FLASH Proton Pencil Beam Scanning Irradiation Minimizes Radiation-Induced Leg Contracture and Skin Toxicity in Mice.
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SUBMITTER: Cunningham S
PROVIDER: S-EPMC7957631 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and purpose:Patient-level benefits of proton beam therapy (PBT) relative to photon therapy for prostate cancer (PC) continue to be the focus of debate. Although trials comparing the two modalities are underway, most are being conducted using "conventional" PBT (passive scattering/uniform scanning [PS/US]) rather than pencil beam scanning (PBS). The dosimetric benefits of PBS are well-known, but comparative data are limited. This analysis compares PBS toxicity rates with those of PS/US in a prospective multicenter registry. Methods:We evaluated acute/late gastrointestinal (GI) and genitourinary (GU) toxicity rates for men with low-to-intermediate risk PC enrolled in PCG 001-09. Acute toxicities with the two techniques were compared using ?2 tests, and the cumulative incidence methods for late toxicity. Multivariable analyses (MVAs) for acute toxicity were performed using logistic regression, and cox proportional hazards models for late toxicity. Results:Patients were treated using PS/US (n?=?1105) or PBS (n?=?238). Acute grade ?2 GI toxicity in PBS did not significantly differ from that with PS/US (2.9% and 2.1%, respectively; P?=?0.47). Acute grade ?2?GU toxicity was significantly higher with PBS (21.9% and 15.1%; P?<?0.01). In MVA, PBS was significantly associated with increased acute grade ?2?GU toxicity (RR?=?1.57, p?<?0.001). Late grade ?2?GI and GU toxicities did not differ significantly between groups. Conclusions:This is the first multi-institutional comparative effectiveness evaluation of PBT techniques in PC. Differences in acute GU toxicity warrant further evaluation, and highlight the urgent need for prospective data using PBT.
| S-EPMC6804653 | biostudies-literature
Project description:PurposeTo compare spatially fractionated radiation therapy (GRID) treatment planning techniques using proton pencil-beam-scanning (PBS) and photon therapy.Materials and methodsPBS and volumetric modulated arc therapy (VMAT) GRID plans were retrospectively generated for 5 patients with bulky tumors. GRID targets were arranged along the long axis of the gross tumor, spaced 2 and 3 cm apart, and treated with a prescription of 18 Gy. PBS plans used 2- to 3-beam multiple-field optimization with robustness evaluation. Dosimetric parameters including peak-to-edge ratio (PEDR), ratio of dose to 90% of the valley to dose to 10% of the peak VPDR(D90/D10), and volume of normal tissue receiving at least 5 Gy (V5) and 10 Gy (V10) were calculated. The peak-to-valley dose ratio (PVDR), VPDR(D90/D10), and organ-at-risk doses were prospectively assessed in 2 patients undergoing PBS-GRID with pretreatment quality assurance computed tomography (QACT) scans.ResultsPBS and VMAT GRID plans were generated for 5 patients with bulky tumors. Gross tumor volume values ranged from 826 to 1468 cm3. Peak-to-edge ratio for PBS was higher than for VMAT for both spacing scenarios (2-cm spacing, P = .02; 3-cm spacing, P = .01). VPDR(D90/D10) for PBS was higher than for VMAT (2-cm spacing, P = .004; 3-cm spacing, P = .002). Normal tissue V5 was lower for PBS than for VMAT (2-cm spacing, P = .03; 3-cm spacing, P = .02). Normal tissue mean dose was lower with PBS than with VMAT (2-cm spacing, P = .03; 3-cm spacing, P = .02). Two patients treated using PBS GRID and assessed with pretreatment QACT scans demonstrated robust PVDR, VPDR(D90/D10), and organs-at-risk doses.ConclusionsThe PEDR was significantly higher for PBS than VMAT plans, indicating lower target edge dose. Normal tissue mean dose was significantly lower with PBS than VMAT. PBS GRID may result in lower normal tissue dose compared with VMAT plans, allowing for further dose escalation in patients with bulky disease.
