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Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
Advances in Brachytherapy Treatment Planning and Delivery
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Advances in Brachytherapy Treatment Planning and Delivery

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A review of advances in Brachytherapy treatment planning and delivery in last decade or so, with main focus on brachytherapy for Prostate cancer, Breast cancer and Cervical cancer

A review of advances in Brachytherapy treatment planning and delivery in last decade or so, with main focus on brachytherapy for Prostate cancer, Breast cancer and Cervical cancer

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  • “In the past decade, there have been major technical innovations in the field of brachytherapy that have revolutionized its use in the management of patients with malignant disease. It is now at the forefront of radiation therapy for prostate cancer, breast cancer, and gynecological cancers1”
  • All the estimates point toward low values of alpha/beta, at least as low as the estimates of Brenner and Hall, and possibly low
    er than the expected values of about 3 Gy for late complications. Hypofractionation trials for intermediate-risk prostatic cancer appear to be indicated.
    The second method gave the definitive result of alpha/beta = 1.49 Gy (95% CI 1.25-1.76) and T(12) = 1.90 h (95% CI 1.42-2.86 h). The first method gave a range from 1.4 to 1.9 Gy and showed that if mean or median dose were used instead of prescribed dose, the estimate of alpha/beta would be substantially below 1 Gy. The third method, although based on early follow-up, was consistent with low values of alpha/beta in the region of 2 Gy or below. The estimate for T(12) is the first value reported for prostate tumors in situ.
    The implications for possibly treating prostatic cancer using fewer and larger fractions are important.
    Direct evidence that prostate tumors show high sensitivity to fractionation (low alpha/beta ratio), similar to late-responding normal tissue.
    Brenner DJ1, Martinez AA, Edmundson GK, Mitchell C, Thames HD, Armour EP.
    alpha/beta = 1.2 Gy
  • Radiation therapy for prostate cancer has been facing a potential paradigm shift since 1999. That is when Brenner and Hall (1) pointed-out that the biological properties of prostate tumours were more like those of very slowly-proliferating late-responding normal tissues (that lead to late complications in normal tissues), than they were to the much more rapidly re-populating carcinomas of most other types of human tumours. This unusual reversal of the relative sensitivities to dose-fraction size, of tumours versus late-responding normal tissues at-risk in conventional radiotherapy, suggested that a few large fractions – hypo-fractionation – might be advantageous for these specific types of tumour (with very low α/β ratios). This is a totally different strategy from the hard-learnt “many-and-small-fractions” strategies that were successful for other types of tumours (which had higher α/β ratios near 10 Gy). Such a great change of perspective was so opposite to conventional habits and instincts of safe practice in radiotherapy that instead of welcoming the opportunity to investigate hypo-fractionation, as a possible opportunity to give more biological damage to prostate tumours (only) and less damage to the normal tissues at-risk by using slightly lower total doses and many fewer fractions, almost 15 years of controversy have arisen.
    To answer the questions: Is the α/β ratio (radiosensitivity to size of dose-per-fraction) really low enough to justify using a few large dose fractions instead of the traditional many small doses? Does this parameter vary with prognostic risk factors?
    METHODS AND MATERIALS:
    Three large statistical overviews are critiqued, with results for 5,000, 6,000 and 14,000 patients with prostate carcinoma, respectively.
    RESULTS:
    These major analyses agree in finding the average α/β ratio to be less than 2 Gy: 1.55, (95% confidence interval=0.46-4.52), 1.4 (0.9-2.2), and the third analysis 1.7 (1.4-2.2) by the ASTRO and 1.6 (1.2-2.2) by Phoenix criteria. All agree that α/β values do not vary significantly with the low, intermediate, high and "all-included" risk factors.
    CONCLUSION:
    The high sensitivity to dose-per-fraction is an intrinsic property of prostate carcinomas and this supports the use of hypo-fractionation to increase the therapeutic gain for these tumours with dose-volume modelling to reduce the risk of late complications in rectum and bladder.
  • What hypofractionated protocols should be tested for prostate cancer?
    Fowler JF1, Ritter MA, Chappell RJ, Brenner DJ.
