Total Lung V20 Research Articles

Risk Stratification by Combination of Heart and Lung Dose in Locally Advanced Non-Small-Cell Lung Cancer after Radiotherapy

Background/Objectives: Despite advancements in treatment for patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC), overall survival (OS) remains poor. The specific effects of varying heart and lung doses on OS in LA-NSCLC patients have not been thoroughly investigated, especially their combined impact on survival. This study aimed to examine the impact on OS of both individual and combined heart and lung doses in patients with LA-NSCLC treated with radiotherapy over a three-year follow-up period. Methods: A total of 120 patients who received definitive radiotherapy for LA-NSCLC (stage III, 92.5%) from January 2015 to January 2020 were retrospectively reviewed. The endpoint in this study was OS. Each patient was followed for a fixed period of three years. Results: Univariate Cox regression analysis showed that OS was significantly related to mean heart dose (MHD, hazard ratio [HR], 3.4 [1.8–6.3]; p < 0.001), pericardium V40 (HR, 3.2 [1.7–6.0]; p < 0.001), and total lung V20 (HR, 2.6 [1.4–5.0]; p = 0.003), and these were independent predictors for worse OS in multivariate analysis. Kaplan–Meier curve analysis with log-rank tests revealed that survival was significantly worse in patients with higher MHD (p < 0.001), pericardium V40 (p < 0.001), and total lung V20 (p = 0.002). Combining MHD and total lung V20, and pericardium V40 and total lung V20 provided enhanced risk stratification for OS (p < 0.001 for both combinations). Conclusions: The combination of heart and lung doses provided enhanced and more detailed risk stratification in prediction of OS for a fixed period of three years in LA-NSCLC patients treated with radiotherapy.

Frequent Friers: Outcomes in Patients Who Receive Multiple Courses of Lung SBRT

Stereotactic body radiation therapy (SBRT) is a definitive therapy for early-stage non-small cell lung cancer and solitary pulmonary metastases with high tolerability and excellent survival rates. With longer survival and patients developing subsequent primaries or oligometastatic disease, patients are receiving multiple repeat lung SBRT courses. This study aims to assess safety and efficacy of high-frequency SBRT (HF-SBRT) to the lung, defined as >3 courses. A retrospective review was performed of patients who received >3 courses of lung SBRT. Logistic regression was performed to identify predictors of radiation pneumonitis (RP) and worsening pulmonary function (WPF). Local control (LC) and overall survival (OS) were evaluated using the Kaplan-Meier method. Ninety-four courses of HF-SBRT to the lung were identified among 28 patients. 78% of patients received 3 SBRT courses, 12% received 4 courses, and 7.1% received >5 courses. Median follow-up was 4.4 years. Median age at time of treatment was 73 years-old; 58% males; 42% had an underlying pulmonary comorbidity; 39% prior lung surgery; 52% history of cardiac disease; 52% prior tobacco use; median ECOG 0. Median SBRT dose was 48 Gy. Median interval between courses was 5.6 months. Zero patients experienced greater than grade 2 acute CTCAE v5 toxicity. 7.2% (7) of patients developed RP at median time of 2.6 months [IQR: 1.4,7.4]; grade 1: 3 patients, grade 2: 1 patient, grade 3: 2 patients. Of patients who developed RP, 42% (3) went on to receive further SBRT without experiencing significant adverse events (AEs). History of pulmonary disease, prior lung surgery, and history of tobacco use strongly correlated with WPF but not RP (WPF p-values: <0.001, 0.003, <0.001, respectively). History of cardiac disease did not correlate with WPF or RP. Receiving bilateral lung SBRT treatment (vs unilateral) trended towards correlation with WPF (p = 0.06) and RP (p = 0.08). Time between SBRT courses did not significantly differ for those who developed RP (p = 0.62) or WPF (p = 0.42). No individual or plan sum dosimetric constraint (GTV, PTV, unilateral lung V5, lung V10, lung V20, unilateral mean lung dose, or total lung V20) significantly differed in those who experienced RP. WPF correlated with the plan sum unilateral lung V10 (p = 0.05). LC at 1-year was 100%, 1 local failure occurred at 13 months; 2-year OS was 91.7%, median OS 5.4 years. Overall, HF-SBRT was well tolerated. Development of RP did not correlate with a specific individual or plan sum dosimetric parameter, with patients receiving subsequent courses of SBRT without increased AEs. WPF increasingly occurred with subsequent SBRT courses and correlated with unilateral plan sum V10. This study suggests that in appropriately selected patients, SBRT after RP can still be provided as definitive care, while further studies should validate this and focus attention on mitigating long-term WPF in patients who receive HF-SBRT.

