Lung Dose Research Articles

A novel predictor for dosimetry data of lung and the radiation pneumonitis incidence prior to SBRT in lung cancer patients

Normal tissue complication probability (NTCP) models for radiation pneumonitis (RP) in lung cancer patients with stereotactic body radiation therapy (SBRT), which based on dosimetric data from treatment planning, are limited to patients who have already received radiation therapy (RT). This study aims to identify a novel predictive factor for lung dose distribution and RP probability before devising actionable SBRT plans for lung cancer patients. A comprehensive correlation analysis was performed on the clinical and dose parameters of lung cancer patients who underwent SBRT. Linear regression models were utilized to analyze the dosimetric data of lungs. The performance of the regression models was evaluated using mean squared error (MSE) and the coefficient of determination (R2). Correlational analysis revealed that most clinical data exhibited weak correlations with dosimetric data. However, nearly all dosimetric variables showed "strong" or "very strong" correlations with each other, particularly concerning the mean dose of the ipsilateral lung (MI) and the other dosimetric parameters. Further study verified that the lung tumor ratio (LTR) was a significant predictor for MI, which could predict the incidence of RP. As a result, LTR can predict the probability of RP without the need to design an elaborate treatment plan. This study, as the first to offer a comprehensive correlation analysis of dose parameters, explored the specific relationships among them. Significantly, it identified LTR as a novel predictor for both dose parameters and the incidence of RP, without the need to design an elaborate treatment plan.

Clinical Factors Influencing the Radiation Dose of Circulating Immune Cells during Radiotherapy for Small Cell Lung Cancer.

Small cell lung cancer (SCLC) has garnered significant attention due to its high malignancy, propensity for distant metastasis, and poor prognosis. Radiotherapy remains the cornerstone of treatment for limited-stage small cell lung cancer (LS-SCLC). However, outcomes with radiotherapy alone or in combination with chemotherapy remain suboptimal. Radiotherapy can induce lymphopenia by directly irradiating hematopoietic organs or destroying mature circulating lymphocytes, leading to immunosuppression and consequently diminishing therapeutic efficacy. The estimated dose of radiation to immune cells (EDRIC) model integrates factors such as hemodynamics, lymphocyte radiosensitivity, and proliferation capacity. This study employs the EDRIC model with enhancements to calculate the circulating immune cell radiation dose. By utilizing the EDRIC methodology, the study explores the correlation between EDRIC and tumor target size, average lung dose, average heart dose, clinical features, and peripheral blood lymphocytopenia during radiotherapy for LS-SCLC, aiming to inform personalized patient treatment strategies. This study analyzed data from 64 LS-SCLC patients who met the inclusion criteria at the General Hospital of Ningxia Medical University from January 2023 to January 2024, all of whom received radical thoracic conventional fractionated radiotherapy. Lymphocyte counts were recorded at the following points: before radiotherapy, at the lowest observed value during radiotherapy, at the end of radiotherapy, and one-month post-radiotherapy. Dosimetric data, including average lung, heart, and body doses, were extracted from the treatment planning system, and the circulating EDRIC was calculated using this model. The relationship between EDRIC values and therapeutic outcomes was analyzed. In LS-SCLC, the EDRIC model effectively predicts lymphocyte count reduction, correlating with planning target volume (PTV; cm3), TNM stage, and the percentage of target lesion shrinkage. Post-radiotherapy, there was a significant decrease in peripheral blood lymphocyte counts, with greater EDRIC values indicating more pronounced lymphocyte reduction.

MRI-based ventilation and perfusion imaging to predict radiation-induced pneumonitis in lung tumor patients at a 0.35 T MR-Linac

