Investigating volumetric repainting to mitigate interplay effect on 4D robustly optimized lung cancer plans in pencil beam scanning proton therapy

Purpose: The interplay effect between dynamic pencil proton beams and motion of the lung tumor presents a challenge in treating lung cancer patients in pencil beam scanning (PBS) proton therapy. The main purpose of the current study was to investigate the interplay effect on the volumetric repainting lung plans with beam delivery in alternating order ( down and up directions), and explore the number of volumetric repaintings needed to achieve acceptable lung cancer PBS proton plan. Method: The current retrospective study included ten lung cancer patients. The total dose prescription to the clinical target volume (CTV) was 70 Gy(RBE) with a fractional dose of 2 Gy(RBE). All treatment plans were robustly optimized on all ten phases in the 4DCT data set. The Monte Carlo algorithm was used for the 4D robust optimization, as well as for the final dose calculation. The interplay effect was evaluated for both the nominal (i.e., without repainting) as well as volumetric repainting plans. The interplay evaluation was carried out for each of the ten different phases as the starting phases. Several dosimetric metrics were included to evaluate the worst-case scenario (WCS) and bandwidth based on the results obtained from treatment delivery starting in ten different breathing phases. Results: The number of repaintings needed to meet the criteria 1 (CR1) of target coverage (D95% ≥ 98% and D99% ≥ 97%) ranged from 2 to 10. The number of repaintings needed to meet the CR1 of maximum dose (ΔD1% \u3c 1.5%) ranged from 2 to 7. Similarly, the number of repaintings needed to meet CR1 of homogeneity index (ΔHI \u3c 0.03) ranged from 3 to 10. For the target coverage region, the number of repaintings needed to meet CR1 of bandwidth ( Conclusion: The number of repaintings required to mitigate the interplay effect in PBS lung cancer (tumor motion \u3c 15 mm) was found to be highly patient dependent. For the volumetric repainting with an alternating order, a patient-specific interplay evaluation strategy must be adopted. Determining the optimal number of repaintings based on the bandwidth and WCS approach could mitigate the interplay effect in PBS lung cancer treatment. Keywords: 4D robust optimization; Monte Carlo; interplay effect; lung cancer; pencil beam scanning

Impact of errors in spot size and spot position in robustly optimized pencil beam scanning proton-based stereotactic body radiation therapy (SBRT) lung plans

Purpose: The purpose of the current study was threefold: (a) investigate the impact of the variations (errors) in spot sizes in robustly optimized pencil beam scanning (PBS) proton-based stereotactic body radiation therapy (SBRT) lung plans, (b) evaluate the impact of spot sizes and position errors simultaneously, and (c) assess the overall effect of spot size and position errors occurring simultaneously in conjunction with either setup or range errors. Methods: In this retrospective study, computed tomography (CT) data set of five lung patients was selected. Treatment plans were regenerated for a total dose of 5000 cGy(RBE) in 5 fractions using a single-field optimization (SFO) technique. Monte Carlo was used for the plan optimization and final dose calculations. Nominal plans were normalized such that 99% of the clinical target volume (CTV) received the prescription dose. The analysis was divided into three groups. Group 1: The increasing and decreasing spot sizes were evaluated for ±10%, ±15%, and ±20% errors. Group 2: Errors in spot size and spot positions were evaluated simultaneously (spot size: ±10%; spot position: ±1 and ±2 mm). Group 3: Simulated plans from Group 2 were evaluated for the setup (±5 mm) and range (±3.5%) errors. Results: Group 1: For the spot size errors of ±10%, the average reduction in D99% for -10% and +10% errors was 0.7% and 1.1%, respectively. For -15% and +15% spot size errors, the average reduction in D99% was 1.4% and 1.9%, respectively. The average reduction in D99% was 2.1% for -20% error and 2.8% for +20% error. The hot spot evaluation showed that, for the same magnitude of error, the decreasing spot sizes resulted in a positive difference (hotter plan) when compared with the increasing spot sizes. Group 2: For a 10% increase in spot size in conjunction with a -1 mm (+1 mm) shift in spot position, the average reduction in D99% was 1.5% (1.8%). For a 10% decrease in spot size in conjunction with a -1 mm (+1 mm) shift in spot position, the reduction in D99% was 0.8% (0.9%). For the spot size errors of ±10% and spot position errors of ±2 mm, the average reduction in D99% was 2.4%. Group 3: Based on the results from 160 plans (4 plans for spot size [±10%] and position [±1 mm] errors × 8 scenarios × 5 patients), the average D99% was 4748 cGy(RBE) with the average reduction of 5.0%. The isocentric shift in the superior-inferior direction yielded the least homogenous dose distributions inside the target volume. Conclusion: The increasing spot sizes resulted in decreased target coverage and dose homogeneity. Similarly, the decreasing spot sizes led to a loss of target coverage, overdosage, and degradation of dose homogeneity. The addition of spot size and position errors to plan robustness parameters (setup and range uncertainties) increased the target coverage loss and decreased the dose homogeneity. Keywords: Monte Carlo; SBRT; lung cancer; proton therapy; robust optimization; robustness; spot position; spot size

