of 4 main ethic groups

• Celebrated 50years of independence last year

Public General Hospitals and National Specialist Centres

“Shaping Medicine for the Future”

National University Cancer Institute, Singapore

• 19-storey building• Radiotherapy Department

located on the 8th Floor• 6 bunkers• 3 Synergy Elekta Linear

Accelarator, Mosaiq, 5 Monaco and 4 Xio TPS

“The research aims to analyse the dosimetric impact of

combined brachytherapy with intensity modulated

radiation therapy (IMRT) or 3 dimensional conformal

radiotherapy (3DCRT) in terms of planned target volume

(PTV) coverage especially the vaginal vault PTV region

and dose to surrounding organs at risk (OARs).”

Content

• Introduction• Material and Methods• Result• Discussion• Conclusion

2. Divider•Introducing new topic Introduction

Introduction

• Radiotherapy for gynaecological cancers is oftendelivered by a combination of brachytherapy andexternal beam irradiation.

• Brachytherapy is used to deliver high doses ofradiation to the primary tumour region where asexternal beam irradiation covers the wholepelvic region.

Complications!

Rectovaginal fistula

Thickening of small bowel wall

IMRT

• Use of intensity modulated radiation therapy (IMRT) hasbeen shown to have advantages in improving targetcoverage and sparing of organs at risks (OARs) whencompared with conventional radiotherapy.

• Allow for better conformity of the high dose region toirregular target volumes as the steep dose gradientcreated can better spare surrounding OARs

• Multiple dose level delivery at one time

Concerns on the use of IMRT for

Gynaecological Cancer

Internal Organ Motion and volume changes during treatment

Tumour Regression

Hot spot in adjacent normal tissue

Concerns on the use of IMRT for gynaecological cancers

Target volume delineation

Improvement in Imaging and Treatment Technology

• Availability of MRI scan for RT planning, cone beam computed tomography (CBCT) an other online monitoring and dose tracking system

IMRT for Gynaecological Cancer

• Consensus Guidelines for Delineation of Clinical Target Volume for IMRT Pelvic Radiotherapy for the Definitive Treatment of Cervix Cancer.

• Results from RTOG 0418 which is a Phase II study designed to determine the transportability of pelvic IMRT to a multi-institutional setting

• RTOG 1203- Randomized Phase III Study Of Standard Vs. IMRT Pelvic Radiation For Post-Operative Treatment Of Endometrial And Cervical Cancer

• Group European de Curie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) guidelines for target volumes delineation and OARS delineation

4. Divider•Introducing new topic 2. Material and Method

Material and Methods

• 21 post operative patients who were previously treated with 3DCRTand brachytherapy were retrospectively planned using IMRT

• Patients underwent CT simulation with full bladder on a Philips BigBore CT scanner in the supine position acquired with 5mm CT slices

• External beam dose given was 50.4Gy in 28 fractions followed bysingle channel brachytherapy of 10Gy at 5mm depth in 2 fractions.

• Plans were reviewed together with imaged-based 3D brachytherapyplans to assess combined dose distribution

Treatment Planning

• Patients were retrospectively planned using IMRT to a total dose of50.4Gy in 28 fraction based on RTOG 1203 planning guidelines

• IMRT was planned using 7 coplanar beams using either 6MV or 10MV dynamic modulated radiotherapy (DMLC) technique on Monacotreatment planning system version 3.2.

• 3DCRT planning was performed using Xio Treatment PlanningSystem version 4.2 with either 6MV or 10MV photon to generate afour-field box technique to cover the whole pelvis.

