Impact of physiological breathing motion for breast cancer radiotherapy with proton beam scanning – An in silico study

This study investigates the impact of breathing motion on proton breast treatment plans. Twelve patients with CT datasets acquired during breath-hold-at-inhalation (BHI), breath-hold-at-exhalation (BHE) and in free-breathing (FB) were included in the study. Proton plans were designed for the left breast for BHI and subsequently recalculated for BHE or designed for FB and recalculated for the extreme breath-hold phases. The plans were compared from the point of view of their target coverage and doses to organs-at-risk. The median amplitude of breathing motion determined from the positions of the sternum was 4.7 mm (range 0.5–14.6 mm). Breathing motion led to a degradation of the dose coverage of the target (heterogeneity index increased from 4–7% to 8–11%), but the degraded values of the dosimetric parameters of interest fulfilled the clinical criteria for plan acceptance. Exhalation decreased the lung burden [average dose 3.1–4.5 Gy (RBE)], while inhalation increased it [average dose 5.8–6.8 Gy (RBE)]. The individual values depended on the field arrangement. Smaller differences were seen for the heart [average dose 0.1–0.2 Gy (RBE)] and the LAD [1.9–4.6 Gy (RBE)]. Weak correlations were generally found between changes in dosimetric parameters and respiratory motion. The differences between dosimetric parameters for various breathing phases were small and their expected clinical impact is consequently quite small. The results indicated that the dosimetric parameters of the plans corresponding to the extreme breathing phases are little affected by breathing motion, thus suggesting that this motion might have little impact for the chosen beam orientations with scanned proton beams.     

Impact of interfractional changes in head and neck cancer patients on the delivered dose in intensity modulated radiotherapy with protons and photons

PurposeTo investigate the influence of interfractional changes on the delivered dose of intensity modulated proton (IMPT) and photon plans (IMXT).Methods and materialsFive postoperative head and neck cancer patients, previously treated with tomotherapy at our institute, were analyzed. The planning study is based on megavoltage (MV) control images. For each patient one IMPT plan and one IMXT plan were generated on the first MV-CT and recalculated on weekly control MV-CTs in the actual treatment position. Dose criteria for evaluation were coverage and conformity of the planning target volume (PTV), as well as mean dose to parotids and maximum dose to spinal cord.ResultsConsiderable dosimetric changes were observed for IMPT and IMXT plans. Proton plans showed a more pronounced increase of maximum dose and decrease of minimum dose with local underdosage occurring even in the center of the PTV (worst IMPT vs. IMXT coverage: 66.7% vs. 85.0%). The doses to organs at risk (OARs) increased during the treatment period. However, the OAR doses of IMPT stayed below corresponding IMXT values at any time. For both modalities treatment plans did not necessarily worsen monotonically throughout the treatment.ConclusionsAlthough absolute differences between planned and reconstructed doses were larger in IMPT plans, doses to OARs were higher in IMXT plans. Tumor coverage was more stable in IMXT plans; IMPT dose distributions indicated a high risk for local underdosage during the treatment course.     

Interlaced proton grid therapy – Linear energy transfer and relative biological effectiveness distributions

PurposeInterlaced beams have previously been proposed for delivering proton grid therapy. This study aims to assess dose-averaged LET (LET_d) and RBE-weighted dose (D_RBE) distributions of such beam geometries, and compare them with conventional intensity modulated proton therapy (IMPT).MethodsIMPT plans and four different interlaced proton grid therapy plans were generated for five patient cases (esophagus, lung, liver, prostate, anus). The constant RBE = 1.1 was assumed for optimization. The LET_d was subsequently Monte Carlo calculated for each plan and used as input for two LET-dependent variable RBE models. The fulfilment of clinical goals, along with DVH and spatial distribution evaluations, were then assessed and compared.ResultsAll plans fulfilled the clinical target goals assuming RBE = 1.1. The target coverage was slightly compromised for some grid plans when assuming the variable RBE models. All IMPT plans, and 18 of 20 grid plans, fulfilled all clinical goals for the organs at risk when assuming RBE = 1.1, whereas most plans failed at least one goal when assuming the variable RBE models. Compared with the IMPT plans, the grid plans demonstrated substantially different LET_d distributions due to the fundamentally different beam geometries. However, D_RBE distributions in the target were similar.ConclusionsDespite the unconventional beam geometries of interlaced proton grid plans, with resulting alternating dose and LET_d patterns, the fulfillment of realistic clinical goals seems to be comparable to regular IMPT plans, both assuming RBE = 1.1 and variable RBE models. In addition, the alternating grid patterns do not seem to give rise to unexpected D_RBE hot-spots.     

