Mean Lung Dose Research Articles

Primary Results of NRG-RTOG1106/ECOG-ACRIN 6697: A Randomized Phase II Trial of Individualized Adaptive (chemo)Radiotherapy Using Midtreatment 18F-Fluorodeoxyglucose Position Emission Tomography/Computed Tomography in Stage III Non-Small Cell Lung Cancer.

NRG-RTOG0617 demonstrated a detrimental effect of uniform high-dose radiation in stage III non-small cell lung cancer. NRG-RTOG1106/ECOG-ACRIN6697 (ClinicalTrials.gov identifier: NCT01507428), a randomized phase II trial, studied whether midtreatment 18F-fluorodeoxyglucose position emission tomography/computed tomography (FDG-PET/CT) can guide individualized/adaptive dose-intensified radiotherapy (RT) to improve and predict outcomes in patients with this disease. Patients fit for concurrent chemoradiation were randomly assigned (1:2) to standard (60 Gy/30 fractions) or FDG-PET-guided adaptive treatment, stratified by substage, primary tumor size, and histology. All patients had midtreatment FDG-PET/CT; adaptive arm patients had an individualized, intensified boost RT dose to residual metabolically active areas. The primary therapeutic end point was 2-year centrally reviewed freedom from local-regional progression (FFLP), defined as no progression in or near the planning target volume and/or regional nodes. FFLP was analyzed on a modified intent-to-treat population at a one-sided Z-test significance level of 0.15. The primary imaging end point was centrally reviewed change in SUVpeak from baseline to midtreatment; its association with FFLP was assessed using the two-sided Wald test on the basis of Cox regression. Of 138 patients enrolled, 127 were eligible. Adaptive-arm patients received a mean 71 Gy in 30 fractions, with mean lung dose 17.9 Gy. There was no significant difference in centrally reviewed 2-year FFLP (59.5% and 54.6% in standard and adaptive arms; P = .66). There were no significant differences in protocol-specified grade 3 toxicities, survival, or progression-free survival (P > .4). Median SUVpeak and metabolic tumor volume (MTV) in the adaptive arm decreased 49% and 54%, from pre-RT to mid-RT PET. However, ΔSUVpeak and ΔMTV were not associated with FFLP (hazard ratios, 0.997; P = .395 and .461). Midtreatment PET-adapted RT dose escalation as given in this study was safe and feasible but did not improve efficacy outcomes.

Dose-Volume Constraints Parameters for Lung Tissue in Thoracic Radiotherapy Following Immune Checkpoint Inhibitor Treatment.

This study aims to identify risk factors associated with symptomatic radiation pneumonitis (RP, Grade ≥ 2) following immunotherapy preceding thoracic radiotherapy (ICI-TRT) and establish safe dose constraints. This retrospective study enrolled patients diagnosed with non-small-cell lung cancer (NSCLC) who underwent thoracic radiotherapy (TRT) following immune checkpoint inhibitors (ICIs) treatment. The primary endpoint was the occurrence of symptomatic RP (Grade ≥ 2), as defined by the Common Terminology Criteria for Adverse Events version 5.0. Clinical and lung dosimetric parameters were analyzed to determine their associations with symptomatic RP. Dosimetric parameters included mean lung dose (MLD) and the percentage of lung volume receiving ≥10 Gy (V10), ≥20 Gy (V20), ≥30 Gy (V30), and ≥40 Gy (V40). Receiver operating characteristic curves were used to predict the risk of developing symptomatic RP to establish optimal threshold values for each dosimetric predictor. Among the 118 patients included, the incidence of symptomatic RP was 25.4%. Tumor locations, intervals between immunotherapy and radiotherapy, and MLD, V10, V20, V30, and V40 were identified as independent risk factors for symptomatic RP. The area under the curve (AUC) values for MLD, V10, V20, V30, and V40 were 0.788 (95% confidence interval [CI] 0.704-0.873), 0.789 (95% CI 0.705-0.874), 0.791 (95% CI 0.706-0.876), 0.784 (95% CI 0.697-0.871), and 0.749 (95% CI 0.656-0.842), respectively. The optimal threshold values for MLD, V10, V20, V30, and V40 were 9.7 Gy, 26.3%, 15.9%, 13.3%, and 8.6%, respectively. These thresholds are lower than current guideline recommendations, and maintaining dosimetric parameters below these values resulted in a cumulative symptomatic RP incidence of <12%. The recommended dose thresholds for MLD, V10, V20, V30, and V40 are lower than the current guidelines, underscoring the importance of radiotherapy planning to minimize symptomatic RP occurrence in patients receiving ICI-TRT.

