Dosimetry Parameters Research Articles

Comparison of Two Light Wavelengths (λ = 660 nm and λ = 780 nm) in the Repair Process of Oral Mucositis Induced by Ionizing Radiation: Clinical and Microscopic Evaluations in Rats

Photobiomodulation (PBM) has been clinically used for the prevention and treatment of oral mucositis (OM). The effect of red and near-infrared wavelengths on OM repair is still misunderstood. The aim of this study was to compare the clinical effect and tissue changes caused by 660 nm and 780 nm exposure in an experimental model of OM. Rats were submitted to gamma irradiation for induction of OM lesions and treated with 660 nm or 780 nm lasers with the same dosimetry parameters (30 mW, 7.5 J/cm2, 10 s, spot size = 0.04 mm, irradiation every two days). Clinical assessment of OM severity and histopathological analyses was performed after 8, 14, and 20 days of the ionizing radiation. OM severity was reduced in the PBM groups, especially when the red laser was used. The histopathological pattern was similar between the PBM groups, showing advanced re-epithelization and more pronounced angiogenesis and collagen deposition compared to the control. The 660 nm group showed a greater collagen matrix area than the 780 nm group at 14 days. In conclusion, PBM at 660 nm and 780 nm improved the repair of ionizing radiation-induced OM. Both wavelengths activated the angiogenesis and collagen deposition, but these tissue effects were more pronounced when 660 nm was used.

Molecular Recognition and In Vivo Detection of Temozolomide and 5-Aminoimidazole-4-carboxamide for Glioblastoma Using Near-Infrared Fluorescent Carbon Nanotube Sensors

There is a pressing need for sensors and assays to monitor chemotherapeutic activity within the human body in real time to optimize drug dosimetry parameters such as timing, quantity, and frequency in an effort to maximize efficacy while minimizing deleterious cytotoxicity. Herein, we develop near-infrared fluorescent nanosensors based on single walled carbon nanotubes for the chemotherapeutic Temozolomide (TMZ) and its metabolite 5-aminoimidazole-4-carboxamide using Corona Phase Molecular Recognition as a synthetic molecular recognition technique. The resulting nanoparticle sensors are able to monitor drug activity in real-time even under in vivo conditions. Sensors can be engineered to be biocompatible by encapsulation in poly(ethylene glycol) diacrylate hydrogels. Selective detection of TMZ was demonstrated using U-87 MG human glioblastoma cells and SKH-1E mice with detection limits below 30 μM. As sensor implants, we show that such systems can provide spatiotemporal therapeutic information in vivo, as a valuable tool for pharmacokinetic evaluation. Sensor implants are also evaluated using intact porcine brain tissue implanted 2.1 cm below the cranium and monitored using a recently developed Wavelength-Induced Frequency Filtering technique. Additionally, we show that by taking the measurement of spatial and temporal analyte concentrations within each hydrogel implant, the direction of therapeutic flux can be resolved. In all, these types of sensors enable the real time detection of chemotherapeutic concentration, flux, directional transport, and metabolic activity, providing crucial information regarding therapeutic effectiveness.

Predictors of Pneumonitis in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Definitive Chemoradiation Followed by Consolidative Durvalumab

PurposeIn patients with locally advanced, unresectable non-small cell lung cancer (NSCLC), the standard of care is concurrent chemoradiation (CRT) followed by consolidative immunotherapy with durvalumab. Pneumonitis is a known adverse event of both radiation therapy and immune checkpoint inhibitors such as durvalumab. We sought to characterize pneumonitis rates and dosimetric predictors of pneumonitis in a real-world population of patients with NSCLC treated with definitive CRT followed by consolidative durvalumab. Methods and MaterialsPatients with NSCLC from a single institution who were treated with definitive CRT followed by consolidative durvalumab were identified. Outcomes of interest included pneumonitis incidence, type of pneumonitis, progression-free survival, and overall survival. ResultsSixty-two patients were included in our data set treated from 2018 to 2021 with a median follow-up of 17 months. The rate of grade 2+ pneumonitis in our cohort was 32.3%, and the rate of grade 3+ pneumonitis was 9.7%. Lung dosimetry parameters including V20 ≥30% and mean lung dose (MLD) >18 Gy were found to be correlated with increased rates of grade 2+ and grade 3+ pneumonitis. Patients with a lung V20 ≥30% had a grade 2+ pneumonitis rate at 1 year of 49.8% compared with 17.8% in patients with a lung V20 <30% (P = .015). Similarly, patients with an MLD >18 Gy had a grade 2+ pneumonitis rate at 1 year of 52.4% compared with 25.8% in patients with an MLD ≤18 Gy (P = .01). Moreover, heart dosimetry parameters including mean heart dose ≥10 Gy were found to be correlated with increased rates of grade 2+ pneumonitis. The estimated 1-year overall survival and progression-free survival of our cohort were 86.8% and 64.1%, respectively. ConclusionsThe modern management of locally advanced, unresectable NSCLC involves definitive chemoradiation followed by consolidative durvalumab. Pneumonitis rates were higher than expected in this cohort, particularly for patients with a lung V20 ≥30%, MLD >18 Gy, and mean heart dose ≥10 Gy, suggesting that more stringent radiation planning dose constraints may be needed.

