Interfractional robustness of scanning carbon ion radiotherapy for prostate cancer: An analysis based on dose distribution from daily in-room CT images.

PURPOSE: We analyzed interfractional robustness of scanning carbon ion radiotherapy (CIRT) for prostate cancer based on the dose distribution using daily in-room computed tomography (CT) images. MATERIALS AND METHODS: We analyzed 11 consecutive patients treated with scanning CIRT for localized prostate cancer in our hospital between December 2015 and January 2016. In-room CT images were taken under treatment conditions in every treatment session. The dose distribution on each in-room CT image was recalculated, while retaining the pencil beam arrangement of the initial treatment plan. Then, the dose-volume histogram (DVH) parameters including the percentage of the clinical target volume (CTV) with 95% and 90% of the prescribed dose area (V95% of CTV, V90% of CTV) and V80% of rectum were calculated. The acceptance criteria for the CTV and rectum were set at V95% of CTV ≥95%, V90% of CTV ≥98%, and V80% of rectum < 10 ml. RESULTS: V95% of CTV, V90% of CTV, and V80% of rectum for the reproduced plans were 98.8 ± 3.49%, 99.5 ± 2.15%, and 4.39 ± 3.96 ml, respectively. Acceptance of V95% of CTV, V90% of CTV, and V80% of rectum was obtained in 123 (94%), 125 (95%) and 117 sessions (89%), respectively. Acceptance of the mean dose of V95% of CTV, V90% of CTV, and V80% of rectum for each patient was obtained in 10 (91%), 10 (91%), and 11 patients (100%), respectively. CONCLUSIONS: We demonstrated acceptable interfractional robustness based on the dose distribution in scanning CIRT for prostate cancer.

Stability of daily rectal movement and effectiveness of replanning protocols for sparing rectal doses based on the daily CT images during proton treatment for prostate cancer.

PURPOSE: To evaluate the optimal period of replanning to spare the rectal dose by investigating daily rectal movements during computed tomography (CT) image-guided proton therapy for prostate cancer. MATERIALS AND METHODS: To evaluate the optimum reference period for replanning, we analyzed 1483 sets of daily CT (dCT) images acquired from 40 prostate cancer patients and measured the daily rectal movement along the anterior-posterior direction based on the simulator CT (sCT) images and dCT images. We calculated daily dose distributions based on initial plans on the sCT images and replans on the dCT images for 13 representative patients, and evaluated daily dose volume histograms (DVHs) for the prostate, seminal vesicles, and rectum. RESULTS: The rectal anterior side on the dCT images around the seminal vesicles largely deviated toward the anterior side relative to the position on the reference sCT images, but the deviation decreased by referring to the dCT images and became nearly zero when we referred to the dCT images after 10-day treatment. The daily DVH values for the prostate showed good dose coverage. For six patients showing rectal movement toward the anterior side, the daily rectal DVH (V77% ) showed a 3.0 ± 1.7 cc excess from the initial plan and this excess was correlated with 9.9 ± 6.8 mm rectal movement. To identify the patients (37.5% in total) for whom the replanning on the 10th-day and 20th-day CT images reduced the V77% excess to 0.4 ± 1.5 cc and -0.2 ± 1.3 cc, respectively, we evaluated the accumulated mean doses with a 1.2 cc criterion. CONCLUSION: Our data demonstrate that the daily movement of the rectal anterior side tends to move toward the anterior side, which results in a rectal overdose, and the mean of the movement gradually decreases with the passage of days. In such cases, replanning with the reference CT after 10 days is effective to spare the rectal dose.

A new target localization method for image-guided radiation therapy of prostate cancer.

