Adam Cunha

IPIP: A new approach to inverse planning for HDR brachytherapy by directly optimizing dosimetric indices

PURPOSE Many planning methods for high dose rate (HDR) brachytherapy require an iterative approach. A set of computational parameters are hypothesized that will give a dose plan that meets dosimetric criteria. A dose plan is computed using these parameters, and if any dosimetric criteria are not met, the process is iterated until a suitable dose plan is found. In this way, the dose distribution is controlled by abstract parameters. The purpose of this study is to develop a new approach for HDR brachytherapy by directly optimizing the dose distribution based on dosimetric criteria. METHODS The authors developed inverse planning by integer program (IPIP), an optimization model for computing HDR brachytherapy dose plans and a fast heuristic for it. They used their heuristic to compute dose plans for 20 anonymized prostate cancer image data sets from patients previously treated at their clinic database. Dosimetry was evaluated and compared to dosimetric criteria. RESULTS Dose plans computed from IPIP satisfied all given dosimetric criteria for the target and healthy tissue after a single iteration. The average target coverage was 95%. The average computation time for IPIP was 30.1 s on an Intel(R) Core 2 Duo CPU 1.67 GHz processor with 3 Gib RAM. CONCLUSIONS IPIP is an HDR brachytherapy planning system that directly incorporates dosimetric criteria. The authors have demonstrated that IPIP has clinically acceptable performance for the prostate cases and dosimetric criteria used in this study, in both dosimetry and runtime. Further study is required to determine if IPIP performs well for a more general group of patients and dosimetric criteria, including other cancer sites such as GYN.

NPIP: A skew line needle configuration optimization system for HDR brachytherapy

PURPOSE In this study, the authors introduce skew line needle configurations for high dose rate (HDR) brachytherapy and needle planning by integer program (NPIP), a computational method for generating these configurations. NPIP generates needle configurations that are specific to the anatomy of the patient, avoid critical structures near the penile bulb and other healthy structures, and avoid needle collisions inside the body. METHODS NPIP consisted of three major components: a method for generating a set of candidate needles, a needle selection component that chose a candidate needle subset to be inserted, and a dose planner for verifying that the final needle configuration could meet dose objectives. NPIP was used to compute needle configurations for prostate cancer data sets from patients previously treated at our clinic. NPIP took two user-parameters: a number of candidate needles, and needle coverage radius, δ. The candidate needle set consisted of 5000 needles, and a range of δ values was used to compute different needle configurations for each patient. Dose plans were computed for each needle configuration. The number of needles generated and dosimetry were analyzed and compared to the physician implant. RESULTS NPIP computed at least one needle configuration for every patient that met dose objectives, avoided healthy structures and needle collisions, and used as many or fewer needles than standard practice. These needle configurations corresponded to a narrow range of δ values, which could be used as default values if this system is used in practice. The average end-to-end runtime for this implementation of NPIP was 286 s, but there was a wide variation from case to case. CONCLUSIONS The authors have shown that NPIP can automatically generate skew line needle configurations with the aforementioned properties, and that given the correct input parameters, NPIP can generate needle configurations which meet dose objectives and use as many or fewer needles than the current HDR brachytherapy workflow. Combined with robot assisted brachytherapy, this system has the potential to reduce side effects associated with treatment. A physical trial should be done to test the implant feasibility of NPIP needle configurations.PURPOSE In this study, the authors introduce skew line needle configurations for high dose rate (HDR) brachytherapy and needle planning by integer program (NPIP), a computational method for generating these configurations. NPIP generates needle configurations that are specific to the anatomy of the patient, avoid critical structures near the penile bulb and other healthy structures, and avoid needle collisions inside the body. METHODS NPIP consisted of three major components: a method for generating a set of candidate needles, a needle selection component that chose a candidate needle subset to be inserted, and a dose planner for verifying that the final needle configuration could meet dose objectives. NPIP was used to compute needle configurations for prostate cancer data sets from patients previously treated at our clinic. NPIP took two user-parameters: a number of candidate needles, and needle coverage radius, δ. The candidate needle set consisted of 5000 needles, and a range of δ values was used to compute different needle configurations for each patient. Dose plans were computed for each needle configuration. The number of needles generated and dosimetry were analyzed and compared to the physician implant. RESULTS NPIP computed at least one needle configuration for every patient that met dose objectives, avoided healthy structures and needle collisions, and used as many or fewer needles than standard practice. These needle configurations corresponded to a narrow range of δ values, which could be used as default values if this system is used in practice. The average end-to-end runtime for this implementation of NPIP was 286 s, but there was a wide variation from case to case. CONCLUSIONS The authors have shown that NPIP can automatically generate skew line needle configurations with the aforementioned properties, and that given the correct input parameters, NPIP can generate needle configurations which meet dose objectives and use as many or fewer needles than the current HDR brachytherapy workflow. Combined with robot assisted brachytherapy, this system has the potential to reduce side effects associated with treatment. A physical trial should be done to test the implant feasibility of NPIP needle configurations.