Background and purpose:Radiation-induced pneumonitis (RP), diagnosed 6–12 weeks after treatment, is a complication of lung tumor radiotherapy. So far, clinical and dosimetric parameters have not been reliable in predicting RP. We propose using non-contrast enhanced magnetic resonance imaging (MRI) based functional parameters acquired over the treatment course for patient stratification for improved follow-up. Materials and methods:23 lung tumor patients received MR-guided hypofractionated stereotactic body radiation therapy at a 0.35T MR-Linac. Ventilation- and perfusion-maps were generated from 2D-cine MRI-scans acquired after the first and last treatment fraction (Fx) using non-uniform Fourier decomposition. The relative differences in ventilation and perfusion between last and first Fx in three regions (planning target volume (PTV), lung volume receiving more than 20Gy (V20) excluding PTV, whole tumor-bearing lung excluding PTV) and three dosimetric parameters (mean lung dose, V20, mean dose to the gross tumor volume) were investigated. Univariate receiver operating characteristic curve - area under the curve (ROC–AUC) analysis was performed (endpoint RP grade≥1) using 5000 bootstrapping samples. Differences between RP and non-RP patients were tested for statistical significance with the non-parametric Mann–Whitney U test (α=0.05). Results:14/23 patients developed RP of grade≥1 within 3 months. The dosimetric parameters showed no significant differences between RP and non-RP patients. In contrast, the functional parameters, especially the relative ventilation difference in the PTV, achieved a p-value<0.05 and an AUC value of 0.84. Conclusion:MRI-based functional parameters extracted from 2D-cine MRI-scans were found to be predictive of RP development in lung tumor patients.

A Four-dimensional Computed Tomography Generated Internal Target Volume Approach to Paediatric High Risk Neuroblastoma to Reduce Organ at Risk and Normal Tissue Irradiation

AimsThe magnitude of upper abdominal organ motion in children may be overestimated by current planning target volumes (PTV). A four-dimensional computed tomography (4DCT) – derived internal target volume (ITV) is frequently used in adult radiotherapy to take respiratory-related organ motion into account. In this study, the dosimetric consequences for target coverage and organs at risk from the use of an ITV approach compared to standard PTV margins in children with high-risk neuroblastoma were investigated. Materials and methods14 patients, median age 4.1 years, range 1.5 – 18.9 years, (9 midline targets, 5 lateralised) each had two dual arc volumetric modulated arc therapy (VMAT) plans (14 ×1.5 Gy) generated. One used an ITV-approach; motion information derived from 4DCT (PTV_itv) with a 5mm ITV to PTV expansion, and the other a PTV margin of 10mm from CTV to PTV (PTV_standard). Differences in absolute PTV volume and organ at risk doses are described. ResultsThe ITV approach resulted in a highly significant reduction in PTV size of 38% (p<0.0001). For midline targets, an ITV approach resulted in a small but statistically significant reduction in combined mean kidney dose of 0.8Gy, p 0.01. Mean heart and lung dose were reduced by an average of 1 Gy with an ITV approach. Non-PTV integral dose from 30.4 Gy L to 27.8 Gy L using an ITV approach. ConclusionAn ITV-approach to respiratory related organ motion management in children can significantly reduce absolute PTV volumes, maintain target coverage and reduce dose delivered to normal tissue in proximity to the target. This is an essential step to maximising the benefits of highly conformal radiotherapy techniques including VMAT for this patient group, and in the future with Proton Therapy.

Proton Pencil Beam Scanning Facilitates the Safe Treatment of Extended Radiation Targets for Hodgkin Lymphoma: A Report from the Proton Collaborative Group Registry.

Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose. Using the Proton Collaborative Group registry, we identified patients with HL treated with PBT to both their mediastinum and axilla, for which DICOM-RT was available. All patients were treated with PBS. To evaluate the dosimetric impact of PBS, we compared delivered PBS plans with VMAT butterfly photon plans optimized to have the same target volume coverage, when feasible. Between 2016 and 2021, twelve patients (median 26 years) received PBS ETRT (median 30.6 Gy (RBE)). Despite the large superior/inferior (SI, median 22.2 cm) and left/right (LR, median 22.8 cm) extent of the ETRT targets, all patients were treated with one isocenter except for two patients (both with SI and LR > 30 cm). Most commonly, anterior beams, with or without posterior beams, were used. Compared to photons, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving lower doses to the lungs and heart, but not to the breast. No acute grade 3+ toxicities were reported, including pneumonitis. Proton ETRT in this small cohort was safely delivered with PBS and was associated with an improved sparing of the heart and lungs compared to VMAT.

Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) – Part I: In Vitro Testing and Characterization

PurposeImproving the deep lung delivery of aerosol surfactant therapy (AST) with a dry powder formulation may enable significant reductions in dose while providing improved efficacy. The objective of Part I of this two-part study was to present the development of a new dry powder aerosol synthetic lung surfactant (SLS) product and to characterize performance based on aerosol formation and realistic in vitro airway testing leading to aerosol delivery recommendations for subsequent in vivo animal model experiments.MethodsA new micrometer-sized SLS excipient enhanced growth (EEG) dry powder formulation was produced via spray drying and aerosolized using a positive-pressure air-jet dry powder inhaler (DPI) intended for aerosol delivery directly to intubated infants with respiratory distress syndrome (RDS) or infant-size test animals.ResultsThe best-case design (D2) of the air-jet DPI was capable of high emitted dose (> 80% of loaded) and formed a < 2 µm mass median aerodynamic diameter (MMAD) aerosol, but was limited to ≤ 20 mg mass loadings. Testing with a realistic in vitro rabbit model indicated that over half of the loaded dose could penetrate into the lower lung regions. Using the characterization data, a dose delivery protocol was designed in which a 60 mg total loaded dose would be administered and deliver an approximate lung dose of 14.7–17.7 mg phospholipids/kg with a total aerosol delivery period < 5 min.ConclusionsA high-efficiency aerosol SLS product was designed and tested that may enable an order of magnitude reduction in administered phospholipid dose, and provide rapid aerosol administration to infants with RDS.

A Multicentric study on a dosimetric comparison of extended SSD technique, VMAT-Based and helical tomotherapy (HT) for total body irradiation (TBI)

PurposeIn study, it was aimed to evaluate the dose volume histograms (DVH) of extended SSD technique, VMAT-based, and helical tomotherapy plans dosimetrically in a multi-institutional context to achieve higher plan quality and to harmonize total body irradiation plans. MethodsFour different clinical centers participated in the study. The CT images of ten patients were used in this study. During the first phase, ten patients enrolled for TBI were planned by multiple centers according to a common protocol. During the second phase, all centers shared their plans’ DVHs. Treatment plans were evaluated according to the critical organ dose limits. Statistical analysis was performed in the SPSS (version 22.0) program (p < 0.05). ResultsIn study, the results indicated that there was a statistically significant and considerable difference in the dose coverage of PTV, beam delivery time and MU, lens doses, and kidney doses between the four techniques (p < 0.001). The mean lung doses of the four centers were below 10 Gy. No significant difference in maximum liver doses between plans was obtained. ConclusionIn conclusion, although four treatment techniques were suitable for TBI treatment, more homogeneous dose distribution, and lower critical organ doses were obtained with the tomotherapy technique. However, treatment time, MU, and dose rate for lung were disadvantages of the tomotherapy technique. When it comes to deciding on the TBI treatment method, it need to be reviewed some important points. It is needed to sufficient data on long-term results to be able to standardize TBI techniques between centers.

Dosimetric impact of intrafraction patient motion on MLC-based 3D-conformal spatially fractionated radiation therapy treatment of large and bulky tumors.

To evaluate the dosimetric impact on spatially fractionated radiation therapy (SFRT) plan quality due to intrafraction patient motion via multi-field MLC-based method for treating large and bulky (≥8cm) unresectable tumors. For large tumors, a cone beam CT-guided 3D conformal MLC-based SFRT method was utilized with 15Gy prescription. An MLC GTV-fitting algorithm provided 1cm diameter apertures with a 2cm center-to-center distance at the isocenter. This generated a highly heterogeneous sieve-like dose distribution within an hour, enabling same-day SFRT treatment. Fifteen previously treated SFRT patients were analyzed (5 head & neck [H&N], 5 chest and lungs, and 5 abdominal and pelvis masses). For each plan, intrafraction motion errors were simulated by incrementally shifting original isocenters of each field in different x-, y-, and z-directions from 1 to 5mm. The dosimetric metrics analyzed were: peak-to-valley-dose-ratio (PVDR), percentage of GTV receiving 7.5Gy, GTV mean dose, and maximum dose to organs-at-risk (OARs). For±1,±2,±3,±4, and±5mm isocenter shifts: PVDR dropped by 3.9%, 3.8%, 4.0%, 4.1%, and 5.5% on average respectively. The GTV(V7.5) remained within 0.2%, and the GTV mean dose remained within 3.3% on average, compared to the original plans. The average PVDR drop for 5mm shifts was 4.2% for H&N cases, 10% for chest and lung, and 2.2% for abdominal and pelvis cases. OAR doses also increased. The maximum dose to the spinal cord increased by up to 17 cGy in H&N plans, mean lung dose (MLD) changed was small for chest/lung, but the bowel dose varied up to 100 cGy for abdominal and pelvis cases. Due to tumor size, location, and characteristics of MLC-based SFRT, isocenter shifts of up to±5mm in different directions had moderate effects on PVDR for H&N and pelvic tumors and a larger effect on chest tumors. The dosimetric impact on OAR doses depended on the treatment site. Site-specific patient masks, Vac-Lok bags, and proper immobilization devices similar to SBRT/SRT setups should be used to minimize these effects.