| S-EPMC9875826 | biostudies-literature
Project description:Background and purposeTo report dosimetry and early adverse effects, aesthetic, and patient-reported outcomes of a prospective study of 3-fraction pencil-beam scanning (PBS) proton accelerated partial irradiation (APBI).Materials and methodsEligibility included women age ≥ 50 years with estrogen receptor positive (ER+), sentinel lymph node negative invasive or in-situ breast cancer measuring ≤2.5 cm. The prescription was 21.9 Gy (RBE 1.1) in 3 daily fractions to the post-operative tumor bed with a 1 cm expansion. Toxicities were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, 10-point Linear Analog Scale Assessment, Patient-Reported Outcomes Version of the CTCAE, and the Harvard Breast Cosmesis Scale.ResultsSeventy-six women were treated between 2015 and 2017. The median breast volume receiving 50% of prescription or more was 28%. Median mean heart, mean ipsilateral lung, and maximum skin dose were 0 Gy, 0.1 Gy, and 20.6 Gy, respectively. With a median follow-up of 12 months, no treatment-related toxicity grade ≥ 2 has been observed. Most common grade 1 adverse events were dermatitis (68%) and skin hyperpigmentation (18%). At 12 months, the only persistent toxicities were one patient with grade 1 breast edema and one patient with a grade 1 seroma. 90% of patients reported quality of life as ≥7 out of 10 (0 indicating "as bad as it can be" and 10 indicating "as good as it can be") and 98% of patients reported excellent or good cosmesis.Conclusion3-fraction PBS proton APBI is well tolerated with low rates of physician and patient reported early adverse effects. Follow-up is ongoing to assess late toxicities and disease control outcomes. Further investigation of this novel adjuvant treatment strategy is warranted.
| S-EPMC6873533 | biostudies-literature
Project description:Proton therapy makes use of the favorable depth-dose distribution with its characteristic Bragg peak to spare normal tissue distal of the target volume. A steep dose gradient would be desired in lateral dimensions, too. The widespread spot scanning delivery technique is based, however, on pencil-beams with in-air spot full-widths-at-half-maximum of typically 1 cm or more. This hampers the sparing of organs-at-risk if small-scale structures adjacent to the target volume are concerned. The trimming of spot scanning fields with collimating apertures constitutes a simple measure to increase the transversal dose gradient. The current study describes the clinical implementation of brass apertures in conjunction with the pencil-beam scanning delivery mode at a horizontal, clinical treatment head based on commercial hardware and software components. Furthermore, clinical cases, which comprised craniopharyngiomas, re-irradiations and ocular tumors, were evaluated. The dosimetric benefits of 31 treatment plans using apertures were compared to the corresponding plans without aperture. Furthermore, an overview of the radiation protection aspects is given. Regarding the results, robust optimization considering range and setup uncertainties was combined with apertures. The treatment plan optimizations followed a single-field uniform dose or a restricted multi-field optimization approach. Robustness evaluation was expanded to account for possible deviations of the center of the pencil-beam delivery and the mechanical center of the aperture holder. Supplementary apertures improved the conformity index on average by 15.3%. The volume of the dose gradient surrounding the PTV (evaluated between 80 and 20% dose levels) was decreased on average by 17.6%. The mean dose of the hippocampi could be reduced on average by 2.9 GyRBE. In particular cases the apertures facilitated a sparing of an organ-at-risk, e.g. the eye lens or the brainstem. For six craniopharyngioma cases the inclusion of apertures led to a reduction of the mean dose of 1.5 GyRBE (13%) for the brain and 3.1 GyRBE (16%) for the hippocampi.