Analysis of clinical and physical dosimetric factors that determine the outcome of severe acute radiation pneumonitis in lung cancer patients

ObjectiveWe conducted a retrospective statistical analysis of clinical and physical dosimetric factors of lung cancer patients who had previously undergone lung and/or mediastinal radiotherapy and died of or survived severe acute radiation pneumonitis (SARP). Our study was the first to reveal the heterogeneity in clinical factors, physical dosimetric factors, and SARP onset time that determined the clinical outcomes of lung cancer patients who developed SARP.Materials and methodsThe clinical characteristics, physical dosimetry factors, and SARP onset time of deceased and surviving patients were retrospectively analyzed. SPSS 20.0 was used for data analysis. Student’s t-test was used for intergroup comparison, and a Mann–Whitney U test was used for data with skewed distribution. Qualitative data were represented using frequencies (%), and Fisher’s exact test or χ2 test was used for intergroup comparison of nonparametric data. Binary logistic analysis was used for univariate and multivariate analyses. Differences with a P < 0.05 were considered statistically significant.ResultsUnivariate analysis revealed that the potential predictors of SARP death were as follows: ipsilateral lung V5 and V30, contralateral lung V5, V10, and V30, total lung V5, V10, and V30, mean lung dose, mean heart dose, and maximum spinal cord dose. Multivariate analysis showed that ipsilateral lung V5 and total lung V5 were predictors that determined the final outcome of SARP patients. In addition, we analyzed the time from the completion of radiotherapy to SARP onset, and found significant difference between the two groups.ConclusionsThere was no decisive correlation between clinical characteristics and SARP outcome (i.e., death or survival) in lung radiotherapy patients. Ipsilateral lung V5 and total lung V5 were independent predictors of death in SARP patients.

Deep-learning based fast and accurate 3D CT deformable image registration in lung cancer.

Deformable Image Registration (DIR) is an essential technique required in many applications of radiation oncology. However, conventional DIR approaches typically take several minutes to register one pair of 3D CT images and the resulting deformable vector fields (DVFs) are only specific to the pair of images used, making it less appealing for clinical application. A deep-learning-based DIR method using CT images is proposed for lung cancer patients to address the common drawbacks of the conventional DIR approaches and in turn can accelerate the speed of related applications, such as contour propagation, dose deformation, adaptive radiotherapy (ART), etc. METHODS: A deep neural network based on VoxelMorph was developed to generate DVFs using CT images collected from 114 lung cancer patients. Two models were trained with the weighted mean absolute error (wMAE) loss and structural similarity index matrix (SSIM) loss (optional) (i.e., the MAE model and the M+S model). In total, 192 pairs of initial CT (iCT) and verification CT (vCT) were included as a training dataset and the other independent 10 pairs of CTs were included as a testing dataset. The vCTs usually were taken 2weeks after the iCTs. The synthetic CTs (sCTs) were generated by warping the vCTs according to the DVFs generated by the pre-trained model. The image quality of the synthetic CTs was evaluated by measuring the similarity between the iCTs and the sCTs generated by the proposed methods and the conventional DIR approaches, respectively. Per-voxel absolute CT-number-difference volume histogram (CDVH) and MAE were used as the evaluation metrics. The time to generate the sCTs was also recorded and compared quantitatively. Contours were propagated using the derived DVFs and evaluated with SSIM. Forward dose calculations were done on the sCTs and the corresponding iCTs. Dose volume histograms (DVHs) were generated based on dose distributions on both iCTs and sCTs generated by two models, respectively. The clinically relevant DVH indices were derived for comparison. The resulted dose distributions were also compared using 3D Gamma analysis with thresholds of 3mm/3%/10% and 2mm/2%/10%, respectively. The two models (wMAE and M+S) achieved a speed of 263.7±163 / 265.8±190ms and a MAE of 13.15±3.8 / 17.52±5.8 HU for the testing dataset, respectively. The average SSIM scores of 0.987±0.006 and 0.988±0.004 were achieved by the two proposed models, respectively. For both models, CDVH of a typical patient showed that less than 5% of the voxels had a per-voxel absolute CT-number-difference larger than 55 HU. The dose distribution calculated based on a typical sCT showed differences of ≤2cGy[RBE] for clinical target volume (CTV) D95 and D5 , within ±0.06% for total lung V5 , ≤1.5cGy[RBE] for heart and esophagus Dmean , and ≤6cGy[RBE] for cord Dmax compared to the dose distribution calculated based on the iCT. The good average 3D Gamma passing rates (>96% for 3mm/3%/10% and>94% for 2mm/2%/10%, respectively) were also observed. A deep neural network-based DIR approach was proposed and has been shown to be reasonably accurate and efficient to register the initial CTs and verification CTs in lung cancer.