Volumetric modulated arc therapy (VMAT) comparison to 3D-conformal technique in lung stereotactic ablative radiotherapy (SABR).

Stereotactic ablative radiotherapy (SABR) can be a curative option for non-small cell lung cancer (NSCLC) and oligometastatic lung disease. Volumetric modulated arc therapy (VMAT) has offered further advancements in terms of radiation dose shaping without compromising treatment times however there is potential for greater low-dose exposure to the lung. This study was to assess whether VMAT lung SABR would result in any increase to the dosimetry parameters compared with three-dimensional conformal radiotherapy (3D-CRT) that could confer increased risk of radiation pneumonitis. A total of 53 and 30 3D-CRT treatment plans of patients treated with 48 Gy in 4 fractions were compared. No statistically significant difference in planning target volumes between the VMAT 29.9 cc (range 12.4-58.5 cc) and 3D-CRT 31.2 cc (range 12.3-58.3 cc) P=0.79. The mean of total lung V5, ipsilateral lung V5 and contralateral lung V5 all showed a trend of being smaller in the VMAT treatment group- 14% versus 15.8%, 25.6% versus 30.4% and 1.6% versus 2.2%, respectively, but all were not statistically significant differences. Mean of the mean lung dose MLD, again showed a trend of being lower in the VMAT treatments but was also non-significant, 2.6 Gy versus 3.0 Gy, P=1.0. Mean V20 was the same in both cohorts, 3.3%. The dosimetry for 3D-CRT and VMAT plans were not significantly different including V5, and therefore we conclude that VMAT treatment is unlikely to be associated with an increased risk of radiation pneumonitis.

Comparative analysis of dosimetry and predictive somatotype parameters of prone and supine whole-breast irradiation among Chinese women after breast-conserving surgery.

Finding a better treatment position (prone or supine) for whole-breast irradiation for Chinese female patients diagnosed with breast cancer by identify the associations between predictive somatotype parameters and dosimetric gains. Two volumetric-modulated arc therapy (VMAT) plans were deployed for whole-breast irradiation in supine and prone position with a total dose of 50 Gy in 25 fractions. Dose-volume parameters were compared and analysed both in the target volume and organs at risk, and equivalent uniform dose-based figure-of-merit (fEUD) models were further used to quantitatively evaluate the overall merits of the two plans. Body shape parameters, including body mass index (BMI), body surface area (BSA), breast shape, cup size, bust size and chest size, were collected. Anatomic features such as the central heart distance (CHD) were measured on supine CT. Spearman's correlation analysis, receiver operating characteristic (ROC) curve analysis, and the linear regression models were conducted. Doses to the heart and left anterior descending coronary artery (LADCA) are greater in left-sided breast cancer (BC) patients in the prone position than in the supine position, and the opposite was true for right-sided BC patients (p<0.001). 19 of 63 patients (5 left-sided and 14 right-sided BC) achieved greater benefit from the prone position according to the fEUD score. Right-sided BC patients with a bust size ≥92.25 cm, drop-type breasts and cup size ≥B are very likely to benefit from prone-position radiotherapy. The CHD is significantly positively associated with △fEUD among right-sided BC patients (rho=0.506, p=0.004). Using a cut-off point of 2.215, the CHD had 71.4% sensitivity and 81.2% specificity in predicting a successful prone plan. Right-sided BC patients had better dosimetric gain in the prone position than left-sided BC patients. The CHD is an especially good and novel predictor that could help to select prone-benefitting right-sided BC patients.

Feasibility of collagen matrix tiles with cesium-131 brachytherapy for use in the treatment of head and neck cancer

Locoregional failure is a unique and challenging problem in head and neck cancer with controversy surrounding the use of re-irradiation in the treatment. We aimed to evaluate the dosimetry and technical parameters in utilizing a collagen matrix with embedded Cesium-131 (Cs-131) radioactive isotope seeds as it relates to dose distribution and dose to carotid artery. Cadaveric feasibility study randomizing Cs-131 strands alone or Cs-131 with collagen matrix to be placed into neck dissection defects. For the dose computation, physicists employed the TG-43 dosimetry calculation algorithm with a point source assumption to compute the dose. Carotid arteries were contoured in MIM-Symphony software and the carotid artery maximum and mean doses were calculated in accordance with TG-43 specifications. Ease of use of collagen matrix tiles on a 7-point Likert scale and mean radiation dose to the carotid artery. Ease of use score was higher in collagen matrix compared to stranded seeds with a mean score of 6.3 +/- 1.2 compared to 4.5 +/- 0.87. Time of implantation was statistically significantly, p = 0.031, lower in the collagen matrix group (M = 5.17 min, SD = 4.62) compared to stranded seeds (M = 15.83 min, SD = 3.24). Mean radiation dose to the carotid artery was 62.8 Gy +/- 9.46 in the collagen matrix group compared to 108.2 Gy +/- 55.6 in the traditional Cs-131 seeds group. We present a feasibility and concept cadaveric study using a collagen matrix with Cesium-131 demonstrating preliminary evidence to support its ease of use, decreased time to implantation, and decreased dose delivered to the carotid artery.