    Recent analyses of clinical results have suggested that the fractionation sensitivity of prostate tumors is remarkably high; corresponding point estimates of the alpha/beta ratio for prostate cancer are around 1.5 Gy, much lower than the typical value of 10 Gy for many other tumors. This low alpha/beta value is comparable to, and possibly even lower than, that of the surrounding late-responding normal tissue in rectal mucosa (alpha/beta nominally 3 Gy, but also likely to be in the 4-5 Gy range). This lower alpha/beta ratio for prostate cancer than for the surrounding late-responding normal tissue creates the potential for therapeutic gain. We analyze here possible high-gain/low-risk hypofractionated protocols for prostate cancer to test this suggestion.
    Hypofractionation: what does it mean for prostate cancer treatment?
    Liao Y1, Joiner M, Huang Y, Burmeister J.
    1Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, USA. yixiang_liao@rush.edu
    Using current radiobiologic models and biologic parameters, we performed an exploratory study of the clinical consequences of hypofractionation in prostate cancer radiotherapy.
    METHODS AND MATERIALS:
    Four hypofractionated treatment regimens were compared with standard fractionation of 2 Gy x 39 for prostate carcinoma using a representative set of anatomical structures. The linear-quadratic model and generalized equivalent uniform dose formalism were used to calculate normalized equivalent uniform dose (gEUD(2)), from which tumor control probability and normal tissue complication probability were calculated, as well as "complication-free tumor control probability" (P+). The robustness of the results was tested for various tumor alpha/beta values and broad interval of biologic parameters such as surviving fraction after a dose of 2 Gy (SF2).
    RESULTS:
    A 2.5% and 5.8% decrease in NTCP for rectum and bladder, respectively, was predicted for the 6.5 Gy/fraction regimen compared with the 2 Gy/fraction. Conversely, TCP for hypofractionated regimens decreased significantly with increasing SF2 and alpha/beta. For tumor cells with SF2 = 0.4-0.5, P+ was superior for nearly all hypofractionated regimens even for alpha/beta values up to 6.5 Gy. For less responsive tumor cells (SF2 = 0.6), hypofractionation regimens were inferior to standard fractionation at much lower alpha/beta.
    CONCLUSION:
    For a sample set of anatomical structures, existing radiobiologic data and models predict improved clinical results from hypofractionation over standard fractionation not only for prostate carcinoma with low alpha/beta but also for high alpha/beta (up to 6.5 Gy) when SF2 < 0.5. Predicted results for specific patients may vary with individual anatomy, and large-scale clinical conclusions can be drawn only after performing similar analysis on an appropriate population of patients.
  • PURPOSE:
    To compare the dose and volume of bladder and rectum treated using high-dose-rate (HDR) prostate implant boost versus conformal external beam radiotherapy boost, and to use the dose-volume information to perform a critical volume tolerance (CVT) analysis and then estimate the potential for further dose escalation using HDR brachytherapy boost.
    METHODS AND MATERIALS:
    Using CT scan data collected before and after patients underwent HDR prostate implant, a 7-field conformal prostate-only external beam treatment plan and HDR brachytherapy treatment plan were constructed for each patient. Doses to the normal structures were calculated. Dose-volume histograms (DVH) were plotted for comparison of the two techniques. Wilcoxon signed rank test was performed at four dose levels to compare the dose to normal structures between the two treatment techniques. The acute and late effects of HDR brachytherapy were calculated based on the linear-quadratic (LQ) model. CVT analyses were performed to calculate the potential dose gain (PDG) using HDR brachytherapy boost.
    RESULTS:
    The volume of bladder and rectum receiving high dose was significantly less from implant boost. On the average, 0.19 cc of the bladder received 100% of the brachytherapy prescription dose, compared with 5.1 cc of the bladder receiving 100% of the prescription dose in the 7-field conformal external beam radiotherapy boost. Similarly, 0.25 cc of the rectum received 100% of the dose with the implant boost, as compared to 2.9 cc in the conformal external beam treatment. The implant also delivered higher doses inside the prostate volume. On average, 47% of the prostate received > or =150% of the prescription dose. The CVT analysis revealed a range of PDG using the HDR brachytherapy boost which depended on the following variables: critical volume (CV), critical volume tolerance dose (CVTD), number of HDR fractions (N), and the dose of external beam radiotherapy (XRT) delivered with brachytherapy boost. The PDG varied from -3.45% to 10.53% for tumor with an alpha-beta ratio of 10 and 7.14% to 64.6% for tumor with an alpha-beta ratio of 1.5 based on the parameters used for calculation in this study.
    CONCLUSIONS:
    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.
