List mode proton imaging relies on accurate reconstruction of the proton most likely path (MLP) through the patient. This typically requires two sets of position sensitive detector systems, one ...upstream (front) and one downstream (rear) of the patient. However, for a clinical implementation it can be preferable to omit the front trackers (single-sided proton imaging). For such a system, the MLP can be computed from information available through the beam delivery system and the remaining rear tracker set. In this work, we use Monte Carlo simulations to compare a conventional double-sided (using both front and rear detector systems) with a single-sided system (only rear detector system) by evaluating the spatial resolution of proton radiographs (pRad) and proton CT images (pCT) acquired with these set-ups. Both the pencil beam spot size, as well as the spacing between spots was also adjusted to identify the impact of these beam parameters on the image quality. Relying only on the pencil beam central position for computing the MLP resulted in severe image artifacts both in pRad and pCT. Using the recently extended-MLP formalism that incorporate pencil beam uncertainty removed these image artifacts. However, using a more focused pencil beam with this algorithm induced image artifacts when the spot spacing was the same as the beam spot size. The spatial resolution tested with a sharp edge gradient technique was reduced by 40% for single-sided (MTF10% = 3.0 lp/cm) compared to double-sided (MTF10% = 4.9 lp/cm) pRad with ideal tracking detectors. Using realistic trackers the difference decreased to 30%, with MTF10% of 4.0 lp/cm for the realistic double-sided and 2.7 lp/cm for the realistic single-sided setup. When studying an anthropomorphic paediatric head phantom both single- and double-sided set-ups performed similarly where the difference in water equivalent thickness (WET) between the two set-ups were less than 0.01 mm in homogeneous areas of the head. Larger discrepancies between the two set-ups were visible in high density gradients like the facial structures. A complete CT reconstruction of a Catphan ® module was performed. Assuming ideal detectors, the obtained spatial resolution was 5.1 lp/cm for double-sided and 3.8 lp/cm for the single-sided setup. Double- and single-sided pRad with realistic tracker properties returned a spatial resolution of 3.8 lp/cm and 3.2 lp/cm, respectively. Future studies should investigate the development of dedicated reconstruction algorithms targeted for single-sided particle imaging.
Background
State-of-the-art radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC) is performed with intensity-modulation during free breathing (FB). Previous studies have found ...encouraging geometric reproducibility and patient compliance of deep inspiration breath hold (DIBH) radiotherapy for LA-NSCLC patients. However, dosimetric comparisons of DIBH with FB are sparse, and DIBH is not routinely used for this patient group. The objective of this simulation study was therefore to compare DIBH and FB in a prospective cohort of LA-NSCLC patients treated with intensity-modulated radiotherapy (IMRT).
Methods
For 38 LA-NSCLC patients, 4DCTs and DIBH CTs were acquired for treatment planning and during the first and third week of radiotherapy treatment. Using automated planning, one FB and one DIBH IMRT plan were generated for each patient. FB and DIBH was compared in terms of dosimetric parameters and NTCP. The treatment plans were recalculated on the repeat CTs to evaluate robustness. Correlations between ΔNTCPs and patient characteristics that could potentially predict the benefit of DIBH were explored.
Results
DIBH reduced the median D
mean
to the lungs and heart by 1.4 Gy and 1.1 Gy, respectively. This translated into reductions in NTCP for radiation pneumonitis grade ≥2 from 20.3% to 18.3%, and for 2-year mortality from 51.4% to 50.3%. The organ at risk sparing with DIBH remained significant in week 1 and week 3 of treatment, and the robustness of the target coverage was similar for FB and DIBH. While the risk of radiation pneumonitis was consistently reduced with DIBH regardless of patient characteristics, the ability to reduce the risk of 2-year mortality was evident among patients with upper and left lower lobe tumors but not right lower lobe tumors.
Conclusion
Compared to FB, DIBH allowed for smaller target volumes and similar target coverage. DIBH reduced the lung and heart dose, as well as the risk of radiation pneumonitis and 2-year mortality, for 92% and 74% of LA-NSCLC patients, respectively. However, the advantages varied considerably between patients, and the ability to reduce the risk of 2-year mortality was dependent on tumor location. Evaluation of repeat CTs showed similar robustness of the dose distributions with each technique.
In this study, the novel iCE radiotherapy treatment planning system (TPS) for automated multi-criterial planning with integrated beam angle optimization (BAO) was developed, and applied to optimize ...organ at risk (OAR) sparing and systematically investigate the impact of beam angles on radiotherapy dose in locally advanced non-small cell lung cancer (LA-NSCLC). iCE consists of an in-house, sophisticated multi-criterial optimizer with integrated BAO, coupled to a broadly used commercial TPS. The in-house optimizer performs fluence map optimization to automatically generate an intensity-modulated radiotherapy (IMRT) plan with optimal beam angles for each patient. The obtained angles and dose-volume histograms are then used to automatically generate the final deliverable plan with the commercial TPS. For the majority of 26 LA-NSCLC patients, iCE achieved improved heart and esophagus sparing compared to the manually created clinical plans, with significant reductions in the median heart Dmean (8.1 vs. 9.0 Gy, p = 0.02) and esophagus Dmean (18.5 vs. 20.3 Gy, p = 0.02), and reductions of up to 6.7 Gy and 5.8 Gy for individual patients. iCE was superior to automated planning using manually selected beam angles. Differences in the OAR doses of iCE plans with 6 beams compared to 4 and 8 beams were statistically significant overall, but highly patient-specific. In conclusion, automated planning with integrated BAO can further enhance and individualize radiotherapy for LA-NSCLC.