Risk analysis of grade ≥ 2 radiation pneumonitis based on radiotherapy timeline in stage III/IV non-small cell lung cancer treated with volumetric modulated arc therapy: a retrospective study

BackgroundRadiotherapy is an important treatment for patients with stage III/IV non-small cell lung cancer (NSCLC), and due to its high incidence of radiation pneumonitis, it is essential to identify high-risk people as early as possible. The present work investigates the value of the application of different phase data throughout the radiotherapy process in analyzing risk of grade ≥ 2 radiation pneumonitis in stage III/IV NSCLC. Furthermore, the phase data fusion was gradually performed with the radiotherapy timeline to develop a risk assessment model.MethodsThis study retrospectively collected data from 91 stage III/IV NSCLC cases treated with Volumetric modulated arc therapy (VMAT). Patient data were collected according to the radiotherapy timeline for four phases: clinical characteristics, radiomics features, radiation dosimetry parameters, and hematological indexes during treatment. Risk assessment models for single-phase and stepwise fusion phases were established according to logistic regression. In addition, a nomogram of the final fusion phase model and risk classification system was generated. Receiver operating characteristic (ROC), decision curve, and calibration curve analysis were conducted to internally validate the nomogram to analyze its discrimination.ResultsSmoking status, PTV and lung radiomics feature, lung and esophageal dosimetry parameters, and platelets at the third week of radiotherapy were independent risk factors for the four single-phase models. The ROC result analysis of the risk assessment models created by stepwise phase fusion were: (area under curve [AUC]: 0.67,95% confidence interval [CI]: 0.52–0.81), (AUC: 0.82,95%CI: 0.70–0.94), (AUC: 0.90,95%CI: 0.80–1.00), and (AUC:0.90,95%CI: 0.80–1.00), respectively. The nomogram based on the final fusion phase model was validated using calibration curve analysis and decision curve analysis, demonstrating good consistency and clinical utility. The nomogram-based risk classification system could correctly classify cases into three diverse risk groups: low-(ratio:3.6%; 0 < score < 135), intermediate-(ratio:30.7%, 135 < score < 160) and high-risk group (ratio:80.0%, score > 160).ConclusionsIn our study, the risk assessment model makes it easy for physicians to assess the risk of grade ≥ 2 radiation pneumonitis at various phases in the radiotherapy process, and the risk classification system and nomogram identify the patient’s risk level after completion of radiation therapy.

PP09 Presentation Time: 10:50 AM: Interobserver Variability of Prostate MRI-Assisted Radiosurgery Postimplant Dosimetry: Comparison with Automatic Postimplant Dosimetry

<h3>Purpose</h3> To quantify the 2 sources of human interobserver variability (IoV) introduced during prostate MRI-assisted radiosurgery postimplant dosimetry, and compare this human variability to automatically generated postimplant dosimetry. <h3>Materials and Methods</h3> Twenty-five patients underwent LDR prostate brachytherapy (LDRPBT) and were imaged with fully balanced SSFP for postimplant dosimetry. Four certified medical dosimetrists (CMDs) identified the radioactive seeds in each of the 25 postimplant MRIs. Seven additional clinical observers, including 3 radiation oncologists (ROs), contoured the prostate and 4 organs at risk (OARs) on the MRIs. Consensus segmentation masks from the 3 ROs' contours were computed for each patient using the simultaneous truth and performance level estimation (STAPLE) algorithm. Thirty unique postimplant dosimetry plans were computed for each patient. Twenty-eight of the dosimetry plans were computed from each unique pair of the CMDs' seed plans and observer contours (4 CMDs × 7 contourers). One dosimetry plan was performed automatically for each patient using custom autosegmentation and automatic seed identification software developed previously. A reference dosimetry plan for each patient was computed using the consensus STAPLE segmentations and the seeds identified by the most experienced CMD. IoV of 5 dosimetry parameters was quantified separately for each IoV source: IoV introduced by seed localization, and IoV introduced by anatomy contouring. The coefficient of variation (CoV) of each dosimetry parameter was quantified for each patient across CMDs using the consensus STAPLE segmentations. Similarly, the CoV of each dosimetry parameter was quantified for each patient across contouring observers using the seed locations determined by the most experienced CMD. Additionally, the differences in dosimetry parameters between the reference and automatic dosimetry plans were quantified. <h3>Results/Discussion</h3> CoVs due to variability of anatomy contouring (CoV_contours) were significantly higher than those due to variability of seed localization (CoV_seeds) for all dosimetry parameters (median CoV_contours vs. median CoV_seeds: prostate D90 - 15.116% vs. 0.651%, p<0.001; prostate V100 - 5.359% vs. 0.365%, p<0.001; prostate V150 - 7.017% vs. 1.252%, p<0.001; rectum V100 - 79.230% vs. 8.688%, p<0.001; EUS V200 - 107.740% vs. 21.176%, p<0.001). CoV_contours were lower when the contouring observers were restricted to only the 3 ROs, but they were still significantly higher than CoV_seeds for all dosimetry parameters. Median differences in prostate D90, prostate V100, prostate V150, rectum V100, and EUS V200 between automatically computed and reference dosimetry parameters were 3.156%, 1.630%, -1.071%, -0.001%, and -0.002%, respectively. Most automatically computed dosimetry parameters were within the expected variability of those produced by human observers (Figure 1). <h3>Conclusion</h3> IoV of contouring constitutes the largest source of IoV in postimplant dosimetry plans performed by clinical observers. When using automatic contouring and seed localization tools, review and refinement of computer predictions will be necessary for some patients. However, automatic dosimetry tools can estimate postimplant dosimetry that is close to, or within, the expected variability of dosimetry plans produced by clinical observers.