| S-EPMC8149965 | biostudies-literature
Project description:BackgroundPencil beam scanning (PBS) proton therapy can provide highly conformal target dose distributions and healthy tissue sparing. However, proton therapy of hepatocellular carcinoma (HCC) is prone to dosimetrical uncertainties induced by respiratory motion. This study aims to develop intra-treatment tumor motion monitoring during respiratory gated proton therapy and combine it with motion-including dose reconstruction to estimate the delivered tumor doses for individual HCC treatment fractions.MethodsThree HCC-patients were planned to receive 58 GyRBE (n=2) or 67.5 GyRBE (n=1) of exhale respiratory gated PBS proton therapy in 15 fractions. The treatment planning was based on the exhale phase of a 4-dimensional CT scan. Daily setup was based on cone-beam CT (CBCT) imaging of three implanted fiducial markers. An external marker block (RPM) on the patient's abdomen was used for exhale gating in free breathing. This study was based on 5 fractions (patient 1), 1 fraction (patient 2) and 6 fractions (patient 3) where a post-treatment control CBCT was available. After treatment, segmented 2D marker positions in the post-treatment CBCT projections provided the estimated 3D motion trajectory during the CBCT by a probability-based method. An external-internal correlation model (ECM) that estimated the tumor motion from the RPM motion was built from the synchronized RPM signal and marker motion in the CBCT. The ECM was then used to estimate intra-treatment tumor motion. Finally, the motion-including CTV dose was estimated using a dose reconstruction method that emulates tumor motion in beam's eye view as lateral spot shifts and in-depth motion as changes in the proton beam energy. The CTV homogeneity index (HI) The CTV homogeneity index (HI) was calculated as D2% - D98%D50% ×100% .ResultsThe tumor position during spot delivery had a root-mean-square error of 1.3 mm in left-right, 2.8 mm in cranio-caudal and 1.7 mm in anterior-posterior directions compared to the planned position. On average, the CTV HI was larger than planned by 3.7%-points (range: 1.0-6.6%-points) for individual fractions and by 0.7%-points (range: 0.3-1.1%-points) for the average dose of 5 or 6 fractions.ConclusionsA method to estimate internal tumor motion and reconstruct the motion-including fraction dose for PBS proton therapy of HCC was developed and demonstrated successfully clinically.
| S-EPMC10019817 | biostudies-literature
Project description:PurposeWe investigate two margin-based schemes for optimization target volumes (OTV), both isotropic expansion (2 mm) and beam-specific OTV, to account for uncertainties due to the setup errors and range uncertainties in pancreatic stereotactic pencil beam scanning (PBS) proton therapy. Also, as 2-mm being one of the extreme sizes of margin, we also study whether the plan quality of 2-mm uniform expansion could be comparable to other plan schemes.Methods and materialsWe developed 2 schemes for OTV: (1) a uniform expansion of 2 mm (OTV2mm) for setup uncertainty and (2) a water equivalent thickness-based, beam-specific expansion (OTVWET) on beam direction and 2 mm expansion laterally. Six LAPC patients were planned with a prescribed dose of 33 Gy (RBE) in 5 fractions. Robustness optimization (RO) plans on gross tumor volumes, with setup uncertainties of 2 mm and range uncertainties of 3.5%, were implemented as a benchmark.ResultsAll 3 optimization schemes achieved decent target coverage with no significant difference. The OTV2mm plans show superior organ at risk (OAR) sparing, especially for proximal duodenum. However, OTV2mm plans demonstrate severe susceptibility to range and setup uncertainties with a passing rate of 19% of the plans meeting the goal of 95% volume covered by the prescribed dose. The proposed dose spread function analysis shows no significant difference.ConclusionsThe use of OTVWET mimics a union volume for all scenarios in robust optimization but saves optimization time noticeably. The beam-specific margin can be attractive to online adaptive stereotactic body proton therapy owing to the efficiency of the plan optimization.
