Advances in Gynecologic Brachytherapy

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Hollie Barker
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1 Advances in Gynecologic Brachytherapy Anuj V Peddada, M.D. Director Department of Radiation Oncology Penrose Cancer Center Colorado Springs, CO USA

2 Brachytherapy Issues in Gyn/onc Cervix Endometrial

3 Rational for Brachytherapy Local Control EBRT 40% vs EBRT + BT 52% (Montana) Pelvic control EBRT 45% vs EBRT + BT 67% (Lanciano) Overall Survival EBRT 20% vs EBRT + BT 45% (Lanciano)

4 Rational for Brachytherapy Adequacy of implant/type of implant Local control Overall survival Total dose delivered Pelvic control Overall survival

5 Manchester Ave dose to obturator LNs (medial parametria) Ave dose to paracervical triangle Tod & Merideth; Brit J Radiol 11:1938

6 LDR Tandem and Ovoid Simulation Films Dummy seeds Contrast in bladder balloon Tandem Ovoid Vaginal packing

7 Good Implant impacts LC & OS Acceptable implant Unacceptable implant 5yr LC 68% 35% 5yr OS 61% 42% A good implant is a BIG difference in LC and OS Corn. Gyn Onc. 1994

8 Cervical Cancer Evolution from 2D 3D

9 Here Is the Reality 2D orthogonal films to 3D visualization

10 Rational for Image-guided Brachytherapy (IGBT) Limitations of 2D technique Maximization of therapeutic ratio Clinical data suggests a benefit Pötter R Radiother Oncol 83: Dimopoulos J IJROBP 75:56, 2009

11 GYN GEC-ESTRO (2005) European Cooperative Group has published guidelines for 3D RTP based largely on the Vienna experience w/ MRI GTV: bright areas on T2 sequences High-risk CTV: cervix + visible/palpable tumor at time of brachy (prescribe to this volume) Goal is D 90 > 100% & V 100 > 90% Intermediate-risk CTV: 1 cm margin around HR- CTV plus initial sites of disease involvement at presentation (should receive 60 Gy)

12 Rational for Image-guided Brachytherapy (IGBT) Dimopoulos J IJROBP 75:56, 2009 Dimopoulos J Radiother Oncol 93:311, 2009 N= 141, median f/u 51 months Two groups; 2-5 cm and > 5 cm Follow-up up with PE and MRI q3 months for 2 years then twice annually Mean D90, D100 was 86±16Gy and 65±10 Gy Investigated impact of D90 and D100 for HR CTV on LC D90 > 87Gy EQD 2 Gy 10 LR 4% D90 < 87 Gy EQD 2 Gy 10 LR 20% *especially for those with >5 cm residual at the time of BT

13 Clinical Impact of MRI assisted dose volume adaptation and dose escalation in brachytherapy of locally advanced cervix cancer Pötter R Radiother Oncol 83: N=145 patients, prospective LC and morbidity were significantly influenced by GEC ESTRO guidelines For limited dz (Ib1-IIB <4-5 cm) the LC was % with severe late morbidity of <5% For advanced disease (IB2, IIB, IIIB >5 cm) LC ~ 82% with severe late morbidity <5% Overall survival for the group 53% to 64% (p=0.03) Late GI or GU (G3,G4) 10% for non-optimized vs 2% for optimized

14 Process Place tandem and ovoid/tandem and ring Perform CT/MRI Contour strutures HRCTV, IRCTV, OAR Implant reconstruction and optimization to Point A Modify doses to maximize dose to HRCTV and minimize dose to OAR

15 ~ D90 (dose covering 90% of volume) in EQD 2 = 70Gy IR-CTV 87Gy HR-CTV 125Gy GTV

16 GYN GEC-ESTRO Dose-volume constraints for normal organs (EBRT + brachy dose, adjusted to a BED / 3 for conventional 2 Gy/fraction): D 2cc rectum < 75 Gy (anterior rectal wall) D 2cc sigmoid < 75 Gy (inferior sigmoid) D 2cc bladder < 90 Gy (posterior bladder wall) D 0.1cc is also recorded, but D 2cc is most clinically relevant in terms of late tox, eg ulceration or fistula (van den Bergh et al.)

Planning CT and MRI were performed and contouring carried out separately (N = 10) CT significantly overestimated the width of the tumor and altered the D90,

18 Planning CT and MRI were performed and contouring carried out separately (N = 10) CT significantly overestimated the width of the tumor and altered the D90, D100 OAR DVH were the same MRI remains standard for contouring IJROBP 2007 Can t see GTV on CT b/c tissue enhancement is same in tumor and in normal cervix.

19 CASE STUDY The patient is a 63 yo with SCCA of the cervix. Presented with a 4.5 cm tumor with extension into the left parametria, FIGO IIB. She received 45Gy EBRT with concurrent CDDP. She presented for implants after external given, no clinical tumor evident by P.E. MRI at brachytherapy also did not demonstrate visible disease. Prescription was for 600 cgy X 5 fractions.

20 Prior to optimization 100% isodose line through the bladder - pink Optimized to cover hrctv and avoid bladder

21 Sagital view with 100% traversing bladder Corrected

22 Beware all values on spreadsheet correct but viewing isodose lines demonstrates problem protruding source

23 Corrected

25 Non-optimised dose in brachytherapy placed on MRI and evaluated Lindegaard JC IJROBP 62:901, 2008 With standard dose plans prescribed to point A results in D90 to the HRCTV from % (n=22), mean 113±30% Doses to OAR were improved with optimization so that DVH constraints met in 16/21 patient vs. 3/21 patients. Confirmed by De Brabandere M Radiother Oncol 88:217, 2008.