PP12 Presentation Time: 11:20 AM: Prognostic Factors of Outcomes in Prostate Cancer Patients Treated with Permanent Implant: A High-Volume Center Experience

<h3>Purpose</h3> This study aims to report prognostic factors of clinical outcomes of prostate cancer (PCa) patients treated with permanent implant prostate brachytherapy (PIPB) at our institution. <h3>Materials and Methods</h3> The study sample consists of 2364 PCa patients treated with PIPB with or without cytoreductive antiandrogen therapy (ADT) between 1994 and 2020. Kaplan-Meier analyses with log-rank tests were performed to assess and compare biochemical relapse (BCR) according to risk stratification factors, dosimetry parameters or physician performing the implant. Univariate and multivariate Cox regression models were used to identify significative prognostic factors for BCR. <h3>Results</h3> The mean age of the patients at treatment time was 63.7±6.9 years. The median follow-up time was 81 months. Most patients had low-risk clinical features with 73.9% having Gleason score under or equal to 6, 92.6% a pre-treatment PSA value under 10, and 93.4% a clinical stage of T2A or lesser. 30.4% of patients were prescribed ADT. The 5 and 10 years BCR-free survival were 95.4 and 90.1%, respectively. Four physicians (RO) with different clinical experience have performed more than 150 PIPB procedures at our institution: 171, 1099, 805 and 240 cases, respectively for RO1 to RO4. On Kaplan-Meier analysis, the four ROs obtained 80.3, 88.5, 93.5 and 87.0 % 10 years BCR-free survival, respectively. When stratifying patients by D'Amico risk groups, no significative difference was found between ROs on log-rank tests. On univariate Cox model, RO1 (HR=3.43, 95%CI: 1.98-5.92) and RO2 (HR=1.85, 95%CI: 1.23-2.79) had significantly higher hazard ratios than RO3. When correcting for different risk stratification factors in multivariate Cox models, only pre-treatment PSA level (HR=1.11, 95%CI: 1.073-1.148, p<0.001) and ADT use (HR=2.179, 95%CI: 1.524-3.116, p<0.001) were identified as prognostic factors for BCR, but the experience of the RO performing the procedure (p=0.258), clinical stage (p=0.135), age (p=0.166) and dosimetry parameters (D90, p=0.121; V100, p=0.312) were not. <h3>Conclusions</h3> The 26 years' experience of PIPB at our institution shows a five, ten years and all-time BCR-free survival of 95.4, 90.1 and 80.4%, respectively, with the latest failure occurring 18 years after treatment. The most important prognostic factor identified in our cohort of patients were pre-treatment PSA level and ADT usage. Whereas clinical tumor stage, patients' age, dosimetry parameters or RO experience were not found to be significant.

GSOR10 Presentation Time: 9:45 AM: Positron Emission Tomography (PET) versus Computed Tomography (CT)-Guided Intracavitary Brachytherapy for Locally Advanced Cervical Cancer: A Randomised Study

<h3>Purpose</h3> This study compared early clinical outcomes in locally advanced cervical cancer (LACC) treated with PET-CT guided intracavitary brachytherapy (ICBT) versus 3D CT guided ICBT after external beam radiation therapy (EBRT). <h3>Materials and Methods</h3> From September 2019 to April 2021, 50 patients with newly diagnosed LACC (FIGO stage IIB to IIIB) who received EBRT (50.4Gy in 28 fractions over 5.5 weeks) with concurrent weekly chemotherapy were randomized into two arms: PET/CT- guided ICBT arm (25 patients) and CT- guided ICBT arm (25 patients). High-risk clinical target volume (HRCTV) in PET-CT arm included cervix along with FDG avid lesion and in CT arm included cervix along with residual disease based on CT scan findings. The prescribed dose of ICRT was 7.0 Gy X 3 fractions (once a week fraction). Rectum, bladder, and sigmoid colon were contoured as organs at risk in both arms. Local control, overall survival, and dosimetry comparison between two arms were evaluated. Common Terminology Criteria for Adverse Events v.4.03 (CTCAE v4.03) was used for reporting early toxicity. <h3>Results</h3> Clinical characteristics like age, stage etc. were comparable in the two arms. The 2- year local control rate was 79.1% in PET-CT arm and 72.7% in CT arm (p-value, 0.3). The 2-year overall survival was 89% in CT arm and 82.9% in PET-CT arm (p-value, 0.6). The mean dose to HRCTV D90 and HRCTV D95 in PET CT arm was 87.7Gy (s=6.1Gy) and 83.04Gy (s=5.5Gy) and in CT arm was 85.6Gy (s=6.4Gy) and 80.6Gy (s=5.7Gy) (p-value, 0.13).The mean dose to bladder, rectum and sigmoid colon in PET-CT arm were 80.3Gy (s=8.2Gy), 70Gy (s=6.1Gy) and 66.2Gy (s=7.4Gy) and in CT arm were 79 Gy (s=6.9Gy), 70.2Gy (s=7.2Gy) and 64.9Gy (s=6.3Gy), (p-value:0.58, 0.88 and 0.55). No Grade III/IV OAR toxicity were reported in both arms. <h3>Conclusion</h3> Though the limited sample size, the results of our randomized study show that PET-CT guided ICBT is feasible in patients with LACC. The clinical outcome (overall survival, local control, and OAR toxicity) and dosimetry parameters were comparable in both arms. Based on marginally better local control in the PET-CT arm, though not statistically significant, we suggest further studies with a larger sample size to evaluate the role of PET-CT in LACC.