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

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

The potential of biology-guided radiation therapy in thoracic cancer: A preliminary treatment planning study.

PurposeWe investigated the feasibility of biology-guided radiotherapy (BgRT), a technique that utilizes real-time positron emission imaging to minimize tumor motion uncertainties, to spare nearby organs at risk.MethodsVolumetric modulated arc therapy (VMAT), intensity-modulated proton (IMPT) therapy, and BgRT plans were created for a paratracheal node recurrence (case 1; 60 Gy in 10 fractions) and a primary peripheral left upper lobe adenocarcinoma (case 2; 50 Gy in four fractions).ResultsFor case 1, BgRT produced lower bronchus V40 values compared to VMAT and IMPT. For case 2, total lung V20 was lower in the BgRT case compared to VMAT and IMPT.ConclusionsBgRT has the potential to reduce the radiation dose to proximal critical structures but requires further detailed investigation.

Treatment patterns and prognosis of patients with inoperable stage III NSCLC after completion of concurrent chemoradiotherapy ± immune checkpoint inhibition: a decade-long single-center historical analysis

PurposeTo investigate the impact of treatment time and patterns in inoperable stage III non-small cell lung cancer (NSCLC) following concurrent chemoradiotherapy (cCRT) ± immune checkpoint inhibitors (ICIs).MethodsPatients were stratified by treatment year: A (2011–2014), B (2015–2017) and C (2018–2020). Tumor- and treatment-related characteristics regarding locoregional recurrence-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) were investigated.ResultsOne hundred and thirty-six consecutive patients were analyzed. All patients completed thoracic radiotherapy (TRT) to a total dose ≥ 60.0 Gy; 36 (26%) patients received ICI. Median PFS in subgroups A, B and C was 8.0, 8.2 and 26.3 months (p = 0.007). Median OS was 19.9 months, 23.4 months and not reached (NR), respectively. In group C, median LRRFS and PFS were 27.2 vs. NR; and 14.2 vs. 26.3 months in patients treated with and without ICI. On multivariate analysis planning target volume (PTV) ≥ 700 cc was a negative prognosticator of LRRFS (HR 2.194; p = 0.001), PFS (HR 1.522; p = 0.042) and OS (HR 2.883; p = 0.001); ICI was a predictor of LRRFS (HR 0.497; p = 0.062), PFS (HR 0.571; p = 0.071) and OS (HR 0.447; p = 0.1). In the non-ICI cohort, multivariate analyses revealed PTV ≥ 700 cc (p = 0.047) and a maximum standardized uptake value (SUVmax) ≥ 13.75 (p = 0.012) were predictors of PFS; PTV ≥ 700 cc (p = 0.017), SUVmax ≥ 13.75 (p = 0.002) and a total lung V20 ≥ 30% (V20 ≥ 30) (p < 0.05) were predictors of OS.ConclusionsPatients treated after 2018 had improved survival regardless of ICI use. Implementation of ICI resulted in further significant increase of all tested survival endpoints. PTV ≥ 700 cc and ICI were only prognosticators for LRRFS, PFS and OS in the analyzed cohort.

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

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

Treatment patterns and prognosis in inoperable stage III NSCLC after concurrent chemoradiotherapy with or without immune checkpoint inhibition: Historical overview.

