CTV Coverage Research Articles

Venezia applicator with oblique needles improves clinical target volume coverage in distal parametrial tumor residue compared to parallel needles only

PurposeResidual distal parametrial involvement after radiochemotherapy is a true challenge for brachytherapists since the width and asymmetry of high-risk clinical target volume (HR-CTV) are difficult to cover properly with a standard implant.Material and methodsDosimetric plans of five patients treated with Venezia advanced gynecological applicator at our institution were reviewed. For each patient, we compared the original plan with a new plan where oblique needles were removed and re-optimized manually. Optimization process was halted when EQD210 D90 HR-CTV reached 90 Gy, when one hard constraint to organs at risk (OARs) was reached according to the EMBRACE II protocol, or when dose-rate of one of OARs exceeded 0.6 Gy/h.ResultsTumors were large; median HR-CTV volume was 64 cc and median distance between tandem and outer contour of HR-CTV was 40 mm. For the five patients, HR-CTV EQD210 D90 was superior in the plan using oblique needles, with a median difference of 6.5 Gy (range, 1.7-8.5 Gy). Median D90 HR-CTV and intermediate-risk CTV (IR-CTV) were significantly increased with oblique needles: 85.9 Gy (range, 83.2-90.3 Gy) vs. 81.5 Gy (range, 77.4-84 Gy), and 68.7 Gy (range, 66.3-72.3 Gy) vs. 67 Gy (range, 64.3-69.1 Gy), p = 0.006 for both. There were no significant differences in the dose to OARs. Plans with only parallel needles had less favorable dose distribution, with cold spots on the outer parametria and higher vaginal activation to compensate parametrial coverage in its inferior part.ConclusionsVeneziaTM applicator permits reproducible application to increase CTV coverage in patients with distal parametrial tumor residue during brachytherapy, while maintaining acceptable dose to OARs.

Dosimetric impact of commercial CT metal artifact reduction algorithms and a novel in-house algorithm for proton therapy of head and neck cancer.

To compare the dosimetric impact of all major commercial vendors' metal artifact reduction (MAR) algorithms to one another, as well as to a novel in-house technique (AMPP) using an anthropomorphic head phantom. The phantom was an Alderson phantom, modified to allow for artifact-filled and baseline (no artifacts) computed tomography (CT) scans using teeth capsules made with metal amalgams or bone-equivalent materials. It also included a cylindrical insert that was accessible from the bottom of the neck and designed to introduce soft tissue features into the phantom that were used in the analysis. The phantom was scanned with the metal teeth in place using each respective vendor's MAR algorithm: OMAR (Philips), iMAR (Siemens), SEMAR (Canon), and SmartMAR (GE); the AMPP algorithm was designed in-house. Uncorrected and baseline (bone-equivalent teeth) image sets were also acquired using a Siemens scanner. Proton spot scanning treatment plans were designed on the baseline image set for five targets in the phantom. Once optimized, the proton beams were copied onto the different artifact-corrected image sets, with no reoptimization of the beams' parameters, to evaluate dose distribution differences in the different MAR-corrected and -uncorrected image sets. Dose distribution differences were evaluated by comparing dose-volume histogram (DVH) metrics, including planning target volume D95 and clinical target volume D99 coverages, V100, D0.03cc, and heterogeneity indexes, along with a qualitative and water equivalent thickness (WET) analysis. Uncorrected CT metal artifacts and commercial MAR algorithms negatively impacted the proton dose distributions of all five target shapes and locations in an inconsistent manner, sometimes overdosing by as much as 11.1% (D0.03) or underdosing by as much as 11.7% (V100) the planning target volumes. The AMPP-corrected images, however, provided dose distributions that consistently agreed with the baseline dose distribution. The dosimetry results also suggest that the commercial MAR algorithms' performances varied more with target location and less with target shape. Once relocated further from the metal, the target showed dose distributions that agreed more with the baseline for all commercial solutions, improving the overdosing by as much as 6%, implying inadequate HU correction from commercial MAR algorithms. In comparison to the baseline, HU profile shapes were considerably altered by commercial algorithms and reference values showed differences that represent stopping power percentage differences of 2.7-10%. The AMPP algorithm plans showed the smallest WET differences with the baseline (0.06cm on average), while the commercial image sets created differences that ranged from 0.11 to 0.54cm. Computed tomography metal artifacts negatively impacted proton dose distributions on all five targets analyzed. The commercial MAR solutions performed inconsistently throughout all targets compared to the metal-free baseline. A lack of CTV coverage and an increased number of hotspots were observed throughout all commercial solutions. Dose distribution errors were related to the proximity to the artifacts, demonstrating the inability of commercial techniques to adequately correct severe artifacts. In contrast, AMPP consistently showed dose distributions that best matched the baseline, likely because it makes use of accurate HU information, as opposed to interpolated data like commercial algorithms.