Constraints used for IMRT planningPTV coverage 97% of PTV received 100% of the dose

0.03cc of any volume within PTV should not receive more than 110%no volume within the PTV that is 0.03cc or larger should receive < 93% of the prescribed dose

Rectum D100%< 40GyBladder D70% < 45GYSmall Bowel D70% < 40GyPelvic Bone D90%< 25GY

D60%<40Gy

**planning objectives used were based on the radiation therapy oncology group (RTOG) 1203 protocol

Contouring

• Accuracy and consistency in the contouring of planning targetvolume (PTV) and organs at risk (OARs) are important in ensuringreliability and generalizability of the planning data

• Delineation of the PTV and OARs for IMRT planning were based onthe Radiation Therapy Oncology Group (RTOG) 1203 Protocol andGYN GEC ESTRO guidelines for 3D brachytherapy

• Study only had one consultant radiation oncologist (RO) to delineatethe PTV and OARs and another consultant RO to verify to avoidintroducing inter-observable variabilities in the study

Evaluation

• Quantitative evaluation of the plans was performed by the use of standard dose-volume histogram (DVH).

• Analysis for IMRT vs 3DCRT includes D97% (dose received by the 97% of the volume), maximum dose at 0.03cc, conformity index (CI) and the dose for bladder, rectum, small bowel and pelvic bones.

• Analysis of IMRT + Brachytherapy vs 3DCRT + Brachytherapy includes D100 and D90 for PTV coverage and maximum dose expressed as D2cc and D1cc for OARs such as bladder, rectum and sigmoid.

IMRT 3DCRTPTV Nodes Max Dose PTV vault Bladder Rectum Small Bowel PTV node Max Dose PTV Vault Bladder Rectum Small Bowel

97% coverage in % 97% coverage 45Gy< 70% 45Gy<100% 40Gy<70% 97% coverage in % 97% coverage 45<70% 45Gy<100% 40Gy<70%

T1 50.54 112.00 51.02 46.3 72.6 35.3 T1 48.59 106.7 46.86 99.7 100 46.3

T2 50.46 113.70 51.29 48 57.9 26.3 T2 48.99 106 48.87 98 96.7 50.5

T3 50.48 113.50 50.93 57.7 76.5 22.4 T3 49.52 109.5 47.91 99.4 97.3 35.3

T4 50.45 114.30 50.92 34.9 74.4 19.8 T4 49.67 106.8 49.67 100 89.7 27.5

T5 50.44 113.70 50.82 67.3 70.6 17.6 T5 47.76 106.7 48.72 100 99.6 26.6

T6 50.46 114.20 51.36 29.3 68.5 26.3 T6 46.35 105 49.73 75.5 100 28.4

T7 50.45 112.70 51.58 66.8 63.5 13.8 T7 46.64 104 49.1 99.3 97.1 16.7

T8 50.64 112.00 51.14 40.7 76 18.7 T8 48.54 105.5 48.54 91.8 77.9 24

T9 50.47 112.20 51.42 18.5 52.1 26.7 T9 48.78 106.5 47.27 88.5 99.6 34.3

T10 50.45 113.00 50.72 26.4 75.4 21.3 T10 47.58 104.7 47.98 80.4 100 45.9

T11 50.48 113.80 50.53 35.2 68.7 27.7 T11 47.48 103.9 47.89 98 98.2 35.5

T12 51.11 113.90 50.80 48.9 65.1 13.4 T12 46.47 105.4 49.69 99.7 98.9 13.8

T13 50.43 111.80 51.26 29.6 75.8 28.1 T13 49.59 107.2 47.97 98.7 98.7 39.6

T14 50.46 113.80 51.27 33.3 97.7 28.4 T14 49.49 105.8 46.78 97.1 92.7 34

T15 50.42 114.90 50.73 37.2 76.7 15.4 T15 49.17 105.5 48.89 100 85.1 22.4

T16 50.46 112.80 51.09 46.8 76.4 31.6 T16 49.49 106.3 48.65 100 100 36.5

T17 50.46 114.00 51.35 32.8 86.4 31.3 T17 49.18 102.3 49.05 100 100 44.7

T18 50.59 112.50 50.99 34.1 70.8 27.7 T18 49.51 107.2 47.95 98.7 100 40

T19 50.48 112.20 50.60 31.1 67.8 24 T19 49.74 105.2 46.36 91 99.9 36.6

T20 50.45 114.00 51.30 26.9 74.7 16.5 T20 49.09 105.8 49.12 96.3 90.9 35.9

T21 50.46 111.80 51.00 34 70.3 35.9 T21 47.37 106.7 48.3 86.8 96.7 18.2

Mean 50.5 113.18 51.05 39.3 72.3 24.2 Mean 48.5 105.8 48.3 95.2 96.1 33.0

SD 0.148 0.2884 12.9 9.3 6.7 SD 1.1 0.96 7.02 5.85 10.16

Comparison between IMRT vs 3DCRT Table 1

Brachytherapy

• Brachytherapy was done using iridium-192 (high-dose-rate) source with standard single channel vaginal applicator