Clinical applications of custom-made vaginal cylinders constructed using three-dimensional printing technology

Purpose Three-dimensional (3D) printing technology allows physicians to rapidly create customized devices for patients. We report our initial clinical experience using this technology to create custom applicators for vaginal brachytherapy. Material and methods Three brachytherapy patients with unique clinical needs were identified as likely to benefit from a customized vaginal applicator. Patient 1 underwent intracavitary vaginal cuff brachytherapy after hysterectomy and chemotherapy for stage IA papillary serous endometrial cancer using a custom printed 2.75 cm diameter segmented vaginal cylinder with a central channel. Patient 2 underwent interstitial brachytherapy for a vaginal cuff recurrence of endometrial cancer after prior hysterectomy, whole pelvis radiotherapy, and brachytherapy boost. We printed a 2 cm diameter vaginal cylinder with one central and six peripheral catheter channels to fit a narrow vaginal canal. Patient 3 underwent interstitial brachytherapy boost for stage IIIA vulvar cancer with vaginal extension. For more secure applicator fit within a wide vaginal canal, we printed a 3.5 cm diameter solid cylinder with one central tandem channel and ten peripheral catheter channels. The applicators were printed in a biocompatible, sterilizable thermoplastic. Results Patient 1 received 31.5 Gy to the surface in three fractions over two weeks. Patient 2 received 36 Gy to the CTV in six fractions over two implants one week apart, with interstitial hyperthermia once per implant. Patient 3 received 18 Gy in three fractions over one implant after 45 Gy external beam radiotherapy. Brachytherapy was tolerated well with no grade 3 or higher toxicity and no local recurrences. Conclusions We established a workflow to rapidly manufacture and implement customized vaginal applicators that can be sterilized and are made of biocompatible material, resulting in high-quality brachytherapy for patients whose anatomy is not ideally suited for standard, commercially available applicators.

Catheter-based ultrasound hyperthermia with HDR brachytherapy for treatment of locally advanced cancer of the prostate and cervix.

A clinical treatment delivery platform has been developed and is being evaluated in a clinical pilot study for providing 3D controlled hyperthermia with catheter-based ultrasound applicators in conjunction with high dose rate (HDR) brachytherapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies. Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within HDR brachytherapy implants during radiation therapy in the treatment of cervix and prostate. A pilot study of the combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling software can monitor and regulate frequency and power to each transducer section as required during the procedure. Interstitial applicators consist of multiple transducer sections of 2-4 cm length × 180 deg and 3-4 cm × 360 deg. heating patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a 6 mm OD plastic tandem catheter within the cervix, consists of 2-3 transducers × dual 180 or 360 deg sectors. 3D temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best configure and position the applicators within the catheters, and to determine optimal base power levels to each transducer section. To date we have treated eight cervix implants and six prostate implants. 100 % of treatments achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the hyperthermia target volume (HTV) and clinical target volume (CTV) are reported. Catheter-based ultrasound hyperthermia with HDR appears feasible with therapeutic temperature coverage of the target volume within the prostate or cervix while sparing surrounding more sensitive regions.

