Normal Tissue Dose Research Articles

Clinical Characterization of a Table Mounted Range Shifter Board for Synchrotron-Based Intensity Modulated Proton Therapy for Pediatric Craniospinal Irradiation.

Purpose: To report our design, manufacturing, commissioning and initial clinical experience with a table-mounted range shifter board (RSB) intended to replace the machine-mounted range shifter (MRS) in a synchrotron-based pencil beam scanning (PBS) system to reduce penumbra and normal tissue dose for image-guided pediatric craniospinal irradiation (CSI). Methods: A custom RSB was designed and manufactured from a 3.5 cm thick slab of polymethyl methacrylate (PMMA) to be placed directly under patients, on top of our existing couch top. The relative linear stopping power (RLSP) of the RSB was measured using a multi-layer ionization chamber, and output constancy was measured using an ion chamber. End-to-end tests were performed using the MRS and RSB approaches using an anthropomorphic phantom and radiochromic film measurements. Cone beam CT (CBCT) and 2D planar kV X-ray image quality were compared with and without the RSB present using image quality phantoms. CSI plans were produced using MRS and RSB approaches for two retrospective pediatric patients, and the resultant normal tissue doses were compared. Results: The RLSP of the RSB was found to be 1.163 and provided computed penumbra of 6.9 mm in the phantom compared to 11.8 mm using the MRS. Phantom measurements using the RSB demonstrated errors in output constancy, range, and penumbra of 0.3%, -0.8%, and 0.6 mm, respectively. The RSB reduced mean kidney and lung dose compared to the MRS by 57.7% and 46.3%, respectively. The RSB decreased mean CBCT image intensities by 86.8 HU but did not significantly impact CBCT or kV spatial resolution providing acceptable image quality for patient setup. Conclusions: A custom RSB for pediatric proton CSI was designed, manufactured, modeled in our TPS, and found to significantly reduce lateral proton beam penumbra compared to a standard MRS while maintaining CBCT and kV image-quality and is in routine use at our center.

Impact of administered amount of peptide on tumor dosimetry at the first cycle of peptide receptor radionuclide therapy (PRRT) in relation to total tumor somatostatin receptor expression

BackgroundThe accumulation of 177Lu-DOTATATE might be influenced by the amount of administered peptide in relation to the tumor somatostatin receptor expression. The effect of the administered peptide mass on the resulting absorbed dose in tumors and normal organs has not previously been assessed in relation to the patients’ tumor load.MethodPatients with small intestinal (n = 141) and pancreatic (n = 62) neuroendocrine tumors (NETs) who underwent PRRT were selected for retrospective evaluation. All patients had received 7.4 GBq 177Lu-DOTATATE, and the amount of administered peptide in the preparation varied from 93 to 456 µg. The absorbed dose in tumors and normal tissue at the first PRRT cycle was calculated, based on SPECT-measurements at day 1, 4, and 7 post-infusion. The total tumor somatostatin receptor expression (tTSSTRE) was calculated on SPECT after 24 h by multiplying the functional tumor volume, delineated by 42% cut-off VOIs of the highest activity, with the SUVmean for the respective tumor VOIs. Spearman’s rank correlation analyzed any relationship between the administered amount of peptide and the absorbed dose in tumors and normal organs, in relation to the patients’ tTSSTRE.ResultsThere was no correlation between the amount of peptide and any of the tested parameters in relation to tTSSTRE.ConclusionIn this retrospective analysis, no correlation between the amount of administered peptide in the 177Lu-DOTATATE preparation and the absorbed radiation doses in tumors and normal tissues was demonstrated in relation to the total tumor SSTR expression.

Trimodal Therapy Using an MR–guided Radiation Therapy Partial Bladder Tumor Boost in Muscle Invasive Bladder Cancer