• 3D treatment planning was done on the Oncentra Masterplan planning system version 4.3.

Brachytherapy Planning

• Treatment is prescribed at 5mm depth from the applicator surface, to a dose of 5Gy per fraction for 2 fractions

• Cover 1/3 to1/2 of the vaginal length from top• Reporting for 3D gynaecological brachytherapy includes the D100 and D90

for the vaginal vault PTV, D1cc and D2cc dose for rectum, bladder and sigmoid

5mm

Combining external beam with brachytherapy

• Due to the different treatment fraction size and dose rate, need to take into account the EQD2- Equivalent dose in 2Gy/Fraction

EQD2= BED/ (1+2/ α/β), where BED is the biological effectivedose and the α/β proposed for target is = 10 and 3 for theOARs

• EQD2 dose from external beam radiotherapy and brachytherapy is summed up to serve as an estimation of the worst case scenario assuming that the points of interest and volumes received the full dose

Statistical Analysis

Null hypothesis:

There is no difference between IMRT and 3DCRT when combined withbrachytherapy in terms of target coverage and dose to OARs and thealternative hypothesis is that there is a difference between IMRT and3DCRT.

Variation in volumetric data and DVH parameter were assessedusing Wilcoxon signed rank test where p<0.5 was consideredsignificant

Total EQD2 IMRT + BT Vs Total 3DCRT + BT

Total EQD2 IMRT + BT Total EQD2 3DCRT + BT

PTV, Gy , α/β =10

Bladder, Gy, α/β =3

Rectum, Gy, α/β =3

Sigmoid, Gy, α/β =3

PTV, Gy , α/β =10

Bladder, Gy, α/β =3

Rectum, Gy, α/β =3

Sigmoid, Gy, α/β =3

D100 D90 D2cc D1cc D2cc D1cc D2cc D1cc D100 D90 D2cc D1cc D2cc D1cc D2cc D1cc

1 T1 60.52 65.45 67.66 70.08 57.94 60.29 59.07 62.06 55.20 62.17 63.72 65.74 57.04 59.14 58.77 61.36

2 T2 52.45 60.34 69.51 71.48 64.78 67.80 62.68 68.01 51.44 57.54 65.95 67.88 63.31 65.47 59.96 64.75

3 T3 54.16 63.06 69.73 71.27 62.71 64.93 66.55 70.78 47.86 60.91 67.36 68.57 62.64 64.63 65.31 69.07

4 T4 49.27 55.11 68.72 71.33 66.68 70.12 54.63 55.19 47.40 51.47 65.64 68.00 65.33 68.28 51.74 52.08

5 T5 58.04 70.44 68.76 71.64 75.38 78.26 55.02 55.90 55.46 68.08 64.36 66.81 72.93 75.29 53.44 54.11

6 T6 53.34 63.70 72.44 76.07 66.15 69.02 56.49 57.48 53.61 61.29 67.19 70.39 64.52 66.89 53.90 54.41

7 T7 52.29 58.51 62.22 64.90 65.46 67.28 59.93 62.18 49.71 56.09 59.59 61.75 62.74 64.04 56.21 58.12

8 T8 50.84 61.30 69.42 73.38 61.25 65.67 56.11 57.55 50.17 59.45 67.68 71.47 62.57 66.75 54.10 55.29

9 T9 53.44 61.82 66.31 69.03 66.69 69.82 56.86 58.57 48.77 57.89 66.26 68.78 65.42 67.63 54.68 56.02