The feasibility and efficacy of new SBRT technique HyperArc for recurrent nasopharyngeal carcinoma: noncoplanar cone-based robotic system vs. noncoplanar high-definition MLC based Linac system

The purpose of this study was to evaluate the feasibility and efficacy of HyperArc (HA) for recurrent nasopharyngeal cancer (NPC) by comparing it with the CyberKnife system (CK). Fifteen patients with recurrent nasopharyngeal cancer who were treated using the noncoplanar cone-based robotic CK system were enrolled. CK was delivered with a median dose of 37.5 Gy in 5 fractions. The delivered CK treatment plans were the sources for the corresponding homogeneous HA (HA-H) and inhomogeneous HA (HA-IH) plans. The HA-H plans were generated to meet the corresponding treatment plan criteria for the CK plans. The HA-IH plans were designed to emulate the corresponding inhomogeneous CK isodose distributions. These three SBRT treatment plans were compared with target coverage, sparing of organs at risk (OARs), and dose distribution metrics. The HA-H and HA-IH plans consistently exhibited CTV and PTV coverage levels similar or better to those of the CK plans but significantly reduced the dose to OARs. Using the HA techniques (both HA-H and HA-IH plans), the mean maximal doses to the spinal cord, brainstem, optic nerves, and optic chiasm were reduced by approximately 60%, compared to the CK plans. The high dose spillage, conformity, and homogeneity indices of the HA-H plans were significantly better than those of the CK plans. The HA-IH plans showed faster dose falloff and similar conformity of the HA-H plans and dose heterogeneity of the CK plans. Here we demonstrated the HA treatment plan system for recurrent NPC is feasible, either homogeneous or inhomogeneous delivery. Excellent sparing of OARs and dosimetric distribution and very efficient delivery make HA an attractive SBRT technique for recurrent NPC treatment.

Robust treatment planning with 4D intensity modulated carbon ion therapy for multiple targets in stage IV non-small cell lung cancer

Intensity modulated particle therapy (IMPT) with carbon ions can generate highly conformal treatment plans; however, IMPT is limited in robustness against range and positioning uncertainty. This is particularly true for moving targets, even though all motion states of a 4DCT are considered in 4D-IMPT. Here, we expand 4D-IMPT to include robust non-linear RBE-weighted optimization to explore its potential in improving plan robustness and sparing critical organs. In this study, robust 4D-optimization—based on worst-case optimization on 9 scenarios—was compared to conventional 4D-optimization with PTV margins using 4D dose calculation and robustness analysis for 21 uncertainty scenarios. Slice-by-slice rescanning was used for motion mitigation. Both 4D-optimization strategies were tested on a cohort of 8 multi-lesion lung cancer patients with the goal of prioritizing OAR sparing in a hypofractionated treatment plan. Planning objectives were to keep the OAR volume doses below corresponding limits while simultaneously achieve CTV coverage with D95% ≥ 95 %. For the conventional plans, average D95% was at 98.7% which fulfilled the target objective in 83.2% of scenarios. For the robust plans, average D95% was reduced to 97.6% which still fulfilled the target objective in 80.7% of cases, but led to significantly improved overall OAR sparing: Volume doses were below the limits in 96.2% of cases for the conventional and 99.5% for the robust plans. When considering the particularly critical smaller airways only, fulfillment rates could be increased from 76.2% to 96% for the robust plans. This study has shown that plan robustness of 4D-IMPT could be improved by using robust 4D-optimization, offering greater control over uncertainties in the actual delivered dose. In some cases, this required sacrificing target coverage for the benefit of better OAR sparing.

Plan-Delivery-Time-Constrained Inverse Optimization for High-Throughput PBS Proton RT

Proton RT remains a limited resource that can only accommodate small number of cancer patients. Given that most modern proton centers use the multi-room shared-beam layout to parallelize patient setup, the major throughput-limiting factor is plan delivery time (primarily dose delivery time and energy switching time). This project will develop novel plan-delivery-time-constrained inverse optimization algorithms to achieve the significant reduction of plan delivery time for high-throughput pencil beam scanning (PBS) proton RT. The PBS dose rate is linearly proportional to the minimum-monitor-unit (MU) constraint. Thus, the increase of MU threshold can increase dose rate and therefore reduce dose delivery time. However, the room to increase this threshold is very limited with a single fixed MU threshold for all PBS spots as is assumed by current methods, since the plan quality is often significantly deteriorated before reaching any meaningful reduction of dose delivery time. To allow a significant reduction of dose delivery time while ensuring the plan quality, we propose to use variable energy-dependent MU thresholds to relax the tradeoff between dose delivery time and plan quality. On the other hand, although energy switching time is the secondary factor for total plan delivery time, it becomes relatively more important as dose delivery time is significantly reduced. Thus, energy switching time is modeled via group sparsity. New optimization algorithms via iterative convex relaxation are developed to solve these non-convex optimization problems. In addition, our methods can provide the efficiency-quality Pareto surface via multi-criteria optimization regarding the tradeoff between delivery efficiency and plan quality. With variable energy-dependent MU thresholds, our new method achieved 46.7%, 32.6%, and 33.3% reduction of dose delivery time respectively for prostate, lung and brain cases. Compared with plans optimized with a single MU threshold that corresponded to a 26.7% reduction of dose delivery time, our new method significantly improved plan quality in terms of both CTV coverage and OAR sparing. Moreover, the dose delivery time was further reduced to 25.7%, 34.9%, and 41.3% respectively, accepting a slightly degraded plan quality that still met all clinical planning constraints. On the other hand, our group-sparsity-regularized method reduced number of energy layers (or equivalently energy switching time) to 78%, 76%, and 61% respectively for prostate, lung and HN cases, while comparable plan quality was preserved. Moreover, the energy switching time was further reduced to 54%, 57%, and 37% respectively, accepting a slightly degraded plan quality that still met all clinical planning constraints. Novel plan-delivery-time-constrained optimization methods have been developed for high-throughput PBS proton RT.