Is clinical target volume necessary for locally advanced non-small cell lung cancer treated with 4D-CT intensity-modulated radiation therapy

BackgroundA dosimetric evaluation is still lacking in terms of clinical target volume (CTV) omission in stage III patients treated with 4D-CT Intensity-Modulated Radiation Therapy (IMRT).Methods49 stage III NSCLC patients received 4D-CT IMRT were reviewed. Target volumes and organs at risk (OARs) were re-delineated. Four IMRT plans were conducted retrospectively to deliver different prescribed dose (74 Gy–60 Gy), and with or without CTV implementation. Dose and volume histogram (DVH) parameters were collected and compared.ResultsIn the PTV-g 60 Gy plan (PTV-g refers to the PTV generated from the internal gross tumor volume), only 5 of 49 patients had the isodose ≥ 50 Gy line covering at least 95% of the PTV-c (PTV-c refers to the PTV generated from the internal CTV) volume. When the prescribed dose was elevated to 74 Gy to the PTV-g, 33 of 49 patients could have the isodose ≥ 50 Gy line covering at least 95% of the PTV-c volume. In terms of OARs protection, the SIB-IMRT plan showed the lowest value of V5, V20, and mean dose of lung, had the lowest V55 of esophagus, and the lowest estimated radiation doses to immune cells (EDIC). The V20, V30, and mean dose of heart was lower in the simultaneous integrated boost (SIB) IMRT (SIB-IMRT) plan than that of the PTV-c 60 Gy plan.ConclusionsCTV omission was not suitable for stage III patients when the prescribed dose to PTV-g was 60 Gy in the era of 4D-CT IMRT. CTV omission plus high dose to PTV-g (74 Gy for example) warranted further exploration. The SIB-IMRT plan had the best protection to normal tissue including lymphocytes, and might be the optimal choice.

Patient, tumour, and dosimetric factors influencing survival in non-small cell lung cancer patients treated with stereotactic ablative body radiotherapy.

We aimed to analyse clinical outcomes of peripheral, early-stage non-small cell lung cancer (NSCLC) patients treated with stereotactic ablative body radiotherapy (SABR), and evaluate potential patient, tumour, and dosimetric variables influencing survival. Data were collected retrospectively from patients treated between September 2012 and December 2016 and followed up until January 2021. Patient demographics, tumour characteristics, SABR dosimetric parameters, and survival data were collected from electronic patient medical records. Descriptive statistics were performed, and SPSS software was used for survival analysis. Eighty-nine patients were included of whom 49.5% were male and 50.5% female. Median age was 74 years. 98.8% of patients had T1-2 tumours and 89.9% underwent 55 Gy in 5 fractions. Median overall survival time was 58.7 months. On uni- and multi-variate analysis, neither patient nor tumour variables showed association with overall survival. However, planning target volume (PTV) and minimum dose to PTV correlated with overall survival. There was a signal for association between mean lung dose and overall survival on multivariate analysis. Our long-term results show SABR is an effective treatment for peripheral, early-stage NSCLC with excellent overall survival, comparable to other series. Our study found only the PTV and minimum dose to PTV had an impact on overall survival, which demonstrates the importance of generating optimal SABR plans. Our work identified lung SABR dosimetric parameters that correlate with survival, which illustrates the importance of producing optimal lung SABR plans.

Predictive Value of Simulated CT Radiomics Combined with Ipsilateral Lung Dosimetry Parameters for Radiation Pneumonitis in Patients with Esophageal Cancer: A Machine Learning-Based Retrospective Study.