Dosimetric and radiobiological impact of intensity modulated proton therapy and RapidArc planning for high-risk prostate cancer with seminal vesicles

INTRODUCTION: The purpose of this study was to evaluate the dosimetric and radiobiological impact of intensity modulated proton therapy (IMPT) and RapidArc planning for high-risk prostate cancer with seminal vesicles. METHODS: Ten high-risk prostate cancer cases were included in this retrospective study. For each case, IMPT plans were generated using multiple field optimisation (MFO) technique (two fields) with XiO treatment planning system (TPS), whereas RapidArc plans were generated using double-arc technique (two full arcs) with Eclipse TPS. IMPT and RapidArc plans were optimised for a total prescription dose of 79.2 Gy (relative biological effectiveness (RBE)) and 79.2 Gy, respectively, using identical dose-volume constraints. IMPT and RapidArc plans were then normalised such that at least 95% of the planning target volume (PTV) received the prescription dose. RESULTS: The mean and maximum PTV doses were comparable in IMPT plans (80.1 ± 0.3 Gy (RBE) and 82.6 ± 1.0 Gy (RBE) respectively) and RapidArc plans (80.3 ± 0.3 Gy and 82.8 ± 0.6 Gy respectively) with P = 0.088 and P = 0.499 respectively. The mean doses of the rectum and bladder were found to be significantly lower in IMPT plans (16.9 ± 5.8 Gy (RBE) and 17.5 ± 5.4 Gy (RBE) respectively) when compared to RapidArc plans (41.9 ± 5.7 Gy and 32.5 ± 7.8 Gy respectively) with P \u3c 0.000 and P \u3c 0.000 respectively. For the rectum, IMPT produced lower V30 (21.0 ± 9.6% vs. 68.5 ± 10.0%; P \u3c 0.000), V50 (14.3 ± 5.8% vs. 45.0 ± 10.0%; P \u3c 0.000) and V70 (6.9 ± 3.4% vs. 12.8 ± 3.6%; P \u3c 0.000) compared to RapidArc. For the bladder, IMPT produced lower V30 (23.2 ± 7.0% vs. 50.9 ± 15.6%; P \u3c 0.000) and V50 (16.6 ± 5.4% vs. 25.1 ± 9.6%; P = 0.001), but similar V70 (9.7 ± 3.5% vs. 10.5 ± 4.2%; P = 0.111) compared to RapidArc. RapidArc produced lower mean dose for both the right femoral head (19.5 ± 4.2 Gy vs. 27.4 ± 4.5 Gy (RBE); P \u3c 0.000) and left femoral head (18.0 ± 4.3 Gy vs. 28.0 ± 5.6 Gy (RBE); P \u3c 0.000). Both IMPT and RapidArc produced comparable bladder normal tissue complication probability (NTCP) (0.6 ± 0.2% vs. 0.5 ± 0.2%; P = 0.152). The rectal NTCP was found to be lower using IMPT (0.8 ± 0.7%) than using RapidArc (1.7 ± 0.7%) with P \u3c 0.000. CONCLUSION: Both IMPT and RapidArc techniques provided comparable mean and maximum PTV doses. For the rectum, IMPT produced better dosimetric results in the low-, medium- and high-dose regions and lower NTCP compared to RapidArc. For the bladder, the NTCP and dosimetric results in the high-dose region were comparable in both sets of plans, whereas IMPT produced better dosimetric results in the low- and medium-dose regions

