Published on March 15, 2014
Advances in Brachytherapy Delivery and Treatment Planning By Vibha Chaswal, Ph.D. (Independent Researcher and Collaborator) USA
Brachytherapy Today! • High precision targeted Radiotherapy Modality with significant patient benefit • High Precision image guided adaptive brachytherapy (IGABT)
Prostate Carcinoma (Over past almost 15 years…)
alpha/beta for prostate tumors • Alpa/beta = 1.5 – 3 Gy • possibly lower than the expected values of about 3 Gy for late complications • Not a rapidly re-populating carcinoma • reversal of the relative sensitivities to dose-fraction size, of tumours versus late-responding normal tissues at-risk in conventional radiotherapy • a few large fractions – hypo-fractionation – might be advantageous for killing prostate carcinoma Brenner DJ, Hall EJ. “Fractionation and protraction for radiotherapy of prostate carcinoma.” Int J Radiat Oncol Biol Phys. Vol 43(5) 1999 Fowler J1, Chappell R, Ritter M., “Is alpha/beta for prostate tumors really low? “, Int J Radiat Oncol Biol Phys. Vol 50(4) 2001
Latest (FINAL?) word on alpha/beta: Fowler et. al. 2013 • Three large statistical overviews are critiqued, with results for 5,000, 6,000 and 14,000 patients with prostate carcinoma • Putting 15 years of controversy to rest, Open doors to opportunity • Agree in finding the average α/β ratio to be less than 2 Gy • hypo-fractionation = therapeutic gain Fowler JF et. al., “Is the α/β ratio for prostate tumours really low and does it vary with the level of risk at diagnosis?” Anticancer Res. Vol 33(3) 2013
HDR-BT of the prostate Hypofractionation and Dose escalation
Prostate HDR Dose Escalation “HDR brachytherapy can provide better sparing of rectum and bladder while delivering a higher dose to the prostate. Even with the increased late effects of high dose per fraction, there is still a potential for dose escalation beyond external radiotherapy limits using HDR brachytherapy.” I C Hsu et. al., “Normal tissue dosimetric comparison between HDR prostate implant boost and conformal external beam radiotherapy boost: potential for dose escalation” Int J Radiat Oncol Biol Phys. Vol 46(4) 2000
Prostate - HDR • TRUS: real-time imaging, good image quality of the prostate boundary, clear visualisation of the needles. • But poor soft-tissue resolution; • A marker wire or aerated gel is inserted into the urinary catheter to visualise the bladder and urethra • The anterior of the rectum is visualised in contact with the ultrasound probe and image quality is improved with the aid of a saline- filled endorectal balloon on the ultrasound probe A Challapalli, E Jones, C Harvey et. al., “ High dose rate prostate brachytherapy: and overview of the rationale, experience, and emerging applications in the treatment of prostate cancer,” BJR, 85(2012)
Treatment Plan Scan: CT/MR • Patient in Tx position, Foley Catheter in place • Contiguous slices with scan thickness ≤ 0.3 cm • MUST include entire prostate + at least 3 slices (9 mm) above and below the prostate • include the perineum for visualization of the catheters from tips to outside the patient • MUST include tips of ALL the catheters • Patient’s external Body contours should not be included in FoV to maximize image quality AMERICAN BRACHYTHERAPY SOCIETY PROSTATE HIGH-DOSE RATE TASK GROUP I-Chow Hsu, MD, Yoshiya Yamada MD, Er ic Vigneault MD, Jean Pouliot, PhD August, 2008
Treatment Planning Essentials • Volumes ICRU Report 58 • Turn off dwell locations outside PTV • Geometric/inverse/Manual optimization • V100 prostate >90% • V75 rectum/Bladder < 1cc • V125 urethra < 1cc • Evaluation Isodoses – 50%, 100%, 150% • DVH – sample minimum of 5000 points/ ROI for cumulative DVH AMERICAN BRACHYTHERAPY SOCIETY PROSTATE HIGH-DOSE RATE TASK GROUP I-Chow Hsu, MD, Yoshiya Yamada MD, Er ic Vigneault MD, Jean Pouliot, PhD August, 2008