In imaged-guided radiation therapy (IGRT), target localization is usually done with rigid-body registration based on anatomy matching. Problems arise when the target volume can only be matched partially due to inter-fractional organ motion and deformation, resulting in deteriorated target coverage and critical structure sparing. A new target localization method is investigated in which the treatment target volume is aligned with the prescription isodose surface. Our study included 15 prostate patients previously treated with intensity-modulated radiation therapy (IMRT). Patient setup and target localization were performed using a CT-on-rails system before and after the IMRT treatment. IMRT plans were generated on the original simulation CTs (15) and the same MUs and leaf sequences were used to compute the dose distributions on post-treatment CTs (98) with the isocenter adjustments based on either anatomical structure matching or prescription isodose surface alignment. When patients were aligned with the traditional anatomy matching method, the dose to 95% of the CTV, D95, received 74.0 - 77.6 Gy and the minimum CTV dose, Dmin, was 61.9 - 71.6 Gy, respectively, in the cumulative dose distributions. The rectal dose-volume constraints were violated in 35.7% of the treatment fractions. When patients were aligned using the new localization method, the dose to 95% of the CTV, D95, received 74.0 - 78.2 Gy and the minimum CTV dose, Dmin, was 68.4 - 71.6 Gy, respectively, in the cumulative dose distributions. The rectal dose-volume constraints were violated in 17.3% of the treatment fractions. Traditional IGRT target localization based on anatomy matching is effective for population-based PTV margins but not ideal for those patients with large inter-fractional prostate rotation/deformation due to large rectal and bladder volume variation. The new method using the prescription isodose surface to align the target volume could improve the target coverage and rectal sparing for these patients, which can be implemented clinically to improve target dose delivery accuracy.

Effectiveness of CT-image guidance in proton therapy for liver cancer and the importance of daily dose monitoring for tumors and organs at risk.

BACKGROUND: It is important to have precise image guidance throughout proton therapy in order to take advantage of the therapy's physical selectivity. PURPOSE: We evaluated the effectiveness of computed tomography (CT)-image guidance in proton therapy for patients with hepatocellular carcinoma (HCC) by assessing daily proton dose distributions. The importance of daily CT image-guided registration and daily proton dose monitoring for tumors and organs at risk (OARs) was investigated. METHODS: A retrospective analysis was conducted using 570 sets of daily CT (dCT) images throughout whole treatment fractions for 38 HCC patients who underwent passive scattering proton therapy with either a 66 cobalt gray equivalent (GyE)/10 fractions (n = 19) or 76 GyE/20 fractions (n = 19) protocol. The actual daily delivered dose distributions were estimated by forward calculation using the dCT sets, their corresponding treatment plans, and the recorded daily couch correction information. We then evaluated the daily changes of the dose indices D99% , V30GyE , and Dmax for the tumor volumes, non-tumorous liver, and other OARs, that is, stomach, esophagus, duodenum, colon, respectively. Contours were created for all dCT sets. We validated the efficacy of the dCT-based tumor registrations (hereafter, "tumor registration") by comparing them with the bone registration and diaphragm registration as a simulation of the treatment based on the positioning using the conventional kV X-ray imaging. The dose distributions and the indices of three registrations were obtained by simulation using the same dCT sets. RESULTS: In the 66 GyE/10 fractions, the daily D99% value in both the tumor and diaphragm registrations agreed with the planned value with 3%-6% (SD), and the V30GyE value for the liver agreed within ±3%; the indices in the bone registration showed greater deterioration. Nevertheless, tumor-dose deterioration occurred in all registration methods for two cases due to daily changes of body shape and respiratory condition. In the 76 GyE/20 fractions, in particular for such a treatment that the dose constraints for the OARs have to be cared in the original planning, the daily D99% in the tumor registration was superior to that in the other registration (p < 0.001), indicating the effectiveness of the tumor registration. The dose constraints, set in the plan as the maximum dose for OARs (i.e., duodenum, stomach, colon, and esophagus) were maintained for 16 patients including seven treated with re-planning. For three patients, the daily Dmax increased gradually or changed randomly, resulting in an inter-fractional averaged Dmax higher than the constraints. The dose distribution would have been improved if re-planning had been conducted. The results of these retrospective analyses indicate the importance of daily dose monitoring followed by adaptive re-planning when needed. CONCLUSIONS: The tumor registration in proton treatment for HCC was effective to maintain the daily dose to the tumor and the dose constraints of OARs, particularly in the treatment where the maintenance for the dose constraints needs to be considered throughout the treatment. Nevertheless daily proton dose monitoring with daily CT imaging is important for more reliable and safer treatment.