Validation of Acuros for total body irradiation at extended distance.

Standardized and accurately reported doses are essential in conventional total body irradiation (TBI), especially lung doses. This study evaluates the accuracy of the Acuros algorithm in predicting doses for extended-distance TBI. Measurements and calculations were done with both 6 and 18 MV. Tissue Maximum Ratio (TMR), output and off axis ratios (OAR) were measured at 200 and 500cm source to detector distance and compared to Acuros calculated values. Two end-to-end tests were carried out, one with an in-house phantom (solid water and Styrofoam) with inserted ion chambers and the other was with the Imaging and Radiation Oncology Core (IROC) TBI anthropomorphic phantom equipped with TLDs. The end-to-end test was done for 6 and 18 MV both with and without lung blocks. The source to midplane distance for both phantoms were at 518 and 508cm respectively. Lung blocks were placed at the phantom surface and a beam spoiler was positioned 30cm from the surface of the phantoms as per our clinical set up. The agreement between measured and calculated TMR, output and off axis ratios for both 6 and 18 MV were within 2%. Ion chamber measurements in both the Styrofoam and solid water for both energies carried out with and without lung blocks were within 2% of calculated values. TLD measured doses for both 6 and 18 MV in the IROC phantom were within 5% of calculated doses which is within the uncertainty of the TLD measurement. The results indicate that the clinical beam model for Acuros 16.1 commissioned at standard clinical distances is capable of calculating doses accurately at extended distances up to 500cm.

Role of adaptive radiotherapy during concomitant chemoradiotherapy for limited-stage small-cell lung cancer.

Tumor shrinkage is frequently observed during conventionally fractionated chemoradiotherapy for limited-stage small-cell lung cancer (SCLC). The specific goals of this study are to evaluate the gross tumor volume (GTV) changes due to treatment-induced tumor reduction during the course of radiotherapy (RT) and to examine its potential use in adaptive radiotherapy (ART) for tumor dose escalation or normal tissue sparing in patients with SCLC. A total of 10 patients with SCLC eligible for chemoradiotherapy underwent computed tomography (CT) scan after Fractions 13 and 23 (at nominal doses of 23.4 Gy and 41.4 Gy, respectively). The GTV was delineated on the repeat CT scans, and two treatment plans were generated with or without adaptation to tumor shrinkage during RT for each patient. Dosimetric and volumetric analyses were performed. The average GTV reduction observed over 13 fractions was 58.5% (range: 13.2%-92.3%; P < 0.001) and over 23 fractions was 70% (range: 36.9%-84.5%; P < 0.001). Compared with the plan without adaptation, ART resulted in mean lung dose relative decreases of 8.7%, mean lung volume receiving ≥20 Gy relative decreases of 5%, mean lung volume receiving ≥5Gy relative decreases of 10%, mean medulla spinalis dose relative decreases of 21 cGy, mean esophagus volume receiving ≥50 Gy relative decreases of 19%, and mean heart volume receiving ≥42 Gy relative decreases of 13%. The benefits of ART were the greatest for tumor volumes ≥30 cm3 and are directly dependent on GTV reduction during treatment. ART for SCLC achieved a significant benefit in terms of organ at risk (OAR) and dose escalation.

Aerosol Delivery Efficiency With High-Flow Nasal Cannula Therapy in Neonatal, Pediatric, and Adult Nasal Upper-Airway and Lung Models.