e20578 Background: To investigate the impact of treatment patterns in inoperable stage III NSCLC following concurrent chemoradiotherapy with or without immune checkpoint inhibition (cCRT±ICI). Methods: Patients were stratified by treatment year and divided into three subgroups: A (2011–2014), B (2015–2017) and C (2018–2020). Patient- and treatment-related characteristics regarding to PFS and OS were analyzed. Survival parameters were calculated from the last day of thoracic radiotherapy (TRT). Results: 136 consecutive enrolled patients were included. Median follow-up (FU) was 35.7 months; median age was 66.9 years. All patients completed TRT to a total dose ≥60.0 Gy; Median radiotherapy planning target volume (PTV) was 700 cc (range: 172.5–2293.2). Thirty-six (26%) patients received ICI. Median PFS in subgroups A, B and C was 8.0, 8.2 and 26.3 months (p = 0.007). Median OS was 19.9 months, 23.4 months and not reached in subgroups A, B and C (p &lt; 0.05). In subgroup C, median PFS was 14.2 vs. 26.3 months in patients treated with and without ICI. On multivariate analysis for the entire cohort, PTV &gt; 700cc was a negative prognosticator of PFS (HR: 1.522; p = 0.042) and OS (HR: 2.671; p = 0.001); ICI was a predictor of improved PFS (HR: 0.571; p = 0.071) and longer OS (HR: 0.401; p = 0.062). In the Non-ICI cohort, multivariate analyses revealed PTV &gt; 700cc (HR: 1.630; p = 0.047) and SUVmax &gt; 13.75 (HR: 1.859; p = 0.012) were predictors of reduced PFS; PTV &gt; 700cc (HR: 1.958; p = 0.017), SUVmax &gt; 13.75 (HR: 2.405; p = 0.002) and total lung V20 &gt; 30 (HR: 3.357; p &lt; 0.05) were predictors of longer OS. Conclusions: Regardless of ICI, patients receiving multimodal therapy after 2018 demonstrated improved survival compared to patients treated earlier. Both PTV &gt; 700cc and ICI were predictive for PFS and OS in the entire cohort.

Investigation of Predictors to Achieve Acceptable Lung Dose in T-Shaped Upper and Middle Esophageal Cancer With IMRT and VMAT.

PurposeThe purpose of this study is to investigate whether there are predictors and cutoff points that can predict the acceptable lung dose using intensity-modulated radiation therapy (IMRT) and volume-modulated arc therapy (VMAT) in radiotherapy for upper ang middle esophageal cancer.Material and MethodsEighty-two patients with T-shaped upper-middle esophageal cancer (UMEC) were enrolled in this retrospective study. Jaw-tracking IMRT plan (JT-IMRT), full-arc VMAT plan (F-VMAT), and pactial-arc VMAT plan (P-VMAT) were generated for each patient. Dosimetric parameters such as MLD and V20 of total lung were compared among the three plannings. Ten factors such as PCTVinferior length and PCTVinferior length/total lung length were calculated to find the predictors and cutoff points of the predictors. All patients were divided into two groups according to the cutoff points, and the dosimetric differences between the two groups of the three plans were compared. ANOVA, receiver operating characteristic (ROC) analysis, and Mann–Whitney U-test were performed for comparisons between datasets. A p <0.05 was considered statistically significant.ResultThe quality of the targets of the three plannings was comparable. The total lung dose in P-VMAT was significantly lower than that in JT IMRT and F-VMAT. Monitor unit (MU) of F-VMAT and P-VMAT was significantly lower than that of JT IMRT. ROC analysis showed that among JT IMRT, F-VMAT, and P-VMAT, PCTVi-L, and PCTVi-L/TLL had diagnostic power to predict the suitability of RT plans according to lung dose constraints of our department. For JT IMRT, the cutoff points of PCTVi-L and PCTVi-L/TLL were 16.6 and 0.59. For F-VMAT, the cutoff points of PCTVi-L and PCTVi-L/TLL were 16.75 and 0.62. For P-VMAT, the cutoff points of PCTVi-L and PCTVi-L/TLL were 15.15 and 0.59. After Mann–Whitney U-test analysis, it was found that among the three plannings, the group with lower PCTVi-L and PCTVi-L/TLL could significantly reduce the dose of total lung and heart (p <0.05).ConclusionPCTVi-L <16.6 and PCTVi-L/TLL <0.59 for JT IMRT, PCTVi-L <16.75 and PCTVi-L/TLL <0.62 for F-VMAT and PCTVi-L <15.15, and PCTVi-L/TLL <0.59 for P-VMAT can predict whether patients with T-shaped UMEC can meet the lung dose limits of our department.

