Spinal Cord Dose Research Articles

Retrospective Analysis of Dosimetric Comparison Between Intensity-Modulated Radiation Therapy and Volumetric-Modulated Arc Therapy in Patients With Esophageal Cancer.

Introduction Esophageal cancer is a significant global health concern, with high incidence and mortality rates, particularly in India, where it ranks among the top causes of cancer-related deaths. Radiotherapy plays a critical role in the treatment of advanced-stage esophageal cancer. This study aims to compare the dosimetric outcomes of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) to evaluate their efficacy and safety in managing mid-esophageal carcinoma. Materials and methods A retrospective study was carried out on thirty patients with middle-third esophageal cancer who received treatment at Rohilkhand Medical College and Hospital, Bareilly, India.The patients, aged between 50 and 70 years (mean age of 66.5 years), were in stages II to III of cancer according to the American Joint Committee on Cancer (AJCC) 2018 guidelines.All patients had histologically confirmed cases of moderately differentiated squamous cell carcinoma. The treatment procedure included immobilization using a thoracic mold, CT simulation with intravenous and oral contrast, and contouring of the gross tumor volume (GTV), clinical target volume (CTV), planning target volume (PTV), and organs at risk (OARs) following the Radiation Therapy Oncology Group (RTOG) 0436 protocol. VMAT planning was done using the Varian Eclipse™Treatment Planning System, while IMRT planning employed a seven-field non-coplanar beam setup. Comparative virtual IMRT plans were generated for these patients. Both VMAT and IMRT plans were evaluated based on dosimetric parameters for the PTV and OARs. Results Both VMAT and IMRT achieved sufficient PTV coverage, with no statistically significant differences in dosimetric parameters (dose to 99 % volume of PTV, dose to 95 %volume of PTV, maximum dose to PTV, minimum dose to PTV). VMAT demonstrated reduced lung and heart doses compared to IMRT; however, the observed differences were not statistically significant.There was a reduction in lung dose with VMAT when evaluating the dose-volume constraints: volume receiving 15 Gy dose (V15) by 11%, volume receiving 20 Gy dose (V20) by 20%, and volume receiving 25 Gy dose (V25) by 41%, though these differences were not statistically significant. Themeanmaximum spinal cord dose was significantly lower with VMAT (19.69 Gy) compared to IMRT (30.80 Gy, p=0.01). Heart dosimetry showed slight improvements with VMAT, particularly in volume receiving 30 Gy dose (V30), volume receiving 40 Gy dose (V40), and mean heart dose, though these differences were not statistically significant. Conclusion Both VMAT and IMRT provided similar PTV coverage. VMAT showed a reduction in spinal cord dose, which was statistically significant, and a trend toward lower lung and heart doses, though these differences were not statistically significant. VMAT appears to be an effective option for treating mid-esophageal carcinomawhile reducing exposure to critical organs.

Phase 1-2 Study of Prone Hypofractionated Accelerated Breast and Nodal Intensity Modulated Radiation Therapy.

In patients with breast cancer, prone radiation therapy (RT) has been shown to reduce heart and lung dose. Though prone positioning is routinely used for whole breast RT, its use when treating the regional lymph nodes is not widespread. In this phase 1/2 trial for stage IB-IIA breast cancer treated with lumpectomy or mastectomy, patients received 40.5 Gy in 15 fractions to the breast or chest wall and regional lymph nodes with an integrated tumor bed boost for lumpectomy patients. Primary endpoints were grade >2 acute toxicity and dosimetric feasibility. Secondary endpoints were the incidence of resimulation to improve dosimetry and late toxicity. Exploratory endpoints were local recurrence, disease-free survival, distant recurrence-free survival, and overall survival. From 2009 to 2016, 97 patients were enrolled (68% lumpectomy and 32% mastectomy), among which 92 were treated in the prone position. Five patients were resimulated and treated supine. Among the prone-treated patients, there were no acute toxicities greater than grade 2. A total of 92%, 98%, and 89% met a planning target volume tumor V48 Gy ≥98%, breast V40.5 Gy ≥95%, and nodal V38.5 Gy ≥95%, respectively. All met the heart V5 Gy <5%, contralateral lung V5 Gy <15%, spinal cord dose maximum (Dmax) ≤37.5 Gy, esophagus V30 Gy <50%, and Dmax ≤40.5 Gy. Ninety-eight percent met the ipsilateral lung V10 Gy. Brachial plexus Dmax <42 Gy was met in 74% with a mean increase of 1.61 Gy (SD, 1.96 Gy) over the target. At a median follow-up of 8 years, grade 2 to 3 late toxicity was 23% for prone patients. There were 2 local recurrences (2%) and no chest wall or nodal recurrences. The 8-year distant recurrence-free survival, disease-free survival, and overall survival were 88% (95% CI, 81%-95%), 86% (95% CI, 78%-95%), and 91% (95% CI, 84%-98%), respectively. Toxicity was low, and outcomes were excellent in this prospective trial of prone hypofractionated nodal RT.