Bladder preservation with trimodal therapy (TMT; maximal tumor resection followed by chemoradiation) is an effective paradigm for select patients with muscle invasive bladder cancer. We report our institutional experience of a TMT protocol using nonadaptive magnetic resonance imaging-guided radiation therapy (MRgRT) for partial bladder boost (PBB). A retrospective analysis was performed on consecutive patients with nonmetastatic muscle invasive bladder cancer who were treated with TMT using MRgRT between 2019 and 2022. Patients underwent intensity modulated RT-based nonadaptive MRgRT PBB contoured on True fast imaging with steady state precession (FISP) images (full bladder) followed sequentially by computed tomography-based RT to the whole empty bladder and pelvic lymph nodes with concurrent chemotherapy. MRgRT treatment time, table shifts, and dosimetric parameters of target coverage and normal tissue exposure were described. Prospectively assessed acute and late genitourinary and gastrointestinal (GI) toxicity were reported. Two-year local control was assessed with Kaplan-Meier methods. Seventeen patients were identified for analysis. PBB planning target volume margins were ≤8 mm in 94% (n=16) of cases. Dosimetric target coverage parameters were favorable and all normal tissue dose constraints were met. For MRgRT PBB fractions, median table shifts were 0.4 cm (range, 0-3.15), 0.45 cm (0-2.65), and 0.75 cm (0-4.8) in the X, Y, and Z planes, respectively. Median treatment time for MRgRT PBB fractions was 9 minutes (range, 6.9-17.4). We identified 32 out of 100 total MRgRT fractions that may have benefitted from online adaptation based on changes in organ position relative to planning target volume, predominantly because of small bowel (13/32, 41%) or rectum (8/32, 25%). Two patients discontinued RT prematurely. The incidence of highest-grade acute genitourinary toxicity was 1 to 2 (69%) and 3 (6%), whereas the incidence of acute GI toxicity was 1 to 2 (81%) and 3 (6%). There were no late grade 3 events; 17.6% had late grade 2 cystitis and none had late GI toxicity. With median follow-up of 18.2 months (95% CI, 12.4-22.5), the local control rate was 92%, and no patient has required salvage cystectomy. Nonadaptive MRgRT PBB is feasible with favorable dosimetry and low resource utilization. Larger studies are needed to evaluate for potential benefits in toxicity and local control associated with this approach in comparison to standard treatment techniques.

D91. Effect of Pre-pectoral Versus Sub-pectoral Implant Placement in Breast Reconstruction on the Delivery of Post-mastectomy Radiation

PURPOSE: The placement of breast implants in a pre-pectoral compared to sub-pectoral plane has become increasingly popular in breast reconstruction, though data are limited on how this affects radiation delivery for locoregional disease control in women with breast cancer. This study aims to assess the dosimetric implications of implant location in women undergoing post-mastectomy radiation therapy (PMRT) after immediate breast reconstruction. METHODS: Patients with breast cancer treated with mastectomy, implant breast reconstruction, and PMRT between 2014-2022 at a single center were included. All patients received either intensity-modulated or 3-D conformal radiation therapy over an average of 5 weeks. Demographic, clinical and treatment data were collected through chart review. Patients were matched 1:1 on cancer sidedness, use of boost, fractionation and extent of radiation fields. Groups were compared using Mann-Whitney U or t-tests for continuous variables, and chi-square or Fisher’s Exact tests for categorical variables, as appropriate. RESULTS: Twenty-seven patients with pre-pectoral and 26 patients with sub-pectoral implants were included. Patients with pre-pectoral reconstruction had lower average implant volumes (452cc vs 503cc) prior to radiation. There was no difference in chest wall coverage (p=0.107), internal mammary node coverage (p=0.215), heart dose (p=0.627) or lung V20Gy (p=0.774). CONCLUSION: In this assessment of radiotherapeutic dosimetry in patients undergoing immediate breast reconstruction, we found no significant difference in target coverage or normal tissue dose based on pre- versus sub-pectoral implant location. This suggests that implant placement can be selected to optimize reconstructive outcomes, without concern for compromise to the oncologic quality of PMRT.

A treatment plan optimization method with direct minimization of number of energy jumps for proton arc therapy

Objective. The optimization of energy layer distributions is crucial to proton arc therapy: on one hand, a sufficient number of energy layers is needed to ensure the plan quality; on the other hand, an excess number of energy jumps (NEJ) can substantially slow down the treatment delivery. This work will develop a new treatment plan optimization method with direct minimization of (NEJ), which will be shown to outperform state-of-the-art methods in both plan quality and delivery efficiency. Approach. The proposed method jointly optimizes the plan quality and minimizes the NEJ. To minimize NEJ, (1) the proton spots x is summed per energy layer to form the energy vector y; (2) y is binarized via sigmoid transform into y 1 ; (3) y 1 is multiplied with a predefined energy order vector via dot product into y 2; (4) y 2 is filtered through the finite-differencing kernel into y 3 in order to identify NEJ; (5) only the NEJ of y 3 is penalized, while x is optimized for plan quality. The solution algorithm to this new method is based on iterative convex relaxation. Main results. The new method is validated in comparison with state-of-the-art methods called energy sequencing (ES) method and energy matrix (EM) method. In terms of delivery efficiency, the new method had fewer NEJ, less energy switching time, and generally less total delivery time. In terms of plan quality, the new method had smaller optimization objective values, lower normal tissue dose, and generally better target coverage. Significance. We have developed a new treatment plan optimization method with direct minimization of NEJ, and demonstrated that this new method outperformed state-of-the-art methods (ES and EM) in both plan quality and delivery efficiency.