To explore how non-surgical esophageal cancer patients can identify high-risk factors for radiation-induced pneumonitis after receiving radiotherapy. We retrospectively included 228 esophageal cancer patients who were unable to undergo surgical treatment but received radiotherapy for the first time. By retrospective analysis and identifying potential risk factors for symptomatic radiation-induced pneumonitis (ie ≥grade 2), as well as delineating the affected lung as an area of interest on localized CT and extracting radiomics features, along with extracting dosimetric parameters from the affected lung area. After feature screening, patients were randomly divided into training and testing sets in a 7-to-3 ratio, and a prediction model was established using machine learning algorithms. Finally, the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to validate the predictive performance of the model. A total of 54 cases of symptomatic radiation pneumonitis occurred in this study, with a total incidence rate of 23.68%. The results of multivariate analysis showed that the occurrence of symptomatic radiation pneumonitis was significantly correlated with the mean lung dose (MLD), esophageal PTVD90, esophageal PTVV50, V5, V10, V15, and V20 in patients. The machine learning prediction model constructed based on candidate prediction variables has a prediction performance interval between 0.751 (95% CI: 0.700-0.802) and 0.891 (95% CI: 0.840-0.942) in the training and validation sets, respectively. Among them, the RFM algorithm has the best prediction performance for radiation-induced pneumonitis, with 0.891 (95% CI: 0.840-0.942) and 0.887 (95% CI: 0.836-0.938) in the training and validation sets, respectively. The combination of localization CT radiomics features and diseased lung dosimetry parameters has good predictive value for radiation-induced pneumonitis in esophageal cancer patients after radiotherapy. Especially, the radiation-induced pneumonitis prediction model constructed using RF algorithm can be more effectively used to guide clinical decision-making in esophageal cancer patients.

Reirradiation of Utracentrally Located Thoracic Tumors Using a 10-Fraction Hypofractionated Stereotactic Body Radiation Therapy Course: A Detailed Dosimetric Analysis

PurposeThere is very little information detailing outcomes and toxicity following re-irradiation for ultracentrally located thoracic tumors, and detailed dosimetric data is non-existent. This data is critical for the safe management of these extremely difficult cases. Materials and MethodsThe records of fifteen individuals undergoing 10-fraction hypofractionated stereotactic body radiotherapy (hfSBRT) for the management of ultracentrally located thoracic tumors between 2009 and 2020 at a single institution were retrospectively reviewed. Treatment outcomes and toxicity were analyzed. A detailed dosimetric analysis of treatment plans and centrally located organs at risk (OARs), from the initial, re-irradiation, and cumulative radiotherapy courses was presented. ResultsAt a median follow up of 10 months, one- and three-year overall survival (OS), progression free survival (PFS) and local control (LC) were 52% and 28%, 33% and 28%, and 76% and 61%, respectively. Treatment related adverse events were low with 5 individuals (33%) developing ≥ grade 2 pneumonitis (Grade 2 = 4, Grade 3 = 1). Dosimetric parameters were not associated with the development of clinically relevant pneumonitis. No adverse events involving central OARs (esophagus, great vessels, primary bronchial tree) were identified. Median cumulative mean lung dose (MLD) was 24 Gy (EQD2) (range: 10-33 Gy), with a V20 of 33% (range: 11-51%). Median esophageal, primary bronchial tree, and great vessel maximum doses (Dmax) were 93.2 Gy (EQD2) (range: 50-148 Gy), 163 Gy (range: 77-204 Gy), and 191 Gy (range: 129-262 Gy), respectively. ConclusionsThe current investigation is the first to provide detailed cumulative dosimetric data from a cohort of patients comprised entirely of ultracentrally located thoracic tumors. Despite unfavorable anatomic tumor location given an intimate association to critical OARs, delivering an ablative dose with a 10-fraction hfSBRT course can serve as a feasible option for these challenging cases.