Treatment Delivery and Image guidance • first HDR fraction delivered on the day of the catheter placement. • multiple fractions: consecutive fractions within 24 hours after the first treatment, but no less than 6 hours between treatments • Visual inspection of the catheters prior to delivery of each treatment is a MUST • Fluoroscopy or CT • Readjust catheters if required • If repositioning or readjustment of TX plan cannot address the catheter displacement, postpone treatment until a satisfactory implant may be done AMERICAN BRACHYTHERAPY SOCIETY PROSTATE HIGH-DOSE RATE TASK GROUP I-Chow Hsu, MD, Yoshiya Yamada MD, Er ic Vigneault MD, Jean Pouliot, PhD August, 2008
A Challapalli, E Jones, C Harvey et. al., BJR, 85(2012)
HDR-BT pre-planning Picture courtesy: Janusz Skowronek, MD, PhD, Greater Poland Cancer Center
HDR-BT real-time planning Picture courtesy: Janusz Skowronek, MD, PhD, Greater Poland Cancer Center
Excitement continues… • New Hypofractionation schemes – UW- Madison and many others! • BrachyView, a novel inbody imaging system for HDR prostate brachytherapy: design and Monte Carlo feasibility study. • Real-time monitoring and verification of in vivo high dose rate brachytherapy using a pinhole camera.
Can’t forget still the gold standard most common Prostate BT procedure……
Prostate LDR – new radioisotopes • Rx: 85 Gy (Cs-131), 110 Gy (I-125), 100 Gy (Pd-103) • Seed strengths employed: 1.6 U (Cs-131) and 1.8 U (Pd-103) 0.54 U (I-125) • 45 treatment plan comparisons. For similar dose coverage (V100 and D90), V200 and V150 reduced. • More “homogeneous” implants using Cs-131
Slide courtesy: R Miller, B R Thomadsen, “Brachytherapy Physics: Everything you need to know and controversial Issues”, AAPM 2009
Slide courtesy: R Miller, B R Thomadsen, “Brachytherapy Physics: Everything you need to know and controversial Issues”, AAPM 2009
Prostate LDR-BT future! - Interesting simulations: “Directional I-125 seed and ROI - Sensitivity profiles based optimization” – UW-Madison MrBoT: “Automatic Brachytherapy Seed Placement Under MRI Guidance” – John Hopkins University Auto-segmentation of prostate (do pubmed search)
Needle placement clinical considerations – Prostate LDR/HDR BT
Breast Brachytherapy evolution in last decade Cox, J. A. & Swanson, T. A. (2013) Current modalities of accelerated partial breast irradiation Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2013.65 Historically, Breast Brachytherapy: treated as "boost” to lumpectomy cavity following external whole breast radiation therapy Now, as Accelerated Partial Breast Irradiation (APBI): sole radiation treatment modality following breast- conserving surgery
APBI: Multicatheter HDR Cox, J. A. & Swanson, T. A. (2013) Current modalities of accelerated partial breast irradiation Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2013.65 The Godmother HDR-breast Brachytherapy technique 3D CT-guidance or TRUS based volumetric implant
APBI: Mammosite (image courtesy of MammoSite, Hologic Inc., Bedford, MA, USA) FDA clearance: 2002 most widely used modern APBI device and with the longest track record, becoming new gold-standard of dosimetry comparison Availability as Single/Multiple central lumen device Ir-192 HDR
APBI: Mammosite J.B. Wojcicka et. al., “Clinical and dosimetric experience with mammosite-based brachytherapy under the RTOG 0413 protocol, JACMP, Vol. 8(4), 2007 Pre- and post-manipulation images of patient: Air-cavity reduction by a net addition of 10 cm3 to the balloon volume And/or massage of the implant area Manipulating the cavity and adjusting the balloon volume may salvage an implant and assist in meeting the strict geometric and dosimetric criteria imposed by the RTOG 0413 protocol.