A Pilot Study of Catheter‐Based Ultrasound Hyperthermia with HDR Brachytherapy for Treatment of Locally Advanced Cancer of the Prostate and Cervix

A clinical treatment delivery platform has been developed and is being evaluated in a clinical pilot study for providing 3D controlled hyperthermia with catheter-based ultrasound applicators in conjunction with high dose rate (HDR) brachytherapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies. Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within HDR brachytherapy implants during radiation therapy in the treatment of cervix and prostate. A pilot study of the combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling software can monitor and regulate frequency and power to each transducer section as required during the procedure. Interstitial applicators consist of multiple transducer sections of 2-4 cm length × 180 deg and 3-4 cm × 360 deg. heating patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a 6 mm OD plastic tandem catheter within the cervix, consists of 2-3 transducers × dual 180 or 360 deg sectors. 3D temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best configure and position the applicators within the catheters, and to determine optimal base power levels to each transducer section. To date we have treated eight cervix implants and six prostate implants. 100 % of treatments achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the hyperthermia target volume (HTV) and clinical target volume (CTV) are reported. Catheter-based ultrasound hyperthermia with HDR appears feasible with therapeutic temperature coverage of the target volume within the prostate or cervix while sparing surrounding more sensitive regions. (NIHR01CA122276).

A method for restricting intracatheter dwell time variance in high-dose-rate brachytherapy plan optimization

PURPOSE To present the algorithm of a modification to the inverse planning simulated annealing (IPSA) optimization engine that allows for restriction of the intracatheter dwell time variance. METHODS AND MATERIALS IPSA was modified to allow user control of dwell time variance within each catheter through a single parameter, the dwell time deviation constraint (DTDC). The minimum DTDC value (DTDC = 0) does not impose any restriction on dwell time variance, and the maximum value (DTDC = 1) restricts all dwell times within each catheter to take on the same value. The final optimization penalty function value was evaluated as a function of DTDC. RESULTS The algorithm proposed fully preserves the inverse planning nature of the IPSA algorithm along with the penalty-based dose optimization workflow. Increasing DTDC creates less variance in dwell time between dwell positions in each catheter and may be used to induce a more smooth change in dwell time with dwell position in each catheter. Nonzero DTDC values always increased the optimization penalty function value. CONCLUSIONS The DTDC was developed as an extension to IPSA to allow restriction of the difference in dwell time between adjacent dwell positions. This results in less variation between neighboring dwell positions which can be clinically desirable. However, the impact of this restriction needs to be considered for its clinical relevance on a case-by-case basis because considerable degradation in dose-volume histogram metrics can result for large DTDC values.

SU‐GG‐T‐47: Dosimetric Equivalence of Non‐Standard Brachytherapy Needle Patterns

Purpose: To determine whether alternative prostate brachytherapy needle patterns can result in similar or improved dose distributions while providing better access and reducing trauma in the treatment of HDR prostate brachytherapy.Method and Materials: Standard prostate cancer HDR brachytherapy uses a regular grid of parallel needle positions to guide the catheter insertion. This geometry does not easily allow the physician to avoid piercing the penile bulb nor does it provide position flexibility in the case of pubic arch interference. In this study, CT datasets from 10 previously‐treated patients were used and catheters were digitized by following three hypothetical catheter patterns: conical, bi‐conical, and fireworks. The conical patterns were used to accommodate a robotic delivery using a single entry point. The bi‐conical and fireworks patterns were specifically designed to avoid the bulb. For each catheter distribution, a plan was optimized with the inverse planning algorithm, IPSA, and compared with the plan used for treatment. Irrelevant of geometry, a plan must fulfill the RTOG‐0321 dose criteria for target dose coverage (V100>90%) and organ‐at‐risk dose sparing (V75<1cc for the bladder and rectum, V125<<1cc for the urethra). Results: The three non‐standard catheter patterns used 16 non‐parallel, straight divergent catheters, with the focal point(s) in the perineum. 30 plans from 10 patients with prostate sizes ranging from 26 to 89 cc were optimized. All non‐standard patterns fulfilled the RTOG criteria when the clinical plan did. In some cases, the dose distribution was improved by better sparing the organs‐at‐risk. Conclusion: Alternative needle patterns can provide the physician with additional ways to treat patients previously considered unsuited for brachytherapytreatment (pubic arch interference) and to improve patient quality of life (avoidance of penile bulb), while fulfilling the RTOG criteria. Conflict of Interest: Research sponsored by the Nucletron Corporation.