Imaging doses for different CBCT protocols on the Halcyon 3.0 linear accelerator – TLD measurements in an anthropomorphic phantom

IntroductionImage guided radiotherapy allows for particularly conformal tumour irradiation through precise patient positioning. Becoming the standard for radiotherapy, this increases imaging doses to the patient. The Halcyon 3.0 linear accelerator (Varian Medical Systems, Palo Alto, CA) requires daily imaging due to its geometry. For this reason, the accelerator is equipped with on-line kV and MV imaging. However, daily CBCT images required for irradiation apply additional radiation, which increases the dose to normal tissue and therefore can affect the patient's secondary cancer risk. In this study, actual organ doses were measured for the kV system, and a comparison of normal tissue doses for all available kV CBCT protocols was presented to demonstrate differences in imaging doses across entities and protocols. In addition, effective dose and secondary cancer risk from imaging are evaluated. Material and methodsMeasurements were performed with thermoluminescent dosimeters in an anthropomorphic phantom positioned according to each entity (brain, head and neck, breast, lung, pelvis). CBCT images were obtained, using all available pre-set protocols without further adjustment of the parameters. Measured doses for each position and each protocol were then compared and secondary cancer risk of relevant and specifically radiosensitive organs was calculated. ResultsIt was found that imaging doses for protocols such as Pelvis and Head could be reduced by up to half using the corresponding Fast and Low Dose modes, respectively. On the other hand, larger field sizes or the Large mode yielded higher doses than their initial protocols. Image Gently was found to spare normal tissue best, however it is not suitable for certain entities due to low image quality or insufficient projection data. DiscussionBy using appropriate kV-CBCT protocols, it is possible to reduce imaging doses to a significant extent and therefore spare healthy tissue. Combined with studies of image quality, the results of this study could lead to adjustments in workflow regarding the choice of protocols used in daily routine. This could prevent unnecessary radiation exposure and reduce secondary cancer risk.

A retrospective study of adjuvant proton radiotherapy for breast cancer after lumpectomy: a comparison of conventional-dose and hypofractionated dose

PurposeThis study aimed to compare the adverse reactions of conventional-dose and hypofractionated dose of proton therapy for breast cancer.Materials and methodsBreast cancer patients treated with proton radiotherapy in conventional-dose or hypofractionated dose were studied retrospectively.ResultFrom January 2017 to December 2019, our center treated 50 patients following lumpectomy with proton radiotherapy. According to the AJCC 8th Edition standard, there were stage I in 26 patients, stage II in 22 patients, and stage III in 2 patients. A total of 14 patients received intensity-modulated proton therapy at a dose of 50 Gy in 25 fractions, followed by a 10 Gy 4 fractionated boost to the lumpectomy cavity, while 36 received 40.05 Gy in 15 fractions, simultaneous integrated boost (SIB) 48 Gy to the lumpectomy cavity. Median follow-up time for 40.05 Gy group was 35.6 months (15–43 months). Median follow-up time for 50 Gy group was 46.8 months (36–68 months). For acute toxicity, the grade 1 and 2 radiodermatitis in conventional-dose group were 35.7% and 57.1%, respectively. In hypofractionated dose group, the grade 1 and 2 radiodermatitis were 91.7% and 8.3%, respectively. The radiodermatitis is hypofractionneted dose better than conventional-dose significantly. Grade 1 radiation-induced esophagitis in conventional-dose group and hypofractionated dose group were 85.71% and 60%, respectively. For late toxicity, no patients developed radiation-induced pneumonitis and rib fracture in conventional-dose group. Three patients presented grade 1 pneumonitis; one patient presented graded 2 pneumonitides and two patients presented rib fracture in hypofractionated dose group. One presented hypothyroidism in hypofractionated dose group. All patients were satisfied with breast shape. The one- and two-year OS and DFS for conventional-dose group were 100 and 100; 100 and 92.9%, respectively. The one- and two-year OS and DFS for hypofractionated dose group were 100 and 100; 100 and 100%, respectively.ConclusionProton radiation therapy can significantly reduce the normal tissue dose in breast cancer patients' hearts, lungs, and other organs. Hypofractionated proton therapy shortens the treatment course with mild radiation-related adverse effects, and has a better effect on addressing the acute adverse reactions than conventional proton radiotherapy.