High-flow nasal cannula (HFNC) systems employ different methods to provide aerosol to patients. This study compared delivery efficiency, particle size, and regional deposition of aerosolized bronchodilators during HFNC in neonatal, pediatric, and adult upper-airway and lung models between a proximal aerosol adapter and distal aerosol circuit chamber. A filter was connected to the upper airway to a spontaneously breathing lung model. Albuterol was nebulized using the aerosol adapter and circuit at different clinical flow settings. The aerosol mass deposited in the upper airway and lung was quantified. Particle size was measured with a laser diffractometer. Regional deposition was assessed with a gamma camera at each nebulizer location and patient model with minimum flow settings. Inhaled lung doses ranged from 0.2-0.8% for neonates, 0.2-2.2% for the small child, and 0.5-5.2% for the adult models. Neonatal inhaled lung doses were not different between the aerosol circuit and adapter, but the aerosol circuit showed marginally greater lung doses in the pediatric and adult patient models. Impacted aerosols and condensation in the non-heated HFNC and aerosol delivery components contributed to the dispersion of coarse liquid droplets, high deposition (11-44%), and occlusion of the supine neonatal upper airway. In contrast, the upright pediatric and adult upper-airway models had minimal deposition (0.3-7.0%) and high fugitive losses (∼24%) from liquid droplets leaking out of the nose. The high impactive losses in the aerosol adapter (56%) were better contained than in the aerosol circuit, resulting in less cannula sputter (5% vs 22%), fewer fugitive losses (18% vs 24%), and smaller inhaled aerosols (5 µm vs 13 µm). The inhaled lung dose was low (1-5%) during HFNC. Approaches that streamline aerosol delivery are needed to provide safe and effective therapy to patients receiving aerosolized medications with this HFNC system.

Single-Session Ablative Transarterial Radioembolization for Patients with Hepatocellular Carcinoma to Streamline Care: An Initial Experience.

Transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) is performed after a mapping angiogram involving infusion of radiolabeled macroaggregated albumin to assess for non-target embolization and pulmonary shunting. The purpose of this case series was to evaluate the safety and feasibility of single-session TARE without the initial procedure. A single-institution case series of 16 consecutive procedures on 15 patients with 18 tumors who underwent an attempted single-session TARE procedures with glass microspheres are presented. A lung shunt fraction (LSF) of 5% was assumed for planning purposes. Sixty-seven percent (10/15) of patients were male with a median age of 72years. Median tumor size was 2.5cm (IQR 2.0-3.2cm). Sixteen of the 18 targeted tumors were untreated prior to the single-session TARE. Rate of technical success was 88% (14/16). Two patients did not ultimately receive a single-session TARE due to intraprocedural findings. The mean administered activity was 2.0GBq, and the mean MIRD dose was 464Gy based on pre-treatment anatomic imaging and 800Gy based on cone-beam CT. There were no cases of radiation pneumonitis. Mean post-procedural calculated lung dose was 4.9Gy (range 3.1-9.3) based on SPECT. An initial experience with single-session TARE using Y-90 glass microspheres without pre-procedural mapping angiography and lung shunt estimation demonstrates that it is a feasible and safe treatment option for select patients with small (< 5cm) HCC. Level 4 case series.

Assessment of Organ-at-risk Sparing in Esophageal Cancer: A Comparative Dosimetric Evaluation of Hybrid, Noncoplanar, and Coplanar RapidArc Plans

Aim: The purpose of this study is to improve the precision of radiation treatment and sparing of organ-at-risk (OAR) in patients with thoracic esophageal cancer (EC) affecting the heart, lung, and spinal cord. To improve and personalize cancer treatment plans, it assesses the dosimetric benefits of coplanar RapidArc (RAc), hybrid arc (RAHyb), and noncoplanar RapidArc (RAnc). Materials and Methods: Fourteen patients with EC were chosen for our investigation from our hospital’s database. RapidArc (RA) plan patients had already received treatment. Retrospectively, additional RAnc and RAHyb plans were made with a prescription dose of 50.4 Gy in 28 fractions for the planning target volume (PTV). A prescription dose of 95% of PTV was used, so that three different treatment planning procedures could be compared. The cumulative dose-volume histogram was used to analyze the plan quality indices homogeneity index (HI), conformity index (CI), conformation number (CN) as well as the OARs doses to the lung, heart, and spinal cord. Results: In comparison to RAc and RAnc techniques, the study indicated that RAHyb plans significantly increased D95%, CI and HI; Dmax and CN did not differ substantially. In addition, compared to RAc (lung: 16.15 ± 0.03 Gy and heart: 23.91 ± 4.67 Gy) and RAnc (lung: 15.24 ± 0.03 Gy and heart 23.82 ± 5.10 Gy) plans, RAHyb resulted in significantly lower mean lung doses (15.10 ± 0.03 Gy) and heart doses (21.33 ± 6.99 Gy). Moreover, the RAHyb strategy showed a statistically significant (P &lt; 0.05) lower average MU (452.7) than both the RAc (517.5) and RAnc (566.2) plans. Conclusion: The D95%, conformity, and homogeneity indices were better for hybrid arc plans compared to RAc and RAnc plans. They also successfully managed to reduce the lung and heart doses as well as the mean MU per fraction.