Automatic Treatment Planning for Radiation Therapy: A Cross-Modality and Protocol Study

PurposeThis study investigates the applicability of 3D dose predictions from a model trained on one modality to a cross-modality automated planning workflow. Additionally, we explore the impact of integrating a multi-criteria optimizer (MCO) on adapting predictions to different clinical preferences. Methods and MaterialsUsing a previously created three-stage UNet in-house model trained on the 2020 AAPM OpenKBP challenge dataset (340 head and neck plans, all planned using 9-field static IMRT), we retrospectively generated dose predictions for 20 patients. These dose predictions were in turn used to generate deliverable IMRT, VMAT, and Tomotherapy plans using the fallback plan functionality in Raystation. The deliverable plans were evaluated against the dose predictions based on primary clinical goals. A new set of plans was also generated using MCO-based optimization with predicted dose values as constraints. Delivery QA was performed on a subset of the plans to assure clinical deliverability. ResultsThe mimicking approach accurately replicated the predicted dose distributions across different modalities, with slight deviations in spinal cord and external contour maximum doses. MCO optimization significantly reduced doses to OARs prioritized by our institution while maintaining target coverage. All tested plans met clinical deliverability standards, evidenced by a gamma analysis passing rate above 98%. ConclusionsOur findings show that a model trained only on IMRT plans can effectively contribute to planning across various modalities. Additionally, integrating predictions as constraints in an MCO-based workflow, rather than direct dose mimicking, enables a flexible, warm-start approach for treatment planning, though the benefit is reduced when the training set differs significantly from an institution's preference. Together, these approaches have the potential to significantly decrease plan turnaround time and quality variance, both at high resource medical centers that can train in-house models, and smaller centers that can adapt a model from another institution with minimal effort.

RAdiotherapy Dose Accumulation Routine (RADAR)-A Novel Dose Accumulation Script With Built-In Uncertainty

PurposeTo incorporate uncertainty into dose accumulation for reirradiation. MethodsThe RADAR script for the Eclipse treatment planning system (Varian Medical Systems, Palo Alto, CA) is described and the voxel-wise ellipsoid search algorithm is introduced as a means of incorporating uncertainty. RADAR is first demonstrated on a test patient reirradiated to the spine illustrating the effect of the uncertainty algorithm. A summary of initial evaluation testing by 11 users, each of whom ran a separate spine reirradiation case, follows. Finally, RADAR run times are reported for different conditions. ResultsIn the demonstration case in which a 3mm ellipsoid search was used, maximum RADAR 2 Gy equivalent (EQD2) accumulated spinal cord dose increased from 7244 cGy to 12689 cGy because the ellipsoid search pulled dose from closer to the adjacent target structure. When the ellipsoid search was restricted to voxels within the spinal cord, the maximum accumulated cord dose was reduced to 6523 cGy and did not exceed the sum of the maximum EQD2 spinal cord doses of the individual plans (6730 cGy). In the evaluation cases, the RADAR EQD2 maximum dose for the spinal cord increased an average of 31.6% with uncertainty applied compared to a conventional dose accumulation and decreased an average of 16.7% compared to a conventional dose accumulation when the uncertainty calculation was restricted to voxels within the spinal cord. RADAR run times depend on the number of plans being added and the type of uncertainty being used. ConclusionRADAR offers a novel way to directly account for uncertainty in dose accumulation by means of a voxel-wise ellipsoid search algorithm. EQD2 dose accumulation with and without dose discounts is also available.

Dosimetric Comparison between the HyperArc and Conventional VMAT in Cervical Spine Stereotactic Radiosurgery.

Background: This research aims to evaluate the usability of the HyperArc (HA) technique in stereotactic radiosurgery for cervical spine metastasis by comparing the dosimetry of the target and organs at risk, specifically the spinal cord, between HA and VMAT and conventional volumetric modulated arc therapy (VMAT). Methods: A RANDO® phantom and QFix EncompassTM and support system were used to simulate three target types (A, B, and C) based on RTOG0631 guidelines. Treatment plans included one VMAT and two HyperArc techniques with different SRS NTO values (100 and 250). Dosimetric parameters such as conformity index (CI), homogeneity index (HI), R50, and spinal cord sparing were analyzed. Gamma analysis was performed using portal dosimetry to validate the dose delivery accuracy. Results: HyperArc plans demonstrated higher conformity, sharper dose fall-off, and improved quality assurance (QA) results compared to VMAT plans. HA with SRS NTO 250 showed even better results in terms of conformity, dose fall-off, and spinal cord dose reduction (V10 and Dmax) compared to HA with SRS NTO 100. Although the mean gamma passing rates were slightly lower, all plans achieved rates above 95%. Conclusion: The findings suggest that HA provides superior dosimetric benefits over VMAT and could be effectively utilized for cervical spine radiation therapy.