Yttrium-90 Radiation Segmentectomy of Hepatocellular Carcinoma: A Comparative Study of the Effectiveness, Safety, and Dosimetry of Glass-Based versus Resin-Based Microspheres

PurposeTo evaluate the differences in safety, effectiveness, and dosimetry between glass-based and resin-based ablative yttrium-90 (90Y) transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC). Materials and MethodsUsing the modified Response Evaluation Criteria in Solid Tumors and Common Terminology Criteria for Adverse Events, both tumor response and adverse events (AEs) were assessed at 3 months after 90Y-TARE. Post procedure 90Y-bremsstrahlung single-photon emission computed tomography/computed tomography voxel-based dosimetry analysis was used to create tumor dose (TD) and normal tissue dose (NTD) volume histograms, and to calculate tumor particle loading and specific activity. The TD and NTD receiver operating characteristic curves evaluated the dose threshold able to predict objective (partial or complete) and complete tumor responses in addition to any-grade and grade ≥3 AE incidences. The chi-square test and Student t-test were used to assess variable differences where appropriate. ResultsBetween 2019 and 2020, 81 patients with HCC (20 in the resin-based cohort and 61 in the glass-based cohort) underwent ablative 90Y-TARE. The resin-based cohort had more males (89% vs 65%, P = .03), lower tumor-to-normal ratio (1.81 ± 0.39 vs 2.22 ± 0.94, P = .03), higher tumor particle loading (40,172 particles/mL ± 28,039 vs 17,081 particles/mL ± 12,555, P = .0001), lower specific activity (158 Bq/particle ± 3 vs 1,058 Bq/particle ± 331, P = .001), and lower mean TD (308 Gy ± 210 vs 794 Gy ± 523, P = .0002) than the glass-based cohort. No significant differences in baseline characteristics or posttreatment AEs were noted. The overall objective and complete response rates were 85% (95% resin-based vs 82% glass-based; P = .1) and 65% (95% resin-based vs 56% glass-based; P = .003), respectively. The mean TD thresholds able to predict the objective and complete responses were 176 Gy and 247 Gy for resin-based radioembolization and 290 Gy and 481 Gy for glass-based radioembolization, respectively. A maximum NTD of 999 Gy predicted any-grade AEs in glass-based ablative 90Y-TARE. ConclusionsCompared with glass-based ablative 90Y-TARE, resin-based ablative 90Y-TARE can offer comparable safety and effectiveness profiles for patients with HCC. The impact of the significantly different tumor particle loading, particle specific activities, and delivered TDs on tumor response outcomes merits further investigation.

(Potential) Mishaps of High-Dose-Rate Vaginal Cuff Brachytherapy

Considering how commonly vaginal cuff brachytherapy is used, there is relatively little literature regarding the potential, albeit low, risk for complications. We present 3 potentially serious mishaps involving cylinder misplacement, dehiscence, and excessive normal tissue irradiation due to unique anatomy. Three patients with potentially serious treatment errors were encountered in the authors’ usual clinical practice. Each patient's records were reviewed for this report. For patient 1, computed tomography (CT) simulation revealed grossly inadequate cylinder insertion, which was most obvious on the sagittal view. For patient 2, CT simulation revealed that the cylinder extended beyond the perforated vaginal cuff and was surrounded by bowel. For patient 3, CT images were used only to verify cylinder depth. A standard library plan based on cylinder diameter and active length was used. In retrospect, the images revealed an unusually thin rectovaginal septum, with the lateral and posterior vaginal wall thickness estimated to be <2 mm. This patient's fractional normal tissue doses were calculated for this report, revealing a rectal maximum dose (per fraction) of 10.8 Gy, maximum dose that 2 cc of the organ receives of 7.4 Gy, and volume of the organ that receives the prescription dose or higher of 2.8 cc. All doses were far in excess of those anticipated for a minimal 0.5-cm vaginal wall depth. Vaginal cuff high-dose-rate brachytherapy is a high-volume, routine procedure. Even in experienced hands, however, it carries a risk of improper cylinder placement, cuff dehiscence, and excessive normal tissue dose, all of which could seriously affect outcomes. These potential mishaps would be better appreciated and avoided with more extensive use of CT-based quality assurance measures.