26 Based on new CTVs, what if tumor can t be covered by T&O or T&R?

27 Wahab, Low et al. (Wash U), 2004 Med Phys AGIMRT: Applicator Guided IMRT Assume 5mm margins for PTV 6.5Gy x 6fractions to Pt A Use IMRT because T&O is inadequate for large tumors! Dosimetry study of 10 patients Ave min dose tumor dose 64.2Gy (AGIMRT) vs 33.6Gy (HDR)

28 Wahab, Low et al. (Wash U), 2004 Med Phys large tumor 217.9cc

29 Low et al. (Wash U), 2002 IJROBP

30 Tandem Ovoid Hotspots 100% 200% 300%

32 2006 IJROBP

35 T&R with needles (Vienna) Varian Nucleotron

36 Rational for Vienna Applicator

37 `

40 DVH parameters and late side effects Georg P IJROBP epub ahead of print, 2010 Rectal toxicity Parameters D 2cc and D 1cc have good predictive value D 2cc >75Gy 20% toxicity vs 5% if less Sigmoid toxicity No prediction because of limited data (only 2 patients with toxicity) Bladder D 2cc predictive for major toxicity D 2cc > 100Gy 13% vs 9% if less

41 Conclusions Need to use GEC-ESTRO and prescribe to a volume Start slowly Start with contouring and tracking doses only until comfortable Streamline process of insertion, imaging, fusion, planning, and optimization Start optimization program

42 Conclusions If interstitial needles (ie, Syed-Neblett) or an IMRT plan, remember to keep high central dose loading (not homogenous)! Join EMBRACE European Study on MRI Based 3D Brachytherapy in Locally Advanced Cervical Cancer

43 Endometrial

44 Early Stage: General Treatment TAH/BSO + pelvic lymph node sampling Depth of MMI Grade of tumor Location of tumor LN status May need adjuvant radiation: Which: Pelvic EBRT or Vaginal brachy??

45 MMI None Inner Middle Outer Grade Pelvic Grade Para-Aortic Creasman. Cancer 1987

46 Other High Risk Factors Risk Factors Beyond the fundus Histology LVSI Size Age Specifically LUS, Cervix Clear cell, UPSC Positive >2cm >60 yrs

47 PORTEC I & II PORTEC I: Low-Int risk IC g1+2; IB g2+3 46Gy/23f vs Obs LF: 4% vs 14% (SS) Conclusion: XRT is needed. (But which kind?) PORTEC II: Int-High risk >60 yrs & IC g1+2, IB g3; IIA g1+2 [No IC g3] 46Gy/23 f vs 21/3f VBT

48 PORTEC II Nout. Lancet 2010 VBT EB P-value LRR 5.1% 2.1% VRR 1.8% 1.6% Pelvic NR 3.8% 0.5% p<0.02 DM 8.3% 5.7% DFS 82.7% 78.1% OS 84.8% 79.6% Diarrhea: QOL better for VBT, 13% vs 54% g1-2 (SS) GU toxicity and sexual fxn: no difference

49 Guidelines No MMI IA <1/2 MMI IB >1/2 MMI Gr 1 None None VBT Gr 2 None None VBT Gr 3 VBT VBT EBRT Low-risk Intermed High May consider EBRT + VB for cervical stromal (II)

Vaginal Cylinder 7Gy @ 5mm depth (100%), but vaginal mucosa gets 150%

50 Vaginal Cylinder 5mm depth (100%), but vaginal mucosa gets 150% Can get vaginal shortening Other, ways to give (eg, 4Gy x6f to vag. mucosa)

51 Vaginal Cylinder 90% use standard segmented cylinder (discrete size) (ABS 2005 survey) ABS: geometry of implant [needs to] remain same for every insertion Treatment device needs to be in direct contact with vaginal surface Is the cylinder pushed into the vaginal apex? Are there other air gaps inside the vagina? What can we see in the CT guided era??

IJROBP 78:1, 2010 25 pts (150 total scans) 2-4Gy at 5mm x 6frxns

52 IJROBP 78:1, pts (150 total scans) 2-4Gy at 5mm x 6frxns CT scan for each insert Results 90/150 air pockets (60%) Ave # = 3.6; 0.34cm 3 Ave dose redxn 27% (9-58%) 10 pts (40%) no air pockets on 1 st frxn, but did on subsequent Bubble at vaginal apex

53 New Applicator Each patient s anatomy is unique Age, parity, post-surgery changes Conical to balloon shape, dog ears Vaginal introitus often smaller than apex

54 Capri device (FDA 2009) 9cm cm

55 Vaginal

58 Advantages of Capri-type device: Removal of air pockets Immobilization from CT to treatment position Better control of dose to bladder/rectum Can also be used to deliver dose at depth laterally (ie, difficult vaginal cases with gross disease Ease of use and patient comfort Disadvantage: ~3cm introitus limit for insertion

59 Conclusions Need to scan patient for every treatment 1 st CT scan can fool you Air pockets do not necessarily dilute out over 6 fractions, but can persist in certain areas, leading to underdosage. 80% of air-pockets are in target area (Note LF is <5% but can be as high as 18%)

Linking DVH-parameters to clinical outcome. Richard Pötter, Medical University of Vienna, General Hospital of Vienna, Austria

Linking DVH-parameters to clinical outcome Richard Pötter, Medical University of Vienna, General Hospital of Vienna, Austria Outline DVH parameters for HR CTV (D90) and OAR (2 ccm) simple integration of