Pencil Beam Scanning Proton Therapy as Single Vocal Cord Irradiation for Early-Stage Glottic Cancer

PurposeSingle vocal cord irradiation (SVCI) is a promising technique to maintain excellent oncologic control and potentially improve upon toxicities for treatment of early-stage glottic squamous cell carcinomas. We sought to investigate whether pencil beam scanning (PBS) proton therapy could improve upon the already favorable dose gradients demonstrated with volumetric modulated arc therapy (VMAT) SVCI. Patients and MethodsA 64-year-old gentleman was treated in our department with 6X-flattening filter-free VMAT SVCI to 58.08 Gy in 16 fractions for a T1a well-differentiated squamous cell carcinoma of the left true vocal cord and tolerated it well with good local control. Comparative PBS plans were created in Raystation for the Varian ProBeam with clinical target volume (CTVs) generated to mimic the prescription target volume extent of the VMAT planning target volumes when accounting for PBS plan robustness (±3 mm translational shifts, 3.5% density perturbation). A 3-field single-field optimization plan was selected as dosimetrically preferable. Dosimetric variables were compared. ResultsSeveral organs at risk doses improved with PBS, including the maximum and mean dose to ipsilateral carotids, maximum and mean dose to contralateral carotid, maximum dose to the spinal cord, maximum and mean dose to inferior constrictor/cricopharyngeus, maximum and mean dose to the uninvolved vocal cord, and mean dose to the thyroid gland. There are tradeoffs in skin dose depending on location relative to the target—with the highest and lowest isodoses extending more into the skin with the VMAT plan but with the moderate isodose lines covering a wider area with the PBS plan, but we deemed it tolerable regardless. ConclusionSVCI is a promising strategy for maintaining the oncologic effectiveness of whole-larynx photon radiation while potentially improving upon the historic toxicity profile. The favorable dose distribution with PBS with respect to organs at risk dosimetry for PBS may allow for further improvements upon VMAT SVCI strategies. Clinical implementation of PBS SVCI may be considered.

Feasibility of Left Anterior Descending Coronary Artery Sparing Radiation Therapy for Locally Advanced Lung Cancer

Efforts to mitigate radiotherapy (RT) associated cardiotoxicity have focused on constraining mean heart dose (MHD). However, recent studies have shown greater predictive power with cardiac substructure dose metrics such as the left anterior descending (LAD) coronary artery volume (V) receiving 15Gy (V15Gy) ≥10%. Herein, we investigated the feasibility of LAD radiation sparing in contemporary IMRT/VMAT lung cancer plans. Single institution retrospective analysis of 54 locally advanced lung cancer patients treated with thoracic RT between February 2018-August 2021. After excluding 33 (5=non-IMRT/VMAT or intentionally LAD-optimized; 28=LAD V15Gy<10%), 21 plans with LAD V15Gy ≥10% were identified for LAD re-optimization with intent to meet LAD V15Gy <10% while maintaining meeting organ-at-risk (OAR) metrics and target coverage with original plan parameters. Dosimetric variables were compared using paired t tests. Most (57.1%, 12/21) were treated with definitive RT, 8/21 (38.1%) with post-operative RT, and one with neoadjuvant RT. The median prescribed RT dose was 60Gy (range 50.4-66Gy) in 30 fractions (range 28-33). LAD re-optimized plans (vs original) led to significant reductions in mean LAD V15Gy (39.4% ±13.9% vs 9.4% ±13.0%; p<0.001) and mean LAD dose (12.9Gy ± 4.6Gy vs 7.6Gy ±2.8Gy; p<0.001). Most (85.7%; 18/21) LAD re-optimized plans achieved LAD V15Gy <10%. There were no statistically significant differences in overall lung, esophageal, or spinal cord dose metrics. Only one re-optimization (1/21) exceeded an OAR constraint that was initially met in the original plan. To our knowledge, this is the first report describing the feasibility of LAD-optimized lung cancer RT planning using the newly identified LAD V15 Gy constraint. We observed that LAD V15Gy <10% is achievable in more than 85% of plans initially exceeding this constraint, with minimal dosimetric tradeoffs. Our results support the feasibility of routine incorporation of the LAD as an OAR in modern thoracic IMRT/VMAT planning.

Dosimetric Impact of Prescription Point Placement in Heterogeneous Medium for Conformal Radiotherapy Dose Calculation with Various Algorithms.

The aim of the study is to compare the accuracy of dose calculation for different dose calculation algorithms with different prescription points (air, tissue, air-tissue interface in carcinoma lung patients and bone, tissue, and bone-tissue interface in carcinoma buccal Mucosa tumors). Forty-one patients with carcinoma lung and buccal mucosa were retrospectively selected for this study. A three-dimensional conformal radiotherapy reference plan was created using the prescription point in the tissue with Monte Carlo (MC) algorithms for both the groups of patients. The reference plan was modified by changing the prescription point and algorithms in the tissue, air, air-tissue interface for lung patients and tissue, bone, and bone-tissue interface for buccal mucosa patients. The dose received by the target volume and other organs at risk (OAR) structures was compared. To find out the statistical difference between different prescription points and algorithms, the statistical tests were performed with repeated measures ANOVA. The target volume receiving 95% dose coverage in lung patients decreased to -3.08%, -5.75%, and -1.87% in the dose prescription point at the air-tissue interface with the dose calculation algorithms like MC, collapsed cone (CC), and pencil beam (PB), respectively, compared to that of the MC tissue. Spinal cord dose was increased in the CC and PB algorithms in all prescription points in patients with lung and buccal mucosa. OAR dose calculated by PB in all prescription points showed a significant deviation compared to MC tissue prescription point. This study will help demonstrate the accuracy of dose calculation for the different dose prescription points with the different treatment algorithms in radiotherapy treatment planning.

