Interstitial Brachytherapy. Low dose rate brachytherapy. Brachytherapy alone cures some cervical cancer. Learning Objectives

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Interstitial Learning Objectives To discuss practical aspects of selection and

trials Akila Viswanathan, MD MPH Johns Hopkins Medicine January 29, 2017 Why

57 of 199 inoperable cases cured treated between 1909-1913 Radium alone JAMA 1915 Pros

Lower risk of normal tissue toxicity than HDR Sublethal damage repair Cons Radioactive

changes more expensive alone cures some cervical cancer ASCO Resource-Stratified

1 Interstitial Learning Objectives To discuss practical aspects of selection and insertion techniques for interstitial brachytherapy and their relation to clinical trials Akila Viswanathan, MD MPH Johns Hopkins Medicine January 29, 2017 Why brachytherapy? 57 of 199 inoperable cases cured treated between Radium alone JAMA 1915 Pros Low dose rate brachytherapy Long half life Inexpensive Cs137 Stable 1-2 insertions Lower risk of normal tissue toxicity than HDR Sublethal damage repair Cons Radioactive safety Exposure to operator National safety Ir-192 shorter half life more frequent changes more expensive alone cures some cervical cancer ASCO Resource-Stratified Guideline Curative modality 50 years before Linac and chemotherapy Cytotoxic rather than cytostatic Cost-effective Bring curative treatment in underresourced environments Chuang et al

combined with External beam improves survival is Necessary Tumor control probability correlated with RT dose and cervix ca volume Fletcher, Shukovsky J Radiol Electrol 56:383-400, 1975 4 y PC 4 y

cancer brachytherapy use 1998-2008 100 Propensity score-matched cohort 80 60 40 20 0 P <.

2 combined with External beam improves survival is Necessary Tumor control probability correlated with RT dose and cervix ca volume Fletcher, Shukovsky J Radiol Electrol 56: , y PC 4 y Survival Lanciano JROBP 20:95, 1991 Local Control Montana Cancer 57:148, 1986 External beam only 45% 19% External Beam + brachytherapy 67% 46% 40% 52% Overall Survival Overall survival by cervical cancer brachytherapy use Propensity score-matched cohort P <.001 No Years 25% reduction in brachytherapy; 13% reduction in survival Mul)variable Cox Regression Characteris)cs Cancer-Specific Survival Overall Survival HR (95% CI) P HR (95% CI) P No 1 (reference) 1 (reference) Yes 0.64 ( ) < ( ) <.001 Stage IB2 1 (reference) 1 (reference) II 1.18 ( ) ( ).18 III 2.28 ( ) < ( ) <.001 IVA 3.50 ( ) < ( ) <.001 Histology SCC 1 (reference) 1 (reference) Adenocarcinoma 1.32 ( ) ( ).005 Other 1.26 ( ) ( ).07 Other significant factors: Age; Marital Status; Race; Ethnicity; Registry SEER, Int J Radiat Oncol Biol Phys 2013;87: Utilization of HDR increased from 13% to 70% LDR SBRT as a boost Node recurrence, sidewall recurrence Higher normal tissue dose Long term complication rate HDR HDR SBRT IJROBP 2005;63(4): IJROBP 2014;89(2):

$SBRT for Recurrent Cervix Ca Deodato et al. Oncol Repo 22:415-419 Dose 30 Gy/6 fractions 1 pt w vaginal recurrence Guckenerger et al.$ recurrence Recurrent endometrial cancer in vagina Extensive distal vaginal involvement from any ca Large pelvic mass Fistula Ovarian recurrence in vagina Large Cervical Ca Vaginal

recurrence Recurrent endometrial cancer in vagina Extensive distal vaginal involvement from any ca Large pelvic mass Fistula Ovarian recurrence in vagina Large Cervical Ca Vaginal

3 SBRT for Recurrent Cervix Ca Deodato et al. Oncol Repo 22: Dose 30 Gy/6 fractions 1 pt w vaginal recurrence Guckenerger et al. Failure 7/11 FAIL 2 Grade 4 fistulae 1 Grade 4 ileus Interstitial 50 Gy + 5 Gy x3 7/10 FAIL Rad onc 94: central recurrences Indications Indications for Interstitial Postop recurrence Recurrent endometrial cancer in vagina Extensive distal vaginal involvement from any ca Large pelvic mass Fistula Ovarian recurrence in vagina Large Cervical Ca Vaginal involvement Sidewall involvement Bladder involvement Vaginal Cancer (>5mm thickness) Vulvar Cancer with vaginal extension Urethral Cancer, Bladder Cancer Applicators for A INTERSTITIAL B Tandem and Ring Tandem use improves OS C Tandem and Ovoids 3