Adaptive planning and toxicities of uniform scanning proton therapy for lung cancer patients

Purpose: Adaptive planning is often needed in lung cancer proton therapy to account for geometrical variations, such as tumor shrinkage and other anatomical changes. The purpose of this study is to present our findings in adaptive radiotherapy for lung cancer using uniform scanning proton beams, including clinical workflow, adaptation strategies and considerations, and toxicities. Methods: We analyzed 165 lung patients treated using uniform scanning proton beams at our center. Quality assurance (QA) plans were generated after repeated computerized tomography (CT) scan to evaluate anatomic and dosimetric change during the course of treatment. Plan adaptation was determined mutually by physicists and physicians after QA plan evaluation, based on several clinical and practical considerations including potential clinical benefit and associated cost in plan adaption. Detailed analysis was performed for all patients with a plan adaptation, including the type of anatomy change, at which fraction the adaption was made, and the strategy for adaptation. Toxicities were compared between patients with and without plan adaptation. Results: In total, 32 adaptive plans were made for 31 patients out of 165 patients, with one patient undergoing adaptive planning twice. Anatomy changes leading to plan adaptation included tumor shrinkage (17), pleural effusion (3), patient weight loss (2), and tumor growth or other anatomy change (9). The plan adaptation occurred at the 15th fraction on average and ranged from the 1st to 31st fraction. Strategies of plan adaptation included range change only (18), re-planning with new patient-specific hardware (9), and others (5). Most toxicities were Grade 1 or 2, with dermatitis the highest toxicity rate. Conclusions: Adaptive planning is necessary in proton therapy to account for anatomy change and its effect on proton penetration depth during the course of treatment. It is important to take practical considerations into account and fully understand the limitations of plan adaptation process and tools to make wise decision on adaptive planning. USPT is a safe treatment for lung cancer patients with no Grade 4 toxicity

Investigating volumetric repainting technique in pencil beam scanning proton therapy

The fundamental goal of radiotherapy is to maximize the radiation dose to enhance the tumor control while minimizing dose to the normal tissues. Proton radiotherapy for clinical use has increased in the last decade. Currently, the use of pencil beam scanning (PBS) proton therapy technology for the treatment of various cancers is gaining popularity. The potential challenge of clinical utilization of PBS proton therapy occurs in the case of mobile tumors such as lung. The mitigation of interplay effect in PBS proton therapy is critical to maintain a higher local control. Volumetric repainting is considered as one of the tumor motion management techniques in PBS proton treatment. Volumetric repainting is accomplished by scanning the entire target volume repeatedly. This thesis examines the application of volumetric repainting in PBS proton therapy, with a particular emphasis on the alternating order repainting technique. The experiments were carried out on an IBA ProteusPLUS PBS proton system operating in a magnetic field regulation mode. The “magnetic field regulation” mode on an IBA ProteusPLUS PBS proton system is capable of delivering a proton beam from the distal end to proximal end and vice-versa, with a faster energy layer switching. There is a lack of published scientific guidelines on the implementation of such commercially available advanced technology in a clinical setting. This thesis work is primarily focused on investigating the feasibility of clinical implementation of volumetric repainting technique in an alternating order to treat lung tumors in PBS proton therapy. Specifically, this thesis work provides the experimental results for a PBS proton beam model as well as addresses the interplay effect, proton dose calculation algorithms, spot size and position errors, treatment plan robustness, radiobiological analysis, and dose-averaged linear energy transfer (LETd) distributions in PBS proton lung cancer patients

Feasibility of Multisolutions Optimization Technique for Real-Time HDR Brachytherapy of Prostate