Evaluation of Safety for Scanning Carbon-Ion Radiotherapy in Hemodialysis Patients With Prostate Cancer.

Background/Aim The efficacy and safety of carbon-ion radiotherapy (CIRT) for prostate cancer have already been demonstrated. The number of hemodialysis (HD) patients is increasing. Although the toxicity of CIRT in HD patients may be more severe, it has been insufficiently investigated. Therefore, we retrospectively analyzed the safety of CIRT for HD patients with prostate cancer in the present study. Materials and methods Five HD patients with prostate cancer who underwent CIRT at the Kanagawa Cancer Center during November 2015-2020 were included in this study. CIRT was delivered by the raster scanning method (sCIRT). Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0. The dose-volume histogram (DVH) parameters of the target volume and normal organs were evaluated between initial planning computed tomography (CT) and in-room CT images. Results In the acute phase, Grade 1 genitourinary toxicity was recorded in one patient. In the late phase, Grade 1 genitourinary toxicity was recorded in two patients. No gastrointestinal toxicities were noted during the follow-up period. In-room CT analysis revealed no significant differences among all DVH parameters of the target volume and normal organs when compared with the treatment plan dose. Conclusions The safety of sCIRT for prostate cancer in HD patients was investigated in the present study. In-room CT analysis suggested the robustness of the treatment plan. According to the present results, sCIRT for prostate cancer can be safely performed in HD patients.

Robust treatment planning in scanned carbon-ion radiotherapy for pancreatic cancer: Clinical verification using in-room computed tomography images.

Purpose: Carbon-ion beam (C-beam) has a sharp dose distribution called the Bragg peak. Carbon-ion radiation therapy, such as stereotactic body radiotherapy in photon radiotherapy, can be completed in a short period by concentrating the radiation dose on the tumor while minimizing the dose to organs at-risk. However, the stopping position of C-beam is sensitive to density variations along the beam path and such variations can lower the tumor dose as well as cause the delivery of an unexpectedly high dose to the organs at risk. We evaluated the clinical efficacy of a robust planning technique considering gastrointestinal gas (G-gas) to deliver accurate radiation doses in carbon-ion radiotherapy for pancreatic cancer. Materials and methods: We focused on the computed tomography (CT) value replacement method. Replacement signifies the overwriting of CT values in the CT images. The most effective replacement method for robust treatment planning was determined by verifying the effects of the three replacement patterns. We selected 10 consecutive patients. Pattern 1 replaces the CT value of the G-gas contours with the value of the region without G-gas (P1). This condition indicates a no-gas state. Pattern 2 replaces each gastrointestinal contour using the mean CT value of each contour (P2). The effect of G-gas was included in the replacement value. Pattern 3 indicates no replacement (P3). We analyzed variations in the target coverage (TC) and homogeneity index (HI) from the initial plan using in-room CT images. We then performed correlation analysis on the variations in G-gas, TC, and HI to evaluate the robustness against G-gas. Results: Analysis of variations in TC and HI revealed a significant difference between P1 and P3 and between P2 and P3. Although no statistically significant difference was observed between P1 and P2, variations, including the median, tended to be fewer in P2. The correlation analyses for G-gas, TC, and HI showed that P2 was less likely to be affected by G-gas. Conclusion: For a treatment plan that is robust to G-gas, P2 mean replacement method should be used. This method does not necessitate any particular software or equipment, and is convenient to implement in clinical practice.

Assessment of setup uncertainty in hypofractionated liver radiation therapy with a breath-hold technique using automatic image registration-based image guidance.