Applicators: Syed Template Applicators: Individualize

insertion to cover parametria No obturator/not for

cover Not for extensive vaginal ca Cylinder with

Obst Gyn 55(4):525-530, 1980 Template and Catheter

countertraction Stitch template Workflow: Diagnostic

Sagittal bssfp Axial T2 axial Final series: T2

6mm thick cover template Stylets, change to Radioque

clockwise U/S and I lesion correlation Dose

4 Applicators: Syed Template Applicators: Individualize Selection Syed Circular formation Martinez Angled insertion to cover parametria No obturator/not for vaginal ca Ring or ovoids with needles Short needles to cover Not for extensive vaginal ca Cylinder with catheters Free hand Customized design Fleming et al. Obst Gyn 55(4): , 1980 Template and Catheter Placement Ultrasound IteraXve InserXon Technique: or Serial mm slice thickness Stitch at vaginal apex for countertraction Stitch template Workflow: Diagnostic series: T2 a/s/c T1 contrast DWI Intra-procedure: bssfp Sagittal bssfp Axial T2 axial Final series: T2 axial/sag/cor for planning 1.6mm thick cover template Stylets, change to Radioque markers for imaging Number steri-strips, attach clockwise U/S and I lesion correlation Dose Distributions Cylinder For postop endo ca Interstitial For gross disease Trans rectal Mahantshetty U et al. Radiotherapy and Oncology Schmid MP et al. Strahlenther Onkol

To safely use HDR, need 3D imaging Opera)ng Room Laparoscopic Guidance Image with Xray, or awer inser)on Suite Fluoroscopy, Ultrasound,, I Simulator with anesthesia Itera)ve Imaging Interven)onal

During BT Local control (%) Disease specific Survival (%) Overall Survival (%) Grade 3-4 Toxicity 118 Xray 74 55 65 22.7 117 78.5* 60 74 2.

73) Chemo, HDR and IBBT reduced relapse Manuel et al.

5 To safely use HDR, need 3D imaging Opera)ng Room Laparoscopic Guidance Image with Xray, or awer inser)on Suite Fluoroscopy, Ultrasound,, I Simulator with anesthesia Itera)ve Imaging Interven)onal with anesthesia Diagnos)c Radiology Normal Xssue rouxnely contoured by respondents who have 3D imaging available a_er applicator placement X-ray versus brachytherapy after chemoradiation # Imaging During BT Local control (%) Disease specific Survival (%) Overall Survival (%) Grade 3-4 Toxicity 118 Xray * Advantage of Image-based intersxxal brachytherapy for vaginal cancer / Xray / Xray / Xray Charra-Brunaud et al. STIC Radioth Oncol pt Xray, 31, 16 DFI MV HR IBBT 0.24 ( ) Chemo, HDR and IBBT reduced relapse Manuel et al. Radiotherapy and Oncology 2016 Sep;120(3): Interstitial in Cervical Cancer First author # Stage Dose LC Imaging Eisbruch 11 IIB-IVA Gy 64% Ishohashi 25 IB2-IVA - 68% Sharma 42 IIB-IVA - 62% Kannan 47 IIB-IVA 75 68% Wang 20 IIB-IIIB 87 90% Lee 17 IIB-IVA 77 88% Pinn- Bingham 116 IB1-IVA 98 85% Viswanathan 6 IIB-IVB 85 83% and Yoshida 29 IIB-IVB - 93% Kamran 56 IIB-IVA 80Gy 97% 87% vs vs Interstitial Cervical Ca Kamran et al ABS

-based brachytherapy data -based HDR brachytherapy Tumor size < 4cm Tumor

contouring larger than with contrast clear OAR delineation interface

uterus 3% decrease in point A dose Tumors < 4cm 4% decrease in point A

6 -based brachytherapy data -based HDR brachytherapy Tumor size < 4cm Tumor size > 4cm -planned brachytherapy: Change in point A dose versus contouring larger than with contrast clear OAR delineation interface bowel/ cervix difficult visualize GTV Bladder HR-V Still treat entire uterus 3% decrease in point A dose Tumors < 4cm 4% decrease in point A dose Tumors > 4cm Rectum Int J Radiat Oncol Biol Phys 2007 Jun 1;68(2):491-8 Cho et al. Gyn Onc epub 2016 RTOG Consensus contour (red) Parametrial extension, good response (red) vs. (blue) IJROBP 2014; 90(2):320-8 IJROBP 2014; 90(2):

org/resources/contouring-atlases/ GYNCervical- Parametrial extension defines whether differs

7 Large tumor, poor response (red) vs. (blue) No parametrial extension Complete response (red) vs. (blue) GYNCervical- Parametrial extension defines whether differs from contours No parametrial extension=identical contours Poor parametrial response = similar contours Good parametrial response = largest discrepancy in contours 7

MRI Guided GYN Brachytherapy: Clinical Considerations

MRI Guided GYN Brachytherapy: Clinical Considerations AAPM Junzo Chino MD Duke Radiation Oncology 8/8/2013 Disclosures none Learning Objectives Historical Context: Film based Brachytherapy Advantages of