Direction modulated brachytherapy (DMBT) for treatment of cervical cancer: A planning study with (192) Ir, (60) Co, and (169) Yb HDR sources.

To evaluate plan quality of a novel MRI-compatible direction modulated brachytherapy (DMBT) tandem applicator using 192 Ir, 60 Co, and 169 Yb HDR brachytherapy sources, for various cervical cancer high-risk clinical target volumes (CTVHR ). The novel DMBT tandem applicator has six peripheral grooves of 1.3-mm diameter along a 5.4-mm thick nonmagnetic tungsten alloy rod. Monte Carlo (MC) simulations were used to benchmark the dosimetric parameters of the 192 Ir, 60 Co, and 169 Yb HDR sources in a water phantom against the literature data. 45 clinical cases that were treated using conventional tandem-and-ring applicators with 192 Ir source (192 Ir-T&R) were selected consecutively from intErnational MRI-guided BRAchytherapy in CErvical cancer (EMBRACE) trial. Then, for each clinical case, 3D dose distribution of each source inside the DMBT and conventional applicators were calculated and imported onto an in-house developed inverse planning optimization code to generate optimal plans. All plans generated by the DMBT tandem-and-ring (DMBT T&R) from all three sources were compared to the respective 192 Ir-T&R plans. For consistency, all plans were normalized to the same CTVHR D90 achieved in clinical plans. The D2 cm3 for organs at risk (OAR) such as bladder, rectum, and sigmoid, and D90, D98, D10, V100, and V200 for CTVHR were calculated. In general, plan quality significantly improved when a conventional tandem (Con.T) is replaced with the DMBT tandem. The target coverage metrics were similar across 192 Ir-T&R and DMBT T&R plans with all three sources (P > 0.093). 60 Co-DMBT T&R generated greater hot spots and less dose homogeneity in the target volumes compared with the 192 Ir- and 169 Yb-DMBT T&R plans. Mean OAR doses in the DMBT T&R plans were significantly smaller (P < 0.0084) than the 192 Ir-T&R plans. Mean bladder D2 cm3 was reduced by 4.07%, 4.15%, and 5.13%, for the 192 Ir-, 60 Co-, and 169 Yb-DMBT T&R plans respectively. Mean rectum (sigmoid) D2 cm3 was reduced by 3.17% (3.63%), 2.57% (3.96%), and 4.65% (4.34%) for the 192 Ir-, 60 Co-, and 169 Yb-DMBT T&R plans respectively. The DMBT T&R plans with the 169 Yb source generally resulted in the greatest OAR sparing when the CTVHR were larger and irregular in shape, while for smaller and regularly shaped CTVHR (<30 cm3 ), OAR sparing between the sources were comparable. The DMBT tandem provides a promising alternative to the Con.T design with significant improvement in the plan quality for various target volumes. The DMBT T&R plans generated with the three sources of varying energies generated superior plans compared to the conventional T&R applicators. Plans generated with the 169 Yb-DMBT T&R produced best results for larger and irregularly shaped CTVHR in terms of OAR sparing. Thus, this study suggests that the combination of the DMBT tandem applicator with varying energy sources can work synergistically to generate improved plans for cervical cancer brachytherapy.

Safigholi H ，Han DY ，Mashouf S ，Soliman A ，Meigooni AS ，Owrangi A ，Song WY ... -  《-》

Direction modulated brachytherapy (DMBT) tandem applicator for cervical cancer treatment: Choosing the optimal shielding material.