BACKGROUND: Target localization in radiation therapy is affected by numerous sources of uncertainty. Despite measures to minimize the breathing motion, the treatment of hypofractionated liver radiation therapy is further challenged by residual uncertainty coming from involuntary organ motion and daily changes in the shape and location of abdominal organs. To address the residual uncertainty, clinics implement image-guided radiation therapy at varying levels of soft-tissue contrast. This study utilized the treatment records from the patients that have received hypofractionated liver radiation therapy using in-room computed tomography (CT) imaging to assess the setup uncertainty and to estimate the appropriate planning treatment volume (PTV) margins in the absence of in-room CT imaging. METHODS: We collected 917 pre-treatment daily in-room CT images from 69 patients who received hypofractionated radiation therapy to the liver with the inspiration breath-hold technique. For each treatment, the daily CT was initially aligned to the planning CT based on the shape of the liver automatically using a CT-CT alignment software. After the initial alignment, manual shift corrections were determined by visual inspection of the two images, and the corrections were applied to shift the patient to the physician-approved treatment position. Considering the final alignment as the gold-standard setup, systematic and random uncertainties in the automatic alignment were quantified, and the uncertainties were used to calculate the PTV margins. RESULTS: The median discrepancy between the final and automatic alignment was 1.1 mm (0-24.3 mm), and 38% of treated fractions required manual corrections of ≥3 mm. The systematic uncertainty was 1.5 mm in the anterior-posterior (AP) direction, 1.1 mm in the left-right (LR) direction, and 2.4 mm in the superior-inferior (SI) direction. The random uncertainty was 2.2 mm in the AP, 1.9 mm in the LR, and 2.2 mm in the SI direction. The PTV margins recommended to be used in the absence of in-room CT imaging were 5.3 mm in the AP, 3.5 mm in the LR, and 5.1 mm in the SI direction. CONCLUSIONS: Manual shift correction based on soft-tissue alignment is substantial in the treatment of the abdominal region. In-room CT can reduce PTV margin by up to 5 mm, which may be especially beneficial for dose escalation and normal tissue sparing in hypofractionated liver radiation therapy.

Study of robust of dose distribution of prostate cancer before carbon ion treatment based on in-room CT / 中华放射肿瘤学杂志

Objective:To analyze the robustness of the dose of clinical target volume (CTV) and tolerance dose of normal tissues after applying in-room CT before carbon ion radiotherapy for prostate cancer.Methods:Thirty prostate cancer patients treated with carbon ion in Shanghai Proton and Heavy Ion Center from January 2020 to June 2021 were enrolled in this study. Five in-room CT images of each patient were selected randomly before treatment. Dose distributions were recalculated using the original plan on in-room CT images and dose volume histogram (DVH) parameters were obtained, including V 95% and V 90% of CTV and V 80% of rectum. The values were compared with the dosimetric parameters of the original plan. Statistical analysis was performed by paired or two independent samples t-tests. Results:The dose distribution was recalculated by applying in-room CT. The mean values of V 95% and V 90% of CTV and V 80% of rectum were 98.1%±1.2% ( P<0.001), 99.9%±0.2% ( P=0.001) and (5.8±1.6) ml ( P<0.001), respectively. The differences were statistically significant compared with those of the original plan. The frequency of V 95%≥95%, V 90%≥98% of CTV, and V 80%<10 ml of rectum was 148 (98.7%), 150 (100.0%) and 147 (98.0%), respectively. Conclusion:Based on in-room CT analysis and the patient management and positioning methods of our research center, the uncertainty of target dose and normal tissue dose in the entire process of prostate cancer carbon ion therapy is small, and the robustness is good.

Value of Three-Dimensional Imaging Systems for Image-Guided Carbon Ion Radiotherapy.

Carbon ion radiotherapy (C-ion RT) allows excellent dose distribution because of the Bragg Peak. Compared with conventional radiotherapy, it delivers a higher dose with a smaller field. However, the dose distribution is sensitive to anatomical changes. Imaging technologies are necessary to reduce uncertainties during treatment, especially for hypofractionated and adaptive radiotherapy (ART). In-room computed tomography (CT) techniques, such as cone-beam CT (CBCT) and CT-on-rails are routinely used in photon centers and play a key role in improving treatment accuracy. For C-ion RT, there is an increasing demand for a three-dimensional (3D) image-guided system because of the limitations of the present two-dimensional (2D) imaging verification technology. This review discusses the current imaging system used in carbon ion centers and the potential benefits of a volumetric image-guided system.

Toward adaptive proton therapy guided with a mobile helical CT scanner.