10 T10 58.67 64.39 67.57 69.94 66.09 68.00 68.74 72.54 53.84 62.21 63.61 65.35 65.20 66.75 66.46 71.35

11 T11 50.19 60.12 64.77 67.06 68.30 71.46 61.27 64.49 51.53 58.53 60.95 62.88 65.23 67.88 58.20 60.90

12 T12 50.96 59.31 67.48 70.50 64.55 67.22 61.09 63.23 47.65 55.58 65.27 67.78 61.28 63.58 56.64 58.28

13 T13 52.31 64.08 70.90 74.36 67.83 69.99 62.01 64.88 42.44 60.12 68.59 71.68 64.33 66.14 59.48 61.88

14 T14 50.97 59.01 66.65 70.40 59.51 61.15 60.02 62.07 48.95 57.07 62.92 66.27 59.47 60.66 56.94 58.67

15 T15 52.50 63.78 64.57 66.81 66.52 69.21 69.75 75.52 50.29 61.01 62.68 64.73 64.98 67.10 66.52 71.95

16 T16 54.11 64.79 70.74 73.02 64.93 69.19 72.44 74.64 53.60 62.07 69.08 71.03 62.72 66.86 71.15 73.06

17 T17 52.75 60.92 61.57 63.48 67.35 70.34 64.94 68.10 49.11 57.31 58.65 61.04 61.72 64.34 61.24 63.90

18 T18 50.96 58.94 61.66 63.08 57.31 59.28 59.96 61.46 46.21 55.71 59.63 60.77 58.09 59.70 57.45 58.69

19 T19 52.61 58.70 60.45 61.98 61.26 63.07 56.04 57.54 49.68 56.87 58.74 60.06 61.33 62.80 55.23 56.27

20 T20 51.85 58.50 62.28 63.79 65.76 67.70 57.00 62.84 46.33 56.70 61.47 62.81 63.72 65.46 54.48 55.83

21 T21 53.84 63.00 68.33 70.58 65.92 68.78 65.75 68.25 48.47 59.28 64.78 66.44 65.41 64.94 61.96 63.94Averag

e 53.15 61.68 66.75 69.25 64.88 67.55 61.25 63.97 49.89 58.92 64.00 66.20 63.33 65.44 58.76 60.95

SD 2.82 3.34 3.49 3.95 3.98 4.23 5.12 6.06 3.24 3.42 3.24 3.60 3.25 3.44 5.10 6.22

Table 2

Result

• When combined with brachytherapy, IMRT resulted in significantly better PTV coverage where the p value < 0.05 for both D100 and D90

• Use of IMRT also resulted in significantly increase in dose to bladder, rectal and sigmoid D1cc and D2cc dose as the p value is less than 0.05 for above organs

• As the p value is less than 0.05, the null hypotheses is rejected as there is significance difference between the IMRT combined doses compared to 3DCRT.

3. Divider•Introducing new topic Discussion

Rectum

Bladder

IMRT 3DCRTRectum Rectum

40Gy< 80% or80%< 45Gy<100%

45Gy<100%T1 72.6 100T2 57.9 96.7T3 76.5 97.3T4 74.4 89.7T5 70.6 99.6T6 68.5 100T7 63.5 97.1T8 76 77.9T9 52.1 99.6T10 75.4 100T11 68.7 98.2T12 65.1 98.9T13 75.8 98.7T14 97.7 92.7T15 76.7 85.1T16 76.4 100T17 86.4 100T18 70.8 100T19 67.8 99.9T20 74.7 90.9T21 70.3 96.7Mean 72.3 96.1SD 9.3 5.85

Table 3

Mea EQD2 IMRT EQD2 3DCRT EQD2 IMRT + BT EDQ2 3DCRT +BTCase study Rectum, Gy, α/β =3 Rectum, Gy, α/β =3 Rectum, Gy, α/β =3 Rectum, Gy, α/β =3

