Robustness and dosimetric verification of hippocampal-sparing craniospinal pencil beam scanning proton plans for pediatric medulloblastoma.

Background and Purpose: Hippocampal-sparing (HS) is a method that can potentially reduce late cognitive complications for pediatric medulloblastoma (MB) patients treated with craniospinal proton therapy (PT). The aim of this study was to investigate robustness and dosimetric plan verification of pencil beam scanning HS PT. Materials and Methods: HS and non-HS PT plans for the whole brain part of craniospinal treatment were created for 15 pediatric MB patients. A robust evaluation of the plans was performed. Plans were recalculated in a water phantom and measured field-by-field using an ion chamber detector at depths corresponding to the central part of hippocampi. All HS and non-HS fields were measured with the standard resolution of the detector and in addition 16 HS fields were measured with high resolution. Measured and planned dose distributions were compared using gamma evaluation. Results: The median mean hippocampus dose was reduced from 22.9 Gy (RBE) to 8.9 Gy (RBE), while keeping CTV V95% above 95 % for all nominal HS plans. HS plans were relatively robust regarding hippocampus mean dose, however, less robust regarding target coverage and maximum dose compared to non-HS plans. For standard resolution measurements, median pass rates were 99.7 % for HS and 99.5 % for non-HS plans (p < 0.001). For high-resolution measurements, median pass rates were 100 % in the hippocampus region and 98.2 % in the surrounding region. Conclusions: A substantial reduction of dose in the hippocampus region appeared feasible. Dosimetric accuracy of HS plans was comparable to non-HS plans and agreed well with planned dose distribution in the hippocampus region.

Pencil beam scanning proton therapy for mediastinal lymphomas in deep inspiration breath-hold: a retrospective assessment of plan robustness.

PURPOSE/BACKGROUND: The aim of this study was to evaluate pencil beam scanning (PBS) proton therapy (PT) in deep inspiration breath-hold (DIBH) for mediastinal lymphoma patients, by retrospectively evaluating plan robustness to the clinical target volume (CTV) and organs at risk (OARs) on repeated CT images acquired throughout treatment.  Methods: Sixteen mediastinal lymphoma patients treated with PBS-PT in DIBH were included. Treatment plans (TPs) were robustly optimized on the CTV (7 mm/4.5%). Repeated verification CTs (vCT) were acquired during the treatment course, resulting in 52 images for the entire patient cohort. The CTV and OARs were transferred from the planning CT to the vCTs with deformable image registration and the TPs were recalculated on the vCTs. Target coverage and OAR doses at the vCTs were compared to the nominal plan. Deviation in lung volume was also calculated. RESULTS: The TPs demonstrated high robust target coverage throughout treatment with D98%,CTV deviations within 2% for 14 patients and above the desired requirement of 95% for 49/52 vCTs. However, two patients did not achieve a robust dose to CTV due to poor DIBH reproducibility, with D98%,CTV at 78 and 93% respectively, and replanning was performed for one patient. Adequate OAR sparing was achieved for all patients. Total lung volume variation was below 10% for 39/52 vCTs. CONCLUSION: PBS PT in DIBH is generally a robust technique for treatment of mediastinal lymphomas. However, closely monitoring the DIBH-reproducibility during treatment is important to avoid underdosing CTV and achieve sufficient dose-sparing of the OARs.

Abdominal compression as motion management for stereotactic radiotherapy of ventricular tachycardia.