The purpose of this study was to evaluate the efficacy of multisolutions optimization algorithm for High Dose Rate (HDR) brachytherapy of prostate. In this retrospective study, we included data from 20 prostate cancer patients who underwent ultrasound based real time HDR Brachytherapy at institution. The treatment plans of all 20 patients were optimized in Oncentra Prostate treatment planning system (TPS) using inverse dose volume histogram based optimization followed by graphical optimization (GRO) in real time. The data of all the patients were retrieved later, and the treatment plans were re-optimized using multisolutions dose volume histogram based optimization (MDVHO) and multisolutions variance based optimization (MVBO) algorithms with same set of dose constraints, same number of catheters, and same contour set as in GRO. Several Pareto optimal solutions were obtained by varying the weighting factors of composite objective function in finite steps of adequate resolutions.  These solutions were then stored in the database of TPS and same decision criteria was employed to pick the final solution using a decision engine. The average values for planning target volume receiving 100% of prescribed dose (V100) for MDVHO, MVBO, and GRO were 95.03%, 86.72% and 97.56%, respectively. The average V100 due to MDVHO was statistically significant (P = 0.002) in comparison to MVBO, whereas the average V100 due to MDVHO and GRO was not statistically significant (P = 0.066). In conclusion, the MDVHO can provide comparable solutions to typical clinical optimizations using GRO within clinically reasonable amount of time. In most of the cases, the plans created by MVBO were not clinically acceptable without users’ further manual intervention

Impact of errors in spot size and spot position in robustly optimized pencil beam scanning proton-based stereotactic body radiation therapy (SBRT) lung plans

Purpose: The purpose of the current study was threefold: (a) investigate the impact of the variations (errors) in spot sizes in robustly optimized pencil beam scanning (PBS) proton-based stereotactic body radiation therapy (SBRT) lung plans, (b) evaluate the impact of spot sizes and position errors simultaneously, and (c) assess the overall effect of spot size and position errors occurring simultaneously in conjunction with either setup or range errors. Methods: In this retrospective study, computed tomography (CT) data set of five lung patients was selected. Treatment plans were regenerated for a total dose of 5000 cGy(RBE) in 5 fractions using a single-field optimization (SFO) technique. Monte Carlo was used for the plan optimization and final dose calculations. Nominal plans were normalized such that 99% of the clinical target volume (CTV) received the prescription dose. The analysis was divided into three groups. Group 1: The increasing and decreasing spot sizes were evaluated for ±10%, ±15%, and ±20% errors. Group 2: Errors in spot size and spot positions were evaluated simultaneously (spot size: ±10%; spot position: ±1 and ±2 mm). Group 3: Simulated plans from Group 2 were evaluated for the setup (±5 mm) and range (±3.5%) errors. Results: Group 1: For the spot size errors of ±10%, the average reduction in D99% for −10% and +10% errors was 0.7% and 1.1%, respectively. For −15% and +15% spot size errors, the average reduction in D99% was 1.4% and 1.9%, respectively. The average reduction in D99% was 2.1% for −20% error and 2.8% for +20% error. The hot spot evaluation showed that, for the same magnitude of error, the decreasing spot sizes resulted in a positive difference (hotter plan) when compared with the increasing spot sizes. Group 2: For a 10% increase in spot size in conjunction with a −1 mm (+1 mm) shift in spot position, the average reduction in D99% was 1.5% (1.8%). For a 10% decrease in spot size in conjunction with a −1 mm (+1 mm) shift in spot position, the reduction in D99% was 0.8% (0.9%). For the spot size errors of ±10% and spot position errors of ±2 mm, the average reduction in D99% was 2.4%. Group 3: Based on the results from 160 plans (4 plans for spot size [±10%] and position [±1 mm] errors × 8 scenarios × 5 patients), the average D99% was 4748 cGy(RBE) with the average reduction of 5.0%. The isocentric shift in the superior–inferior direction yielded the least homogenous dose distributions inside the target volume. Conclusion: The increasing spot sizes resulted in decreased target coverage and dose homogeneity. Similarly, the decreasing spot sizes led to a loss of target coverage, overdosage, and degradation of dose homogeneity. The addition of spot size and position errors to plan robustness parameters (setup and range uncertainties) increased the target coverage loss and decreased the dose homogeneity

Investigating volumetric repainting to mitigate interplay effect on 4D robustly optimized lung cancer plans in pencil beam scanning proton therapy