287 OUTCOMES OF DEFINITIVE CHEMORADIOTHERAPY IN LONG SEGMENT ESOPHAGEAL CANCERS FROM A TERTIARY CANCER CENTRE IN INDIA

Abstract Definitive chemoradiotherapy (CTRT) is the standard of care for unresectable esophageal cancer. Long segment esophageal primary disease makes it challenging to deliver radiation doses needed to achieve good local control without exceeding normal tissue tolerance to the surrounding organs at risk (OAR). We report our experience and outcomes of such patients where the RT doses were reduced from our institutional standard of 63Gy to 50.4Gy. Methods Between Jan 2017 and Dec 2019, 30/232 consecutive esophageal cancer patients were identified with long segment disease that required dose reduction from 63 to 50.4Gy and were included in this analysis. For this study, we divided nodal regions by their location into cervical, mediastinal, and gastro-hepatic. We generated and compared dosimetric parameters of the standard dose (63Gy) plan with that of treated low-dose plan (50.4Gy) using paired t-test. We also evaluated the patterns of recurrence and have reported them as local relapse (LR), loco-regional relapse (LRR), and distant metastases (DM). Results The median age was 55.5 years; 16 (53.3%) were males and 28 (93.3%) had squamous carcinoma. Single nodal site was involved in 6(20%), 2 sites in 20(66.7%) and 3 sites in 4 (13.3%). Median GTV and PTV length were 7.9 cm (IQR:6.4–9.7 cm) and 18.8 cm (IQR:14.08–22.31 cm) respectively. Median OAR doses with standard Vs treated plan achieved were: Total lung V20 and V5:28 Vs 22.14% (p = 0.00), and 81 Vs 70.5% (p = 0.005) respectively, and heart V20:70.92% Vs 64.7% (p = 0.000). No patients experienced ≥grade2 lung toxicity. After a median follow up of 8.4 months, 3 patients experienced LRR and 1 developed DM. Conclusion Treatment of long segment esophageal cancers warrants dose reduction to avoid higher doses to OAR like lung and heart. Early loco-regional and distant failures suggest need for improved treatment strategies or dose escalation with more conformal techniques like proton therapy. Longer follow-up is necessary to assess the median LR, LRR rates and overall survival for this reduced dose group as compared to the standard dose group.

Regression models for predicting physical and EQD2 plan parameters of two methods of hybrid planning for stage III NSCLC

Background/purposeTo establish regression models of physical and equivalent dose in 2 Gy per fraction (EQD2) plan parameters of two kinds of hybrid planning for stage III NSCLC.MethodsTwo kinds of hybrid plans named conventional fraction radiotherapy & stereotactic body radiotherapy (C&S) and conventional fraction radiotherapy & simultaneous integrated boost (C&SIB) were retrospectively made for 20 patients with stage III NSCLC. Prescription dose of C&S plans was 2 Gy × 30f for planning target volume of lymph node (PTVLN) and 12.5 Gy × 4f for planning target volume of primary tumor (PTVPT), while prescription dose of C&SIB plans was 2 Gy × 26f for PTVLN and sequential 2 Gy × 4f for PTVLN combined with 12.5 Gy × 4f for PTVPT. Regression models of physical and EQD2 plan parameters were established based on anatomical geometry features for two kinds of hybrid plans. The features were mainly characterized by volume ratio, min distance and overlapping slices thickness of two structures. The possibilities of regression models of EQD2 plan parameters were verified by spearman’s correlation coefficients between physical and EQD2 plan parameters, and the influence on the consistence of fitting goodness between physical and EQD2 models was investigated by the correlations between physical and EQD2 plan parameters. Finally, physical and EQD2 models predictions were compared with plan parameters for two new patients.ResultsPhysical and EQD2 plan parameters of PTVLN CI60Gy have shown strong positive correlations with PTVLN volume and min distance(PT to LN), and strong negative correlations with PTVPT volume for two kinds of hybrid plans. PTV(PT+LN) CI60Gy is not only correlated with above three geometry features, but also negatively correlated with overlapping slices thickness(PT and LN). When neck lymph node metastasis was excluded from PTVLN volume, physical and EQD2 total lung V20 showed a high linear correlation with corrected volume ratio(LN to total lung). Meanwhile, physical total lung mean dose (MLD) had a high linear correlation with corrected volume ratio(LN to total lung), while EQD2 total lung MLD was not only affected by corrected volume ratio(LN to total lung) but also volume ratio(PT to total lung). Heart D5, D30 and mean dose (MHD) would be more susceptible to overlapping structure(heart and LN). Min distance(PT to ESO) may be an important feature for predicting EQD2 esophageal max dose for hybrid plans. It’s feasible for regression models of EQD2 plan parameters, and the consistence of the fitting goodness of physical and EQD2 models had a positive correlation with spearman’s correlation coefficients between physical and EQD2 plan parameters. For total lung V20, ipsilateral lung V20, and ipsilateral lung MLD, the models could predict that C&SIB plans were higher than C&S plans for two new patients.ConclusionThe regression models of physical and EQD2 plan parameters were established with at least moderate fitting goodness in this work, and the models have a potential to predict physical and EQD2 plan parameters for two kinds of hybrid planning.