Mammosite: Single Lumen Vs Multiple lumen Mammosite implant
Contura Multi-Lumen Balloon catheter • surgeons and radiation oncologists are familiar and comfortable with Balloon type devices now • Drainage channels: air and blood around the cavity could be removed before treatment, potentially reducing air pockets and seroma formation (image courtesy) Bard Medical Systems
SAVI: Strut Adjusted Volume Implant (not balloon) CT image of a SAVI applicator inside of a lumpectomy cavity. Single-entry multi-channel catheter system *S Gurdalli, “Dosimetric comparison of three brachytherapy applicators for partial breast irradiation”, World congress of brachytherapy 2008 Dose modulation up to 11 channels Improved skin dose sparing as compared with Mammosite and Contoura*
APBI: Clearpath single entry Multicatheter device (Hybrid) Both HDR as well as LDR compatible facilities without high-rate- rate equipment can now offer APBI Strands of I-125 seeds are inserted in the outer catheters Patients must wear a fully shielded bra if low-dose continuous release treatment is given
Electronic brachytherapy • FDA clearance: 2006 • Balloon brachytherapy with electronic 50 kilo- voltage x-ray source • No radio-isotopes • miniature x-ray tube that is inserted into the balloon catheter and delivers the radiation therapy
Electronic brachytherapy • Minimal Shielding • No rigorous radiation source regulations • IORT with EBX - TARGIT trial
References • C F Njeh et. al. “Accelerated Partial Breast Irradiation (APBI): A review of available techniques” Radiation Oncology, 5:90, 2010 • Brent Herron et. al. “A Review of Radiation Therapy’s Role in Early- Stage Breast Cancer and an Introduction to Electronic Brachytherapy” • *S Gurdalli, “Dosimetric comparison of three brachytherapy applicators for partial breast irradiation”, World congress of brachytherapy 2008 • J.B. Wojcicka et. al., “Clinical and dosimetric experience with mammosite-based brachytherapy under the RTOG 0413 protocol, JACMP, Vol. 8(4), 2007 • Cox, J. A. & Swanson, T. A. (2013) Current modalities of accelerated partial breast irradiation Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2013.65
Cervical Cancer (Aha!)
Cervical cancer Brachytherapy plays fundamental role in the therapeutic approach of patients with FIGO stage I-IV cervical carcinoma High precision image guided (Dose Adaptive) Brachytherapy
Brachytherapy of the cervix • AP-PA radiographs to volumetric imaging guided – CT, CBCT, TRUS, MRI • On road from Point-dose prescription to Volume-based prescription….. • IGABT: Image Guided Adaptive Brachytherapy • HDR: Intracavitary (most common), Interstitial-intracavitary or interstitial only
Image Guidance • Image guidance for applicator placement – Fluoroscopy, TRUS, radiographs… • Volumetric image set for treatment planning CT, MRI, CBCT • Fluro radiographs before/after CT/MRI for applicator positional assessment • Volumetric CT image set for post-implant assessment
Intracavitary BT for Cervical cancer • Traditionally, Rx and Tx planning: Either reference points (points A and B) or reference isodoses (60Gy according to ICRU recommendations) to report doses to the target volume. • Doses to critical organs were reported at bladder and rectum ICRU points. • long-standing clinical experience has yielded an acceptable therapeutic ratio
Good to better…...