Phase II Clinical Trial of Second Course of Stereotactic Body Radiotherapy for Spinal Metastases

Purpose: The optimal method for the second course of stereotactic body radiotherapy (SBRT) for spinal metastases remains poorly established. This single-center, single-arm, phase II trial was conducted to propose a safe and effective salvage spine SBRT. Methods: The patients initially treated with SBRT for spine-targeted protocol treatment, or for areas adjacent to the spine, were enrolled. The second SBRT dose was 30 Gy delivered in five fractions; the spinal cord dose constraint was 15.5 Gy at the maximum point dose. The brachial or lumbosacral plexuses were dose-constrained to &lt;30 Gy if the boundary between the nerves and tumors was detected. The primary endpoint was dose-limiting toxicity (DLT) (grade ≥ 3 severe radiation-related toxicity) within a year after the second SBRT. Results: The second SBRT was administered to the same spinal level in 12 patients and to an adjacent spinal level in 8 patients. SBRT2 was performed for 14 painful lesions, 10 MESCC, and 6 oligometastases, with some lesions having multiple indications. The median interval between SBRT sessions was 21 months (range: 6–51 months). The median follow-up duration was 14 months. No radiation myelopathy or local failure was reported during the follow-up period. DLT was confirmed in two patients (10%) within a year, both of whom developed grade 3 lumbosacral plexopathy. These two patients received SBRT twice to the S1–2 and S1–5 vertebrae, respectively, and both experienced paralysis of the tibialis anterior muscle (L5 level). Grade 3 late adverse effects (including lumbosacral plexopathy and vertebral compression fracture) were observed in 25% of the patients throughout the entire follow-up period. Conclusions: The second spine SBRT achieved good local control without causing myelopathy. However, one-quarter of the patients experienced grade 3 late adverse effects, suggesting that the treatment protocol carries a risk of toxicity.

Dosimetric comparison of proton therapy and CyberKnife in stereotactic body radiation therapy for liver cancers

Stereotactic body radiation therapy (SBRT) has been increasingly used for the ablation of liver tumours. CyberKnife and proton beam therapy (PBT) are two advanced treatment technologies suitable to deliver SBRT with high dose conformity and steep dose gradients. However, there is very limited data comparing the dosimetric characteristics of CyberKnife to PBT for liver SBRT. PBT and CyberKnife plans were retrospectively generated using 4DCT datasets of ten patients who were previously treated for hepatocellular carcinoma (HCC, N = 5) and liver metastasis (N = 5). Dose volume histogram data was assessed and compared against selected criteria; given a dose prescription of 54 Gy in 3 fractions for liver metastases and 45 Gy in 3 fractions for HCC, with previously published consensus-based normal tissue dose constraints. Comparison of evaluation parameters showed a statistically significant difference for target volume coverage and liver, lungs and spinal cord (p < 0.05) dose, while chest wall and skin did not indicate a significant difference between the two modalities. A number of optimal normal tissue constraints was violated by both the CyberKnife and proton plans for the same patients due to proximity of tumour to chest wall. PBT resulted in greater organ sparing, the extent of which was mainly dependent on tumour location. Tumours located on the liver periphery experienced the largest increase in organ sparing. Organ sparing for CyberKnife was comparable with PBT for small target volumes.

Dose-Painting Proton Radiotherapy Guided by Functional MRI in Non-enhancing High-Grade Gliomas

AimsThis study aimed to demonstrate the feasibility and evaluate the dosimetric effect and clinical impact of dose-painting proton radiotherapy (PRT) guided by functional MRI in non-enhancing high-grade gliomas (NE-HGGs). Materials and methodsThe 3D-ASL and T2 FLAIR MR images of ten patients with NE-HGGs before radiotherapy were studied retrospectively. The hyperintensity on T2 FLAIR was used to generate the planning target volume (PTV), and the high-perfusion volume on 3D-ASL (PTV-ASL) was used to generate the simultaneous integrated boost (SIB) volume. Each patient received pencil beam scanning PRT and photon intensity-modulated radiotherapy (IMRT). There were five plans in each modality: (1) Uniform plans (IMRT60 vs. PRT60): 60Gy in 30 fractions to the PTV. (2)–(5) SIB plans (IMRT72, 84, 96, 108 vs. PRT72, 84, 96, 108): Uniform plan plus additional dose boost to PTV-ASL in 30 fractions to 72, 84, 96, 108 Gy. The dosimetric differences between various plans were compared. The clinical effects of target volume and organs at risk (OARs) were assessed using biological models for both tumor control probability (TCP) and normal tissue complication probability (NTCP). ResultsCompared with the IMRT plan, the D2 and D50 of the PRT plans with the same prescription dose increased by 1.27–4.12% and 0.64–2.01%, respectively; the R30 decreased by > 32%; the dose of brainstem and chiasma decreased by > 27% and >32%; and the dose of normal brain tissue (Br-PTV), optic nerves, eyeballs, lens, cochlea, spinal cord, and hippocampus decreased by > 50% (P < 0.05). The maximum necessary dose was 96GyE to achieve >98% TCP for PRT, and it was 84Gy to achieve >91% TCP for IMRT. The average NTCP of Br-PTV was 1.30% and 1.90% for PRT and IMRT at the maximum dose escalation, respectively. The NTCP values of the remaining OARs approached zero in all PRT plans. ConclusionThe functional MRI-guided dose escalation using PRT is feasible while sparing the OARs constraints and demonstrates a potential clinical benefit by improving TCP with no or minimal increase in NCTP for tissues outside the PTV. This retrospective study suggested that the use of PRT-based SIB guided by functional MRI may represent a strategy to provide benefits for patients with NE-HGGs.