A typical proton CT (pCT) detector comprises a tracking system, used to measure the proton position before and after the imaged object, and an energy/range detector to measure the residual proton ...range after crossing the object. The Bergen pCT collaboration was established to design and build a prototype pCT scanner with a high granularity digital tracking calorimeter used as both tracking and energy/range detector. In this work the conceptual design and the layout of the mechanical and electronics implementation, along with Monte Carlo simulations of the new pCT system are reported. The digital tracking calorimeter is a multilayer structure with a lateral aperture of 27 cm × 16.6 cm, made of 41 detector/absorber sandwich layers (calorimeter), with aluminum (3.5 mm) used both as absorber and carrier, and two additional layers used as tracking system (rear trackers) positioned downstream of the imaged object; no tracking upstream the object is included. The rear tracker’s structure only differs from the calorimeter layers for the carrier made of ∼200 μm carbon fleece and carbon paper (carbon-epoxy sandwich), to minimize scattering. Each sensitive layer consists of 108 ALICE pixel detector (ALPIDE) chip sensors (developed for ALICE, CERN) bonded on a polyimide flex and subsequently bonded to a larger flexible printed circuit board. Beam tests tailored to the pCT operation have been performed using high-energetic (50–220 MeV/u) proton and ion beams at the Heidelberg Ion-Beam Therapy Center (HIT) in Germany. These tests proved the ALPIDE response independent of occupancy and proportional to the particle energy deposition, making the distinction of different ion tracks possible. The read-out electronics is able to handle enough data to acquire a single 2D image in few seconds making the system fast enough to be used in a clinical environment. For the reconstructed images in the modeled Monte Carlo simulation, the water equivalent path length error is lower than 2 mm, and the relative stopping power accuracy is better than 0.4%. Thanks to its ability to detect different types of radiation and its specific design, the pCT scanner can be employed for additional online applications during the treatment, such as in-situ proton range verification.
•Dose constraints validated for DNIRS may become too strict when applied for DLEM.•CNAO’s initial ON constraints of D1% ≤40 Gy(RBE)/D20% ≤28 Gy(RBE) were overcautious.•Translation of CNAO treatment ...plans to DNIRS aided the proposal of new constraints.•Updated ON constraints at CNAO are DLEM|1% ≤45 Gy(RBE)/DLEM|20% ≤37 Gy(RBE).•It is valuable to analyze and report CIRT outcome in both DNIRS and DLEM.
Until now, carbon ion RT (CIRT) dose constraints for the optic nerve (ON) have only been validated and reported in the NIRS RBE-weighted dose (DNIRS). The aim of this work is to improve CNAO’s RBE-weighted dose (DLEM) constraints by analyzing institutional toxicity data and by relating it to DNIRS.
A total of 65 ONs from 38 patients treated with CIRT to the head and neck region in the period 2013–14 were analyzed. The absorbed dose (DAbs) of the treatment plans was reproduced and subsequently both DLEM and DNIRS were applied, thus relating CNAO clinical toxicity to DNIRS.
Median FU was 47 (26–67) months. Visual acuity was preserved for the 56 ONs in which the old constraints were respected. Three ONs developed visual decline at DLEM|1% ≥71 Gy(RBE)/DLEM|20% ≥68 Gy(RBE), corresponding to DNIRS|1% ≥68 Gy(RBE)/DNIRS|20% ≥62 Gy(RBE). Dose recalculation revealed that NIRS constraints of DNIRS|1% ≤40 Gy(RBE)/DNIRS|20% ≤28 Gy(RBE) corresponded to DLEM|1% ≤50 Gy(RBE)/DLEM|20% ≤40 Gy(RBE). Reoptimization of treatment plans with these new DLEM constraints showed that the dose distribution still complied with NIRS constraints when evaluated in DNIRS. However, due to uncertainties in the method, and to comply with the EQD2-based constraints used at GSI/HIT, a more moderate constraint relaxation to DLEM|1% ≤45 Gy(RBE)/DLEM|20% ≤37 Gy(RBE) has been implemented in CNAO clinical routine since October 2018.
New DLEM constraints for the ON were derived by analyzing CNAO toxicity data and by linking our results to the experience of NIRS and GSI/HIT. This work demonstrates the value of recalculating and reporting results in both DLEM and DNIRS.