Phase I study of dose escalation to dominant intraprostatic lesions using high-dose-rate brachytherapy

Purpose Radiation dose escalation for prostate cancer improves biochemical control but is limited by toxicity. Magnetic resonance spectroscopic imaging (MRSI) can define dominant intraprostatic lesions (DIL). This phase I study evaluated dose escalation to MRSI-defined DIL using high-dose-rate (HDR) brachytherapy. Material and methods Enrollment was closed early due to low accrual. Ten patients with prostate cancer (T2a-3b, Gleason 6-9, PSA < 20) underwent pre-treatment MRSI, and eight patients had one to three DIL identified. The eight enrolled patients received external beam radiation therapy to 45 Gy and HDR brachytherapy boost to the prostate of 19 Gy in 2 fractions. MRSI images were registered to planning CT images and DIL dose-escalated up to 150% of prescription dose while maintaining normal tissue constraints. The primary endpoint was genitourinary (GU) toxicity. Results The median total DIL volume was 1.31 ml (range, 0.67-6.33 ml). Median DIL boost was 130% of prescription dose (range, 110-150%). Median urethra V120 was 0.15 ml (range, 0-0.4 ml) and median rectum V75 was 0.74 ml (range, 0.1-1.0 ml). Three patients had acute grade 2 GU toxicity, and two patients had late grade 2 GU toxicity. No patients had grade 2 or higher gastrointestinal toxicity, and no grade 3 or higher toxicities were noted. There were no biochemical failures with median follow-up of 4.9 years (range, 2-8.5 years). Conclusions Dose escalation to MRSI-defined DIL is feasible. Toxicity was low but incompletely assessed due to limited patients’ enrollment.

SU‐GG‐T‐15: Inverse Planning Optimization for Hybrid Brachytherapy Plans Using Multiple Seed Types

Purpose: The purpose of this work is to develop a brachytherapy inverse planning algorithm that can generate: 1) Hybrid plans with seeds of one isotope but of different activity levels; 2) Hybrid plans with seeds of two or more different isotopes.Method and Materials: A stand‐alone research version of the inverse planning algorithm, IPSA, was modified to sample different isotopes at each source position at specific moments during the iteration process. The user specifies the isotope sources desired using the TG43 formalism. The algorithm probes this space and evaluates the resulting dose distribution, compares it to the best distribution yet attained, keeps or rejects it, and finally continues to the next iteration. To test the program, plans for prostate volumes (19, 28, 35, 44, and 48 cc) were generated with a single activity and with different combinations of two activities (e.g. 0.25 and 0.4 mCi). Dosimetric indices were compared. Results: We have developed an inverse planning tool that allows the user to incorporate multiple isotopes into any brachytherapy plan. The optimization time is approximately 20% longer than for the standard optimization due to a larger parameter space, but still well under one minute. For all three prostate implants considered, the target volume receiving 100% of the prescribed dose was within 2% for every plan and always above the clinically acceptable 90%. Also the urethra volume receiving 120% of the prescribed dose was always below the clinically acceptable value of 1 cc. Conclusion: An inverse planning algorithm was developed as an extension to IPSA with the ability to incorporate multiple activities or isotopes into the permanent implant optimization process. Studies of the hybrid plans using two activities are shown here; studies involving two separate isotopes are under progress to determine the clinical potential. Conflict of Interest: Work supported by Nucletron.