Purpose: The interplay effect between dynamic pencil proton beams and motion of the lung tumor presents a challenge in treating lung cancer patients in pencil beam scanning (PBS) proton therapy. The main purpose of the current study was to investigate the interplay effect on the volumetric repainting lung plans with beam delivery in alternating order (“down” and “up” directions), and explore the number of volumetric repaintings needed to achieve acceptable lung cancer PBS proton plan. Method: The current retrospective study included ten lung cancer patients. The total dose prescription to the clinical target volume (CTV) was 70 Gy(RBE) with a fractional dose of 2 Gy(RBE). All treatment plans were robustly optimized on all ten phases in the 4DCT data set. The Monte Carlo algorithm was used for the 4D robust optimization, as well as for the final dose calculation. The interplay effect was evaluated for both the nominal (i.e., without repainting) as well as volumetric repainting plans. The interplay evaluation was carried out for each of the ten different phases as the starting phases. Several dosimetric metrics were included to evaluate the worst-case scenario (WCS) and bandwidth based on the results obtained from treatment delivery starting in ten different breathing phases. Results: The number of repaintings needed to meet the criteria 1 (CR1) of target coverage (D95% ≥ 98% and D99% ≥ 97%) ranged from 2 to 10. The number of repaintings needed to meet the CR1 of maximum dose (ΔD1% \u3c 1.5%) ranged from 2 to 7. Similarly, the number of repaintings needed to meet CR1 of homogeneity index (ΔHI \u3c 0.03) ranged from 3 to 10. For the target coverage region, the number of repaintings needed to meet CR1 of bandwidth (\u3c100 cGy) ranged from 3 to 10, whereas for the high-dose region, the number of repaintings needed to meet CR1 of bandwidth (\u3c100 cGy) ranged from 1 to 7. Based on the overall plan evaluation criteria proposed in the current study, acceptable plans were achieved for nine patients, whereas one patient had acceptable plan with a minor deviation. Conclusion: The number of repaintings required to mitigate the interplay effect in PBS lung cancer (tumor motion \u3c 15 mm) was found to be highly patient dependent. For the volumetric repainting with an alternating order, a patient-specific interplay evaluation strategy must be adopted. Determining the optimal number of repaintings based on the bandwidth and WCS approach could mitigate the interplay effect in PBS lung cancer treatment

Impact of different tillage methods on growth, development and productivity of maize (Zea mays)-wheat (Tritcum aestivum) cropping system

An experiment was conducted on a silty clay loam soil of Palampur during 2009–2011, to study the effect of different tillage methods in maize (Zea mays L.) wheat {Triticum aestivum (L.) emend. Fiori & Paol.} cropping system. Results revealed that in maize crop, tillage methods in kharif season resulted in significantly highest emergence count (27.1 plant/m2) under manual seed drill. While, multi-crop planter recorded in significantly taller plants (55.4 cm) at 30 DAS; higher dry matter accumulation 81.0, 990.0 and 4184.4 g/m2 at 30, 60 and 90 DAS, respectively and CGR (30.3 g/day/m2) at 30-60 DAS. Tillage methods in rabi season resulted in higher emergence count (17.6 plant/m2) under zero tillage. This treatment also recorded advanced emergence by 1.2 to 1.5 days. In wheat crop, tillage methods in kharif season resulted in significantly highest emergence count (307.6 plant/m2), taller plants (13.1 cm) at 30 DAS, dry matter accumulation (625.3 g/m2) at 120 DAS and CGR (14.4 g/day/m2) at 90-120 DAS under conventional tillage. While, tillage methods in rabi season resulted in significantly highest emergence count (369.5 plants/m2), tallest plants (17.7, 92.6 and 101.0 cm at 60, 120 and at harvest, respectively) with multi-crop planter. While, zero tillage recorded significantly higher CGR (15.8 g/day/m2) and RGR (0.027 g/g/day) during 120-harvest stage. Zero tillage produced statistically at par crop yield and rainwater-use efficiency of both crops with other tillage treatments. Hence, zero tillage can be as good as other intensive tillage system besides lower input cost and environmental security