A novel nomogram containing acute radiation esophagitis predicting radiation pneumonitis in thoracic cancer receiving radiotherapy

BackgroundRadiation-induced pneumonitis (RP) is a non-negligible and sometimes life-threatening complication among patients with thoracic radiation. We initially aimed to ascertain the predictive value of acute radiation-induced esophagitis (SARE, grade ≥ 2) to symptomatic RP (SRP, grade ≥ 2) among thoracic cancer patients receiving radiotherapy. Based on that, we established a novel nomogram model to provide individualized risk assessment for SRP.MethodsThoracic cancer patients who were treated with thoracic radiation from Jan 2018 to Jan 2019 in Shandong Cancer Hospital and Institute were enrolled prospectively. All patients were followed up during and after radiotherapy (RT) to observe the development of esophagitis as well as pneumonitis. Variables were analyzed by univariate and multivariate analysis using the logistic regression model, and a nomogram model was established to predict SRP by “R” version 3.6.0.ResultsA total of 123 patients were enrolled (64 esophageal cancer, 57 lung cancer and 2 mediastinal cancer) in this study prospectively. RP grades of 0, 1, 2, 3, 4 and 5 occurred in 29, 57, 31, 0, 3 and 3 patients, respectively. SRP appeared in 37 patients (30.1%). In univariate analysis, SARE was shown to be a significant predictive factor for SRP (P < 0.001), with the sensitivity 91.9% and the negative predictive value 93.5%. The incidence of SRP in different grades of ARE were as follows: Grade 0–1: 6.5%; Grade 2: 36.9%; Grade 3: 80.0%; Grade 4: 100%. Besides that, the dosimetric factors considering total lung mean dose, total lung V5, V20, ipsilateral lung mean dose, ipsilateral lung V5, and mean esophagus dose were correlated with SRP (all P < 0.05) by univariate analysis. The incidence of SRP was significantly higher in patients whose symptoms of RP appeared early. SARE, mean esophagus dose and ipsilateral mean lung dose were still significant in multivariate analysis, and they were included to build a predictive nomogram model for SRP.ConclusionsAs an early index that can reflect the tissue’s radiosensitivity visually, SARE can be used as a predictor for SRP in patients receiving thoracic radiation. And the nomogram containing SARE may be fully applied in future’s clinical work.

Abstract PS15-12: Initial outcomes of adjuvant proton pencil beam scanning radiation for patients with breast cancer requiring comprehensive nodal irradiation within a single institution