Impact of Radiation on Dysphagia-Related Structures: A Dosimetric and Clinical Comparative Analysis of Three-Dimensional Conformal Radiotherapy (3D-CRT) and Intensity-Modulated Radiation Therapy (IMRT) Techniques in Patients With Head and Neck Cancer.

Introduction Head and neck squamous cell carcinoma (HNSCC)is a significant health concern in India, with around one million new cases annually. The prevalence of HNSCC is notably high in Asia, especially in India, due to habitslike tobacco chewing, betel nut usage, and alcohol consumption. Treatment typically involves a combination of surgery, radiation, chemotherapy, and biological therapy, aiming for tumor control while preserving function and quality of life. However, survivors often face long-term side effectslike difficulty swallowing, leading to complicationssuch as aspiration pneumonia. Intensity-modulated radiotherapy (IMRT) has shown promise in improving outcomes by sparing critical swallowing structures. Efforts to minimize radiation-related dysphagia are crucial for enhancing patients' quality of life post-treatment. Our study focuses on examining dosimetric parameters associated with dysphagia aspiration, alongside evaluating dysphagia grades in both treatment groups using the RTOGscale. Material and methods Patients with histologically confirmed non-metastatic head and neck carcinomas were included in our study in November 2018-April 2020. A total of 56 patients were taken into our study with 28 in each arm. They underwent radical radiotherapy (RT) with a total dose of 66-70 Gy, with or without concurrent chemotherapy, meeting specific inclusion criteria and excluding those receiving reirradiation or with distant metastasis. Patients were divided into two groups: Group I received three-dimensional conformal radiotherapy (3D-CRT), and Group II received IMRT. Treatment planning involved immobilization, CT imaging, delineation of target volumes and organs at risk, and contouring of swallowing structures. Dose-volume histogram parameters (mean dose, maximum dose, V30, V70, V80, D50, and D80) were used to assess mean dose to swallowing structures outside the planning target volume (PTV), with a mean dose constraint of 50 Gy. Dysphagia was evaluated using the RTOGcriteria at baseline, during treatment, and six months post-treatment. Statistical analysis was performed using SPSS, with significance set at p < 0.05. Results In our study, the mean age at presentation differed slightly between the IMRT and 3D-CRT arms: 58 years versus 55 years, respectively. A higher proportion of patients in both arms experienced symptoms for three to six months, with 53.6% in 3D-CRT and 42.9% in IMRT. Stage distribution varied, with IV being most common in 3D-CRT and stage II in IMRT. Approximately 56% of patients in both groups had a history of smoking. Significant differences were observed in spinal cord dose between 3DCRT and IMRT techniques (p < 0.001). Similarly, a significant difference was found in the mean dose received by dysphagia aspiration-related structures (DARSs) between the 3D-CRT and IMRT arms (p = 0.04). Patients in the IMRT arm exhibited superior dysphagia grades compared to those in the 3D-CRT arm, with statistical significance observed in the third month (p = 0.008) and sixth month (p = 0.048). Conclusion Our study found a notable decrease in the mean DARS dose and reduced dysphagia severity at three and six months in the IMRT group compared to the 3D-CRT group. However, due to the diverse study population, establishing a definitive correlation between the DARS dose and dysphagia severity was challenging. Future large-scale studies are needed to validate these findings for improved preservation of DARS structures.

Relative biological effectiveness of oxygen ion beams in the rat spinal cord: Dependence on linear energy transfer and dose and comparison with model predictions

Background and purposeIon beams exhibit an increased relative biological effectiveness (RBE) with respect to photons. This study determined the RBE of oxygen ion beams as a function of linear energy transfer (LET) and dose in the rat spinal cord. Materials and methodsThe spinal cord of rats was irradiated at four different positions of a 6 cm spread-out Bragg-peak (LET: 26, 66, 98 and 141 keV/µm) using increasing levels of single and split oxygen ion doses. Dose-response curves were established for the endpoint paresis grade II and based on ED50 (dose at 50 % effect probability), the RBE was determined and compared to model predictions. ResultsWhen LET increased from 26 to 98 keV/µm, ED50 decreased from 17.2 ± 0.3 Gy to 13.5 ± 0.4 Gy for single and from 21.7 ± 0.4 Gy to 15.5 ± 0.5 Gy for split doses, however, at 141 keV/µm, ED50 rose again to 15.8 ± 0.4 Gy and 17.2 ± 0.4 Gy, respectively. As a result, the RBE increased from 1.43 ± 0.05 to 1.82 ± 0.08 (single dose) and from 1.58 ± 0.04 to 2.21 ± 0.08 (split dose), respectively, before declining again to 1.56 ± 0.06 for single and 1.99 ± 0.06 for split doses at the highest LET. Deviations from RBE-predictions were model-dependent. ConclusionThis study established first RBE data for the late reacting central nervous system after single and split doses of oxygen ions. The data was used to validate the RBE-dependence on LET and dose of three RBE-models. This study extends the existing data base for protons, helium and carbon ions and provides important information for future patient treatments with oxygen ions.