CT-based BT: ICRU Point Doses vs Volumetric Doses • 20 patients • The median EBRT dose 45Gy. • CT-MRI compatible T&O BT, median dose 24 Gy, Treatment planning using 3D CT image set • bladder, rectum and sigmoid were retrospectively contoured • OAR doses assessed by DVH criteria were higher than ICRU point doses S K Vinod et. al., “A comparison of ICRU point doses and volumetric doses of organs at risk (OARs) in brachytherapy for cervical cancer” J Med Imaging Radiat Oncol. Vol 55(3) 2011
CBCT guided promise! • 3D planning in the brachytherapy suite using a cone beam CT (CBCT) scanner dedicated to brachytherapy • No patient movement between imaging and treatment procedures • adequate image quality to reconstruct the applicators in the treatment planning system • More practical and feasible Reniers B, Verhaegen F., “Technical note: cone beam CT imaging for 3D image guided brachytherapy for gynecological HDR brachytherapy.” Med Phys. 38(5)2011
Slide courtesy: J Siewerdsen and G-H Chen, Johns Hopkins University and UW- Madison
Most Promising IGBT…. MRI guided Intracavitary BT with its excellent soft tissue contrast! Futuristic for many…..but on road to future!
MRI-BT R Potter et. al. “Present status and future of high precision image guided adaptive brachytherapy for cervix carcinoma” Acta Oncologica, Vol 47, 2008 Red: >10% dose deviation for at least 10% of the patients Green: <10% dose deviation for at least 90% of the patients.
Let’s look at • Dosimetric impacts of: - Applicator displacement - Applicator reconstruction uncertainties - Different HR-CTV volume definitions - Awesomeness of 3T-MRI images! U-Iowa MRI- BT group Rocks!
MRI Guided ICBT Dosimetric impact of Applicator displacement and Applicator reconstruction uncertainties J. Schindel et. al., “Dosimetric impact of Applicator displacements and applicator reconstruction uncertainties on 3D image-guided brachytherapy for cervical cancer” J Contemp Brachytherapy Vol 5(4) 2013
Simulating displacement • Cranial-caudal applicator shifts only • + shift => longer guide wire travel => Cranial (T) and Posterior (o) • ± 1.5, ±3, ±5, ±6, ±7.5, ±10, ± 20 mm increments after dose calculation • Compare a shifted plan with an unshifted one • Assessment of impact on both Point A plans and MRIG-CBT plans
Simulating Recon uncertainty • applicator shifts along central axis only • + shift => longer guide wire travel => Cranial (T) and Posterior (o) • ± 1.5, ±3, ±5, ±6, ±7.5, ±10, ± 20 mm increments after dose calculation
Methods • Compare a shifted plan with an unshifted one • Assessment of impact on both Point A plans and MRIG-CBT plans • Point A plan based on reference optimization lines and manual optimization • MRIG-CBT plans using hybrid-inverse optimization • Dosimetric parameters: HR-CTV (D100, D90), Rectum D2cc, Bladder D2cc, Sigmoid D2cc, ICRU rectum and bladder points
Dosimetric impact of Applicator displacement • The dosimetric impact of simulated applicator displacements (<±1.5mm) on sigmoid, bladder, HR-CTV, and point A were significantly larger in MRIG-CBT plans as compared with point A plans. • Rectal D2cc most sensitive parameter • RoT: For dosimetric change < 10% … limit Applicator Displacement <± 1.5mm
Dosimetric impact of Applicator recon-uncertainty • Rectal D2cc most sensitive parameter (3mm => 15% error) • HR-CTV and Point A relatively less sensitive (10% => 7.5mm) • ICRU bladder point more sensitive than Bladder D2cc • RoT: For dosimetric change < 10% … limit Reconstruction uncertainty <± 3 mm
MRI-BT Consequences of different high-risk CTV sizes J Anderson et. al., “High resolution (3 Tesla) MRI-guided conformal brachytherapy for cervical cancer: consequences of different high- risk CTV sizes.” J Contemp Brachytherapy Vol 5(2) 2013
On High Resolution (3 Tesla) MRI datasets
MRI-BT • MRIG-CBT plans displayed considerable improvement for tumor coverage and OAR sparing over conventional treatment. • When the HR-CTV volume exceeded 40 cc, its improvements were diminished when using a conventional intracavitary applicator
CT versus MRI for Volumetric treatment planning • CT-based or MRI-based scans at brachytherapy are adequate for OAR DVH analysis. • However, CT tumor contours can significantly overestimate the tumor width, resulting in significant differences in the D(90), D(100), and volume treated to the prescription dose or greater for the HR-CTV compared with that using MRI. • MRI remains the standard for CTV definitionViswanathan AN, “Computed tomography versus magnetic resonance imaging-based contouring in cervical cancer brachytherapy: results of a prospective trial and preliminary guidelines for standardized contours.” Int J Radiat Oncol Biol Phys. Vol 68(2) 2007
Issue with imaging based volumetric brachytherapy techniques Dosage consensus? Dose to point A Equivalence to HR-CTV on MRI Equivalence to CT based CTV via MR - road ???