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.

Real-World Acute Toxicity and 90-Day Mortality in Patients With Stage I NSCLC Treated With Stereotactic Body Radiotherapy

IntroductionStereotactic body radiotherapy (SBRT) has firmly established its role in stage I NSCLC. Clinical trial results may not fully apply to real-world scenarios. This study aimed to uncover the real-world incidence of acute toxicity and 90-day mortality in patients with SBRT-treated stage I NSCLC and develop prediction models for these outcomes. MethodsProspective data from the Dutch Lung Cancer Audit for Radiotherapy (DLCA-R) were collected nationally. Patients with stage I NSCLC (cT1-2aN0M0) treated with SBRT in 2017 to 2021 were included. Acute toxicity was assessed, defined as grade greater than or equal to 2 radiation pneumonitis or grade greater than or equal to 3 non-hematologic toxicity less than or equal to 90 days after SBRT. Prediction models for acute toxicity and 90-day mortality were developed and internally validated. ResultsAmong 7279 patients, the mean age was 72.5 years, with 21.6% being above 80 years. Most were male (50.7%), had WHO scores 0 to 1 (73.3%), and had cT1a-b tumors (64.6%), predominantly in the upper lobes (65.2%). Acute toxicity was observed in 280 (3.8%) of patients and 90-day mortality in 122 (1.7%). Predictors for acute toxicity included WHO greater than or equal to 2, lower forced expiratory volume in 1 second and diffusion capacity for carbon monoxide, no pathology confirmation, middle or lower lobe tumor location, cT1c-cT2a stage, and higher mean lung dose (c-statistic 0.68). Male sex, WHO greater than or equal to 2, and acute toxicity predicted higher 90-day mortality (c-statistic 0.73). ConclusionsThis nationwide study revealed a low rate of acute toxicity and an acceptable 90-day mortality rate in patients with SBRT-treated stage I NSCLC. Notably, advanced age did not increase acute toxicity or mortality risk. Our predictive models, with satisfactory performance, offer valuable tools for identifying high-risk patients.

Comparison of Lung and Contralateral Scattered Breast Dose between Field-in-Field and Wedge Techniques in Patients with Early Breast Cancer

Purpose: This study aims to evaluate the dosimetric result of the Field-In-Field (FIF) plans compared with Tangential Wedged Beams (TWB) plans for whole breast radiotherapy of patients. Materials and Methods: In this survey, we entered fifty patients with breast-conserving surgery and postoperative whole-breast radiotherapy. FIF and a TWB plan were made for each patient to compare dosimetric outcomes. Results: The Homogeneity Index (HI) and Conformity Index (CI) were specified for the evaluation of Planning Target Volume (PTV). The mean dose of the ipsilateral lung and contra-lateral breast for the evaluation of organs at risk dose were used. The FIF plans had significantly lower HI (p &lt; 0.01) and CI (p &lt; 0.01) than those of the TWB plans. It means in the dosimetric comparisons of the PTV, the FIF plans were better than the TWB plans. The V10lung (31.152vs. 32.72%, p &lt; 0.01), V20lung (25.6064vs. 26.6%, p &lt; 0.01) V30lung (17.4% vs. 18.4%, p &lt; 0.01) were lower with the FIF plans compared with those of the TWB plans, with statistical significance. The FIF plans had a lower mean dose for the lung than those of TWB plans (1225.48 vs. 1670.32 cGy) but no statistical significance (p=0.06). The mean dose in the contra-lateral of the breast in FIF plans was lower than in TWB plans (61.666 vs. 163.45 cGy), with statistical significance (p &lt; 0.01). Conclusion: The FIF plans increased the dose homogeneity, and conformity of the target volume for the whole-breast irradiation compared with the TWB plans. Moreover, the doses of organs at risk (ipsilateral lung and contralateral breast) were reduced with FIF plans.