Proton or photon radiosurgery for cardiac ablation of ventricular tachycardia? Breath and ECG gated robust optimization

PurposeVentricular tachycardia (VT) is a life-threatening heart disorder. The aim of this preliminary study is to assess the feasibility of stereotactic body radiation therapy (SBRT) photon and proton therapy (PT) plans for the treatment of VT, adopting robust optimization technique for both irradiation techniques.MethodsECG gated CT images (in breath hold) were acquired for one patient. Conventional planning target volume (PTV) and robust optimized plans (25GyE in single fraction) were simulated for both photon (IMRT, 5 and 9 beams) and proton (SFO, 2 beams) plans. Robust optimized plans were obtained both for protons and photons considering in the optimization setup errors (5 mm in the three orthogonal directions), range (±3.5%) and the clinical target volume (CTV) motion due to heartbeat and breath-hold variability.ResultsThe photon robust optimization method, compared to PTV-based plans, showed a reduction in the average dose to the heart by about 25%; robust optimization allowed also reducing the mean dose to the left lung from 3.4. to 2.8 Gy for 9-beams configuration and from 4.1 to 2.9 Gy for 5-beams configuration. Robust optimization with protons, allowed further reducing the OAR doses: average dose to the heart and to the left lung decreased from 7.3 Gy to 5.2 GyE and from 2.9 Gy to 2.2 GyE, respectively.ConclusionsOur study demonstrates the importance of the optimization technique adopted in the treatment planning system for VT treatment. It has been shown that robust optimization can significantly reduce the dose to healthy cardiac tissues and that PT further increases this gain.     

In silico comparison of photons versus carbon ions in single fraction therapy of lung cancer

PurposeStereotactic body image guided radiation therapy (SBRT) shows good results for lung cancer treatment. Better normal tissue sparing might be achieved with scanned carbon ion therapy (PT). Therefore an in silico trial was conducted to find potential advantages of and patients suited for PT.MethodsFor 19 patients treated with SBRT, PT plans were calculated on 4D-CTs with simulated breathing motion. Prescribed single fraction dose was 24 Gy and OAR constraints used for photon planning were respected. Motion was mitigated by rescanning and range-adapted ITVs. Doses were compared to the original SBRT plans.ResultsCTV coverage was the same in SBRT and PT. The field-specific PTV including range margins for PT was 1.5 (median, 25–75% 1.3–2.1) times larger than for SBRT. Nevertheless, maximum point dose and mean dose in OARs were higher in SBRT by 2.8 (1.6–3.7) Gy and 0.7 (0.3–1.6) Gy, respectively. Patients with a CTV >2.5 cc or with multiple lung lesions showed larger differences in OAR doses in favor of PT.ConclusionsPatients receive less dose in critical OARs such as heart, spinal cord, esophagus, trachea and aorta with PT, while maintaining the same target coverage. Patients with multiple or larger lesions are particularly suited for PT.     

“Cancer risk after breast proton therapy considering physiological and radiobiological uncertainties” by Raptis et al. (Physica Medica 76 (2020) 1–6)

The paper by Raptis et al. concludes that proton therapy has an advantage over photon therapy with respect to the induction of a second cancer. Furthermore, the authors conclude that physiological movements and radiobiological parameters do not affect the general trend of lower risk associated with proton therapy. The work is based on a modeling framework which is different from most previously used models on the same subject. This invited commentary puts the findings of the paper in context with other published modeling studies on second cancer risk after proton and photon radiation therapy for breast cancer.     

Gated carbon-ion scanning treatment for pancreatic tumour with field specific target volume and organs at risk

ObjectiveTo assess the feasibility of treatment planning for pancreatic tumours subject to respiratory motion using field-specific target volumes (FTV) and field-specific organs at risk (FOAR) using four-dimensional computed tomography (4DCT).MethodsFourteen pancreatic cancer patients underwent 4DCT. Radiation oncologists contoured the gross tumour volume (GTV), clinical target volume (CTV), spinal cord, duodenum, kidneys, and stomach. The gating duty cycle was set to 30 % around exhalation. FTV and FOAR were calculated using the 4DCT dataset. Planning target volumes (PTV) and planning organs at risk volumes (PRV) were defined as equal to FTV and FOAR, respectively. A dose of 55.2 Gy relative biological effectiveness (RBE) was planned to target the PTV from four beam angles. A single field uniform dose (SFUD) plan was selected. The dose distribution, including intrafractional motion changes, was generated.ResultsThe mean volume of target receiving 95 % of the planned doses was 96.4 ± 4.1 % to the GTV and 94.7 ± 0.9 % to the CTV. The highest dose to 2 cc of duodenal volume was 27.5 Gy (RBE). The volume of the stomach receiving ⩾30 Gy (RBE) was <7.0 cc in all patients. All metrics for OARs satisfied dose constraints.ConclusionDose to the CTV was covered sufficiently by the 4DCT-generated FTV, and dose to OARs was reduced by 4DCT-generated FOAR. This methodology may prevent adverse reactions while preserving local tumour control.     