Novel Technique for Intensity Modulated Proton Therapy With Custom Oral Device is Associated With Reduced Oral Cavity Doses and Favorable Outcomes

Particle therapies are well-suited for the adjuvant treatment of lip and buccal mucosa malignancies. Intensity modulated radiation therapy (IMRT) is often utilized but can result in increased moderate doses to sensitive organs including the oral cavity. Herein, we describe a novel treatment utilizing Intensity Modulated Proton Therapy (IMPT) with custom oral dental putty devices employed to protect non-target oral cavity by limiting the range of IMPT beams. We hypothesized that this technique would allow for optimal treatment of the post-operative bed and regional lymphatics/cranial nerves with very low non-target oral cavity doses. We also proposed that this oral cavity sparing would be more pronounced with IMPT than IMRT. On an IRB-approved retrospective review, we identified patients treated at our institution with this novel IMPT and oral device technique for the treatment of lower lip and buccal mucosa malignancies. Patient and tumor characteristics along with dosimetric and outcomes data were collected. Each patient had a comparative volumetric modulated arc therapy (VMAT) plan generated for comparison of non-target oral cavity sparing with the same planning scans including dental putty. Five patients were treated with IMPT and a custom oral device with a median follow up of 5.2 months (range, 1.1–21.5). Three patients were treated for squamous cell carcinoma (SCC) of the lip and two for adenoid cystic carcinoma (ACC) of the lip or buccal mucosa. Three patients had regional lymph nodes included in the target (SCC), and two had V3 electively covered (ACC). To date, there were no grade ³3 acute or subacute toxicities, there have been no failures and all patients remain alive. There was no appreciable difference in CTV coverage between the VMAT and IMPT plans. Table 1 includes V10Gy, V20Gy, V30Gy, and mean oral cavity dose, all of which were statistically significantly lower with IMPT than VMAT (p<0.01). Compared to VMAT, oral cavity mean dose decreased with IMPT from a median of 29.8Gy (range, 23.2 – 32.6) to 14.3Gy (range 6.21 – 19.7) (p<0.01). Use of IMPT with custom dental putty oral devices for dose attenuation is a novel, effective, and simple technique to reduce toxicity for patients with lower lip and buccal head and neck malignancies requiring radiation coverage of regional lymphatics and/or cranial nerves. While follow up is limited, outcomes and acute/subacute toxicity rates to date are excellent with a decrease of ∼50% mean dose to the oral cavity when compared with VMAT.Tabled 1Abstract 2813; TableOral Cavity Dosimetric ValueIMRT: Median (range)IMPT: Median (range)V10Gy (%)97.0 (87.7 – 100.0)42.9 (17.2 – 58.8)V20Gy (%)62.0 (46.5 – 86.0)30.3 (11.0 – 39.2)V30Gy (%)35.7 (20.5 – 53.2)18.3 (7.4 – 27.4)Mean Dose (Gy)29.8 (23.2 – 32.6)14.3 (6.21 – 19.7) Open table in a new tab

Characterization of Photon IMRT Robustness as a Benchmark for Proton Therapy Planning

Robustness evaluation is increasingly used in proton therapy to assess CTV coverage in the setting of expected setup and range uncertainty errors. However, no standard exists to describe an acceptable degree of plan robustness in proton therapy. The aim of this study is to quantify photon intensity modulated radiation therapy (IMRT) robustness parameters, as this could aid proton planning and evaluation. Prostate cancer was selected as a model to evaluate the dosimetric effect of setup errors in IMRT due to its simple geometry and consistent arrangement of organs at risk (OARs). Consecutive prostate adenocarcinoma patients treated with definitive photon IMRT at a single institution in 2019 were retrospectively reviewed. IMRT consisted of 70 Gy in 28 fractions to the prostate alone. In all patients, an isotropic CTV to PTV margin of 7 mm was used, except 4 mm posteriorly. Each plan was normalized such that 100% of the prescribed dose covered 95% of the PTV. Planning goals included rectal V70Gy < 3 cc, rectal V60Gy < 10 cc, and bladder V60Gy < 10%. Patient setup errors were simulated using the treatment planning system’s tool by shifting the isocenter relative to the patient in each of the cardinal directions. The degree of each shift equaled the magnitude of the CTV to PTV expansion in that same direction. Range uncertainty was set to 0%. For each case, dosimetric data for the CTV and OARs (rectum and bladder) were extracted from dose-volume histogram (DVH) curves of the nominal plan and the six cardinal shifts. A total of 27 patients were included. The mean CTV coverage (and standard deviation [SD]) of the nominal plan for V100% and V95% were 99.6% (1.2%) and 100% (0.0%), respectively. Mean CTV coverage (SD) for the worst-case shift (most commonly in the inferior direction) for V100% and V95% were 97.2% (2.9%) and 99.7% (0.5%), respectively. Other parameters examined included the mean [SD] CTV D95% (71.2 Gy [0.7 Gy] nominal; 70.7 Gy [0.6 Gy] worst case) and CTV D50% (72.3 Gy [0.6 Gy] nominal; 71.9 Gy [0.6 Gy] worst case). The mean (SD) nominal rectal V70Gy and V60Gy were 2.37 cc (1.02 cc) and 7.74 cc (2.46 cc), respectively. In the worst case (corresponding to a 4 mm posterior shift), mean values increased to 7.06 cc (2.13 cc) and 13.83 cc (3.91 cc) for rectal V70Gy and V60Gy, respectively. The mean (SD) bladder V60Gy nominal and worst case were 7.8% (4.9%) and 14.8% (10.1%). Paired two tailed t-tests comparing the nominal to worst case DVHs were significant for each of the above dosimetric parameters (p <0.01). Photon IMRT planning uses PTV margins to inherently provide robustness to patient setup errors. While we found that the prostate remains relatively well covered in various setup uncertainty scenarios, OARs routinely exceeded institutional constraints in the worst case. Robustness metrics obtained from photon IMRT plans could serve as a benchmark for proton therapy robustness analysis and robust optimization.