  • HDR brachytherapy (HDR-BT) in treatment of prostate cancer is most frequently used together with external beam radiation therapy (EBRT) as a boost (increasing the treatment dose precisely to the tumor). In the early stages of the disease (low, sometimes intermediate risk group), HDR-BT is more often used as monotherapy. There are no significant differences in treatment results (overall survival rate - OS, local recurrence rate - LC) between radical prostatectomy, EBRT and HDR-BT.
    TRUS: real-time imaging, good image quality of the prostate boundary, clear visualisation of the needles.
    But poor soft-tissue resolution;
    therefore, a marker wire or aerated gel is inserted into the urinary catheter in order 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.
  • (Urology and Radiology Departments, URobotics Laboratory, The Johns Hopkins University, School of Medicine, Baltimore, MD) an IEEE publication*
    Abstract:
    The paper presents a robotic method of performing low dose rate prostate brachytherapy under magnetic resonance imaging (MRI) guidance. The design and operation of a fully automated MR compatible seed injector is presented. This is used with the MrBot robot for transperineal percutaneous prostate access. A new image-registration marker and algorithms are also presented. The system is integrated and tested with a 3T MRI scanner. Tests compare three different registration methods, assess the precision of performing automated seed deployment, and use the seeds to assess the accuracy of needle targeting under image guidance. Under the ideal conditions of the in vitro experiments, results show outstanding image-guided needle and seed placement accuracy.
    end-effector mounted on a MR compatible robotic manipulator – THE MrBot
    new type of pneumatic actuators (PneuStep)
    This paper presents the MR compatible automated seed placement end-effector, image registration and guidance algorithms - seed placement in agar and ex vivo models
    5 degree of freedom (DOF) (3T+2R) placement: all directions (3T) and its orientation about two directions normal to the needle axis (2R)
  • Longest followup
  • You can see how the struts of the applicator rest nicely along edges of the cavity.
  • ClearPath (North American Scientific Inc, Chatsworth, CA) is a hybrid device that combines the advantage of a balloon catheter with multicatheter brachytherapy. The ClearPath device consists of 6 expandable tubes around a central catheter that accepts the HDR iridium-192 source. These catheters can be adjusted by rotating a knob at the base of the device to conform to the lumpectomy cavity.
    After ClearPath catheter placement, a rubber sleeve is sutured to the patient and the base of the catheter is cut off, leaving only the catheters exposed. This avoids cumbersome exposed catheters (a frequent source of patient discomfort and complaint) and allows reduction in the received radiation skin dose without compromising target volume such as in situations where inadequate skin distance may preclude APBI with other techniques (MammoSite).[72] Because ClearPath is a relatively new clinical device, no clinical outcome data currently exist.
    Dosimetric comparisons of ClearPath technology with MammoSite therapy have demonstrated similar target volume coverage with increased normal tissue-sparing
  • IORT with EBX: The treatment prescription is the delivery of 20 Gy to the balloon surface. The treatment is accomplished in 10-25 minutes based on the balloon size, fill volume, and the x-ray source calibration. The duration of the entire procedure including lumpectomy, sentinel lymph node biopsy, balloon catheter placement, radiation therapy, and closing the incisions is approximately two hours.
    The results of the TARGIT trial will help determine whether IORT is an equivalent alternative to standard whole breast external beam radiation therapy. If IORT methods, including EBX, are established as a standard treatment option, this may allow increased access to breast conserving therapy, as well as, improved quality of life and decreased medical costs for patients with a diagnosis of early-stage breast cancer.
    TARGIT trial is a phase III prospective, randomized trial comparing single fraction IORT delivered via EBX to conventional whole breast external beam radiation therapy. Sixteen international institutions are enrolling patients in the trial. Eligible patients include patients >35 years of age with T1-T3, N0 tumors eligible for breast conserving therapy.
  • Traditionally, prescription and treatment planning in intracavitary brachytherapy for cervix cancer have used either reference points (mainly 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. This practice has been supported by a long-standing clinical experience that has yielded an acceptable therapeutic ratio.
  • In brachytherapy for cervix cancer, doses to organs at risk (OARs) are traditionally calculated using the ICRU-38 point doses to rectum and bladder. Three-dimensional image-guided brachytherapy allows assessment of OAR dose with dose volume histograms (DVHs). The purpose of this study was to analyse the correlation between DVHs and ICRU point doses.