Voluntary breath-hold reduces dose to organs at risk in radiotherapy of left-sided breast cancer

AimTo compare the dose to organs at risk with free breathing (FB) or voluntary breath-hold (VBH) during radiotherapy of patients with left sided breast cancer.BackgroundRadiotherapy reduces the risk of breast-cancer-specific mortality but the effects on other organs increase non-cancer-specific mortality. Radiation exposure to the heart, in particular in patients with left sided breast cancer, can be reduced by breath hold methods that increase the distance between the heart and the radiation field.Materials and MethodsThree-dimensional conformal radiotherapy (3D-CRT) dose plans for the left breast and organs at risk including the heart, left anterior descending coronary artery (LAD) and ipsilateral lung were compared with FB and VBH in ten patients with left sided breast cancer.ResultsThe mean doses to the heart and LAD were reduced by 50.4 % (p < 0.001) and 58.8 % (p = 0.006), respectively, in VBH relative to FB. The mean dose to the ipsilateral lung was reduced by 13.8 % (p = 0.11) in VBH relative to FB. The planning target volume (PTV) coverage was at least 95 % in both FB and VBH (p = 0.78).ConclusionThe VBH technique significantly reduces the dose to organs at risk in 3D-CRT treatment plans of left sided breast cancer.     

Dose distribution comparison in volumetric-modulated arc therapy plans for head and neck cancers with and without an external body contour extended technique

AimThis study compared volumetric-modulated arc therapy (VMAT) plans for head and neck cancers with and without an external body contour extended technique (EBCT).BackgroundDose calculation algorisms for VMAT have limitations in the buildup region.Materials and methodsThree VMAT plans were enrolled, with one case having a metal artifact from an artificial tooth. The proper dose was calculated using Eclipse version 11.0. The body contours were extended 2 cm outward from the skin surface in three-dimensional space, and the dose was recalculated with an anisotropic analytical algorithm (AAA) and Acuros XB (AXB). Monitor units (MUs) were set, and the dose distributions in the planning target volume (PTV), clinical target volume, and organ at risk (OAR) and conformity index (CI) with and without an EBCT were compared. The influence of a metal artifact outside of the thermoplastic head mask was also compared.ResultsThe coverage of PTV by the 95% dose line near the patient’s skin was increased drastically by using an EBCT. Plan renormalization had a negligible impact on MUs and doses delivered to OARs. CI of PTV with a 6-MV photon beam was closer to 1 than that with a 10-MV photon beam when both AAA and AXB were used in all cases. Metal artifacts outside the head mask had no effect on dose distribution.ConclusionsAn EBCT is needed to estimate the proper dose at object volumes near the patient’s skin and can improve the accuracy of the calculated dose at target volumes.     

Effect of patient positioning on carbon-ion therapy planned dose distribution to pancreatic tumors and organs at risk

PurposePancreatic tumor treatment dose distribution variations associated with supine and prone patient positioning were evaluated.MethodsA total of 33 patients with pancreatic tumors who underwent CT in the supine and prone positions were analyzed retrospectively. Gross tumor volume (GTV), planning target volume (PTV), and organs at risk (OARs) (duodenum and stomach) were contoured. The prescribed dose of 55.2 Gy (RBE) was planned from four beam angles (0°, 90°, 180°, and 270°). Patient collimator and compensating boli were designed for each field. Dose distributions were calculated for each field in the supine and prone positions. To improve dose distribution, patient positioning was selected from supine or prone for each beam field.ResultsCompared with conventional beam angle and patient positioning, D2cc of 1st-2nd portion of duodenum (D1-D2), 3rd-4th portion of duodenum (D3-D4), and stomach could be reduced to a maximum of 6.4 Gy (RBE), 3.5 Gy (RBE), and 4.5 Gy (RBE) by selection of patient positioning. V10 of D1-D2, D3-D4, and stomach could be reduced to a maximum of 7.2 cc, 11.3 cc, and 11.5 cc, respectively. D95 of GTV and PTV were improved to a maximum of 6.9% and 3.7% of the prescribed dose, respectively.ConclusionsOptimization of patient positioning for each beam angle in treatment planning has the potential to reduce OARs dose maintaining tumor dose in pancreatic treatment.     