Volumetric Modulated Arc Therapy Versus Three-Dimensional Conformal Radiotherapy for Breast Cancer Patients Treated with Regional Nodal Irradiation

Locally advanced breast cancer is often treated with adjuvant radiotherapy to the chest wall or breast and the regional nodes following surgery. Intensity-modulated radiotherapy (IMRT) can improve target coverage and spare organ at risk, but the efficacy and safety of IMRT for locally advanced breast cancer have not been clarified. We aimed to compare the dosimetric parameters and clinical outcomes between 3D-CRT and volumetric modulated arc therapy (VMAT) for breast cancer. The hypothesis is that VMAT has better target coverage without increasing toxicities. Breast cancer patients who received adjuvant radiotherapy with regional nodes irradiation between July 2016 and December 2019 were included. Patients with a right-sided disease were treated with three-dimensional conformal radiotherapy (3D-CRT), whereas patients with a left-sided disease were treated with VMAT to reduce heart dose. Patients who received bilateral radiotherapy were excluded. Radiotherapy was delivered to the chest wall or breast, and supraclavicular region with or without internal mammary nodes. A dose of 50 Gy in 25 fractions was prescribed to the reference point for 3D-CRT, and to cover 75% of the PTV for VMAT. Single full or two partial arcs with 6MV were used for VMAT. Clinical outcome and dosimetric data were collected retrospectively from medical records. Toxicities were assessed by CTCAE ver.4.0. A total of 74 consecutive patients were included in this study. Thirty-five left-sided breast cancer patients received VMAT, and 39 right-sided breast cancer patients received 3D-CRT. The median follow-up was 591 days. The median age was 50 years. Grade 2 or higher acute dermatitis were observed in 10 patients (29%) with VMAT versus 17 patients (44%) with 3D-CRT (P = 0.18). Grade 3 acute dermatitis occurred in one patient in the 3D-CRT group. Grade 2 radiation pneumonitis occurred in one patient in each group (P = 1.0). Acute radiation esophagitis occurred in 25 patients only in the VMAT group. CTV coverage (CTV V47.5Gy, D95%, D75%) was significantly better for VMAT (86%, 42 Gy, 49 Gy) compared to 3D-CRT (72%, 29 Gy, 46 Gy) (all P < 0.01). Total lung V20 Gy was lower for VMAT versus 3D-CRT (11Gy versus 13 Gy, P < 0.01), whereas total lung V5 Gy and mean dose were higher for VMAT (34 Gy and 7.8 Gy) compared to 3D-CRT (22 Gy and 6.9 Gy) (P < 0.01, 0.01). Because of the laterality, the dose to the heart and esophagus was higher in the VMAT group (P < 0.01, 0.01). Five patients experienced recurrence (two distant metastases in the VMAT group and two distant and one local and distant metastases in the 3D-CRT group). VMAT for breast radiotherapy with regional nodal irradiation had better target coverage and lower lung V20 Gy at the expense of a small increase in the lung mean dose and V5 Gy. VMAT can be safely administered with similar toxicity to 3D-CRT.

Initial Outcomes And Treatment-Associated Toxicities Using Stereotactic MRI-Guided Adaptive Radiation Therapy For Pancreatic Cancer Patients Treated At A Single Institution

High dose stereotactic body radiotherapy (SBRT) may offer improved outcomes for pancreatic cancer patients, but treatment delivery remains a challenge due to tumor proximity to organs-at-risk (OAR) and daily anatomic variability. Stereotactic MRI-guided adaptive radiation therapy (SMART) with real-time tumor tracking allows for improved dose delivery and OAR sparing by accounting for anatomic changes with each treatment. This study reports initial outcomes, treatment-associated toxicities, and dosimetric outcomes in locally advanced, metastatic, and/or recurrent pancreatic cancer patients treated using SMART. We performed a retrospective analysis of locally advanced, metastatic, and/or recurrent pancreatic cancer patients who underwent adaptive planning with MRI-guided radiation treatments. Charts were reviewed for follow-up, imaging, and laboratory values, including CA19-9 and absolute lymphocyte count. A plan was generated for each patient after initial CT and MR-simulation. At each treatment, MR imaging was obtained for the daily anatomy and the initial (unadapted) plan was compared to obtain a predicted dose to target volumes and OARs using a prescribed dose ranging from 30-50 Gy in 3-5 fractions. If constraints were not met or coverage was inadequate, an adaptive plan was generated based on the anatomy imaged on the day of treatment. From June 2018 to February 2020, a total of 23 patients were analyzed. With a median follow up of 5 months, we observed 15/19 (79%) with local control, 12/19 (63%) distal metastatic control, and a median overall survival of 19 months from cancer diagnosis. We observed no grade 3 or higher treatment related toxicities. Two patients were found to have an absolute lymphocyte count less than 0.5 x 103 cells/μl within six months of radiation, and 11/17 (65%) had lower CA19-9 six months after radiation treatment compared to before treatment. Of the 23 patients treated, there were 71 adaptive plans available for analysis. Compared to unadapted plans, adaptive fractions had improved coverage of PTV (84.94% vs. 73.36% at 100% of prescribed dose) and CTV (94.62% vs 88.08% at 95% of prescribed dose). Unadapted plans were more likely to exceed OAR constraints with 63 of 71 (89%) unadapted fractions predicted to violate prescribed duodenal, stomach, or small bowel constraints. Moreover, 34/71 (48%) of unadapted fractions violated constraints for 2 of 3 abdominal OARs and 10/71 (14%) violated constraints for all 3 compared to none for adapted fractions. Stereotactic adaptive MRI-guided radiotherapy demonstrated minimal treatment-related toxicities, enhanced tumor volume coverage, and improved adherence to OAR constraints in pancreatic cancer patients. Additional follow up is needed to further assess outcomes of these patients.