A Comparative Analysis of Implant-sparing Plan Versus Conventional Plans Utilizing Helical Tomotherapy in Breast Cancer Patients Undergoing Breast Reconstruction.

To compare implant sparing irradiation with conventional radiotherapy (RT) using helical (H) and TomoDirect (TD) techniques in breast cancer patients undergoing immediate breast reconstruction (IBR). The dosimetric parameters of 40 patients with retropectoral implants receiving 50.4 Gy delivered in 28 fractions were analyzed. Three plans were created: H plan using conventional planning target volume (PTV) that included the chest wall, skin, and implant; TD plan using conventional PTV; and Hs plan using implant-sparing PTV. The H, TD, and Hs plans were compared for PTV doses, organ-at-risk (OAR) doses, and treatment times. Dose distribution in the Hs plan was less homogeneous and uniform than that in the H and TD plans. The TD plan had lower lung, heart, contralateral breast, spinal cord, liver, and esophagus doses than the Hs plan. Compared to the Hs plan, the H plan had lower lung volume receiving 5Gy (V5) (39.1±3.9 vs. 41.2±3.9 Gy; p<0.001), higher V20 (12.3±1.3 vs. 11.5±2.6 Gy; p=0.02), and higher V30 (7.5±1.6 vs. 4.4±1.7 Gy; p<0.001). H plan outperformed Hs plan in heart dosimetric parameters except V20. The Hs plan had significantly lower mean implant doses (43.4±2.1 Gy) than the H plan (51.4±0.5 Gy; p<0.001) and the TD plan (51.9±0.6 Gy; p<0.001). Implementing an implant sparing technique for silicone dose reduction decreases lung doses. Conventional H and TD plans outperform the implant sparing helical plan dosimetrically. Because capsular contracture during RT is unpredictable, long-term clinical outcomes are required to determine whether silicon should be spared.

Understanding the Radiation Dose Variability in Nasopharyngeal Cancer: An Organs-at-Risk Approach.

Objective This study aims to thoroughly assess the radiation dose distributionto critical organs in patients with nasopharyngeal carcinoma, focusing on the correlation between the radiation dosages for the various organs at risk (OARs) in nasopharyngeal cancer patients. Methods We meticulously analysed a dataset comprising 38 nasopharyngeal carcinoma patients, focusing on radiation dosages measured in Gray (Gy) and volumetric data in cubic centimetres (cc) of critical organs, including the lens, brainstem, spinal cord, optic nerve, optic chiasm, and cochlea. A detailed exploratory data analysis approach encompassed univariate, bivariate, and multivariate techniques. Results Our analysis revealed several key findings. The mean and median values across various dose measurements were closely aligned, indicating symmetrical distributions with minimal skewness. The histograms further corroborated this, showing evenly distributed dose values across different anatomical regions. The correlation matrix highlighted varying degrees of interrelationships between the doses, with some showing strong correlations while others exhibited minimal or no correlation. The 3D scatter plot provided a view of the multi-dimensional dose relationships, with a specific focus on the spinal cord, lens, and brainstem doses. The bivariate scatter plotsrevealed symmetrical distributions between the right and left lens doses and more complex relationships involving the brainstem and spinal cord, illustrating the intricacies of dose distribution in radiation therapy. Conclusion Our findings reveal distinct radiation exposure patterns to OARs of nasopharyngeal carcinoma. This research emphasises the need for tailored radiation therapy planning to achieve optimal clinical outcomes while safeguarding vital organs.

Proton therapy (PT) combined with concurrent chemotherapy for locally advanced non-small cell lung cancer with negative driver genes