Background and purpose: Stereotactic body radiotherapy (SBRT) has emerged as a promising treatment for patients with ventricular tachycardia (VT) who do not respond to standard treatments. However, the management of respiratory motion during treatment remains a challenge. This study aimed to investigate the effect of abdominal compression (AC) on respiratory induced motion in the heart. Materials and methods: A patient cohort of 18 lung cancer patients was utilized, where two four-dimensional computed tomography (4DCT) scans were performed for each patient, one with and one without AC. The patient setup consisted of an AC plate together with a stereotactic body frame. The left coronary artery, the left anterior descending artery, the lateral wall of the left ventricle, the heart apex, the carina, and the right and left diaphragm were delineated in max expiration and max inspiration phases in both 4DCT scans. The center of mass shift from expiration to inspiration phase was determined to assess the AC's impact on respiratory motion. Results: A significant reduction in motion in the superior-inferior direction was found for all heart structures when AC was used. The median respiratory motion of the heart structures decreased by approximately 1-3 mm with AC in the superior-inferior direction, and approximately 60% of the patients had a motion reduction ≥3 mm in the left ventricle wall. Conclusion: These findings suggest that AC has the potential to improve the motion management of SBRT for VT patients, by reducing the respiratory induced motion in the heart.

Surface guided electron FLASH radiotherapy for canine cancer patients.

BACKGROUND: During recent years FLASH radiotherapy (FLASH-RT) has shown promising results in radiation oncology, with the potential to spare normal tissue while maintaining the antitumor effects. The high speed of the FLASH-RT delivery increases the need for fast and precise motion monitoring to avoid underdosing the target. Surface guided radiotherapy (SGRT) uses surface imaging (SI) to render a 3D surface of the patient. SI provides real-time motion monitoring and has a large scanning field of view, covering off-isocentric positions. However, SI has so far only been used for human patients with conventional setup and treatment. PURPOSE: The aim of this study was to investigate the performance of SI as a motion management tool during electron FLASH-RT of canine cancer patients. METHODS: To evaluate the SI system's ability to render surfaces of fur, three fur-like blankets in white, grey, and black were used to imitate the surface of canine patients and the camera settings were optimized for each blanket. Phantom measurements using the fur blankets were carried out, simulating respiratory motion and sudden shift. Respiratory motion was simulated using the QUASAR Respiratory Motion Phantom with the fur blankets placed on the phantom platform, which moved 10 mm vertically with a simulated respiratory period of 4 s. Sudden motion was simulated with an in-house developed phantom, consisting of a platform which was moved vertically in a stepwise motion at a chosen frequency. For sudden measurements, 1, 2, 3, 4, 5, 6, 7, and 10 Hz were measured. All measurements were both carried out at the conventional source-to-surface distance (SSD) of 100 cm, and in the locally used FLASH-RT setup at SSD = 70 cm. The capability of the SI system to reproduce the simulated motion and the sampling time were evaluated. As an initial step towards clinical implementation, the feasibility of SI for surface guided FLASH-RT was evaluated for 11 canine cancer patients. RESULTS: The SI camera was capable of rendering surfaces for all blankets. The deviation between simulated and measured mean peak-to-peak breathing amplitude was within 0.6 mm for all blankets. The sampling time was generally higher for the black fur than for the white and grey fur, for the measurement of both respiratory and sudden motion. The SI system could measure sudden motion within 62.5 ms and detect motion with a frequency of 10 Hz. The feasibility study of the canine patients showed that the SI system could be an important tool to ensure patient safety. By using this system we could ensure and document that 10 out of 11 canine patients had a total vector offset from the reference setup position <2 mm immediately before and after irradiation. CONCLUSIONS: We have shown that SI can be used for surface guided FLASH-RT of canine patients. The SI system is currently not fast enough to interrupt a FLASH-RT beam while irradiating but with the short sampling time sudden motion can be detected. The beam can therefore be held just prior to irradiation, preventing treatment errors such as underdosing the target.

Faster and more accurate patient positioning with surface guided radiotherapy for ultra-hypofractionated prostate cancer patients.