PURPOSE: To evaluate the feasibility of image-guided adaptive proton therapy (IGAPT) with a mobile helical-CT without rails. METHOD: CT images were acquired with a 32-slice mobile CT (mCT) scanning through a 6 degree-of-freedom robotic couch rotated isocentrically 90 degrees from an initial setup position. The relationship between the treatment isocenter and the mCT imaging isocenter was established by a stereotactic reference frame attached to the treatment couch. Imaging quality, geometric integrity and localization accuracy were evaluated according to AAPM TG-66. Accuracy of relative stopping power ratio (RSPR) was evaluated by comparing water equivalent distance (WED) and dose calculations on anthropomorphic phantoms to that of planning CT (pCT). Feasibility of image-guided adaptive proton therapy was demonstrated on fractional images acquired with the mCT scanner. RESULTS: mCT images showed slightly lower spatial resolution and a higher contrast-to-noise ratio compared to pCT images from the standard helical CT scanner. The geometric accuracy of the mCT was <1 mm. Localization accuracy was <0.4 mm and <0.3° with respect to 2DkV/kV matching. WED differences between mCT and pCT images were negligible, with discrepancies of 0.8 ±â€¯0.6 mm and 1.3 ±â€¯0.9 mm for brain and lung phantoms respectively. 3D gamma analysis (3% and 3 mm) passing rate was >95% on dose computed on mCT, with respect to dose calculation on pCT. CONCLUSION: Our study has demonstrated that the geometric integrity, image quality and RSPR accuracy of the mCT are sufficient for IGAPT.

Current state and future applications of radiological image guidance for particle therapy.

In this review paper, we first give a short overview of radiological image guidance in photon radiotherapy, placing emphasis on the fact that linac based radiotherapy has outpaced particle therapy in the adoption of volumetric image guidance. While cone beam computed tomography (CBCT) has been an established technique in linac treatment rooms for almost two decades, the widespread adoption of volumetric image guidance in particle therapy, whether by means of CBCT or in-room CT imaging, is recent. This lag may be attributable to the bespoke nature and lower number of particle therapy installations, as well as the differences in geometry between those installations and linac treatment rooms. In addition, for particle therapy the so called shift invariance of the dose distribution rarely applies. An overview of the different volumetric image guidance solutions found at modern particle therapy facilities is provided, covering gantry, nozzle, C-arm, and couch-mounted CBCT as well different in-room CT configurations. A summary of the use of in-room volumetric imaging data beyond anatomy-based positioning is also presented as well as the necessary corrections to CBCT images for accurate water equivalent thickness calculation. Finally, the use of non-ionizing imaging modalities is discussed.

Positioning accuracy and daily dose assessment for prostate cancer treatment using in-room CT image guidance at a proton therapy facility.

PURPOSE: To evaluate the effectiveness of CT image-guided proton radiotherapy for prostate cancer by analyzing the positioning uncertainty and assessing daily dose change due to anatomical variations. MATERIALS AND METHODS: Patients with prostate cancer were treated by opposed lateral proton beams based on a passive scattering method using an in-room CT image-guided system. The system employs a single couch for both CT scanning and beam delivery. The patient was positioned by matching the boundary between the prostate and the rectum's anterior region identified in the CT images to the corresponding boundary in the simulator images after bone matching. We acquired orthogonal kV x-ray images after couch movement and confirmed the body position by referring to the bony structure prior to treatment. In offline analyses, we contoured the targeted anatomical structures on 375 sets of daily in-room CT images for 10 patients. The uncertainty of the image-matching procedure was evaluated using the prostate contours and actual couch corrections. We also performed dose calculations using the same set of CT images, and evaluated daily change of dose-volume histograms (DVHs) to compare the effectiveness of the treatment using prostate matching to the bone-matching procedure. RESULTS: The isocenter shifts by prostate matching after bone matching were 0.5 ± 1.8 and -0.8 ± 2.6 mm along the superior-inferior (SI) and anterior-posterior (AP) directions, respectively. The body movement errors (σ) after couch movement were 0.7, 0.5, and 0.3 mm along the lateral, SI and AP direction, respectively, for 30 patients. The estimated errors (σ) in the prostate matching were 1.0 and 1.3 mm, and, in conjunction with the movement errors, the total positioning uncertainty was estimated to be 1.0 and 1.4 mm along the SI and AP directions, respectively. Daily DVH analyses showed that in the prostate matching, 98.7% and 86.1% of the total 375 irradiations maintained a dose condition of V95%  > 95% for the prostate and a dose constraint of V77%  < 18% for the rectum, whereas 90.4% and 66.1% of the total irradiations did so when bone matching was used. The dose constraint of the rectum and dose coverage of the prostate were better maintained by prostate matching than bone matching (P < 0.001). The daily variation in the dose to the seminal vesicles (SVs) was large, and only 40% of the total irradiations maintained the initial planned values of V95% for high-risk treatment. Nevertheless, the deviations from the original value were -4 ± 7% and -5 ± 11% in the prostate and bone matching, respectively, and a better dose coverage of the SV was achieved by the prostate matching. CONCLUSION: The correction of repositioning along the AP and SI direction from conventional bone matching in CT image-guided proton therapy was found to be effective to maintain the dose constraint of the rectum and the dose coverage of the prostate. This work indicated that prostate cancer treatment by prostate matching using CT image guidance may be effective to reduce the rectal complications and achieve better tumor control of the prostate. However, an adaptive approach is desirable to maintain better dose coverage of the SVs.