    METHODS:
    Using the PLATO™ planning system, the bladder, rectum and sigmoid were retrospectively contoured on 62 CT datasets for 20 patients treated with definitive radiotherapy. The median external beam radiotherapy dose was 45 Gy. Brachytherapy was delivered using a CT-MRI compatible tandem and ovoids to a median dose of 24 Gy in three fractions. DVHs were calculated, and the minimum dose to 2 cc of tissue receiving the highest dose (D(2cc) ) was recorded and compared with the ICRU point doses (D(ICRU) ).
    RESULTS:
    The mean rectal D(ICRU) was 4.01 Gy compared with D(2cc) of 4.28 Gy. The mean bladder D(ICRU) was 6.74 Gy compared with D(2cc) of 8.65 Gy. The mean sigmoid D(2cc) was 4.58 Gy. The mean dose ratios (D(2cc) /D(ICRU) ) were 1.08 for rectum and 1.39 for bladder. D(ICRU) correlated with D(2cc) for rectum (r = 0.76, P = 0.001) and for bladder (r = 0.78, P = 0.01).
    CONCLUSION:
    OAR doses assessed by DVH criteria were higher than ICRU point doses. The significant correlation between D(2cc) and D(ICRU) has allowed us to set DVH dose constraints for CT-based brachytherapy and thus begin the transition from two-dimensional to three-dimensional image-guided brachytherapy planning.
  • PURPOSE:
    This paper focuses on a novel image guidance technique for gynecological brachytherapy treatment. The present standard technique is orthogonal x-ray imaging to reconstruct the 3D position of the applicator when the availability of CT or MR is limited. Our purpose is to introduce 3D planning in the brachytherapy suite using a cone beam CT (CBCT) scanner dedicated to brachytherapy. This would avoid moving the patient between imaging and treatment procedures which may cause applicator motion. This could be used to replace the x-ray images or to verify the treatment position immediately prior to dose delivery.
    METHODS:
    The sources of CBCT imaging artifacts in the case of brachytherapy were identified and removed where possible. The image quality was further improved by modifying the x-ray tube voltage, modifying the compensator bowtie filter and optimizing technical parameters such as the detector gain or tube current.
    RESULTS:
    The image quality was adequate to reconstruct the applicators in the treatment planning system. The position of points A and the localization of the organs at risk (OAR) ICRU points is easily achieved. This allows identification of cases where the rectum had moved with respect to the ICRU point which would require asymmetrical source loading. A better visualization is a first step toward a better sparing of the OAR.
    CONCLUSIONS:
    Treatment planning for gynecological brachytherapy is aided by CBCT images. CBCT presents advantages over CT: acquisition in the treatment room and in the treatment position due to the larger clearance of the CBCT, thereby reducing problems associated to moving patients between rooms.
  • Figure shows the percentage doserelative to the TPS as a function of random and systemic longitudinal reconstruction uncertainties.
    Red area: >10% dose deviation for at least 10% of the patients
    Green: <10% dose deviation for at least 90% of the patients.
  • To simulate whole T&O was virtually shifted in a cranial (+) and caudal (-) direction in ± 1.5, ±3, ±5, ±6, ±7.5, ±10, ± 20 mm increments after dose calculation. Simply put, the whole T&O was shifted cranio-caudally while dwell times and positions are kept unchanged.
    Due to tight gauze packing and angle of the tandem torque is rare and this represents the most common shift scenario.
  • For recon uncertainty a tandem and 2 ovoids were shifted along their central axis. This was done because mostly the recon uncertainties exist along the central axis when the applicator libraries are used.
    Unlike the ring and tandem applicator where the uncertainties are mostly associated with rotational movement of the ring, ovoids recon based uncertainties occur in posterior-anterior direction along the central axis of the Ov-Tandem.
    + shift is when guide wire travels longer (cranial shift for tandem, posterior shift for ovoid) than expected and – shift is when a guide wire travels shorter (caudal shift for tandem, anterior shift for ovoid) than expected.
  • To evaluate conventional brachytherapy (BT) plans using dose-volume parameters and high resolution (3 Tesla) MRI datasets, and to quantify dosimetric benefits and limitations when MRI-guided, conformal BT (MRIG-CBT) plans are generated.