Liver SBRT dose accumulation to assess the impact of anatomic variations on normal tissue doses and toxicity in patients treated with concurrent sorafenib

Background and PurposeUnexpected liver volume reductions occurred during trials of liver SBRT and concurrent sorafenib. The aims were to accumulate liver SBRT doses to assess the impact of these anatomic variations on normal tissue dose parameters and toxicity. Materials and MethodsThirty-two patients with hepatocellular carcinoma (HCC) or metastases treated on trials of liver SBRT (30–57 Gy, 6 fractions) and concurrent sorafenib were analyzed. SBRT doses were accumulated using biomechanical deformable registration of daily cone-beam CT. Dose deviations (accumulated-planned) for normal tissues were compared for patients with liver volume reductions > 100 cc versus stable volumes, and accumulated doses were reported for three patients with grade 3–5 luminal gastrointestinal toxicities. ResultsPatients with reduced (N = 12) liver volumes had larger mean deviations of 0.4–1.3 Gy in normal tissues, versus −0.2–0.4 Gy for stable cases (N = 20), P > 0.05. Deviations > 5% of the prescribed dose occurred in both groups. Two HCC patients with toxicities to small and large bowel had liver volume reductions and deviations to the maximum dose of 4% (accumulated 36.9 Gy) and 3% (accumulated 33.4 Gy) to these organs respectively. Another HCC patient with a toxicity of unknown location plus tumor rupture, had stable liver volumes and deviations to luminal organs of −6% to 4.5% (accumulated < 30.5 Gy). ConclusionLiver volume reductions during SBRT and concurrent sorafenib were associated with larger increases in accumulated dose to normal tissues versus stable liver volumes. These dosimetric changes may have further contributed to toxicities in HCC patients who have higher baseline risks.

Patient anatomy-specific trade-offs between sub-clinical disease coverage and normal tissue dose reduction in head-and-neck cancer

PurposeRisk of subclinical disease decreases with increasing distance from the GTV in head- and-neck squamous cell carcinoma (HNSCC). Depending on individual patient anatomy, OAR sparing could be improved by reducing target coverage in regions with low risk of subclinical spread. Using automated multi-criteria optimization, we investigate patient-specific optimal trade-offs between target periphery coverage and OAR sparing. MethodsVMAT plans for 39 HNSCC patients were retrospectively created following our clinical three-target-level protocol: high-risk (PTV1), intermediate-risk (PTV2, 5 mm expansion from PTV1), and elective (PTV3). A baseline plan fulfilling clinical constraints (D 99 % ≥95 % for all PTVs) was compared to three plans with reduced PTV2 coverage (goals: PTV2 D 99 % ≥90 % or 85 %, or no PTV2) at the outer edge of PTV2. Plans were compared on PTV D 99 %, OAR D mean, and NTCP (xerostomia/dysphagia). ResultsTrade-offs between PTV2 coverage and OAR doses varied considerably between patients. For plans with PTV2 D 99 % -goal 90 %, median PTV2 D 99 % was 91.5 % resulting in xerostomia (≥grade 4) and dysphagia (≥grade 2) NTCP decrease of median [maximum] 1.9 % [5.3 %] and 1.1 % [4.1 %], respectively, compared to nominal PTV2 D 99 % -goal 95 %. For PTV2 D 99 % -goal 85 % median PTV D 99 % was 87 % with NTCP improvements of 4.6 % [9.9 %] and 1.5 % [5.4 %]. For no-margin plans, PTV2 D 99 % decreased to 83.3 % with NTCP reductions of 5.1 % [10.2 %] and 1.4 % [6.1 %]. ConclusionClinically relevant, patient-specific reductions in OARs and NTCP were observed at limited cost in target under-coverage at the outermost PTV edge. Given the observed inter-patient variations, individual evaluation is warranted to determine whether trade- offs would benefit a specific patient.

Improving Quality of Life with Brachytherapy for Urological Malignancies

Brachytherapy for localised prostate, muscle-invasive bladder and penile cancer is well established, providing high tumour dose delivery and minimising normal tissue doses compared with external beam techniques. In prostate cancer, the main impact on quality of life relates to diminished sexual function and irritative or obstructive urinary symptoms, which are seen up to 15 years after treatment. Significant changes in bowel function are rare. Compared with radical prostatectomy or external beam radiotherapy, irritative or obstructive urinary symptoms are more prominent, whereas incontinence is less than after radical prostatectomy and bowel changes are less than after external beam radiotherapy. For muscle-invasive bladder cancer, when compared with radical cystectomy, although no difference is seen for urinary symptoms or fatigue, role and social functioning scores are higher and there is better post-treatment sexual function in both men and women. Compared with surgical treatment for penile cancer, brachytherapy results in better erectile function scores than after glansectomy and partial penectomy and high quality of life scores, with good satisfaction ratings for cosmetic appearance.

Dosimetric Effects of Dynamic Jaw Tracking and Collimator Angle Optimization in Non-Coplanar Cranial Arc Radiotherapy.