D2cc D1cc D2cc D1cc D2cc D1cc D2cc D1cc

T1 51.3 51.6 50.4 50.4 57.9 60.3 57.0 59.1

T2 50.4 51.4 48.9 49.0 64.8 67.8 63.3 65.5

T3 51.7 52.0 51.6 51.7 62.7 64.9 62.6 64.6

T4 50.8 51.4 49.4 49.6 66.7 70.1 65.3 68.3

T5 52.0 52.6 49.6 49.6 75.4 78.3 72.9 75.3

T6 52.7 53.2 51.0 51.1 66.2 69.0 64.5 66.9

T7 51.6 52.1 48.9 48.9 65.5 67.3 62.7 64.0

T8 48.8 49.4 50.1 50.5 61.3 65.7 62.6 66.7

T9 51.2 52.2 50.0 50.0 VS 66.7 69.8 65.4 67.6

T10 50.9 51.3 50.0 50.1 66.1 68.0 65.2 66.8

T11 53.8 54.5 50.8 50.9 68.3 71.5 65.2 67.9

T12 51.0 51.5 47.7 47.8 64.6 67.2 61.3 63.6

T13 51.9 52.4 48.4 48.5 67.8 70.0 64.3 66.1

T14 50.7 51.3 50.6 50.8 59.5 61.1 59.5 60.7

T15 51.6 52.3 50.1 50.2 66.5 69.2 65.0 67.1

T16 50.9 51.7 48.7 49.4 64.9 69.2 62.7 66.9

T17 53.3 53.8 47.7 47.8 67.4 70.3 61.7 64.3

T18 50.1 50.6 50.9 51.0 57.3 59.3 58.1 59.7

T19 51.1 51.5 51.1 51.2 61.3 63.1 61.3 62.8

T20 51.3 51.7 49.3 49.4 65.8 67.7 63.7 65.5

T21 51.4 52.2 50.9 48.4 65.9 68.8 65.4 64.9

Mean 51.4 51.9 49.8 49.8 64.9 67.6 63.3 65.4

Table 4

Limitation

• Current TPS doesn’t allow for summation or deformable registration of multiple brachytherapy plans or combined external beam treatment plan with brachytherapy plan. The evaluation of dose is based on the summation of the DVH value.

• Assessment of IMRT plans is based on the dosimetry and DVH of the planning CT scan taken before the start of treatment, hence does not necessarily represent the actual dose delivered to the tumour and OARs if intrafraction and interfraction organ motion, tumour regression and set-up reproducibility

Conclusions

• Use of IMRT in gynaecological cancer can help to improve target coverage to the vaginal cuff and reduce bladder, rectum and small bowel dose when compared with 3DCRT.

• Combined mean EQD2 dose of D1cc and D2cc of bladder, rectum and small bowel is however significantly higher in IMRT compared to 3DCRT.

• Hence, during IMRT planning may need to evaluate the D1cc and D2cc dose of the OARs to limit these dose to avoid exceeding tolerance dose when combine with brachytherapy

References

• Heron DE, Gerszten K, Selvaraj RN. et al. Conventional 3D conformal versus intensity- modulated radiotherapy for the adjuvant treatment of gynecologic malignancies: a comparative dosimetric study of dose-volume histograms. Gynecol Oncol 2003:91: 39-45.

• Lim K, Kelly V, Stewart J. et al Pelvic Radiotherapy for cancer of the cervix: Is what you plan actually what you deliver? Int J of Radiat Oncol, Biol, Phys 2009; 74:304-312

• Macdonald DM, Lin LL, Biehl K, Mutic S, Nantz R, Grigsby W. Combined intensity modulated radiation therapy and brachytherapy in the treatment of cervical cancer. Int J of Radiat Oncol, Biol, Phys 2008;71:618-624

• Mundt AJ et al. (2002)-Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies. International Journal of Radiation Oncology Biology Physics. 52(5),1330-1309

• Potter R, Haie-Meder, C, Limbergen EV, et al. Recommendations from gynaecological (GYN) GEC ESTRO working group (II): Concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy- 3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology. Radiother and Oncol 2006;78:67-77

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