Abstract Background:Following lumpectomy or mastectomy, locally advanced breast cancer (LABC)requires adjuvant radiation (RT) to the chest wall (CW) and comprehensiveregional nodal basins (CNI). Proton therapy (PBT) has demonstrated dosimetricadvantages in heart, lung, and esophageal exposures compared to photon RT, butlittle is published regarding oncologic outcomes of PBT for LABC. Methods:Consecutive patients treated from 2016-2019 wereretrospectively reviewed. Men and women over the age of 18 requiring adjuvantRT with CNI were included; all patients had at least 6 months of follow up fromRT completion. Initial treatment volumes, excluding boosts to scars or grossdisease, (CTV_init) included CW-CNI per the RADCOMP atlas. CTV_init coveragewas prescribed as 95% CTV_init at 100% Rx dose. All patients were treated with proton pencil-beam scanning RT (PBS-PBT),typically with a two-field anterior SFO technique. Patient, tumor, and dosimetric characteristics wereanalyzed. Tumoral control and survival rates were estimated by the Kaplan Meiermethod. Toxicities were recorded prospectively by treating physicians andreviewed retrospectively. Local recurrence was defined as in-breast, or skin/chestwall; regional recurrence was defined as a nodal failure. Results:One hundred patients were included with a median follow upof 15.4 months (6-42). Ninety-eight percent were female, and 61% were white.Median age was 52 years, and 94% of patients had an ECOG PS ≤1.AJCC 8th edition anatomic staging was predominantly stage II (49%)or III (48%).Sixty-five percent of patients were treated for left-sideddisease; 7% of patient received bilateral RT; 87% received cytotoxicchemotherapy (63% neoadjuvant, 37% adjuvant). Twenty six patients receivedconcurrent systemic therapy with trastuzumab (H)/pertuzumab (P)(38% ),capecitabine (29%), H-emtansine (21%), or H (12%). The median initial RT dosewas 50.4 (45-50.4) while median total RT dose was 50.4Gy (45-70.2). Forty-twopercent of patient underwent an RT boost to nodal areas and/or the scar. Allpatients were treated in 1.8 or 2.0Gy fractions. Eighty-seven percent oflesions were invasive ductal carcinomas; 52% were ER+/Her2-, 17% weretriple-negative (TNBC), and 31% were Her2+.Nine (9%) of patients experienced a ≥G3 acute toxicity, all in theform of radiation dermatitis. There was one acute G4 incidence of skinnecrosis. There were no ≥G3 late toxicities or documented major cardiac events atthe time of last follow up. Median doses to critical organs at risk (OARs) were asfollows: mean heart 0.9Gy (&amp;lt;0.1 - 3.9), V25 heart 0.9% (0 - 6.6) ipsilaterallung V20 15% (4.6 - 29.2) ipsilateral lung V5 41.1% (17.5 - 62.2), volume ofthe esophagus receiving 70% Rx dose 0.1cc (0 - 5.3). For bilateral plans, themedian total lung V20 was 15.6% (6.6 - 23.5) and V5 was 41.5% (18.5 - 45.0). Overall, there were 3 local, 3 regional, and 8 distantfailures. All local failures were TNBC; regional and distant failures wereequally distributed between histologies. All distant failures occurred in patientswith at least AJCC 8th Edition anatomic stage IIIA. Actuarial ratesof 2-year local, regional, locoregional, and distant failures were 4% (±3),2% (±2),6% (±3%),and 11% (±4).Two-year actuarial survival was 94% (±3).Conclusions:We present a large series of patients with high-risk or LABCtreated with adjuvant PBS-PBT and CNI. Our series includes significant percentagesof TNBC, non-white patients, and patients requiring dose-escalated RT boosts overalldemonstrating promising initial oncologic outcomes and very favorable acutetoxicity and dosimetric profiles. Continued follow up is warranted to confirmlong-term oncologic outcomes. Citation Format: Cristina DeCesaris, Ariel Pollock, Emily Kowalski, Kayla Paulosky, Sung Choi, Mark Mishra, Elizabeth Nichols. Initial outcomes of adjuvant proton pencil beam scanning radiation for patients with breast cancer requiring comprehensive nodal irradiation within a single institution [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-12.

Dosimetric Evaluation of Simplified Knowledge-Based Plan with an Extensive Stepping Validation Approach in Volumetric-Modulated Arc Therapy-Stereotactic Body Radiotherapy for Lung Cancer.

Purpose:We investigated the performance of the simplified knowledge-based plans (KBPs) in stereotactic body radiotherapy (SBRT) with volumetric-modulated arc therapy (VMAT) for lung cancer.Materials and Methods:For 50 cases who underwent SBRT, only three structures were registered into knowledge-based model: total lung, spinal cord, and planning target volume. We performed single auto-optimization on VMAT plans in two steps: 19 cases used for the model training (closed-loop validation) and 16 new cases outside of training set (open-loop validation) for TrueBeam (TB) and Halcyon (Hal) linacs. The dosimetric parameters were compared between clinical plans (CLPs) and KBPs: CLPclosed, KBPclosed-TB and KBPclosed-Hal in closed-loop validation, CLPopen, KBPopen-TB and KBPopen-Hal in open-loop validation.Results:All organs at risk were comparable between CLPs and KBPs except for contralateral lung: V5 of KBPs was approximately 3%–7% higher than that of CLPs. V20 of total lung for KBPs showed comparable to CLPs; CLPclosed vs. KBPclosed-TB and CLPclosed vs. KBPclosed-Hal: 4.36% ± 2.87% vs. 3.54% ± 1.95% and 4.36 ± 2.87% vs. 3.54% ± 1.94% (P = 0.54 and 0.54); CLPopen vs. KBPopen-TB and CLPopen vs. KBPopen-Hal: 4.18% ± 1.57% vs. 3.55% ± 1.27% and 4.18% ± 1.57% vs. 3.67% ± 1.26% (P = 0.19 and 0.27). CI95 of KBPs with both linacs was superior to that of the CLP in closed-loop validation: CLPclosed vs. KBPclosed-TB vs. KBPclosed-Hal: 1.32% ± 0.12% vs. 1.18% ± 0.09% vs. 1.17% ± 0.06% (P < 0.01); and open-loop validation: CLPopen vs. KBPopen-TB vs. KBPopen-Hal: 1.22% ± 0.09% vs. 1.14% ± 0.04% vs. 1.16% ± 0.05% (P ≤ 0.01).Conclusions:The simplified KBPs with limited number of structures and without planner intervention were clinically acceptable in the dosimetric parameters for lung VMAT-SBRT planning.