The stereotactic treatment of single cranial targets using noncoplanar volumetric modulated arc therapy (VMAT) allows for effective dose delivery to the target, while sparing normal brain tissue. In this study, the dosimetric effect of adding dynamic jaw tracking and automatic collimator angle selection in the optimization of single target cranial VMAT plans was investigated. Twenty-two cranial targets, previously treated with VMAT without dynamic jaw tracking and automatic collimator angle optimization (CAO) were chosen for replanning. Target volumes ranged from 0.441cc to 25.863cc with doses between 18Gy and 30Gy delivered in 1 to 5 fractions. Original plans were reoptimized with automatic CAO, keeping all other objectives the same (CAO plans). Next, original plans were reoptimized with both dynamic jaw tracking and CAO (DJT plans). Original, CAO, and DJT target doses were compared using the Paddick gradient index (GI) and the Paddick inverse conformity index (ICI), while normal tissue dose was compared using the volume of the normal brain receiving 5Gy, 10Gy, and 12Gy. The normal tissue volume was normalized to target size to allow cross comparison between plans. A one-sided t-test was performed to determine whether the changes in the plan metrics were statistically significant. CAO plans had improved GIs compared to the originals (p = 0.03) with insignificant changes in other plan metrics (p > 0.20). The addition of dynamic jaw tracking in DJT plans greatly improved ICIs and normal brain metrics (p < 0.01) compared to the CAO plans with minor improvement in ICIs (p = 0.07). The combined effect of adding dynamic jaw tracking and collimator optimization led to improvements in all metrics of the DJT plans when compared to the original (p < 0.02). The addition of dynamic jaw tracking and CAO led to improvements in both target and normal tissue dose metrics for single-target noncoplanar cranial VMAT plans.

Noncoplanar Volumetric Modulated Arc Therapy for Hepatocellular Carcinoma Based on a Cage-Like Radiotherapy System: A Simulation Study.

The incorporation of noncoplanar beam arrangements has been proposed in liver radiotherapy modalities, which can reduce the dose in normal tissues compared to coplanar techniques. Noncoplanar radiotherapy techniques for hepatocellular carcinoma treatment based on the Linac design have a limited effective arc angle to avoid collisions. To propose a novel noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system and investigate its performance in hepatocellular carcinoma patients. The computed tomography was deflected 90° to meet the structure of a cage-like radiotherapy system and design the noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system plan in the Pinnacle3 planning system. An noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system plan was customized for each of 10 included hepatocellular carcinoma patients, with 6 dual arcs ranging from -30° to 30°. Six couch angles were set with an interval of 36° and distributed along with the longest diameter of planning target volume. The dosimetric parameters of noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system plan were compared with the noncoplanar volumetric modulated arc therapy and volumetric modulated arc therapy plan. The 3 radiotherapy techniques regarding planning target volume were statistically different for D98%, D2%, conformity index, and homogeneity index with χ2 = 9.692, 14.600, 8.600, and 12.600, and P = .008, .001, .014, and .002, respectively. Further multiple comparisons revealed that noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system significantly reduced the mean dose (P = .005) and V5 (P = .005) of the normal liver, the mean dose (P = .005) of the stomach, and V30 (P = .028) of the lung compared to noncoplanar volumetric modulated arc therapy. Noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system significantly reduced the mean dose (P = .005) and V5 (P = .005) of the normal liver, the mean dose (P = .017) of the spinal cord, V50 (P = .043) of the duodenum, the maximum dose (P = .007) of the esophagus, and V30 (P = .047) of the whole lung compared to volumetric modulated arc therapy. The results indicate that noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system protects the normal liver, stomach, and lung better than noncoplanar volumetric modulated arc therapy and protects the normal liver, spinal cord, duodenum, esophagus, and lung better than volumetric modulated arc therapy. The noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system technique with the arrangement of noncoplanar arcs provided optimal dosimetric gains compared with noncoplanar volumetric modulated arc therapy and volumetric modulated arc therapy, except for the heart. Noncoplanar volumetric modulated arc therapy technique based on a cage-like radiotherapy system should be considered in more clinically challenging cases.

A novel X-Ray and γ-Ray combination strategy for potential dose escalation in patients with locally advanced pancreatic cancer.