INTRODUCTION: The aim of this study was to evaluate if surface guided radiotherapy (SGRT) can decrease patient positioning time for localized prostate cancer patients compared to the conventional 3-point localization setup method. The patient setup accuracy was also compared between the two setup methods. MATERIALS AND METHODS: A total of 40 localized prostate cancer patients were enrolled in this study, where 20 patients were positioned with surface imaging (SI) and 20 patients were positioned with 3-point localization. The setup time was obtained from the system log files of the linear accelerator and compared between the two methods. The patient setup was verified with daily orthogonal kV images which were matched based on the implanted gold fiducial markers. Resulting setup deviations between planned and online positions were compared between SI and 3-point localization. RESULTS: Median setup time was 2:50 min and 3:28 min for SI and 3-point localization, respectively (p < 0.001). The median vector offset was 4.7 mm (range: 0-10.4 mm) for SI and 5.2 mm for 3-point localization (range: 0.41-17.3 mm) (p = 0.01). Median setup deviation in the individual translations for SI and 3-point localization respectively was: 1.1 mm and 1.9 mm in lateral direction (p = 0.02), 1.8 and 1.6 mm in the longitudinal direction (p = 0.41) and 2.2 mm and 2.6 mm in the vertical direction (p = 0.04). CONCLUSIONS: Using SGRT for positioning of prostate cancer patients provided a faster and more accurate patient positioning compared to the conventional 3-point localization setup.

Pencil beam scanning proton therapy of Hodgkin's lymphoma in deep inspiration breath-hold: A case series report.

BACKGROUND: Most patients with Hodgkin's lymphoma are young and have a favourable prognosis, therefore it is of high importance to decrease the radiation doses to normal tissues received during radiotherapy. A combination of proton therapy and deep inspiration breath-hold technique (DIBH) can improve the sparing effect and thereby reduce the risk of late effects. CASE PRESENTATION: The two first patient cases treated with proton therapy in DIBH at the Skandion Clinic, Uppsala, Sweden, are presented here. Proton treatment plans were compared to photon plans based on doses to target and organs at risk. Several CT scans were acquired during the treatment course and inter breath-hold variations were evaluated based on anatomical distances and dosimetric comparisons. CONCLUSIONS: The results from our first patients treated with proton therapy in DIBH imply that the treatment strategy is robust and has the potential to reduce dose to normal tissue.

Surface guided radiotherapy (SGRT) improves breast cancer patient setup accuracy.

PURPOSE: The purpose of the study was to investigate if surface guided radiotherapy (SGRT) can decrease setup deviations for tangential and locoregional breast cancer patients compared to conventional laser-based setup (LBS). MATERIALS AND METHODS: Both tangential (63 patients) and locoregional (76 patients) breast cancer patients were enrolled in this study. For LBS, the patients were positioned by aligning skin markers to the room lasers. For the surface based setup (SBS), an optical surface scanning system was used for daily setup using both single and three camera systems. To compare the two setup methods, the patient position was evaluated using verification imaging (field images or orthogonal images). RESULTS: For both tangential and locoregional treatments, SBS decreased the setup deviation significantly compared to LBS (P < 0.01). For patients receiving tangential treatment, 95% of the treatment sessions were within the clinical tolerance of ≤ 4 mm in any direction (lateral, longitudinal or vertical) using SBS, compared to 84% for LBS. Corresponding values for patients receiving locoregional treatment were 70% and 54% for SBS and LBS, respectively. No significant difference was observed comparing the setup result using a single camera system or a three camera system. CONCLUSIONS: Conventional laser-based setup can with advantage be replaced by surface based setup. Daily SGRT improves patient setup without additional imaging dose to breast cancer patients regardless if a single or three camera system was used.

Comparative treatment planning study for mediastinal Hodgkin's lymphoma: impact on normal tissue dose using deep inspiration breath hold proton and photon therapy.