Dosimetric and NTCP advantages of robust proton therapy over robust VMAT for Stage III NSCLC in the immunotherapy era

AimsTo assess the robustness and to define the dosimetric and NTCP advantages of pencil-beam-scanning proton therapy (PBSPT) compared with VMAT for unresectable Stage III non-small lung cancer (NSCLC) in the immunotherapy era. Material and methods10 patients were re-planned with VMAT and PBSPT using: 1) ITV-based robust optimization with 0.5 cm setup uncertainties and (for PBSPT) 3.5 % range uncertainties on free-breathing CT 2) CTV-based RO including all 4DCTs anatomies. Target coverage (TC), organs at risk dose and TC robustness (TCR), set at V95%, were compared. The NTCP risk for radiation pneumonitis (RP), 24-month mortality (24MM), G2 + acute esophageal toxicity (ET), the dose to the immune system (EDIC) and the left anterior descending (LAD) coronary artery V15 < 10 % were registered. Wilcoxon test was used. ResultsBoth PBSPT methods improved TC and TCR (p < 0.01). The mean lung dose and lung V20 were lower with PBSPT (p < 0.01). Median mean heart dose reduction with PBSPT was 8 Gy (p < 0.001). PT lowered median LAD V15 (p = 0.004).ΔNTCP > 5 % with PBSPT was observed for two patients for RP and for five patients for 24 MM. ΔNTCP for ≥ G2 ET was not in favor of PBSPT for all patients. PBSPT halved median EDIC (4.9/5.1 Gy for ITV/CTV-based VMAT vs 2.3 Gy for both ITV/CTV-based PBSPT, p < 0.01). ConclusionsPBSPT is a robust approach with significant dosimetric and NTCP advantages over VMAT; the EDIC reduction could allow for a better integration with immunotherapy. A clinical benefit for a subset of NSCLC patients is expected.

Establishing Updated Safety Standards for Independent 99mTc-MAA SPECT/CT Treatment Planning in Radioembolization

Significant improvements within radioembolization imaging and dosimetry permit the development of an accurate and personalized pretreatment plan using technetium 99m-labeled macroaggregated albumin (99mTc-MAA) and single-photon emission computed tomography (SPECT) combined with anatomical CT (SPECT/CT). Despite these potential advantages, the clinical transition to pretreatment protocols with SPECT/CT is hindered by their unknown safety constraints. This study aimed to address this issue by establishing novel dose limits for 99mTc-MAA SPECT/CT to enable quantitative pretreatment planning. Stratification criteria to determine images most viable for dosimetry analysis were created from a cohort of 85 patients. SPECT/CT, cone beam CT, and activity calculations derived from the local deposition method were used to create an accurate pretreatment protocol. Planar and SPECT/CT images were compared using linear regression and modified Bland-Altman analyses to convert accepted planar dose limits to SPECT/CT. To validate these new dose limits, activity calculations based on SPECT/CT were compared with those calculated with the body surface area and planar methods for three treatment plans. A total of 38 of 85 patients were deemed viable for dosimetry analysis. SPECT yielded greater lung shunt fractions (LSFs) than planar imaging when LSFs were <4.89%, whereas SPECT yielded lower LSFs than planar imaging when LSFs were >4.89%. Planar to SPECT/CT dose conversions were 0.76×, 0.70×, and 0.55× for the whole liver, normal liver, and lungs, respectively. Patients with SPECT LSFs ≤4.89% were safely treated with the direct application of planar lung dose limits. Activity calculations with the newly established SPECT/CT dose limits were greater than those of the body surface area method by a median range of 33.1% to 61.9% and were lower than planar-based activity calculations by a median range of 12.5% to 13.7% for the whole liver and by 29.4% to 32.2% for the normal liver. This study demonstrated a safe method for translating dose limits from 99mTc-MAA planar imaging to SPECT/CT. A robust pretreatment protocol was further developed guided by the current knowledge in the field. Established SPECT/CT dose limits safely treated 97.5% of patients and permitted the application of independent pretreatment planning with 99mTc-MAA SPECT/CT.