PurposeTo discuss the optimal treatment modality for inoperable locally advanced Non-Small Cell Lung Cancer patients with poor physical status, impaired cardio-pulmonary function, and negative driver genes, and provide clinical evidence.Materials and methodsRetrospective analysis of 62 cases of locally advanced non-small cell lung cancer patients with negative driver genes treated at Tsukuba University Hospital(Japan) and Qingdao University Affiliated Hospital(China).The former received proton therapy with concurrent chemotherapy, referred to as the proton group, with 25 cases included; while the latter underwent X-ray therapy with concurrent chemoradiotherapy followed by 1 year of sequential immunomodulatory maintenance therapy, referred to as the X-ray group, with 37 cases included.The treatment response and adverse reactions were assessed using RECIST v1.1 criteria and CTCAE v3.0, and radiotherapy planning and evaluation of organs at risk were performed using the CB-CHOP method.All data were subjected to statistical analysis using GraphPad Prism v9.0, with a T-test using P < 0.05 considered statistically significant.Results(1)Target dose distribution: compared to the X-ray group, the proton group exhibited smaller CTV and field sizes, with a more pronounced bragg peak.(2)Organs at risk dose: When comparing the proton group to the X-ray group, lung doses (V5, V20, MLD) and heart doses (V40, Dmax) were lower, with statistical significance (P < 0.05), while spinal cord and esophagus doses showed no significant differences between the two groups (P > 0.05).(3)Treatment-related toxicities: The incidence of grade 3 or higher adverse events in the proton group and X-ray group was 28.6% and 4.2%, respectively, with a statistically significant difference (P < 0.05). In terms of the types of adverse events, the proton group primarily experienced esophagitis and pneumonia, while the X-ray group primarily experienced pneumonia, esophagitis, and myocarditis. Both groups did not experience radiation myelitis or esophagotracheal fistula.(4)Efficacy evaluation: The RR in the proton group and X-ray group was 68.1% and 70.2%, respectively (P > 0.05), and the DCR was 92.2% and 86.4%, respectively (P > 0.05), indicating no significant difference in short-term efficacy between the two treatment modalities.(5)Survival status: The PFS in the proton group and X-ray group was 31.6 ± 3.5 months (95% CI: 24.7 ~ 38.5) and 24.9 ± 1.55 months (95% CI: 21.9 ~ 27.9), respectively (P > 0.05), while the OS was 51.6 ± 4.62 months (95% CI: 42.5 ~ 60.7) and 33.1 ± 1.99 months (95% CI: 29.2 ~ 37.1), respectively (P < 0.05).According to the annual-specific analysis, the PFS rates for the first to third years in both groups were as follows: 100%, 56.1% and 32.5% for the proton group vs. 100%, 54.3% and 26.3% for the X-ray group. No statistical differences were observed at each time point (P > 0.05).The OS rates for the first to third years in both groups were as follows: 100%, 88.2%, 76.4% for the proton group vs. 100%, 91.4%, 46.3% for the X-ray group. There was no significant difference in the first to second years (P > 0.05), but the third year showed a significant difference (P < 0.05). Survival curve graphs also depicted a similar trend.ConclusionThere were no significant statistical differences observed between the two groups in terms of PFS and OS within the first two years. However, the proton group demonstrated a clear advantage over the X-ray group in terms of adverse reactions and OS in the third year. This suggests a more suitable treatment modality and clinical evidence for populations with frail health, compromised cardio-pulmonary function, post-COVID-19 sequelae, and underlying comorbidities.

CTNI-01. LONG-TERM RESULTS FROM A PHASE 1 TRIAL OF SPINE SBRT IN INOPERABLE PATIENTS WITH CORD COMPRESSION

Abstract PURPOSE/OBJECTIVE We seek to establish the feasibility of using spine stereotactic radiosurgery (SSRS) allowing for spinal cord dose constraint relaxation as the primary management of metastatic epidural spinal cord compression (MESCC) in inoperable patients monitoring for radiation myelopathy (RM) and radiographic local control (LC). MATERIAL/METHODS Patients with radiation naïve MESCC were enrolled on this prospective Phase 1 trial. Single fraction SSRS was delivered to a dose of 18 or 24 Gy. Spinal cord constraint relaxation was performed in sequential cohorts from an initial allowable Dmax cohort of 10 Gy up to 16 Gy only if tumor progression occurred without RM. RESULTS Thirty two patients enrolled on the trial of which 4, 12, 8 and 8 were in the 10 Gy, 12 Gy, 14 Gy and 16 Gy cord Dmax cohorts, respectively. At baseline, there were 10 sites with MESCC Grade 1B, 10 sites with Grade 1C, 9 sites with Grade 2, 2 sites with Grade 1A, and 1 site with Grade 3 disease. Of the 28 evaluable patients, the median overall survival was 32.3 months (range 5.8-122.6 mo). The 1-year and 5-year LC was 84.5% and 79.5%. The 2-year LC did not statistically differ between the 14-16 Gy cord Dmax combined cohorts and the 10-12 Gy cord Dmax combined cohorts (92.9% vs. 62.9%, p = 0.15). With a median clinical follow-up of 22.7 months (range 3-122.3 mo), there were no cases of RM including in the 13 patients who survived at least 3 years. In the cohort receiving a cord Dmax of 16 Gy, there were no cases of RM with a median follow-up of 18.6 mo (range 9.0-97.1 mo). CONCLUSION With long-term follow-up, these data demonstrate that SSRS is a safe and effective tool in patients with MESCC. Cord constraint relaxation may be considered in inoperable patients with MESCC.

Pretreatment Spinal Column Dose Estimation for Spinal SBRT Using Octavius Four-dimensional Phantom and Dose-volume Histograms Four-dimensional Feature: A Dosimetric Analysis.

The aim of this study was to estimate the spinal column dose for spinal Stereotactic body radiation therapy (SBRT) before patient treatment using the PTW dosimetry Octavius dose-volume histograms (DVH) four-dimensional (4D) feature. Twenty-three patients were included in the study, and a volumetric modulated arc therapy plan with 6MV flattening filter-free (6FFF) was generated for each patient in the Eclipse planning system using the Anisotropic Analytical Algorithm (AAA) algorithm (Varian Medical Systems, Palo Alto, CA) for the TrueBeam STx LINAC machine. The Octavius 4D system was used to estimate the spinal cord dose by delivering the plans to the 4D phantom. The measured dose was compared with the Eclipse treatment planning system (TPS) (Varian Medical Systems, Palo Alto, CA) dose. The spinal cord max and mean doses estimated using Varisoft DVH 4D are in close agreement with the TPS calculated max and mean doses. The deviation between measured dose and TPS dose is ±5% for the spinal max dose, and the deviation between measured dose and TPS dose is ± 3% for the spinal mean dose. The study demonstrates that the PTW Octavius 4D phantom and DVH 4D feature can be used as a tool to estimate spinal cord dose before the treatment in spinal SBRT plans. The system provides an independent dose measurement that is comparable to the TPS dose. The close agreement between measured and calculated doses validates the use of this system as a critical organ dose verification tool.