BACKGROUND: Late effects induced by radiotherapy (RT) are of great concern for mediastinal Hodgkin's lymphoma (HL) patients and it is therefore important to reduce normal tissue dose. The aim of this study was to investigate the impact on the normal tissue dose and target coverage, using various combinations of intensity modulated proton therapy (IMPT), volumetric modulated arc therapy (VMAT) and 3-dimensional conformal RT (3D-CRT), planned in both deep inspiration breath hold (DIBH) and free breathing (FB). MATERIAL AND METHODS: Eighteen patients were enrolled in this study and planned with involved site RT. Two computed tomography images were acquired for each patient, one during DIBH and one during FB. Six treatment plans were created for each patient; 3D-CRT in FB, 3D-CRT in DIBH, VMAT in FB, VMAT in DIBH, IMPT in FB and IMPT in DIBH. Dosimetric impact on the heart, left anterior descending (LAD) coronary artery, lungs, female breasts, target coverage, and also conformity index and integral dose (ID), was compared between the different treatment techniques. RESULTS: The use of DIBH significantly reduced the lung dose for all three treatment techniques, however, no significant difference in the dose to the female breasts was observed. Regarding the heart and LAD doses, large individual variations were observed. For VMAT, the mean heart and LAD doses were significantly reduced using DIBH, but no significant difference was observed for 3D-CRT and IMPT. Both IMPT and VMAT resulted in improved target coverage and more conform dose distributions compared to 3D-CRT. IMPT generally showed the lowest organs at risk (OAR) doses and significantly reduced the ID compared to both 3D-CRT and VMAT. CONCLUSIONS: The majority of patients benefited from treatment in DIBH, however, the impact on the normal tissue dose was highly individual and therefore comparative treatment planning is encouraged. The lowest OAR doses were generally observed for IMPT in combination with DIBH.

Normal tissue sparing potential of scanned proton beams with and without respiratory gating for the treatment of internal mammary nodes in breast cancer radiotherapy.

Proton therapy has shown potential for reducing doses to normal tissues in breast cancer radiotherapy. However data on the impact of protons when including internal mammary nodes (IMN) in the target for breast radiotherapy is comparatively scarce. This study aimed to evaluate normal tissue doses when including the IMN in regional RT with scanned proton beams, with and without respiratory gating. The study cohort was composed of ten left-sided breast patients CT-scanned during enhanced inspiration gating (EIG) and free-breathing (FB). Proton plans were designed for the target including or excluding the IMN. Targets and organs-at-risk were delineated according to RTOG guidelines. Comparison was performed between dosimetric parameters characterizing target coverage and OAR radiation burden. Statistical significance of differences was tested using a paired, two-tailed Student's t-test. Inclusion of the IMN in the target volume led to a small increase of the cardiopulmonary burden. The largest differences were seen for the ipsilateral lung where the mean dose increased from 6.1 to 6.6 Gy (RBE) (P < 0.0001) in FB plans and from 6.9 to 7.4 Gy (RBE) (P = 0.003) in EIG plans. Target coverage parameters were very little affected by the inclusion of IMN into the treatment target. Radiotherapy with scanned proton beams has the potential of maintaining low cardiovascular burden when including the IMN into the target, irrespective of whether respiratory gating is used or not.

Motion induced interplay effects for VMAT radiotherapy.

The purpose of this study was to develop a method to simulate breathing motion induced interplay effects for volumetric modulated arc therapy (VMAT), to verify the proposed method with measurements, and to use the method to investigate how interplay effects vary with different patient- and machine specific parameters. VMAT treatment plans were created on a virtual phantom in a treatment planning system (TPS). Interplay effects were simulated by dividing each plan into smaller sub-arcs using an in-house developed software and shifting the isocenter for each sub-arc to simulate a sin6 breathing motion in the superior-inferior direction. The simulations were performed for both flattening-filter (FF) and flattening-filter free (FFF) plans and for different breathing amplitudes, period times, initial breathing phases, dose levels, plan complexities, CTV sizes, and collimator angles. The resulting sub-arcs were calculated in the TPS, generating a dose distribution including the effects of motion. The interplay effects were separated from dose blurring and the relative dose differences to 2% and 98% of the CTV volume (ΔD98% and ΔD2%) were calculated. To verify the simulation method, measurements were carried out, both static and during motion, using a quasi-3D phantom and a motion platform. The results of the verification measurements during motion were comparable to the results of the static measurements. Considerable interplay effects were observed for individual fractions, with the minimum ΔD98% and maximum ΔD2% being -16.7% and 16.2%, respectively. The extent of interplay effects was larger for FFF compared to FF and generally increased for higher breathing amplitudes, larger period times, lower dose levels, and more complex treatment plans. Also, the interplay effects varied considerably with the initial breathing phase, and larger variations were observed for smaller CTV sizes. In conclusion, a method to simulate motion induced interplay effects was developed and verified with measurements, which allowed for a large number of treatment scenarios to be investigated. The simulations showed large interplay effects for individual fractions and that the extent of interplay effects varied with the breathing pattern, FFF/FF, dose level, CTV size, collimator angle, and the complexity of the treatment plan.