Efficient bone marrow irradiation and low uptake by non-haematological organs with an yttrium-90-anti-CD66 antibody prior to haematopoietic stem cell transplantation

We report the results of a Phase I radiation dose escalation study using an yttrium-90 (90Y) labelled anti-CD66 monoclonal antibody given with standard conditioning regimen for patients receiving haematopoietic stem cell transplants for myeloid leukaemia or myeloma. The 90Y-labelled anti-CD66 was infused prior to standard conditioning. In total, 30 patients entered the trial and 29 received 90Y-labelled mAb, at infused radiation activity levels of 5, 10, 25, or 37.5 megaBequerel (MBq)/kg lean body weight. A prerequisite for receiving the 90Y-labelled mAb was favourable dosimetry determined by single-photon emission computerised tomography (SPECT) dosimetry following administration of indium-111 (111In) anti-CD66. Estimated absorbed radiation doses delivered to the red marrow demonstrated a linear relationship with the infused activity of 90Y-labelled mAb. At the highest activity level of 37.5 MBq/kg, mean estimated radiation doses for red marrow, liver, spleen, kidneys and lungs were 24.6 ± 5.6 Gy, 5.8 ± 2.7 Gy, 19.1 ± 8.0 Gy, 2.1 ± 1.1 and 2.2 ± 0.9, respectively. All patients engrafted, treatment-related mortality 1-year post-transplant was zero. Toxicities were no greater than those anticipated for similar conditioning regimens without targeted radiation. The ability to substantially intensify conditioning prior to haematopoietic stem cell transplantation without increasing toxicity warrants further testing to determine efficacy. clinicaltrials.gov identifier: NCT01521611.

Overall survival following heterogeneous FDG-guided dose-escalation for locally advanced NSCLC in the international phase III NARLAL2 trial.

LBA8069 Background: The survival and loco-regional control for patients (pts) with locally advanced non-small cell lung cancer (LA_NSCLC) treated with radiotherapy (RT) are dismal despite adjuvant Durvalumab. However, there have been concerns about dose escalation for these pts since the unexpected result of the dose-escalation trial RTOG0617. A novel approach is therefore warranted to escalate the dose to the tumor. A possible approach is to use the principle from stereotactic body radiotherapy (SBRT) with inhomogeneous dose distribution. SBRT has demonstrated excellent local control in early-stage lung cancer. The international multicenter NARLAL2 (novel approach to RT for LA_NSCLC) phase III trial on dose escalation, randomized pts with LA_NSCLC between standard 66 Gy/ 33 fractions (F) versus heterogeneous FDG-PET driven dose escalation, aiming at mean dose to GTV-tumorPET 95 Gy/ 33 F and mean dose to GTV-nodePET 74 Gy/ 33 F while strictly respecting dose to organs at risk. We here present the data on overall survival (OS) 1 year after the end of recruitment. Methods: Pts aged ≥18 years with LA_NSCLC were recruited from seven institutions in Denmark and Norway. Eligibility criteria included ECOG PS 0-1, histological or cytological confirmed NSCLC stage IIB-IIIB, signed informed consent, and a clinically acceptable plan for RT with conventional 66 Gy/ 33 F. PET-CT and brain MR were part of staging. Pts were randomly assigned to either treatment group (1:1, stratified for center and histology). The trial aimed to have iso-lung toxicity within the treatment arms by creating two RT plans (before randomization) for each patient (one for each treatment arm) with matching mean lung dose and lung V20Gy. The follow-up (FU) were scheduled weekly during RT, every 3rd month for 2 years, and every 6th month for another 3 years after randomization. At FU visit a CT-scan and toxicity scoring were performed. All interim analyses were passed without interventions (toxicity and OS). The trial's primary endpoint was time to loco-regional failure from randomization. Secondary endpoints included OS, acute, and late toxicity. The sample size calculations requested 350 pts to be enrolled in the study. Recruitment of the pre-planned number of pts finalized in March 2023. The trial was registered with ClinicalTrials.gov (NCT02354274). Results: From January 2015 to March 2023, 350 pts were randomized: 177 and 173 pts in standard and escalated arms respectively. The two groups were well-balanced regarding age, gender, stage, and PS. The dose to GTV-tumor was 66.5 Gy [66.2, 67.1] (median [IQR]) in the standard arm and 88.1 Gy [84.9, 90.4] in the escalated arm. Median OS were 35.8 months (m) and 51.6 m for pts treated in the standard and escalated arm, respectively ( p = 0.36). Median FU time 50.8 m (reverse Kaplan-Meier). Conclusions: Dose escalation is safe in the NARLAL2 setting with respect to OS. Clinical trial information: NCT02354274 .