To investigate the dose modulation capability of a novel MRI-compatible direction modulated brachytherapy (DMBT) tandem applicator design with various high-density shielding materials for brachytherapy treatment of cervical cancer. The shield materials that have been evaluated are tantalum (Ta), pure tungsten (W), gold (Au), rhenium (Re), osmium (Os), platinum (Pt), iridium (Ir), and W' tungsten alloy (95%W, 3.5%Ni, 1.5%Cu). The recently proposed six-channel DMBT tandem is composed of nonmagnetic tungsten alloy (W') rod with diameter of 5.4 mm and coated with 0.3-mm thick bio-safe plastic sheath. The tandem shielding material can, however, be individually replaced with various other shields to create directional radiation. Monte Carlo N-Particle (MCNP) code was used to calculate the three-dimensional (3D) dose distributions in a water phantom for an HDR 192 Ir (mHDR-v2) source inside each DMBT tandem with various shields and a plastic conventional tandem (Con.T). Then, the 3D dose distributions were imported into an in-house-coded inverse planning optimization algorithm to obtain optimal plans for 12 clinical cases chosen at random from the international RetroEMBRACE dataset involving conventional tandem and ring (Con.T&R) applicators. All plans generated by the DMBT tandem and ring (DMBT&R) with the tungsten alloy [DMBT(W')&R] were compared with the corresponding Con.T&R plans, to generate benchmark results. These benchmark results were then considered as reference plans for other shields performances. Plans were normalized to receive the same high-risk clinical target volume (CTVHR ) D90 . The D100 , D10 , and V100 for CTVHR , and D2cm3 for organs at risk (OARs) of bladder, sigmoid, and rectum were calculated and compared. Transmission factor (TF), that is, the dose in the backside of the DMBT shield over that in the front opening, at a 5 cm distance, were 36.6%, 34.8%, 31.9%, 28.9%, 27.9%, 26.2%, 26.2%, and 25.5%, for Ta, W', W, Re, Au, Os, Pt, and Ir shields, respectively. On average, the CTVHR values for D100 , V100 , D10 were not significantly different across all DMBT&R shields and the Con.T&R plans (P > 0.219). For the D2cm3 , the benchmark results showed significant reductions (P < 0.03), that is, on average, -8.3% for bladder, -10.7% for rectum, and -10.1% for sigmoid, compared to the Con.T&R plans. However, the various shields showed little improvement from the tungsten alloy (W'), where on average, rectum (bladder) [sigmoid] D2cm3 were reduced by -1.32% (-0.85%) [-1.01%], -1.25% (-0.78%) [-0.91%], -1.22% (-0.75%) [-0.86%], -0.94% (-0.60%) [-0.70%], -0.84% (-0.51%) [-0.59%], and -0.38% (-0.24%) [-0.23%] for Ir, Pt, Os, Au, Re, and W shields, relative to the benchmark W' DMBT plans, respectively. These corresponding values for Ta increased by +0.28% (+0.08%) [+0.25%], respectively. The Ir, Pt, Os, Au, Re, and W shielding materials, respectively, in descending order, lead to better OAR sparing than the DMBT(W')&R plans. However, the amount of improvement is limited and clinically insignificant. This finding suggests that the initial W' shield remains a suitable choice given the proven MR compatibility, for use in MR-guided adaptive brachytherapy of cervical cancer.

Safigholi H ，Han DY ，Soliman A ，Song WY ... -  《-》

Direction-modulated brachytherapy for high-dose-rate treatment of cervical cancer. I: theoretical design.

To demonstrate that utilization of the direction-modulated brachytherapy (DMBT) concept can significantly improve treatment plan quality in the setting of high-dose-rate (HDR) brachytherapy for cervical cancer. The new, MRI-compatible, tandem design has 6 peripheral holes of 1.3-mm diameter, grooved along a nonmagnetic tungsten-alloy rod (ρ = 18.0 g/cm(3)), enclosed in Delrin tubing (polyoxymethylene, ρ = 1.41 g/cm(3)), with a total thickness of 6.4 mm. The Monte Carlo N-Particle code was used to calculate the anisotropic (192)Ir dose distributions. An in-house-developed inverse planning platform, geared with simulated annealing and constrained-gradient optimization algorithms, was used to replan 15 patient cases (total 75 plans) treated with a conventional tandem and ovoids (T&O) applicator. Prescription dose was 6 Gy. For replanning, we replaced the conventional tandem with that of the new DMBT tandem for optimization but left the ovoids in place and kept the dwell positions as originally planned. All DMBT plans were normalized to match the high-risk clinical target volume V100 coverage of the T&O plans. In general there were marked improvements in plan quality for the DMBT plans. On average, D2cc for the bladder, rectum, and sigmoid were reduced by 0.59 ± 0.87 Gy (8.5% ± 28.7%), 0.48 ± 0.55 Gy (21.1% ± 27.2%), and 0.10 ± 0.38 Gy (40.6% ± 214.9%) among the 75 plans, with best single-plan reductions of 3.20 Gy (40.8%), 2.38 Gy (40.07%), and 1.26 Gy (27.5%), respectively. The high-risk clinical target volume D90 was similar, with 6.55 ± 0.96 Gy and 6.59 ± 1.06 Gy for T&O and DMBT, respectively. Application of the DMBT concept to cervical cancer allowed for improved organ at risk sparing while achieving similar target coverage on a sizeable patient population, as intended, by maximally utilizing the anatomic information contained in 3-dimensional imaging. A series of mechanical and clinical validations are to be followed.

Han DY ，Webster MJ ，Scanderbeg DJ ，Yashar C ，Choi D ，Song B ，Devic S ，Ravi A ，Song WY ... -  《-》

Direction Modulated Brachytherapy for Treatment of Cervical Cancer. II: Comparative Planning Study With Intracavitary and Intracavitary-Interstitial Techniques.