Dosimetric effects of intrafractional isocenter variation during deep inspiration breath-hold for breast cancer patients using surface-guided radiotherapy.

The aim of this study was to investigate potential dose reductions to the heart, left anterior descending coronary artery (LAD), and ipsilateral lung for left-sided breast cancer using visually guided deep inspiration breath-hold (DIBH) with the optical surface scanning system Catalyst™, and how these potential dosimetric benefits are affected by intrafractional motion in between breath holds. For both DIBH and free breathing (FB), treatment plans were created for 20 tangential and 20 locoregional left-sided breast cancer patients. During DIBH treatment, beam-on was triggered by a region of interest on the xiphoid process using a 3 mm gating window. Using a novel nonrigid algorithm, the Catalyst™ system allows for simultaneous real-time tracking of the isocenter position, which was used to calculate the intrafractional DIBH isocenter reproducibility. The 50% and 90% cumulative probabilities and maximum values of the intrafractional DIBH isocenter reproducibility were calculated and to obtain the dosimetric effect isocenter shifts corresponding to these values were performed in the treatment planning system. For both tangential and locoregional treatment, the dose to the heart, LAD and ipsilateral lung was significantly reduced for DIBH compared to FB. The intrafractional DIBH isocenter reproducibility was very good for the majority of the treatment sessions, with median values of approximately 1 mm in all three translational directions. However, for a few treatment sessions, intrafractional DIBH isocenter reproducibility of up to 5 mm was observed, which resulted in large dosimetric effects on the target volume and organs at risk. Hence, it is of importance to set tolerance levels on the intrafractional isocenter motion and not only perform DIBH based on the xiphoid process.

Respiratory gating for proton beam scanning versus photon 3D-CRT for breast cancer radiotherapy.

Background Respiratory gating and proton therapy have both been proposed to reduce the cardiopulmonary burden in breast cancer radiotherapy. This study aims to investigate the additional benefit of proton radiotherapy for breast cancer with and without respiratory gating. Material and methods Twenty left-sided patients were planned on computed tomography (CT)-datasets acquired during enhanced inspiration gating (EIG) and free-breathing (FB), using photon three-dimensional conformal radiation therapy (3D-CRT) and scanned proton beams. Ten patients received treatment to the whole breast only (WBO) and 10 were treated to the breast and the regional lymph nodes (BRN). Dosimetric parameters characterizing the coverage of target volumes and the cardiopulmonary burden were compared using a paired, two-tailed Student's t-test. Results Protons ensured comparable or better target coverage than photons in all patients during both EIG and FB. The heterogeneity index decreased from 12% with photons to about 5% with protons. The mean dose to the ipsilateral lung was reduced in BRN patients from 12 Gy to 7 Gy (RBE) in EIG and from 14 Gy to 6-7 Gy (RBE) in FB, while for WBO patients all values were about 5-6 Gy (RBE). The mean dose to heart decreased by a factor of four in WBO patients [from 1.1 Gy to 0.3 Gy (RBE) in EIG and from 2.1 Gy to 0.5 Gy (RBE) in FB] and 10 in BRN patients [from 2.1 Gy to 0.2 Gy (RBE) in EIG and from 3.4 Gy to 0.3 Gy (RBE) in FB]. Similarly, the mean and the near maximum dose to the left anterior descending artery (LAD) were significantly lower (p < 0.05) with protons in comparison with photons. Conclusion Proton spot scanning has a high potential to reduce the irradiation of organs at risk and other normal tissues for most patients, beyond what could be achieved with EIG and photon therapy. The largest dose sparing has been seen for BRN patients, both in terms of cardiopulmonary burden and integral dose.