Treatment of locally advanced pancreatic cancer (LAPC) has long been calling for advances in technology of radiotherapy. Patients who received radiotherapy still had high risks of local recurrence, while suffering from gastrointestinal side effects. Based on the inherent characteristics of the x-ray and γ-Ray radiation techniques, here we proposed and investigated an unexplored radiation therapy. To investigate the potential clinical benefit of a novel x-ray and γ-Ray combination radiation technique in patients with LAPC. Retrospective intensity-modulated radiotherapy (IMRT) treatment plans of 10 LAPC patients were randomly selected to compare with dual-modality plans. The prescribed dose to PGTV was 60.2Gy. The PGTV dose was further escalated in dual-modality plan while maintaining clinically tolerable dose to organs at risk (OARs). Dosimetric comparisons were made and analyzed for three treatment plans (tomotherapy, standard dual-modality plan, escalated dual-modality plan) to assess the ability to increase dose to target volume while minimizing dose in adjacent OARs. Finally, radiobiological models were utilized for comparison. All strategies resulted in dosimetrically acceptable plans. Dual-modality plans were present with similar conformity index (CI) and significantly lower gradient index (GI) compared with tomotherapy (3.64±0.37vs. 4.14±0.61, p=0.002; 3.64±0.42vs. 4.14±0.61, p=0.003). Dmean of PGTV (65.46±3.13vs. 61.56±1.00, p=0.009; 77.98±5.86vs. 61.56±1.00, p<0.001) and PCTV (55.04±2.14vs. 53.93±1.67, p=0.016; 58.24±3.24vs. 53.93±1.67, p=0.001) were significantly higher, while Dmean of the stomach was reduced in both dual-modality plans (17.98±10.23vs. 19.34±9.75, p=0.024; 17.62±9.92vs. 19.34±9.75, p=0.040). The lower V30Gy in the liver (4.83±5.87vs. 6.23±6.68, p=0.015; 4.90±5.93vs. 6.23±6.68, p=0.016) and lower V45Gy of the small intestine (3.35±3.30vs. 4.06±3.87, p=0.052) were found in dual-modality plans. Meanwhile, radiobiological models demonstrated higher probability of tumor control (29.27%±9.61% vs. 18.34%±4.70%, p<0.001; 44.67%±18.16% vs. 18.34%±4.70%, p=0.001) and lower probability of small intestine complication (2.16%±2.30% vs. 1.25%±2.72%, p=0.048) in favor of dual-modality strategy. A novel dual-modality strategy of x-ray and γ-Ray combination radiation appears reliable for target dose escalation and normal tissue dose reduction. This strategy might be beneficial for local tumor control and the protection of normal organs in patients with LAPC.

Comparison of out-of-field normal tissue dose estimates for pencil beam scanning proton therapy: MCNP6, PHITS, and TOPAS

Monte Carlo (MC) methods are considered the gold-standard approach to dose estimation for normal tissues outside the treatment field (out-of-field) in proton therapy. However, the physics of secondary particle production from high-energy protons are uncertain, particularly for secondary neutrons, due to challenges in performing accurate measurements. Instead, various physics models have been developed over the years to reenact these high-energy interactions based on theory. It should thus be acknowledged that MC users must currently accept some unknown uncertainties in out-of-field dose estimates. In the present study, we compared three MC codes (MCNP6, PHITS, and TOPAS) and their available physics models to investigate the variation in out-of-field normal tissue dosimetry for pencil beam scanning proton therapy patients. Total yield and double-differential (energy and angle) production of two major secondary particles, neutrons and gammas, were determined through irradiation of a water phantom at six proton energies (80, 90, 100, 110, 150, and 200 MeV). Out-of-field normal tissue doses were estimated for intracranial irradiations of 1-, 5-, and 15-year-old patients using whole-body computational phantoms. Notably, the total dose estimates for each out-of-field organ varied by approximately 25% across the three codes, independent of its distance from the treatment volume. Dose discrepancies amongst the codes were linked to the utilized physics model, which impacts the characteristics of the secondary radiation field. Using developer-recommended physics, TOPAS produced both the highest neutron and gamma doses to all out-of-field organs from all examined conditions; this was linked to its highest yields of secondary particles and second hardest energy spectra. Subsequent results when using other physics models found reduced yields and energies, resulting in lower dose estimates. Neutron dose estimates were the most impacted by physics model choice, and thus the variation in out-of-field dose estimates may be even larger than 25% when considering biological effectiveness.

Treatment Planning of Bulky Tumors Using Pencil Beam Scanning Proton GRID Therapy.

To compare spatially fractionated radiation therapy (GRID) treatment planning techniques using proton pencil-beam-scanning (PBS) and photon therapy. PBS 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. PBS 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. The 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.

Comparison of normal tissue doses in deep inspiration breath-hold and free breathing methods for radiotherapy of left-sided breast cancer using 4D-XCAT digital phantom.