Intensity modulated proton therapy (IMPT) could yield high linear energy transfer (LET) in critical structures and increased biological effect. For head and neck cancers at the skull base this could ...potentially result in radiation-associated brain image change (RAIC). The purpose of the current study was to investigate voxel-wise dose and LET correlations with RAIC after IMPT.
For 15 patients with RAIC after IMPT, contrast enhancement observed on T1-weighted magnetic resonance imaging was contoured and coregistered to the planning computed tomography. Monte Carlo calculated dose and dose-averaged LET (LETd) distributions were extracted at voxel level and associations with RAIC were modelled using uni- and multivariate mixed effect logistic regression. Model performance was evaluated using the area under the receiver operating characteristic curve and precision-recall curve.
An overall statistically significant RAIC association with dose and LETd was found in both the uni- and multivariate analysis. Patient heterogeneity was considerable, with standard deviation of the random effects of 1.81 (1.30-2.72) for dose and 2.68 (1.93-4.93) for LETd, respectively. Area under the receiver operating characteristic curve was 0.93 and 0.95 for the univariate dose-response model and multivariate model, respectively. Analysis of the LETd effect demonstrated increased risk of RAIC with increasing LETd for the majority of patients. Estimated probability of RAIC with LETd = 1 keV/µm was 4% (95% confidence interval, 0%, 0.44%) and 29% (95% confidence interval, 0.01%, 0.92%) for 60 and 70 Gy, respectively. The TD15 were estimated to be 63.6 and 50.1 Gy with LETd equal to 2 and 5 keV/µm, respectively.
Our results suggest that the LETd effect could be of clinical significance for some patients; LETd assessment in clinical treatment plans should therefore be taken into consideration.
BACKGROUNDKnowledge-based planning (KBP) is a method for automated radiotherapy treatment planning where appropriate optimization objectives for new patients are predicted based on a library of ...training plans. KBP can save time and improve organ at-risk sparing and inter-patient consistency compared to manual planning, but its performance depends on the quality of the training plans. We used another system for automated planning, which generates multi-criteria optimized (MCO) plans based on a wish list, to create training plans for the KBP model, to allow seamless integration of knowledge from a new system into clinical routine. Model performance was compared for KBP models trained with manually created and automatic MCO treatment plans.MATERIAL AND METHODSTwo RapidPlan models with the same 30 locally advanced non-small cell lung cancer patients included were created, one containing manually created clinical plans (RP_CLIN) and one containing fully automatic multi-criteria optimized plans (RP_MCO). For 15 validation patients, model performance was compared in terms of dose-volume parameters and normal tissue complication probabilities, and an oncologist performed a blind comparison of the clinical (CLIN), RP_CLIN, and RP_MCO plans.RESULTSThe heart and esophagus doses were lower for RP_MCO compared to RP_CLIN, resulting in an average reduction in the risk of 2-year mortality by 0.9 percentage points and the risk of acute esophageal toxicity by 1.6 percentage points with RP_MCO. The oncologist preferred the RP_MCO plan for 8 patients and the CLIN plan for 7 patients, while the RP_CLIN plan was not preferred for any patients.CONCLUSIONRP_MCO improved OAR sparing compared to RP_CLIN and was selected for implementation in the clinic. Training a KBP model with clinical plans may lead to suboptimal output plans, and making an extra effort to optimize the library plans in the KBP model creation phase can improve the plan quality for many future patients.
Manual volumetric modulated arc therapy (VMAT) treatment planning for high-risk prostate cancer receiving whole pelvic radiotherapy (WPRT) with four integrated dose levels is complex and time ...consuming. We have investigated if the radiotherapy planning process and plan quality can be improved using a well-tuned model developed through a commercial system for knowledge-based planning (KBP).
Treatment plans from 69 patients treated for high-risk prostate cancer with manually planned VMAT were used to develop an initial KBP model (RapidPlan, RP). Prescribed doses were 50, 60, 67.5, and 72.5 Gy in 25 fractions to the pelvic lymph nodes, prostate and seminal vesicles, prostate gland, and prostate tumour(s), respectively. This RP model was in clinical use from July 2019 to February 2020, producing another set of 69 clinically delivered treatment plans for a new patient group, which were used to develop a second RP model. Both models were validated on an independent group of 40 patients. Plan quality was compared by D
98%
and the Paddick conformity index for targets, mean dose (D
mean
) and generalised equivalent uniform dose (gEUD) for bladder, bowel bag and rectum, and number of monitor units (MU).
Target coverage and conformity was similar between manually created and RP treatment plans. Compared to the manually created treatment plans, the final RP model reduced average D
mean
and gEUD with 2.7 Gy and 1.3 Gy for bladder, 1.2 Gy and 0.9 Gy for bowel bag, and 2.7 Gy and 0.8 Gy for rectum, respectively (p < .05). For rectum, the interpatient variation (i.e., 95% confidence interval) of DVHs was reduced by 23%.
KBP improved plan quality and consistency among treatment plans for high-risk prostate cancer. Model tuning using KBP-based clinical plans further improved model outcome.
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