Efficacy and Toxicity of Stereotactic Body Radiation Therapy Treatment of Multiple Lung Lesions

<h3>Purpose/Objective(s)</h3> As the role of SBRT in caring for patients with complex cancer presentations continues to expand, it is paramount to elucidate how many courses of lung SBRT are safe and what factors predict toxicity. Our study seeks to evaluate the dose-volume factors and associated toxicities for treatment of multiple lung tumors with SBRT. <h3>Materials/Methods</h3> This retrospective IRB approved study was conducted using our institutional database of patients who underwent SBRT for multiple lung lesions between 2012 to 2020. 64 patients underwent SBRT for multiple tumors for a total of 137 tumors treated. We compared dosimetry and clinical outcome parameters of these patients to a paired set of 50 randomly selected patients who received SBRT for a solitary lung lesion. Variables collected include patient age, gender, cancer stage, tumor histology, SBRT dose, dosimetric parameters, toxicities from SBRT, and progression-free survival (PFS). Acute toxicity was defined as any toxicity related to lung SBRT occurring <90 days from the start of SBRT and late toxicity was beyond 90 days from the end of SBRT. Statistical analysis was performed using statistical software. <h3>Results</h3> 137 pulmonary lesions in 64 patients (2+ lesions in every patient) were treated using SBRT at our institution. Of these 137 lesions, 122/137 (89.1%) were primary lung tumors and 15/137 (10.9%) were metastatic lesions. Out of the 137 lesions, 9.5% were classified as SCLC, 43.1% as adenocarcinoma, 36.5% as squamous cell carcinoma, and 10.9% as distant metastases. The mean prescription dose for multi-lesion patients was 50 Gy delivered in 3-5 fractions versus 50 Gy in 5 fractions in the single lesion group. The mean V5 (47.3% vs. 25.7%, p<0.05), V10 (26.8.3% vs. 15.4%, p<0.05), V20 (10.2% vs. 4.5%, p<0.05), and mean lung dose (10.05 Gy vs. 5.29 Gy, p<0.05) were significantly greater in multi-lesion patients compared to single lesion patients, respectively. Fatigue and dyspnea were the most commonly reported acute toxicities; 56.2% multi-lesion patients experienced fatigue and 18.8% experienced dyspnea while 22.0% of single lesion patients experienced fatigue and 12.0% experienced dyspnea (p=0.315). No late toxicities were documented. 126/137 (92.0%) of the lung lesions treated with multiple SBRT treatments demonstrated local control, while 11/137 (8.0%) had local recurrence. 1-year PFS was 92.2% in the multi-lesion group versus 84.0% in the single lesion group. There was no significant correlation between pulmonary toxicity and histology in the single lesion and multi-lesion groups. <h3>Conclusion</h3> Our results suggest that SBRT treatment of multiple pulmonary tumors is safe and feasible without increasing in acute or late pulmonary toxicity. While there is significant difference in all lung parameters between these two groups, it did not translate into increasing toxicity. Further studies are needed to understand the relation between radiation dose parameters and incidence of pulmonary toxicity.

Investigation of the Constancy of the Dosimetric Parameters of the Proton Therapy System

Purpose: Determination of fluctuation ranges of dosimetry parameters of the proton therapy system&#x0D; (PTS) to clarify the permissible limit deviations.&#x0D; Methods and materials: The basis for the quality assurance program (QA) of the PTS is the report of the&#x0D; American Association of Physicists in Medicine AAPM TG-224. According to this report, the QA program is a living, adaptive document that needs to be refined, corrected and optimized taking into account the features of the PTS being in use and the available dosimetry equipment. After setting-up&#x0D; checks within the framework of the daily QA program, it became possible to automatically collect data&#x0D; containing dosimetry parameters of the PTS for subsequent analysis. It was decided to investigate the&#x0D; stability over time of some dosimetry parameters of the PTS in order to determine the ranges of their&#x0D; fluctuations and, as a result, to clarify the permissible deviations of these parameters.&#x0D; Results: The stability of the parameters associated with the constancy of the proton beam energy selection was studied. As a result, the study showed that the values of the parameters associated with the&#x0D; constancy of the proton beam energy selection fluctuated within much smaller limits compared to&#x0D; those proposed in TG-224.&#x0D; Conclusion: The obtained result may allow us to reconsider the approach to proton therapy planning&#x0D; system in the FSBI FSCCRO of the FMBA of Russia, in particular, to the choice of PTV margins. The new&#x0D; refined tolerances for the maximum deviations of the analyzed parameters are proposed in this research work

Intensity-modulated radiotherapy does not induce volumetric changes of the Bichat fat pad in nasopharyngeal cancer.