| S-EPMC8463829 | biostudies-literature
Project description:BackgroundPencil beam scanning (PBS) proton therapy offers dosimetric advantages for several treatment sites, including head and neck (H&N). However, to achieve the optimal target coverage and robustness, these plans can be complex and time consuming to develop and optimize. Automating the treatment planning process can ensure a high-quality and standardized plan, reduce burden to the planner, and decrease time-to-treatment. We utilized in-house scripting to automate a four-field multi-field optimization (MFO) H&N planning technique.Methods and materialsTen bilateral H&N patients were planned in RayStation v6 with a four-field modified-X beam configuration using MFO planning. Automation included creation of avoidance structures to control spot placement and development of standardized beams, PBS spot settings, robust optimization objectives, and patient-specific predicted planning constraints. Each patient was planned both with and without automation to evaluate differences in planning time, perceived effort and plan quality, plan robustness, and OAR sparing.ResultsOn average, scripted plans required 3.2 h, compared to 4.3 h without the script. There was no difference in target coverage or plan robustness with or without automation. Automation significantly reduced mean dose to the oral cavity, parotids, esophagus, trachea, and larynx. Perceived effort was scaled from 1 (minimum effort) to 100 (maximum effort), and automation reduced perceived effort by 42% (p < 0.05). Two non-scripted plans required re-planning due to errors.ConclusionsAutomation of this multi-beam, the MFO proton planning process reduced planning time and improved OAR sparing compared to the same planning process without scripting. Scripting generation of complex structures and planning objectives reduced burden on the planner. With most current treatment planning software, this automation is simple to implement and can standardize quality of care across all treatment planners.
| S-EPMC8833278 | biostudies-literature
Project description:Healthy tissue-sparing effects of FLASH (≥40 Gy/s, ≥4-8 Gy/fraction) radiotherapy (RT) make it potentially useful for whole breast irradiation (WBI), since there is often a lot of normal tissue within the planning target volume (PTV). We investigated WBI plan quality and determined FLASH-dose for various machine settings using ultra-high dose rate (UHDR) proton transmission beams (TBs). While five-fraction WBI is commonplace, a potential FLASH-effect might facilitate shorter treatments, so hypothetical 2- and 1-fraction schedules were also analyzed. Using one tangential 250 MeV TB delivering 5 × 5.7 Gy, 2 × 9.74 Gy or 1 × 14.32 Gy, we evaluated: (1) spots with equal monitor units (MUs) in a uniform square grid with variable spacing; (2) spot MUs optimized with a minimum MU-threshold; and (3) splitting the optimized TB into two sub-beams: one delivering spots above an MU-threshold, i.e., at UHDRs; the other delivering the remaining spots necessary to improve plan quality. Scenarios 1-3 were planned for a test case, and scenario 3 was also planned for three other patients. Dose rates were calculated using the pencil beam scanning dose rate and the sliding-window dose rate. Various machine parameters were considered: minimum spot irradiation time (minST): 2 ms/1 ms/0.5 ms; maximum nozzle current (maxN): 200 nA/400 nA/800 nA; two gantry-current (GC) techniques: energy-layer and spot-based. For the test case (PTV = 819 cc) we found: (1) a 7 mm grid achieved the best balance between plan quality and FLASH-dose for equal-MU spots; (2) near the target boundary, lower-MU spots are necessary for homogeneity but decrease FLASH-dose; (3) the non-split beam achieved >95% FLASH for favorable (not clinically available) machine parameters (SB GC, low minST, high maxN), but <5% for clinically available settings (EB GC, minST = 2 ms, maxN = 200 nA); and (4) splitting gave better plan quality and higher FLASH-dose (~50%) for available settings. The clinical cases achieved ~50% (PTV = 1047 cc) or >95% (PTV = 477/677 cc) FLASH after splitting. A single UHDR-TB for WBI can achieve acceptable plan quality. Current machine parameters limit FLASH-dose, which can be partially overcome using beam-splitting. WBI FLASH-RT is technically feasible.