Morbidity dynamics in proton–photon or photon radiation therapy for locally advanced prostate cancer

Aim

This study evaluated the frequency and long-term dynamics of early and late post irradiation damage after proton–photon or photon therapy for locally advanced prostate cancer.

Clinical verification of treatment planning dose calculation in lung SBRT with GATE Monte Carlo simulation code

PurposeThis study aims to use GATE/Geant4 simulation code to evaluate the performance of dose calculations with Anisotropic Analytical Algorithm (AAA) in the context of lung SBRT for complex treatments considering images of patients.MethodsFour cases of non-small cell lung cancer treated with SBRT were selected for this study. Irradiation plans were created with AAA and recalculated end to end using Monte Carlo (MC) method maintaining field configurations identical to the original plans. Each treatment plan was evaluated in terms of PTV and organs at risk (OARs) using dose-volume histograms (DVH). Dosimetric parameters obtained from DVHs were used to compare AAA and MC.ResultsThe comparison between the AAA and MC DVH using gamma analysis with the passing criteria of 3%/3% showed an average passing rate of more than 90% for the PTV structure and 97% for the OARs. Tightening the criteria to 2%/2% showed a reduction in the average passing rate of the PTV to 86%. The agreement between the AAA and MC dose calculations for PTV dosimetric parameters (V₁₀₀; V₉₀; Homogeneity index; maximum, minimum and mean dose; CI_Paddick and D_2cm) was within 18.4%. For OARs, the biggest differences were observed in the spinal cord and the great vessels.ConclusionsIn general, we did not find significant differences between AAA and MC. The results indicate that AAA could be used in complex SBRT cases that involve a larger number of small treatment fields in the presence of tissue heterogeneities.     

RBE variation in prostate carcinoma cells in active scanning proton beams: In-vitro measurements in comparison with phenomenological models

PurposeIn-vitro radiobiological studies are essential for modelling the relative biological effectiveness (RBE) in proton therapy. The purpose of this study was to experimentally determine the RBE values in proton beams along the beam path for human prostate carcinoma cells (Du-145). RBE-dose and RBE-LET_d (dose-averaged linear energy transfer) dependencies were investigated and three phenomenological RBE models, i.e. McNamara, Rørvik and Wilkens were benchmarked for this cell line.MethodsCells were placed at multiple positions along the beam path, employing an in-house developed solid phantom. The experimental setup reflected the clinical prostate treatment scenario in terms of field size, depth, and required proton energies (127.2–180.1 MeV) and the physical doses from 0.5 to 6 Gy were delivered. The reference irradiation was performed with 200 kV X-ray beams. Respective (α/β) values were determined using the linear quadratic model and LET_d was derived from the treatment planning system at the exact location of cells.Results and ConclusionIndependent of the cell survival level, all experimental RBE values were consistently higher in the target than the generic clinical RBE value of 1.1; with the lowest RBE value of 1.28 obtained at the beginning of the SOBP. A systematic RBE decrease with increasing dose was observed for the investigated dose range. The RBE values from all three applied models were considerably smaller than the experimental values. A clear increase of experimental RBE values with LET_d parameter suggests that proton LET must be taken into consideration for this low (α/β) tissue.     

Range optimization for target and organs at risk in dynamic adaptive passive scattering proton beam therapy – A proof of concept

PurposeThe purpose of this study was to design and develop a new range optimization for target and organs at risk (OARs) in dynamic adaptive proton beam therapy (PBT).MethodsThe new range optimization for target and OARs (RO-TO) was optimized to maintain target dose coverage but not to increase the dose exposure of OARs, while the other procedure, range optimization for target (RO-T), only focused on target dose coverage. A retrospective analysis of a patient who received PBT for abdominal lymph node metastases was performed to show the effectiveness of our new approach. The original plan (OP), which had a total dose of 60 Gy (relative biological effectiveness; RBE), was generated using six treatment fields. Bone-based registration (BR) and tumor-based registration (TR) were performed on each pretreatment daily CT image dataset acquired once every four fractions, to align the isocenter.ResultsBoth range adaptive approaches achieved better coverage (D_95%) and homogeneity (D_5%−D_95%) than BR and TR only. However, RO-T showed the greatest increases in D_2cc and D_mean values of the small intestine and stomach and exceeded the limitations of dose exposure for those OARs. RO-TO showed comparable or superior dose sparing compared with the OP for all OARs.ConclusionsOur results suggest that BR and TR alone may reduce target dose coverage, and that RO-T may increase the dose exposure to the OARs. RO-TO may achieve the planned dose delivery to the target and OARs more efficiently than the OP. The technique requires testing on a large clinical dataset.     