To evaluate morphological and functional changes in the Bichat fat pad (BFP) after curative concurrent chemoradiotherapy in nasopharyngeal cancer (NPC) patients. We retrospectively analyzed the volumetric, metabolic, and dosimetry parameters of BFPs in 7NPC patients who underwent intensity-modulated radiotherapy (IMRT) between 2015 and 2020. Inclusion criteria were i)histologically confirmed diagnosis of NPC, ii)follow-up period of at least 12months, iii)no history of previous irradiation or surgery in the maxillofacial area, and ìv)availability of pre- and posttreatment MRI and 18F‑FDGPET-CT performed in our Institution. All patients had stageIII-IVA disease (n = 7) and received platinum-based chemotherapy. Planned doses in 30daily fractions/5days per week were 66 Gy (2.2 Gy/die 5days/week) to the gross tumor volume, 66 Gy (2.1-2.2 Gy/die 5days/week) to the gross nodal volume, 60 Gy (2 Gy/die 5days week) to clinical target volume (CTV)1, and 54 Gy (1.8 Gy/die 5days/week) to CTV2. All patients completed the planned radiotherapy course in amedian time of 42days (range 42-43). Relationships between BFP volumes and the following DVH parameters were evaluated: mean dose, maximum dose (Dmax), and percentage of BFP volume receiving more than 5to 65 Gy (V5to V65). The pre-RT volumes of the left and right BFPs were 12.24cc (range 6.51-20.01cc) and 11.55cc (range 5.78-17.53cc), respectively. The mean volumes of left BFPPRE and BFPPOST were 12.24cc (range6.51-20.01cc) and 13.85cc (range7.54-20.21 cc), respectively, with no significant statistical differences (P > 0.05). No statistically significant correlations were found between dosimetry features and BFP volumetric changes (all P > 0.05). Our original results showed that chemoradiotherapy does not induce significant volumetric changes of the BFP. Further investigations are needed to evaluate the effects of higher radiation doses on BFP. This is the first real-world study on this issue.

A Feasibility Study of Deep Learning-Based Auto-Segmentation Directly Used in VMAT Planning Design and Optimization for Cervical Cancer.

PurposeTo investigate the dosimetric impact on target volumes and organs at risk (OARs) when unmodified auto-segmented OAR contours are directly used in the design of treatment plans. Materials and MethodsA total of 127 patients with cervical cancer were collected for retrospective analysis, including 105 patients in the training set and 22 patients in the testing set. The 3D U-net architecture was used for model training and auto-segmentation of nine types of organs at risk. The auto-segmented and manually segmented organ contours were used for treatment plan optimization to obtain the AS-VMAT (automatic segmentations VMAT) plan and the MS-VMAT (manual segmentations VMAT) plan, respectively. Geometric accuracy between the manual and predicted contours were evaluated using the Dice similarity coefficient (DSC), mean distance-to-agreement (MDA), and Hausdorff distance (HD). The dose volume histogram (DVH) and the gamma passing rate were used to identify the dose differences between the AS-VMAT plan and the MS-VMAT plan.Results Average DSC, MDA and HD95 across all OARs were 0.82–0.96, 0.45–3.21 mm, and 2.30–17.31 mm on the testing set, respectively. The D99% in the rectum and the Dmean in the spinal cord were 6.04 Gy (P = 0.037) and 0.54 Gy (P = 0.026) higher, respectively, in the AS-VMAT plans than in the MS-VMAT plans. The V20, V30, and V40 in the rectum increased by 1.35% (P = 0.027), 1.73% (P = 0.021), and 1.96% (P = 0.008), respectively, whereas the V10 in the spinal cord increased by 1.93% (P = 0.011). The differences in other dosimetry parameters were not statistically significant. The gamma passing rates in the clinical target volume (CTV) were 92.72% and 98.77%, respectively, using the 2%/2 mm and 3%/3 mm criteria, which satisfied the clinical requirements.ConclusionsThe dose distributions of target volumes were unaffected when auto-segmented organ contours were used in the design of treatment plans, whereas the impact of automated segmentation on the doses to OARs was complicated. We suggest that the auto-segmented contours of tissues in close proximity to the target volume need to be carefully checked and corrected when necessary.