| S-EPMC10177419 | biostudies-literature
Project description:PurposeCarbon ion radiotherapy (CIRT) has emerged as a promising treatment modality for hepatocellular carcinoma (HCC). However, evidence of using the pencil beam scanning (PBS) technique to treat moving liver tumors remains lacking. The present study investigated the efficacy and toxicity of PBS CIRT in patients with HCC.MethodsBetween January 2016 and October 2021, 90 consecutive HCC patients treated with definitive CIRT in our center were retrospectively analyzed. Fifty-eight patients received relative biological effectiveness-weighted doses of 50-70 Gy in 10 fractions, and 32 received 60-67.5 Gy in 15 fractions, which were determined by the tumor location and normal tissue constraints. Active motion-management techniques and necessary strategies were adopted to mitigate interplay effects efficiently. Oncologic outcomes and toxicities were evaluated.ResultsThe median follow-up time was 28.6 months (range 5.7-74.6 months). The objective response rate was 75.0% for all 90 patients with 100 treated lesions. The overall survival rates at 1-, 2- and 3-years were 97.8%, 83.3% and 75.4%, respectively. The local control rates at 1-, 2- and 3-years were 96.4%, 96.4% and 93.1%, respectively. Radiation-induced liver disease was not documented, and 4 patients (4.4%) had their Child-Pugh score elevated by 1 point after CIRT. No grade 3 or higher acute non-hematological toxicities were observed. Six patients (6.7%) experienced grade 3 or higher late toxicities.ConclusionThe active scanning technique was clinically feasible to treat HCC by applying necessary mitigation measures for interplay effects. The desirable oncologic outcomes as well as favorable toxicity profiles presented in this study will be a valuable reference for other carbon-ion centers using the PBS technique and local effect model-based system, and add to a growing body of evidence about the role of CIRT in the management of HCC.
| S-EPMC10759913 | biostudies-literature
Project description:Proton radiotherapy using minibeams of sub-millimeter dimensions reduces side effects in comparison to conventional proton therapy due to spatial fractionation. Since the proton minibeams widen with depth, the homogeneous irradiation of a tumor can be ensured by adjusting the beam distances to tumor size and depth to maintain tumor control as in conventional proton therapy. The inherent advantages of protons in comparison to photons like a limited range that prevents a dosage of distal tissues are maintained by proton minibeams and can even be exploited for interlacing from different beam directions. A first animal study was conducted to systematically investigate and quantify the tissue-sparing effects of proton pencil minibeams as a function of beam size and dose distributions, using beam widths between ? = 95, 199, 306, 411, 561 and 883 ?m (standard deviation) at a defined center-to-center beam distance (ctc) of 1.8 mm. The average dose of 60 Gy was distributed in 4x4 minibeams using 20 MeV protons (LET ~ 2.7 keV/?m). The induced radiation toxicities were measured by visible skin reactions and ear swelling for 90 days after irradiation. The largest applied beam size to ctc ratio (?/ctc = 0.49) is similar to a homogeneous irradiation and leads to a significant 3-fold ear thickness increase compared to the control group. Erythema and desquamation was also increased significantly 3-4 weeks after irradiation. With decreasing beam sizes and thus decreasing ?/ctc, the maximum skin reactions are strongly reduced until no ear swelling or other visible skin reactions should occur for ?/ctc < 0.032 (extrapolated from data). These results demonstrate that proton pencil minibeam radiotherapy has better tissue-sparing for smaller ?/ctc, corresponding to larger peak-to-valley dose ratios PVDR, with the best effect for ?/ctc < 0.032. However, even quite large ?/ctc (e.g. ?/ctc = 0.23 or 0.31, i.e. PVDR = 10 or 2.7) show less acute side effects than a homogeneous dose distribution. This suggests that proton minibeam therapy spares healthy tissue not only in the skin but even for dose distributions appearing in deeper layers close to the tumor enhancing its benefits for clinical proton therapy.
| S-EPMC6876838 | biostudies-literature