Predictive Factors for Response to Adaptive Therapy in Thoracic Stereotactic Ablative Radiotherapy

Online adaptive radiotherapy (ART) has been increasingly adopted for clinical use. However, ART for thoracic malignancies has lagged beyond its implementation for other primary cancers. Efforts are needed to identify optimal patients for ART by finding trends for changes in tumor position, shape, or proximity to OARs are needed. We hypothesized tumor size, histology, pre-RT SUV value, and intrathoracic location could influence how tumors change during cone beam computed tomography (CBCT)-based ART Stereotactic Ablative Radiotherapy (SAbR) for thoracic disease. Data was collected from a prospective registry of patients who received CBCT-ART and SAbR for primary and secondary lung tumors. Dosimetry data was obtained from the simulation planning and the daily adaptive workflow. Central lung tumors were defined as those located within 2 cm of the bronchial tree. Plans were either delivered as per simulation or through the online adaptive workflow delivery (AD). Change in planning tumor volumes (PTV) were calculated between initial and final fractions (ΔPTV). A total of 42 patients with a median age of 67 (range 17-90) and median 8.3 months follow up, treated between June 2021 and December 2022 were included. Most patients had NSCLC or presumed NSCLC (73.85%, 31/42), and most lesions were peripheral (61.9%, 26/42) versus central (31%, 13/42) or apical (7.1%, 3/42). Mean dose and median fractions were 52.5 Gy (SD 8.07) and 5 (range 3-5) while median initial (i) PTV was 31.75 cm3 (IQR 42.3 cm3). On average, ΔPTV decreased by 4.9% (SD 21) and volume shrunk by 5 cm3 (SD 14.5). AD improved per fraction PTV coverage and conformality while esophageal, cardiac, and spinal cord dose were significantly decreased (all p < 0.05), and most fractions were delivered with AD (73.4%, 138/188). AD was aborted most often for small iPTVs. ΔPTV grew >10% for two lesions though their iPTV were < 10 cm3. 12/42 ΔPTV were >10% smaller by the end of RT and corresponded to larger iPTVs. Age, lung primary, metastatic disease, smoking status, and tumor location were not predictive for >10% decrease in ΔPTV. Among 24 biopsy-proven NSCLC ΔPTV was >10% smaller in 6/12 patients (50%) with adenocarcinoma and only in 2/12 (16.7%) with SCC, although this was not significant on χ2 testing (p = 0.08). There were no differences in local, regional, distant failure or death comparing those with a ΔPTV of >10% vs <10% (all p > 0.1). Comparing pre-treatment PET SUV and tumor response, lower SUVs appear to be associated with more PTV shrinkage, with no significant PTV change plateauing at SUV 20. However, this analysis was limited by the number of patients with high SUV values. CBCT-ART SAbR is associated with improved PTV coverage, target conformality, and reduced OAR dose. Large iPTV and adenocarcinomas were more likely to decrease >10%. High metabolic activity appeared predictive for a lack of significant ΔPTV. Further clinical and radiographic features should be explored to predict response to ART.

Dosimetric Analysis of CBCT-Based Weekly Online Adaptive Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer

Anatomic and geometric changes are common during a radiotherapy course amongst patients receiving conventional fractionated radiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC). These changes may cause significant deviation from initial reference plan resulting in over-treatment of normal tissue or under-coverage of the target. Cone-beam computed tomography (CBCT)-based online adaptive radiotherapy (ART) platforms allow for response to these changes and is being increasingly used in the clinic though less so for intrathoracic disease. We hypothesized weekly CBCT-ART would improve target coverage and decrease dose to organs at risk (OAR) in patients with LA-NSCLC. Data was collected from a prospective registry of 23 LA-NSCLC patients treated to 60 Gy in 30 fractions with CBCT-ART between June 2021 and December 2022. For weekly ART (Wk-ART), online plan adaptation started on week two. The adapted plan was then used to treat patients with image guidance until the next ART. For comparison, doses were recalculated with the initial reference plan on the SCT with updated contours to derive non-adapted (non-ART) dosimetry for each week. The final dosimetric parameters were obtained by averaging weekly coverage (ITV, PTV) and critical OAR (Lung, esophagus, heart, spinal cord) doses for non-ART and weekly ART treatments respectively for each patient. Paired student t-test was performed to compare the dosimetric parameters between non-ART and Wk-ART. We observed an average 29% ± 19% (median: 26%) reduction in ITV volume through the radiotherapy course, with 48% (11/23) of patients showing >30% reduction. Most significant volume reductions (16%) were observed between the third and fourth adaptation. Weekly ART showed significant (p<1×10-3) improvements in ITV and PTV coverage, and showed improved clinically relevant lung, esophageal, cardiac, and lung dosimetry (Table 1), especially in the later stages of treatment when the tumor showed significant shrinkage. The average time from contour review to quality assurance completed is 8.5±1.2 min. CBCT-ART provides robust ART plan quality and efficient workflow. There are significant improvements in target coverage and OAR sparing in LA-NSCLC treated with weekly CBCT-ART and these are driven by the significant volume reduction of the ITV throughout treatment course.