Risk factors and clinical characteristics of pneumonitis among patients with ALK-rearranged non-small cell lung cancer who received alectinib and thoracic radiotherapy.

e20591 Background: Alectinib and thoracic radiotherapy (TRT) are important modalities in the management of ALK-rearranged non-small cell lung cancer. We therefore aimed to assess the incidence and risk factors of pneumonitis when these two treatments were combined. Methods: Patients with ALK-rearranged non-small cell lung cancer, receiving alectinib and TRT from January 2018 to December 2020 were reviewed, and the clinical and dosimetry data were collected. Logistic regression analyses were performed to evaluate risk factors associated with treatment-related pneumonitis (TRP). The prediction ability of dosimetry parameters for pneumonitis were examined by receiver-operating characteristic (ROC) curve analyses. Results: Of the 25 enrolled patients, 16 (64%) developed pneumonitis, and 12 (48%) developed grade 2 or higher pneumonitis. Logistics regression analyses revealed chemotherapy (OR = 8.750, 95% CI 1.207 - 63.428, p = 0.032), higher ipsilateral V5 (OR = 1.060, 95%CI 1.002 - 1.122, p = 0.043) and total lung V5 (OR = 1.083, 95%CI 1.000 - 1.174, p = 0.05) to be risk factors for TRP. Total lung V10, total lung V5, and ipsilateral V5 were strong predictors of TRP among the dosimetry parameters (AUC = 0.800, 0.786 and 0.781, respectively). After developing pneumonitis, 52% of patients recovered or improved, but one patient died due to respiratory failure. Conclusions: The combined use of alectinib and TRT significantly increased the risk of pneumonitis. Clinicians should consider the elevated risks and related dosimetric factors when deciding on combination treatment for ALK-rearranged NSCLC patients.

Individualized clinical target volume delineation and efficacy analysis in unilateral nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT): 10-year summary.

To evaluate the long-term local control, failure patterns, and toxicities after individualized clinical target volume (CTV) delineation in unilateral nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Unilateral NPC was defined as a nasopharyngeal mass confined to one side of the nasopharynx and did not exceed the midline. From November 2003 to December 2017, 95 patients were retrospectively included. All patients received IMRT. The CTVs were determined based on the distance from the gross tumor. The contralateral para-pharyngeal space and skull base orifices were spared from irradiation. There were three local recurrences and eight regional recurrences in 10 patients during an 84-month follow-up. All local recurrences were within PGTVnx, and all in-field recurrences. No recurrences were found in traditional high-risk areas including contralateral the para-pharyngeal space and skull base orifices. The 10-year local-recurrence-free survival, regional-recurrence-free survival and overall survival were 96.2%, 90.5% and 84.7%, respectively. The dosimetry parameters of the tumor-contralateral organs were all lower than the values of the tumor-ipsilateral side (P < 0.05). The late toxicities occurred mainly in the tumor-ipsilateral organs, including radiation-induced temporal lobe injury, impaired visuality, hearing loss and subcutaneous fibrosis. Individualized CTV delineation in unilateral NPC could yield excellent long-term local control with limited out-of-field recurrences, reduced dose to tumor- contralateral organs and mild late toxicities, which is worthy of further exploration.

Perihippocampal failure after hippocampal-avoidance whole-brain radiotherapy in cancer patients with brain metastases: Results of a retrospective analysis.

Perihippocampal failure is a rare clinical scenario in brain metastatic cancer patients following hippocampal-avoidance (HA) whole-brain radiotherapy (HA-WBRT). The clinical features have not been fully identified because clinical data on intracranial failure after HA-WBRT are limited. It is thus necessary to accumulate clinical data.We retrospectively analyzed cancer patients with brain metastases who were diagnosed between January 2014 and September 2020 at a regional referral hospital. The medical records of patients who underwent HA-WBRT were reviewed. The clinical features of intracranial recurrence were described. Dosimetry parameters were compared in terms of deviation from the recommended protocol of the Radiation Therapy Oncology Report 0933.Twenty-four eligible patients with brain metastases who underwent HA-WBRT were identified; 13 (54%) were male. Seventeen patients (71%) had lung cancer, 6 (25%) had breast cancer, and 1 (4%) had liver cancer. The median overall survival was 12 months. Three patients developed intracranial failure during clinical follow-up, and 2 relapsed with intracranial failure in the perihippocampal region at 13 and 22 months, respectively. The perihippocampal failure rate was about 8%. One patient with small cell lung cancer received HA-prophylactic cranial irradiation; the minimum and maximum doses to the hippocampi were 6.8 and 10.7 Gy, respectively. Another patient with brain metastases from lung adenocarcinoma received HA-WBRT; the minimum and maximum doses to the hippocampi were 5.4 and 10.6 Gy, respectively.We reported unusual cases of intracranial failure in the perihippocampal region following HA-WBRT. Perihippocampal failure could be attributed to an under-dose of radiation partially or be resulted from aggressiveness of cancer per se. Further research on this topic is encouraged.