Adaptive SBRT by 1.5T MR-linac for prostate cancer: On the accuracy of dose delivery in view of the prolonged session time.

Adaptive Stereotactic Body Radiotherapy (SBRT) of prostate cancer (PC) by online 1.5T MRi-guidance prolongs session-time, due to contouring and planning tasks, thus increasing the risk of prostate motion. Hence, the interest to verify the adequacy of the delivered dose. For twenty PC patients treated by 35Gy (Dp) in five fractions, daily pre- and post- delivery MRi scans were respectively used for adapt-to-shape (ATS) optimization, and re-computation of the delivered irradiation (Drec). Two expansion recipes, from Clinical (CTV) to Planning target volume (PTV), which slightly differed in the posterior margin were used for groups I and II, of ten patients each. Plans had to assure D95%≥95%Dp to PTV, and D1cc≤Dp to rectum, bladder, penile bulb, and urethral planning-risk-volume (urethral-PRV). The adequacy of the delivered dose was estimated by inter-fraction average (ifa) of dose-volume metrics computed from Drec. A cumulative dose (Dsum) was calculated from the five daily Drec deformed onto the simulation MRi. For each patient, CTV coverage resulted in D95%>95%Dp when estimated as ifa by Drec. No significant difference for D95% and D99% metrics to CTV resulted between groups I and II. D1cc was<Dp for rectum, urethral-PRV, and penile bulb, whereas<103.5%Dp for the bladder. Significant correlations resulted between metrics computed by Dsum and as ifa by Drec, by both linear-correlation analysis, and Receiver-Operating-Characteristic curve analysis. Our results for PC-SBRT confirm the adequacy of the delivered dose by ATS with 1.5T MR-linac, and the consistency between dose-volume metrics computed by Drec and Dsum.

Intensity-modulated proton therapy (IMPT) interplay effect evaluation of asymmetric breathing with simultaneous uncertainty considerations in patients with non-small cell lung cancer.

Intensity-modulated proton therapy (IMPT) is sensitive to uncertainties from patient setup and proton beam range, as well as interplay effect. In addition, respiratory motion may vary from cycle to cycle, and also from day to day. These uncertainties can severely degrade the original plan quality and potentially affect patient's outcome. In this work, we developed a new tool to comprehensively consider the impact of all these uncertainties and provide plan robustness evaluation under them. We developed a comprehensive plan robustness evaluation tool that considered both uncertainties from patient setup and proton beam range, as well as respiratory motion simultaneously. To mimic patients' respiratory motion, the time spent in each phase was randomly sampled based on patient-specific breathing pattern parameters as acquired during the four-dimensional (4D)-computed tomography (CT) simulation. Spots were then assigned to one specific phase according to the temporal relationship between spot delivery sequence and patients' respiratory motion. Dose in each phase was calculated by summing contributions from all the spots delivered in that phase. The final 4D dynamic dose was obtained by deforming all doses in each phase to the maximum exhalation phase. Three hundred (300) scenarios (10 different breathing patterns with 30 different setup and range uncertainty scenario combinations) were calculated for each plan. The dose-volume histograms (DVHs) band method was used to assess plan robustness. Benchmarking the tool as an application's example, we compared plan robustness under both three-dimensional (3D) and 4D robustly optimized IMPT plans for 10 nonrandomly selected patients with non-small cell lung cancer. The developed comprehensive plan robustness tool had been successfully applied to compare the plan robustness between 3D and 4D robustly optimized IMPT plans for 10 lung cancer patients. In the presence of interplay effect with uncertainties considered simultaneously, 4D robustly optimized plans provided significantly better CTV coverage (D95% , P=0.002), CTV homogeneity (D5% -D95% , P=0.002) with less target hot spots (D5% , P=0.002), and target coverage robustness (CTV D95% bandwidth, P=0.004) compared to 3D robustly optimized plans. Superior dose sparing of normal lung (lung Dmean , P=0.020) favoring 4D plans and comparable normal tissue sparing including esophagus, heart, and spinal cord for both 3D and 4D plans were observed. The calculation time for all patients included in this study was 11.4±2.6min. A comprehensive plan robustness evaluation tool was successfully developed and benchmarked for plan robustness evaluation in the presence of interplay effect, setup and range uncertainties. The very high efficiency of this tool marks its clinical adaptation, highly practical and versatile nature, including possible real-time intra-fractional interplay effect evaluation as a potential application for future use.