Effects of organ motion on proton prostate treatments, as determined from analysis of daily CT imaging for patient positioning.

PURPOSE: We quantified interfractional movements of the prostate, seminal vesicles (SVs), and rectum during computed tomography (CT) image-guided proton therapy for prostate cancer and studied the range variation in opposed lateral proton beams. MATERIALS/METHODS: We analyzed 375 sets of daily CT images acquired throughout the proton therapy treatment of ten patients. We analyzed daily movements of the prostate, SVs, and rectum by simulating three image-matching strategies: bone matching, prostate center (PC) matching, and prostate-rectum boundary (PRB) matching. In the PC matching, translational movements of the prostate center were corrected after bone matching. In the PRB matching, we performed PC matching and correction along the anterior-posterior direction to match the boundary between the prostate and the rectum's anterior region. In each strategy, we evaluated systematic errors (Σ) and random errors (σ) by measuring the daily movements of certain points on each anatomic structure. The average positional deviations in millimeter of each point were determined by the Van Herk formula of 2.5Σ + 0.7σ. Using these positional deviations, we created planning target volumes of the prostate and SVs and analyzed the daily variation in the water equivalent length (WEL) from the skin surface to the target along the lateral beam directions using the density converted from the daily CT number. Based on this analysis, we designed prostate cancer treatment planning and evaluated the dose volume histograms (DVHs) for these strategies. RESULTS: The SVs' daily movements showed large variations over the superior-inferior direction, as did the rectum's anterior region. The average positional deviations of the prostate in the anterior, posterior, superior, inferior, and lateral sides (mm) in bone matching, PC matching, and PRB matching were (8.9, 9.8, 7.5, 3.6, 1.6), (5.6, 6.1, 3.5, 4.5, 1.9), and (8.6, 3.2, 3.5, 4.5, 1.9) (mm), respectively. Moreover, the ones of the SV tip were similarly (22.5, 15.5, 11.0, 7.6, 6.0), (11.8, 8.4, 7.8, 5.2, 6.3), and (9.9, 7.5, 7.8, 5.2, 6.3). PRB matching showed the smallest positional deviations at all portions except for the anterior portion of the prostate and was able to markedly reduce the positional deviations at the posterior portion. The averaged WEL variations at the distal and proximal sides of planning target volumes were estimated 7-9 mm and 4-6 mm, respectively, and showed the increasing of a few millimeters in PC and PRB matching compared to bone matching. In the treatment planning simulation, the DVH values of the rectum in PRB matching were reduced compared to those obtained with other matching strategies. CONCLUSION: The positional deviations for the prostate on the posterior side and the SVs were smaller by PRB matching than the other strategies and effectively reduced the rectal dose. 3D dose calculations indicate that PRB matching with CT image guidance may do a better job relative to other positioning methods to effectively reduce the rectal complications. The WEL variation was quite large, and the appropriate margin (approx. 10 mm) must be adapted to the proton range in an initial planning to maintain the coverage of target volumes throughout entire treatment.