464 A Novel High Dose Rate Brachytherapy Device for Preventing Local Recurrence of Pancreatic Cancer Dosimetry Verification

OBJECTIVES/GOALS: To demonstrate safety and limit damage to off-target organs, we will be determining dosimetry parameters through experimentation and Monte Carlo simulations with our brachy therapy applicator designed to improve upon current designs to treat a 3-dimensional volume. METHODS/STUDY POPULATION: Low-cost materials were used to manufacture our High Dose Rate (HDR) applicator and a readily available after loading system was used to load our configuration with a radioactive source. The dosimetry of our device was analyzed using commercially available software and external beam therapy films to generate depth dose profiles and superficial dose distribution. Additionally, we attempt to confirm Task Group No. 43 (TG-43) dosimetry parameters using Monte Carlo simulations for our device. These data were compared with currently available applicators used for intraoperative radiotherapy. RESULTS/ANTICIPATED RESULTS: We anticipate that we will be able to validate dosimetry parameters for our device in preparation for clinical use. We aim to show our dose distributions align well with proposed target volumes while considering the composition and shape of our applicator. We hope to demonstrate that, unlike current applicators, our design is more effective at treating a 3-dimensional target volume. DISCUSSION/SIGNIFICANCE: By 2040, pancreatic cancer will be the second-largest cause of cancer-related deaths. Even with current brachytherapy applicators, 30-40% of pancreatic cancer seems to recur near the surgical site after surgery. By preventing local recurrence, we hope to improve patient outcomes.

Dosimetric Study of Deep Learning-Guided ITV Prediction in Cone-beam CT for Lung Stereotactic Body Radiotherapy.

PurposeThe purpose of this study was to evaluate the accuracy of a lung stereotactic body radiotherapy (SBRT) treatment plan with the target of a newly predicted internal target volume (ITVpredict) and the feasibility of its clinical application. ITVpredict was automatically generated by our in-house deep learning model according to the cone-beam CT (CBCT) image database.MethodA retrospective study of 45 patients who underwent SBRT was involved, and Mask R-CNN based algorithm model helped to predict the internal target volume (ITV) using the CBCT image database. The geometric accuracy of ITVpredict was verified by the Dice Similarity Coefficient (DSC), 3D Motion Range (R3D), Relative Volume Index (RVI), and Hausdorff Distance (HD). The PTVpredict was generated by ITVpredict, which was registered and then projected on free-breath CT (FBCT) images. The PTVFBCT was margined from the GTV on FBCT images gross tumor volume on free-breath CT (GTVFBCT). Treatment plans with the target of Predict planning target volume on CBCT images (PTVpredict) and planning target volume on free-breath CT (PTVFBCT) were respectively re-established, and the dosimetric parameters included the ratio of the volume of patients receiving at least the prescribed dose to the volume of PTV (R100%), the ratio of the volume of patients receiving at least 50% of the prescribed dose to the volume of PTV in the Radiation Therapy Oncology Group (RTOG) 0813 Trial (R50%), Gradient Index (GI), and the maximum dose 2 cm from the PTV (D2cm), which were evaluated via Plan4DCT, plan which based on PTVpredict (Planpredict), and plan which based on PTVFBCT (PlanFBCT).ResultThe geometric results showed that there existed a good correlation between ITVpredict and ITV on the 4-dimensional CT [ITV4DCT; DSC= 0.83 ±0.18]. However, the average volume of ITVpredict was 10% less than that of ITV4DCT (p = 0.333). No significant difference in dose coverage was found in V100% for the ITV with 99.98 ± 0.04% in the ITV4DCT vs. 97.56 ± 4.71% in the ITVpredict (p = 0.162). Dosimetry parameters of PTV, including R100%, R50%, GI and D2cm showed no statistically significant difference between each plan (p > 0.05).ConclusionDosimetric parameters of Planpredict are clinically comparable to those of the original Plan4DCT. This study confirmed that the treatment plan based on ITVpredict produced by our model could automatically meet clinical requirements. Thus, for patients undergoing lung SBRT, the model has great potential for using CBCT images for ITV contouring which can be used in treatment planning.

Evaluation of the efficacy of CT-guided 3D template-assisted 125I seed implantation in the treatment of unresectable STS: a multicenter retrospective study

To observe the safety and efficacy of CT-guided 3D template-assisted radioactive 125I seed implantation in the treatment of unresectable advanced soft tissue sarcoma (STS). Sixty-two patients who underwent continuous 3D template-assisted radioactive 125I seed implantation for the treatment of unresectable advanced STS from August 2017 to August 2018 were selected from four tumor treatment centers for retrospective analysis. The postoperative adverse reactions and tumor response were recorded, and the postoperative complications were observed and treated at the same time. The overall survival (OS) rate was determined. All patients successfully completed 125I seed implantation. In practice, the median number of puncture needles used during the operation was 20, and the median number of 125I particles was 88. There were no statistical differences in the relative dosimetry parameters before and after the operation (P > 0.05). Tumor evaluation was performed 6 months after the operation. The effective rate was 61.3%, and the local control rate was 93.5%. As of March 2020, the 1-year survival rate was 85.2%, and the 2-year survival rate was 49.0%. The OS was 23 months. CT-guided 3D template-assisted 125I seed implantation for the treatment of unresectable STS has a high local control rate, thereby further prolonging the OS of patients with unresectable STS.