Online adaptive dose restoration in intensity modulated proton therapy of lung cancer to account for inter-fractional density changes.

In proton therapy, inter-fractional density changes can severely compromise the effective delivery of the planned dose. Such dose distortion effects can be accounted for by treatment plan adaptation, that requires considerable automation for widespread implementation in clinics. In this study, the clinical benefit of an automatic online adaptive strategy called dose restoration (DR) was investigated. Our objective was to assess to what extent DR could replace the need for a comprehensive offline adaptive strategy. The fully automatic and robust DR workflow was evaluated in a cohort of 14 lung IMPT patients that had a planning-CT and two repeated 4D-CTs (rCT1,rCT2). Initial plans were generated using 4D-robust optimization (including breathing-motion, setup and range errors). DR relied on isodose contours generated from the initial dose and associated patient specific weighted objectives to mimic this initial dose in repeated-CTs. These isodose contours, with their corresponding objectives, were used during re-optimization to compensate proton range distortions disregarding re-contouring. Robustness evaluations were performed for the initial, not-adapted and restored (adapted) plans. The resulting DVH-bands showed overall improvement in DVH metrics and robustness levels for restored plans, with respect to not-adapted plans. According to CTV coverage criteria (D95%>95%Dprescription) in not-adapted plans, 35% (5/14) of the cases needed offline adaptation. After DR, Median(D95%) was increased by 1.1 [IQR,0.4] Gy and only one patient out of 14 (7%) still needed offline adaptation because of important anatomical changes. DR has the potential to improve CTV coverage and reduce offline adaptation rate.

On adaptation cost and tractability in robust adaptive radiation therapy optimization.

In this paper, a framework for online robust adaptive radiation therapy (ART) is discussed and evaluated. The purpose of the presented approach to ART is to: (a) handle interfractional geometric variations following a probability distribution different from the a priori hypothesis, (b) address adaptation cost, and (c) address computational tractability. A novel framework for online robust ART using the concept of Bayesian inference and scenario reduction is introduced and evaluated in a series of simulated cases on a one-dimensional phantom geometry. The initial robust plan is generated from a robust optimization problem based on either expected-value or worst-case optimization approach using the a priori hypothesis of the probability distribution governing the interfractional geometric variations. Throughout the course of treatment, the simulated interfractional variations are evaluated in terms of their likelihood with respect to the a priori hypothesis of their distribution and violation of user-specified tolerance limits by the accumulated dose. If an adaptation is considered, the a posteriori distribution is computed from the actual variations using Bayesian inference. Then, the adapted plan is optimized to better suit the actual interfractional variations of the individual case. This adapted plan is used until the next adaptation is triggered. To address adaptation cost, the proposed framework provides an option for increased adaptation frequency. Computational tractability in robust planning and ART is addressed by an approximation algorithm to reduce the size of the optimization problem. According to the simulations, the proposed framework may improve target coverage compared to the corresponding nonadaptive robust approach. In particular, Bayesian inference may be useful to individualize plans to the actual interfractional variations. Concerning adaptation cost, the results indicate that mathematical methods like Bayesian inference may have a greater impact on improving individual treatment quality than increased adaptation frequency. In addition, the simulations suggest that the concept of scenario reduction may be useful to address computational tractability in ART and robust planning in general. The simulations indicate that the adapted plans may improve target coverage and OAR protection at manageable adaptation and computational cost within the novel framework. In particular, adaptive strategies using Bayesian inference appear to perform best among all strategies. This proof-of-concept study provides insights into the mathematical aspects of robustness, tractability, and ART, which are a useful guide for further development of frameworks for online robust ART.

Pelvic radiation therapy with volumetric modulated arc therapy and intensity-modulated radiotherapy after renal transplant: A report of 3 cases.

Describe characteristics and outcomes of three patients treated with pelvic radiation therapy after kidney transplant. The incidence of pelvic cancers in kidney transplant (KT) recipients is rising. Currently it is the leading cause of death. Moreover, treatment is challenging because anatomical variants, comorbidities, and associated treatments, which raises the concern of using radiotherapy (RT). RT has been discouraged due to the increased risk of urethral/ureteral stricture and KT dysfunction. We reviewed the electronic health records and digital planning system of patients treated with pelvic RT between December 2013 and December 2018 to identify patients with previous KT. We describe three successful cases of KT patients in which modern techniques allowed full standard RT for pelvic malignances (2 prostate and 1 vaginal cancer) with or without elective pelvic nodal RT, without allograft toxicity at short and long follow-up (up to 60 months). When needed, RT modern techniques remain a valid option with excellent oncologic results and acceptable toxicity. Physicians should give special considerations to accomplish all OAR dose constraints in the patient's specific setting. Recent publications recommend KT mean dose <4 Gy, but graft proximity to CTV makes this unfeasible. We present 2 cases where dose constraint was not achieved, and to a short follow-up of 20 months renal toxicity has not been documented. We recommend the lowest possible mean dose to the KT, but never compromising the CTV coverage, since morbimortality from recurrent or progressive cancer disease outweighs the risk of graft injury.