Comparison of doses and NTCP to risk organs with enhanced inspiration gating and free breathing for left-sided breast cancer radiotherapy using the AAA algorithm.

BACKGROUND: The purpose of this study was to investigate the potential dose reduction to the heart, left anterior descending (LAD) coronary artery and the ipsilateral lung for patients treated with tangential and locoregional radiotherapy for left-sided breast cancer with enhanced inspiration gating (EIG) compared to free breathing (FB) using the AAA algorithm. The radiobiological implication of such dose sparing was also investigated. METHODS: Thirty-two patients, who received tangential or locoregional adjuvant radiotherapy with EIG for left-sided breast cancer, were retrospectively enrolled in this study. Each patient was CT-scanned during FB and EIG. Similar treatment plans, with comparable target coverage, were created in the two CT-sets using the AAA algorithm. Further, the probability of radiation induced cardiac mortality and pneumonitis were calculated using NTCP models. RESULTS: For tangential treatment, the median V25Gy for the heart and LAD was decreased for EIG from 2.2% to 0.2% and 40.2% to 0.1% (p < 0.001), respectively, whereas there was no significant difference in V20Gy for the ipsilateral lung (p = 0.109). For locoregional treatment, the median V25Gy for the heart and LAD was decreased for EIG from 3.3% to 0.2% and 51.4% to 5.1% (p < 0.001), respectively, and the median ipsilateral lung V20Gy decreased from 27.0% for FB to 21.5% (p = 0.020) for EIG. The median excess cardiac mortality probability decreased from 0.49% for FB to 0.02% for EIG (p < 0.001) for tangential treatment and from 0.75% to 0.02% (p < 0.001) for locoregional treatment. There was no significant difference in risk of radiation pneumonitis for tangential treatment (p = 0.179) whereas it decreased for locoregional treatment from 6.82% for FB to 3.17% for EIG (p = 0.004). CONCLUSIONS: In this study the AAA algorithm was used for dose calculation to the heart, LAD and left lung when comparing the EIG and FB techniques for tangential and locoregional radiotherapy of breast cancer patients. The results support the dose and NTCP reductions reported in previous studies where dose calculations were performed using the pencil beam algorithm.

Photon activation therapy of RG2 glioma carrying Fischer rats using stable thallium and monochromatic synchrotron radiation.

75 RG2 glioma-carrying Fischer rats were treated by photon activation therapy (PAT) with monochromatic synchrotron radiation and stable thallium. Three groups were treated with thallium in combination with radiation at different energy; immediately below and above the thallium K-edge, and at 50 keV. Three control groups were given irradiation only, thallium only, or no treatment at all. For animals receiving thallium in combination with radiation to 15 Gy at 50 keV, the median survival time was 30 days, which was 67% longer than for the untreated controls (p = 0.0020) and 36% longer than for the group treated with radiation alone (not significant). Treatment with thallium and radiation at the higher energy levels were not effective at the given absorbed dose and thallium concentration. In the groups treated at 50 keV and above the K-edge, several animals exhibited extensive and sometimes contra-lateral edema, neuronal death and frank tissue necrosis. No such marked changes were seen in the other groups. The results were discussed with reference to Monte Carlo calculated electron energy spectra and dose enhancement factors.