Blood biomarkers for cardiac damage during and after radiotherapy for esophageal cancer: A prospective cohort study

PurposeThe aim of this study was to test the hypothesis that the levels of High Sensitive Troponin T (HS-TNT) and N-terminal Brain Natriuretic Peptide (NT-ProBNP) increase after radiation therapy in a dose dependent way and are predictive for clinical cardiac events. Materials and MethodsBlood samples during and after radiotherapy of 87 esophageal cancer patients were analysed regarding the course of HS-TNT and NT-ProBNP levels and their relationship with clinical toxicity endpoints and radiation dose volume parameters. ResultsHS-TNT values at the end of treatment correlated with the mean heart dose (p = 0.02), whereas the rise of NT-ProBNP correlated with the mean lung dose (p = 0.01). Furthermore, the course of both HS-TNT (p < 0.001) and NT-ProBNP (p < 0.01) levels were significantly different for patients who developed new cardiac events as opposed to those without new cardiac events. ConclusionSignificant correlations were found for both biomarkers with radiation dose and clinical toxicity endpoints after treatment. Therefore, these markers might be of additional value in NTCP models for cardiac events and might help us unravelling the mechanisms behind these toxicity endpoints.

Cumulative rib fracture risk after stereotactic body radiotherapy in patients with localized non-small cell lung cancer

IntroductionRib fracture is a known complication after stereotactic body radiotherapy (SBRT). Patient-related parameters are essential to provide patient-tailored risk estimation, however, their impact on rib fracture is less documented compared to dosimetric parameters. This study aimed to predict the risk of rib fractures in patients with localized non-small cell lung cancer (NSCLC) post-SBRT based on both patient-related and dosimetric parameters with death as a competing risk. Materials and methodsIn total, 602 patients with localized NSCLC treated with SBRT between 2010–2020 at Odense University Hospital, Denmark were included. All patients received SBRT with 45–66 Gray (Gy)/3 fractions. Rib fractures were identified in CT-scans using a word embedding model. The cumulative incidence function was based on cause-specific Cox hazard models with variable selection based on cross-validation model likelihood performed using 50 bootstraps. ResultsIn total, 19 % of patients experienced a rib fracture. The cumulative risk of rib fracture increased rapidly from 6-54 months post-SBRT. Female gender, bone density, near max dose to the rib, V30 and V40 to the rib, gross tumor volume, and mean lung dose were significantly associated with rib fracture risk in univariable analysis. The final multi-variable model consisted of V20 and V30 to the rib and mean lung dose. ConclusionFemale gender and low bone density in male patients are significant predictors of rib fracture risk. The final model predicting cumulative rib fracture risk of 19 % in patients with localized NSCLC treated with SBRT contained no patient-related parameters, suggesting that dosimetric parameters are the primary drivers.

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.

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.

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.

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.

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.

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.

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 .

Radiation pneumonitis prediction with dual-radiomics for esophageal cancer underwent radiotherapy

BackgroundTo integrate radiomics and dosiomics features from multiple regions in the radiation pneumonia (RP grade ≥ 2) prediction for esophageal cancer (EC) patients underwent radiotherapy (RT).MethodsTotal of 143 EC patients in the authors’ hospital (training and internal validation: 70%:30%) and 32 EC patients from another hospital (external validation) underwent RT from 2015 to 2022 were retrospectively reviewed and analyzed. Patients were dichotomized as positive (RP+) or negative (RP-) according to CTCAE V5.0. Models with radiomics and dosiomics features extracted from single region of interest (ROI), multiple ROIs and combined models were constructed and evaluated. A nomogram integrating radiomics score (Rad_score), dosiomics score (Dos_score), clinical factors, dose-volume histogram (DVH) factors, and mean lung dose (MLD) was also constructed and validated.ResultsModels with Rad_score_Lung&Overlap and Dos_score_Lung&Overlap achieved a better area under curve (AUC) of 0.818 and 0.844 in the external validation in comparison with radiomics and dosiomics models with features extracted from single ROI. Combining four radiomics and dosiomics models using support vector machine (SVM) improved the AUC to 0.854 in the external validation. Nomogram integrating Rad_score, and Dos_score with clinical factors, DVH factors, and MLD further improved the RP prediction AUC to 0.937 and 0.912 in the internal and external validation, respectively.ConclusionCT-based RP prediction model integrating radiomics and dosiomics features from multiple ROIs outperformed those with features from a single ROI with increased reliability for EC patients who underwent RT.