Data clustering to select clinically-relevant test cases for algorithm benchmarking and characterization

Algorithm benchmarking and characterization are an important part of algorithm development and validation prior to clinical implementation. However, benchmarking may be limited to a small collection of test cases due to the resource-intensive nature of establishing ‘ground-truth’ references. This study proposes a framework for selecting test cases to assess algorithm and workflow equivalence. Effective test case selection may minimize the number of ground-truth comparisons required to establish robust and clinically relevant benchmarking and characterization results.To demonstrate the proposed framework, we clustered differences between two independent workflows estimating during-treatment dose objective violations for 15 head and neck cancer patients (15 planning CTs, 105 on-unit CBCTs). Each workflow used a different deformable image registration algorithm to estimate inter-fractional anatomy and contour changes. The Hopkins statistic tested whether workflow output was inherently clustered and k-medoid clustering formalized cluster assignment. Further statistical analyses verified the relevance of clusters to algorithm output. Data at cluster centers (‘medoids’) were considered as candidate test cases representative of workflow-relevant algorithm differences.The framework indicated that differences in estimated dose objective violations were naturally grouped (Hopkins = 0.75, providing 90% confidence). K-medoid clustering identified five clusters which stratified workflow differences (MANOVA: p < 0.001) in estimated parotid gland D50%, spinal cord/brainstem Dmax, and high dose CTV coverage dose violations (Kendall’s tau: p < 0.05). Systematic algorithm differences resulting in workflow discrepancies were: parotid gland volumes (ANOVA: p < 0.001), external contour deformations (t-test: p = 0.022), and CTV-to-PTV margins (t-test: 0.009), respectively. Five candidate test cases were verified as representative of the five clusters.The framework successfully clustered workflow outputs and identified five test cases representative of clinically relevant algorithm discrepancies. This approach may improve the allocation of resources during the benchmarking and characterization process and the applicability of results to clinical data.

Clinical implementation in proton therapy of multi-field optimization by a hybrid method combining conventional PTV with robust optimization

To implement a robust multi-field optimization (MFO) technique compatible with the application of a Monte Carlo (MC) algorithm and to evaluate its robustness. Nine patients (three brain, five head-and-neck, one spine) underwent proton treatment generated by a novel robust MFO technique. A hybrid (hMFO) approach was implemented, planning dose coverage on isotropic PTV compensating for setup errors, whereas range calibration uncertainties are incorporated into PTV robust optimization process. hMFO was compared with single-field optimization (SFO) and full robust multi-field optimization (fMFO), both on the nominal plan and the worst-case scenarios assessed by robustness analysis. The SFO and the fMFO plans were normalized to hMFO on CTV to obtain iso-D95 coverage, and then the organs at risk (OARs) doses were compared. On the same OARs, in the normalized nominal plans the potential impact of variable relative biological effectiveness (RBE) was investigated. hMFO reduces the number of scenarios computed for robust optimization (from twenty-one in fMFO to three), making it practicable with the application of a MC algorithm. After normalizing on D95 CTV coverage, nominal hMFO plans were superior compared to SFO in terms of OARs sparing (p < 0.01), without significant differences compared to fMFO. The improvement in OAR sparing with hMFO with respect to SFO was preserved in worst-case scenarios (p < 0.01), confirming that hMFO is as robust as SFO to physical uncertainties, with no significant differences when compared to the worst case scenarios obtained by fMFO. The dose increase on OARs due to variable RBE was comparable to the increase due to physical uncertainties (i.e. 4–5 Gy(RBE)), but without significant differences between these techniques. hMFO allows improving plan quality with respect to SFO, with no significant differences with fMFO and without affecting robustness to setup, range and RBE uncertainties, making clinically feasible the application of MC-based robust optimization.

Impact of internal target volume definition for pencil beam scanned proton treatment planning in the presence of respiratory motion variability for lung cancer: A proof of concept

PurposeMotion management is crucial in scanned proton therapy for mobile tumours. Current motion mitigation approaches rely on single 4DCTs before treatment, ignoring respiratory variability. We investigate the consequences of respiratory variations on internal target volumes (ITV) definition and motion mitigation efficacy, and propose a probabilistic ITV based on 4DMRI. Materials and methodsFour 4DCT(MRI) datasets, each containing 40 variable cycles of synthetic 4DCTs, were generated by warping single-phase CTs of two lung patients with motion fields extracted from two 4DMRI datasets. Two-field proton treatment plans were optimised on ITVs based on different parts of the 4DCT(MRI)s. 4D dose distributions were calculated by considering variable respiratory patterns. Different probabilistic ITVs were created by incorporating the voxels covered by the CTV in at least 25%, 50%, or 75% (ITV25, ITV50, ITV75) of the cycles, and compared with the conservative ITV encompassing all possible CTV positions. ResultsDepending on the selected planning 4DCT, ITV volumes vary up to 20%, resulting in significant variation in CTV coverage for 4D treatments. Target coverage and homogeneity improved with the conservative ITV, but was associated with significantly increased lung dose (~1%). ITV25 and ITV50 led to acceptable plan quality in most cases without lung dose increments. ITV75 best minimised lung dose, but was insufficient to ensure coverage under all motion scenarios. ConclusionIrregular respiration significantly affects CTV coverage when ITVs are only defined by single 4DCTs. A probabilistic ITV50 provides an adequate compromise between target coverage and lung dose for most motion and patient scenarios investigated.