    MATERIAL AND METHODS:
    Fifty-five clinical high-dose-rate BT plans from 14 cervical cancer patients were retrospectively studied. All conventional plans were created using MRI with titanium tandem-and-ovoid applicator (T&O) for delivery. For each conventional plan, a MRIG-CBT plan was retrospectively generated using hybrid inverse optimization. Three categories of high risk (HR)-CTV were considered based on volume: non-bulky (< 20 cc), low-bulky (> 20 cc and < 40 cc) and bulky (≥ 40 cc). Dose-volume metrics of D90 of HR-CTV and D2cc and D0.1cc of rectum, bladder, and sigmoid colon were analyzed.
    RESULTS:
    Tumor coverage (HR-CTV D90) of the conventional plans was considerably affected by the HR-CTV size. Sixteen percent of the plans covered HR-CTV D90 with the prescription dose within 5%. At least one OAR had D2cc values over the GEC-ESTRO recommended limits in 52.7% of the conventional plans. MRIG-CBT plans showed improved target coverage for HR-CTV D90 of 98 and 97% of the prescribed dose for non-bulky and low-bulky tumors, respectively. No MRIG-CBT plans surpassed the D2cc limits of any OAR. Only small improvements (D90 of 80%) were found for large targets (> 40 cc) when using T&O applicator approach.
    CONCLUSIONS:
    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.
  • To evaluate conventional brachytherapy (BT) plans using dose-volume parameters and high resolution (3 Tesla) MRI datasets, and to quantify dosimetric benefits and limitations when MRI-guided, conformal BT (MRIG-CBT) plans are generated.
    MATERIAL AND METHODS:
    Fifty-five clinical high-dose-rate BT plans from 14 cervical cancer patients were retrospectively studied. All conventional plans were created using MRI with titanium tandem-and-ovoid applicator (T&O) for delivery. For each conventional plan, a MRIG-CBT plan was retrospectively generated using hybrid inverse optimization. Three categories of high risk (HR)-CTV were considered based on volume: non-bulky (< 20 cc), low-bulky (> 20 cc and < 40 cc) and bulky (≥ 40 cc). Dose-volume metrics of D90 of HR-CTV and D2cc and D0.1cc of rectum, bladder, and sigmoid colon were analyzed.
    RESULTS:
    Tumor coverage (HR-CTV D90) of the conventional plans was considerably affected by the HR-CTV size. Sixteen percent of the plans covered HR-CTV D90 with the prescription dose within 5%. At least one OAR had D2cc values over the GEC-ESTRO recommended limits in 52.7% of the conventional plans. MRIG-CBT plans showed improved target coverage for HR-CTV D90 of 98 and 97% of the prescribed dose for non-bulky and low-bulky tumors, respectively. No MRIG-CBT plans surpassed the D2cc limits of any OAR. Only small improvements (D90 of 80%) were found for large targets (> 40 cc) when using T&O applicator approach.
    CONCLUSIONS:
    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.
  • Dana farber (Boston)
    Ten patients underwent both MRI and CT after applicator insertion. The dose received by at least 90% of the volume (D(90)), the minimal target dose (D(100)), the volume treated to the prescription dose or greater for tumor for the high-risk (HR) and intermediate-risk (IR) clinical target volume (CTV) and the dose to 0.1 cm3, 1 cm3, and 2 cm3 for the OARs were evaluated. A standardized approach to contouring on CT (CT(Std)) was developed, implemented (HR- and IR-CTV(CTStd)), and compared with the MRI contours.
    Computed tomography-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 definition
  • certain patients are not suitable for it due to extensive disease in the cervix, obliteration of the cervical os, narrow vagina, extension of disease into the lower vagina and parametrical disease beyond the high dose range of the ICRT applicators
    The Martinez Universal Perineal Interstitial Template (MUPIT) is designed for interstitial placement of needlesfor brachytherapy. The periphery of the template has angled holes for the needles to reach the widest tumor spread. Rectal and vaginal cylinders are included to provide better template stability and additional treatment options.
  • certain patients are not suitable for it due to extensive disease in the cervix, obliteration of the cervical os, narrow vagina, extension of disease into the lower vagina and parametrical disease beyond the high dose range of the ICRT applicators
    The Martinez Universal Perineal Interstitial Template (MUPIT) is designed for interstitial placement of needlesfor brachytherapy. The periphery of the template has angled holes for the needles to reach the widest tumor spread. Rectal and vaginal cylinders are included to provide better template stability and additional treatment options.