And…for patients ineligible for ICBT
TRUS guided Interstitial Brachytherapy of the cervix *D N Sharma et. al. “Use of trans-rectal ultrasound for high dose rate interstitial brachytherapy for patients of carcinoma of uterine cervix” J Gynecol Oncol.Vol 21(1) 2010 For patients ineligible for ICBT 25 patient study (40 TRUS guided Interstitial plans) TRUS guidance: 1.full volumetric extent of disease 2.Image guided Needle insertion MUPIT template With or without central Tandem Plate stitched to the skin Martinez Universal Perineal Interstitial Template (MUPIT)- Nucletron
Interstitial BT for Cervical cancer • For patients ineligible for ICBT
TRUS guided Interstitial Brachytherapy of the cervix D N Sharma et. al. “Use of trans-rectal ultrasound for high dose rate interstitial brachytherapy for patients of carcinoma of uterine cervix” J Gynecol Oncol.Vol 21(1) 2010 Needle tip against gut-wall needles in the cervical tumor region covering it adequately.
TRUS Interstitial BT….. • Treatment Planning using CT imaging • Not a point-dose Rx • Dose prescribed at the periphery of the target volume • 2 sessions (one session per week), dose of 10 Gy/fx • The rationale of using high dose per fraction is the short treatment time, equal effectiveness, convenient and least morbid.* Thick red - target area Thin red - prescription isodose D N Sharma et. al. “Use of trans-rectal ultrasound for high dose rate interstitial brachytherapy for patients of carcinoma of uterine cervix” J Gynecol Oncol.Vol 21(1) 2010
TRUS interstitial volumetric BT Severe late toxicity was observed in 3 (12%) patients One patient had vesico-vaginal fistula and required diversion colostomy one patient with bowel obstruction and one patient Grade 3 proctitis, were managed conservatively. Overall pelvic control rate was 64% Group 1, Group II, and Group III had pelvic control rate of 80%, 50%, and 56%, respectively 9 pelvic failures 3 patients associated distant metastasis TRUS is most practical and effective imaging device for guiding the IBT procedure for cervical cancer patients, especially in developing countries
TRUS and MRI Comparison of the target width and thickness showed a high correlation between TRUS and MRI, indicating the potential of TRUS for target definition in image-guided adaptive brachytherapy. M. P Schmid et. al. “Feasibility of transrectal ultrasonography for assessment of cervical cancer”, Strahlentherapie und Onkologie, Vol 189(2) 2013
Last but not the least Another milestone… Transition from a pure point-dose based dose calculation algorithm to a hybrid model based Dose calculation! “ACUROS Brachytherapy” Monte Carlo akin dose accuracy and faster Initial plan based on TG-43. Coupled with inhomogeneity correction Better representation of Patient Brachy dose
I bet I am out of time now!
But not so much to not extend my heartfelt thanks to all the authors I have cited and to Bruce R Thomadsen for a quick review of this review!