To evaluate normal lung and heart tissue doses for treatment of left-sided breast cancer in deep inspiration breath-hold (DIBH) and free breathing (FB) as a function of breast size and diaphragm displacement using 4D-XCAT digital phantom in a simulation study. 4D-XCAT digital phantom was used to create 36 left-sided breast cancer digital phantom datasets with different breast height (BH) of 40, 50, and 60 mm, breast length (BL) of 16, 17, and 18 mm, and diaphragm excursion of 20, 25, 30, and 35 mm. For each dataset, DIBH and FB treatment plans were prepared using planning computerized radiotherapy-three dimensional (PCRT-3D) treatment planning system (TPS) with superposition computational algorithm. Dose differences in DIBH and FB plans were assessed in terms of mean lung dose (MLD), the lung volume receiving ≤20 Gy (V20), normal tissue complication probability (NTCP) of the lung, mean heart dose (MHD), and the heart volume receiving ≤30 (V30). DIBH reduced mean dose and V20 and NTCP of the lung in all cases, by up to 4.37 Gy, 7.62%, and 18.95%. Mean dose and V30 of the heart were also significantly reduced by 5.02 Gy and 8.23%. The use of DIBH for left-sided breast cancer radiotherapy offers excellent possibilities for sparing critical normal tissue without compromising radiation dose to the target.

Dosimetric comparison of volumetric modulated arc therapy with TrueBeam LINAC and hypofractionated radiosurgery with gamma knife ICON for large (>10 cm3) skull base meningiomas.

Multi Fractionated stereotactic radiosurgery (MF-SRS) of Linac has an essential role in the treatment of skull base meningiomas (sbMNG). However, Gamma Knife Icon (GK) allows MF-SRS using mask immobilization with onboard image guidance. This dosimetric study aims to investigate whether equivalent plan quality can be achieved with Volumetric Modulated Arc Therapy (VMAT) in patients with large sbMNG (>10 cm3) previously treated with GK. Twenty patients with the median target volume of 19.7cm3 are re-planned by using VMAT with 20 Gy in 5 fractions. Plan qualities are compared to tumor coverage, paddick conformity index (PCI), gradient index (GI), V4 Gy, V10 Gy, V12 Gy, optic chiasm V20 Gy, brainstem V23 Gy, optic nerve V25 Gy volumes, and maximum doses for all. Additionally, beam-on time and approximate planning time are also analyzed and compared. All plans provide adequate clinical requirements. First, the CI is comparable for the GK and VMAT (0.99±0.01 vs. 1.13±0.20; p = 0.18). Second, VMAT has a significantly higher GI than GK (3.81±0.35 vs. 2.63±0.09; p < 0.001). Third, the PCI is significantly higher in GK than VMAT (0.76±0.05 vs. 0.70±0.07; p < 0.001). The lower GI of the GK also results in significantly lower V4 Gy (156.1±43.8 vs. 207.5±40.1 cm3, p < 0.001) and V10 Gy (26.1±9.0 vs. 28.9±7.7 cm3, p < 0.001) compared to VMAT. Last, the VMAT reduces beam-on time (4.8±0.5 vs. 19±1.1 min.; p < 0.001). Although both systems have succeeded in creating effective plans in clinical practice, the GK reveals more effective lower normal brain tissue doses. However, the shorter treatment time with LINAC, excluding the total procedure time, can be considered advantageous over GK.

Dosimetric and biological comparisons of single planning and double plannings for bilateral lung cancer SBRT planning based on the Cyber-Knife system.

The aim is to investigate the influence of single planning (Plan S) and double plannings (Plan D) on bilateral lung cancer stereotactic body radiation therapy planning from the perspective of dosimetry and biology respectively. Methods Cases with bilateral lung cancer patients who had undergone SBRT with the Cyber-Knife were enrolled, and a single planning and double plannings were designed in the Multiplan@4.2 treatment planning system equipped with the Cyber-Knife system. The single plan was to optimize the two target volumes in a separate plan, while the dual plan is to optimize two target volumes respectively in two separate plans, then perform dose superposition. Then based on the dosimetric results, the biological parameters were calculated. Thus the quality of SBRT plans for those bilateral lung cancer designed by the two methods were compared and evaluated according to the dosimetric and biological results. The dose distribution of both planning target volumes and surrounding organs at risk in Plan S and Plan D could meet the clinical prescription requirements. The target conformity index and the new conformity index of PTV were closer to 1 in the Double plannings, and the dose gradient GI in the Plan D was smaller than Plan S. For organs at risks, the doses received by the Plan D were relatively small. In terms of biological models, for the equivalent uniform dose of normal lung tissue, heart and esophagus, the Plan D was 6.51% (P=0.045), 19.8% (P=0.022), 27.08% (P>0.05) lower than Plan S respectively. The results showed that the equivalent uniform dose of normal tissue in the Plan D was lower relative to Plan S. Dosimetric and biological results show that both the use of Plan D have an advantage of protecting normal tissues, and it was suggested that to design double plannings for bilateral lung cancer stereotactic body radiation therapy planning based on Cyber-Knife in the clinical practice.