A comparison study between single- and dual-energy CT density extraction methods for neurological proton monte carlo treatment planning

Monte Carlo proton dose calculations requires mass densities calculated from the patient CT image. This work investigates the impact of different single-energy CT (SECT) and dual-energy CT (DECT) to density conversion methods in proton dose distributions for brain tumours.Material and methods: Head CT scans for four patients were acquired in SECT and DECT acquisition modes. Commercial software was used to reconstruct DirectDensity™ images in Relative Electron Densities (RED, ) and to obtain DECT-based pseudo-monoenergetic images (PMI). PMI and SECT images were converted to RED using piecewise linear interpolations calibrated on a head-sized phantom, these fits were referred to as “PMI2RED” and “CT2RED”. Two DECT-based calibration methods (“Hünemohr-15it” and “Saito-15it”) were also investigated. images were converted to mass-densities () to investigate differences and one representative patient case was used to make a proton treatment plan. Using CT2RED as reference method, dose distribution differences in the target and in five organs-at-risk (OARs) were quantified.Results: In the phantom study, Saito-15it and Hünemohr-15it produced the lowest root-mean-square error (0.7%) and DirectDensity™ the highest error (2.7%). The proton plan evaluated in the Saito-15it and Hünemohr-15it datasets showed the largest relative differences compared to initial CT2RED plan down to −6% of the prescribed dose. Compared to CT2RED, average range differences were calculated: −0.1 ± 0.3 mm for PMI2RED; −0.8 ± 0.4 mm for Hünemohr-15it, and −1.2 ± 0.4 mm for Saito-15it.Conclusion: Given the wide choice of available conversion methods, studies investigating the density accuracy for proton dose calculations are necessary. However, there is still a gap between performing accuracy studies in reference phantoms and applying these methods in human CT images. For this treatment case, the PMI2RED method was equivalent to the conventional CT2RED method in terms of dose distribution, CTV coverage and OAR sparing, whereas Hünemohr-15it and Saito-15it presented the largest differences.

153 The Impact of Advanced Image Registration and 3-D EQD2 Dose Conversion on PTV and CTV Coverage in the Retreatment of Nasopharyngeal Cancer: A Case Study

153 The Impact of Advanced Image Registration and 3-D EQD2 Dose Conversion on PTV and CTV Coverage in the Retreatment of Nasopharyngeal Cancer: A Case Study

Multi-Criteria Hybrid Proton-Photon Inverse Planning for Oropharyngeal Cancer

To evaluate a recently developed hybrid proton-photon inverse planning technique (HYBRID) with conventional photon-only (PHOTON) and proton-only (PROTON) planning for HN cancer patients using multi-criteria optimization (MCO). The hypothesis is that HYBRID will provide more favorable CTV coverage and OAR sparing than PHOTON or PROTON for HN cancer. HYBRID simultaneously optimizes proton and photon variables in addition to their numbers of fractions, during which the photon dose covers PTV that implicitly accounts for setup uncertainty, and the proton dose and the total dose cover CTV that explicitly account for range and setup uncertainty via robust optimization. HYBRID optimally allocates protons and photons to improve total planning objective: the coverage of CTV is fine-tuned to minimize hot and cold spots and improve dose uniformity by photons owing to its robustness to delivery uncertainties; the sparing of OARs is improved using both protons and photons of complementary characteristics with more degrees of freedom for dose shaping. HYBRID was compared with PHOTON and PROTON for 10 HN patients treated with definitive radiation for locally advanced oropharyngeal cancer. The highest CTV was treated to 70Gy in 35 fractions using SIB with 2-3 CTVs. All three planning methods were solved with the same objectives and the same normalization (D98=100% to CTV for the worst case). The following table summarizes optimization objectives (normalized to the total of HYBRID (100.0 in the table)) and dosimetric quantities from MCO: better CTV coverage vs more OAR sparing by adjusting objective weights, where the best values are highlighted in bold. HYBRID provided the best total objectives (the sum of CTV and OAR objectives), and also the best OAR and CTV objectives for almost all cases (CTV objective slightly worse than PHOTON for 1 case); under the similar CTV coverage (D98), HYBRID had the lowest maximum dose (Dmax); in terms of mean or integral OAR dose (Dmean), HYBRID was the best for submandibular and larynx, the best for parotid under MCO with more OAR sparing, and in between PHOTON and PROTON for oral cavity and body. In average, HYBRID had 10 proton and 25 photon fractions. HYBRID offered the lowest total minimization objectives for all 10 oropharyngeal cancer patients, and the lowest OAR and CTV objectives as well for 9 patients. In particular, MCO-based HYBRID had the lowest mean dose for parotid, submandibular gland and larynx.Abstract 2970; Table 1QuantityBetter CTV CoverageMore OAR SparingPHOTONPROTONHYBRIDPHOTONPROTONHYBRIDObjectiveCTV51.5237.642.134.9194.330.3OAR72.7126.557.999.8130.769.7TOTAL124.3364.1100.0134.6325.0100.0CTVD98 (%)100.0100.8100.2100.0100.9100.4Dmax (%)107.5109.6105.7110.0120.0108.1ParotidDmean (Gy)23.520.421.717.216.714.7Oral CavityDmean (Gy)30.322.126.723.217.118.4SubmandibularDmean (Gy)31.029.327.419.521.916.4LarynxDmean (Gy)30.034.128.318.924.616.7BodyDmean (Gy)6.53.75.66.63.75.7 Open table in a new tab