  • 2.5 mm apart
    Thick red line depicts the target area obtained by line joining the outermost needles. The thin red line represents the prescription isodose (100% isodose line).
    Such an HDR dose fractionation schedule has already been tried for ICRT by Patel et al. They have used a dose of 9 Gy to point A in 2 weekly fractions and reported successful clinical results. Therefore an HDR dose of 8 to 10 Gy is biologically equivalent and clinically effective dose. Additionally, with single high dose of 10 Gy (un-fractionated), the treatment is completed within 2 to 3 hours which has several advantages like least trauma, least probability of bleeding, infection, fistulas etc. At the same time, it is highly convenient and comfortable to patient.
  • T2-weighted MRI and TRUS were performed on 17 patients with locally advanced cervical cancer at the same timepoint—either at the time of diagnosis, or at the time of brachytherapy before or after insertion of the applicator. Patients treated from 2009 to 2011 were selected for this study based on the availability of MRI and TRUS at the defined time points. The target was defined as the complete macroscopic tumor mass and the remaining cervix and was measured on transversal planes. Descriptive statistics and a linear regression analysis were performed for the groups.
    Linear regression analysis for target width and thickness between TRUS and MRI demonstrated a correlation with R2 = 0.842 and R2 = 0.943, respectively.
  • Transcript

    • 1. Advances in Brachytherapy Delivery and Treatment Planning By Vibha Chaswal, Ph.D. (Independent Researcher and Collaborator) USA
    • 2. Brachytherapy Today! • High precision targeted Radiotherapy Modality with significant patient benefit • High Precision image guided adaptive brachytherapy (IGABT)
    • 3. Prostate Carcinoma (Over past almost 15 years…)
    • 4. 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
    • 5. 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
    • 6. HDR-BT of the prostate Hypofractionation and Dose escalation
    • 7. 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
    • 8. 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)
    • 9. 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
    • 10. 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
    • 11. 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
    • 12. A Challapalli, E Jones, C Harvey et. al., BJR, 85(2012)
    • 13. HDR-BT pre-planning Picture courtesy: Janusz Skowronek, MD, PhD, Greater Poland Cancer Center
    • 14. HDR-BT real-time planning Picture courtesy: Janusz Skowronek, MD, PhD, Greater Poland Cancer Center
    • 15. 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.
    • 16. Can’t forget still the gold standard most common Prostate BT procedure……
    • 17. 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
    • 18. Slide courtesy: R Miller, B R Thomadsen, “Brachytherapy Physics: Everything you need to know and controversial Issues”, AAPM 2009
    • 19. Slide courtesy: R Miller, B R Thomadsen, “Brachytherapy Physics: Everything you need to know and controversial Issues”, AAPM 2009
    • 20. 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)
    • 21. Needle placement clinical considerations – Prostate LDR/HDR BT
    • 22. Breast Cancer
    • 23. 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
    • 24. 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
    • 25. 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
    • 26. 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.
    • 27. Mammosite: Single Lumen Vs Multiple lumen Mammosite implant
    • 28. 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
    • 29. 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*
    • 30. 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
    • 31. 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
    • 32. Electronic brachytherapy • Minimal Shielding • No rigorous radiation source regulations • IORT with EBX - TARGIT trial
    • 33. 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
    • 34. Cervical Cancer (Aha!)
    • 35. 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
    • 36. 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
    • 37. 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
    • 38. 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
    • 39. Good to better…...
    • 40. 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
    • 41. 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
    • 42. Slide courtesy: J Siewerdsen and G-H Chen, Johns Hopkins University and UW- Madison
    • 43. Most Promising IGBT…. MRI guided Intracavitary BT with its excellent soft tissue contrast! Futuristic for many…..but on road to future!
    • 44. 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.
    • 45. 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!
    • 46. 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
    • 47. 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
    • 48. 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
    • 49. 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
    • 50. 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
    • 51. 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
    • 52. 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
    • 53. On High Resolution (3 Tesla) MRI datasets
    • 54. 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
    • 55. 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
    • 56. 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 ???
    • 57. And…for patients ineligible for ICBT
    • 58. 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
    • 59. Interstitial BT for Cervical cancer • For patients ineligible for ICBT
    • 60. 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.
    • 61. 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
    • 62. 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
    • 63. 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
    • 64. 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
    • 65. I bet I am out of time now!
    • 66. 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!
    • 67. THANK YOU!

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