A radiobiological model for the relative biological effectiveness of high-dose-rate 252Cf brachytherapy

While there is significant clinical experience using both low- and high-dose-rate 252Cf brachytherapy, there are minimal data regarding values for the neutron relative biological effectiveness (RBE) with both modalities. The aim of this research was to derive a radiobiological model for 252Cf neutron RBE and to compare these results with neutron RBE values used clinically in Russia. The linear-quadratic (LQ) model was used as the basis to characterize cell survival after irradiation, with identical cell killing rates (S(N) = S(gamma)) between 252Cf neutrons and photons used for derivation of RBE. Using this equality, a relationship among neutron dose and LQ radiobiological parameter (i.e., alpha(N), beta(N), alpha(gamma), beta(gamma)) was obtained without the need to specify the photon dose. These results were used to derive the 252Cf neutron RBE, which was then compared with Russian neutron RBE values. The 252Cf neutron RBE was determined after incorporating the LQ radiobiological parameters obtained from cell survival studies with fast neutrons and teletherapy photons. For single-fraction high-dose-rate neutron doses of 0.5, 1.0, 1.5 and 2.0 Gy, the total biologically equivalent doses were 1.8, 3.4, 4.7 and 6.0 RBE Gy with 252Cf neutron RBE values of 3.2, 2.9, 2.7 and 2.5, respectively. Using clinical data for late-responding reactions from 252Cf, Russian investigators created an empirical model that predicted high-dose-rate 252Cf neutron RBE values ranging from 3.6 to 2.9 for similar doses and fractionation schemes and observed that 252Cf neutron RBE increases with the number of treatment fractions. Using these relationships, our results were in general concordance with high-dose-rate 252Cf RBE values obtained from Russian clinical experience.     

Evaluation of energy deposition and secondary particle production in proton therapy of brain using a slab head phantom

AimEvaluation of energy deposition of protons in human brain and calculation of the secondary neutrons and photons produced by protons in proton therapy.BackgroundRadiation therapy is one of the main methods of treating localized cancer tumors. The use of high energy proton beam in radiotherapy was proposed almost 60 years ago. In recent years, there has been a revival of interest in this subject in the context of radiation therapy. High energy protons suffer little angular deflection and have a well-defined penetration range, with a sharp increase in the energy loss at the end of their trajectories, namely the Bragg peak.Materials and methodsA slab head phantom was used for the purpose of simulating proton therapy in brain tissue. In this study simulation was carried out using the Monte Carlo MCNPX code.ResultsBy using mono energetic proton pencil beams, energy depositions in tissues, especially inside the brain, as well as estimating the neutron and photon production as a result of proton interactions in the body, together with their energy spectra, were calculated or obtained. The amount of energy escaped from the head by secondary neutrons and photons was determined.ConclusionsIt was found that for high energy proton beams the amount of escaped energy by neutrons is almost 10 times larger than that by photons. We estimated that at 110 MeV beam energy, the overall proton energy “leaked” from the head by secondary photons and neutrons to be around 1%.     

Hybrid volumetric modulated arc therapy for chest wall irradiation: For a good plan,get the right mixture

PurposeTo find the optimal dose weighting for hybrid volumetric modulated arc therapy (H-VMAT), a combination of conventional 3DCRT and VMAT plans for left sided chest wall and supraclavicular radiation therapy.Methods & materials20 left-sided breast cancer patients who received adjuvant radiotherapy were considered for this study. To find the optimal weighting, 5 H-VMAT plans were generated for each study case by combining different dose proportions of 3DCRT and VMAT plans including: 90% 3DCRT/10% VMAT, 80% 3DCRT/20% VMAT, 70% 3DCRT/30% VMAT, 60% 3DCRT/40% VMAT, 50% 3DCRT/50% VMAT. Further field-in-field, optimal H-VMAT and VMAT alone plans were compared.ResultsAll H-VMAT plans achieved the expected target coverage. A higher conformity index was achieved for 50% 3DCRT/50% VMAT plan, while better homogeneity index was achieved for 80% 3DCRT/20% VMAT plan. Mean and low doses were less in 90% 3DCRT/10% VMAT plan. Compared with other proportions, 80% 3DCRT/20% VMAT and 70% 3DCRT/30% VMAT weighted H-VMAT plans achieved balanced results for PTVs and OARs.ConclusionThe optimal dose mixture for H-VMAT technique is 70% to 80% for 3DCRT and 20% to 30% for VMAT. The optimal H-VMAT achieved balanced results for the PTVs and OARs compared with field-in-field and VMAT alone plans.