To perform a comprehensive comparative planning study evaluating the utility of the proposed direction modulated brachytherapy (DMBT) tandem applicator against standard applicators, in the setting of image guided adaptive brachytherapy of cervical cancer. A detailed conceptual article was published in 2014. The proposed DMBT tandem applicator has 6 peripheral grooves of 1.3-mm width, along a 5.4-mm-thick nonmagnetic tungsten alloy rod of density 18.0 g/cm(3), capable of generating directional dose profiles. We performed a comparative planning study with 45 cervical cancer patients enrolled consecutively in the prospective observational EMBRACE study. In all patients, MRI-based planning was performed while utilizing various tandem-ring (27 patients) and tandem-ring-needles (18 patients) applicators, in accordance with the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology recommendations. For unbiased comparisons, all cases were replanned with an in-house-developed inverse optimization code while enforcing a uniform set of constraints that are reflective of the clinical practice. All plans were normalized to the same high-risk clinical target volume D90 values achieved in the original clinical plans. In general, if the standard tandem was replaced with the DMBT tandem while maintaining all other planning conditions the same, there was consistent improvement in the plan quality. For example, among the 18 tandem-ring-needles cases, the average D2cm(3) reductions achieved were -2.48% ± 11.03%, -4.45% ± 5.24%, and -5.66% ± 6.43% for the bladder, rectum, and sigmoid, respectively. An opportunity may also exist in avoiding use of needles altogether for when the total number of needles required is small (approximately 2 to 3 needles or less), if DMBT tandem is used. Integrating the novel DMBT tandem onto both intracavitary and intracavitary-interstitial applicator assembly enabled consistent improvement in the sparing of the OARs, over a standard "single-channel" tandem, though individual variations in benefit were considerable. Although at an early stage of development, the DMBT concept design is demonstrated to be useful and pragmatic for potential clinical translation.

Han DY ，Safigholi H ，Soliman A ，Ravi A ，Leung E ，Scanderbeg DJ ，Liu Z ，Owrangi A ，Song WY ... -  《-》

A novel minimally invasive dynamic-shield, intensity-modulated brachytherapy system for the treatment of cervical cancer.

To present a novel, MRI-compatible dynamicshield intensity modulated brachytherapy (IMBT) applicator and delivery system using 192 Ir, 75 Se, and 169 Yb radioisotopes for the treatment of locally advanced cervical cancer. Needle-free IMBT is a promising technique for improving target coverage and organs at risk (OAR) sparing. The IMBT delivery system dynamically controls the rotation of a novel tungsten shield placed inside an MRI-compatible, 6-mm wide intrauterine tandem. Using 36 cervical cancer cases, conventional intracavitary brachytherapy (IC-BT) and intracavitary/interstitial brachytherapy (IC/IS-BT) (10Ci 192 Ir) plans were compared to IMBT (10Ci 192 Ir; 11.5Ci 75 Se; 44Ci 169 Yb). All plans were generated using the Geant4-based Monte Carlo dose calculation engine, RapidBrachyMC. Treatment plans were optimized then normalized to the same high-risk clinical target volume (HR-CTV) D90 and the D2cc for bladder, rectum, and sigmoid in the research brachytherapy planning system, RapidBrachyMCTPS. Plans were renormalized until either of the three OAR reached dose limits to calculate the maximum achievable HR-CTV D90 and D98 . Compared to IC-BT, IMBT with either of the three radionuclides significantly improves the HR-CTV D90 and D98 by up to 5.2% ± 0.3% (P < 0.001) and 6.7% ± 0.5% (P < 0.001), respectively, with the largest dosimetric enhancement when using 169 Yb followed by 75 Se and then 192 Ir. Similarly, D2cc for all OAR improved with IMBT by up to 7.7% ± 0.6% (P < 0.001). For IC/IS-BT cases, needle-free IMBT achieved clinically acceptable plans with 169 Yb-based IMBT further improving HR-CTV D98 by 1.5% ± 0.2% (P = 0.034) and decreasing sigmoid D2cc by 1.9% ± 0.4% (P = 0.048). Delivery times for IMBT are increased by a factor of 1.7, 3.3, and 2.3 for 192 Ir, 75 Se, and 169 Yb, respectively, relative to conventional 192 Ir BT. Dynamic shield IMBT provides a promising alternative to conventional IC- and IC/IS-BT techniques with significant dosimetric enhancements and even greater improvements with intermediate energy radionuclides. The ability to deliver a highly conformal, OAR-sparing dose without IS needles provides a simplified method for improving the therapeutic ratio less invasively and in a less resource intensive manner.

Morcos M ，Antaki M ，Viswanathan AN ，Enger SA ... -  《-》