Acute Radiation-induced Esophagitis as a Novel and Early Predictor for Radiation-Induced Pneumonitis: A Real-World Study

Radiation-induced pneumonitis (RP) is a non-negligible and life-threatening complication in patients undergoing thoracic radiation. We have observed that many patients with severe RP (SRP, grade≥2) were accompanied with severe acute radiation-induced esophagitis (SARE, grade≥2) in clinic. The aim of this study was to ascertain the application value of SARE to SRP and establish a novel and visible nomogram model for it. Patients with thoracic cancer who were treated with thoracic radiation from Jan.2018 to Jan.2019 in Shandong Cancer Hospital and Institute were enrolled prospectively. All patients were followed up during and after radiotherapy (RT) to observe the appearance of esophagitis and pneumonitis. Variables were analyzed by univariate and multivariate analysis using the logistic regression model, and a nomogram model was established to predict SRP by "R” version 3.6.0. A total of 123 patients were enrolled (64 esophageal cancer, 57 lung cancer and 2 mediastinal cancer) in this study prospectively. With a median follow-up of 3.3 months (range 1–14.2 months), RP grades of 0, 1, 2, 3, 4 and 5 occurred in 29, 57, 31, 0, 3 and 3 patients, respectively. SRP appeared in 37 patients (30.1%). In univariate analysis, SARE was shown to be a significant predictive factor for SRP (P < 0.001). The incidence of SRP in different grades of ARE were as follows: Grade 0-1:6.52%; Grade 2: 36.92%; Grade 3: 80.00%; Grade 4: 100%. Besides that, the dosimetric factors considered total lung mean dose, total lung V5, V20; ipsilateral lung mean dose, ipsilateral lung V5, and mean esophagus dose to be correlated with SRP (all P < 0.005) in univariate analysis. The incidence of SRP was significantly higher in patients whose symptoms of RP appeared early. SARE (HR 34.408, P = 0.001), mean esophagus dose and ipsilateral mean lung dose were still significant in multivariate analysis, and they were included to build a predictive nomogram model for SRP. SARE was the first intuitive index that can reflect the radiation sensitivity of normal tissue visually. It could be a significant predictor to SRP for patients receiving thoracic radiation, which can be earlier and easier than previously reported laboratory or clinical indicators. And the nomogram model could assist in doctor’s decision and guide to make personalized radiation dose prescription.

Adaptive Radiotherapy in Locally Advanced Lung Cancers – Real World Scenario from a Tertiary Cancer Center

Concurrent chemo-radiation (CTRT) for locally advanced lung cancer (LALC) leads to dynamic changes in tumor volume and location especially in patients with large tumor or atelectasis. Using adaptive radiotherapy (ART) prevents under dosage of the tumor and over dosage of the organs at risk (OAR). One hundred forty patients of LALC from Jan 2017 to Dec 2019 were treated with concurrent CTRT. A four-dimensional computed tomography (4D CT) scan was acquired and contouring of gross target volume (GTV) was guided by PET-scan fusion. All patients were planned to receive 60Gy/30 daily fractions with volumetric modulated arc therapy. Cone-beam CT (CBCT) for set-up verification was performed at least twice weekly. Change in anatomy and tumor response was determined on CBCT during weekly radiotherapy audit. Patients suitable for ART were re-simulated and re-planned. GTV now consisted of residual tumor and 5mm isotropic clinical target volume (CTV) was generated and manually extended to include areas suspicious for residual disease. Dose delivered prior to ART and time needed to execute ART (calculated from the day of re-simulation to the day of starting ART) were documented. The volumetric and dosimetric changes were analyzed using paired t-test between the 2 plans for full prescription dose. We also evaluated local control for this cohort. Out of 140 patients, 35 (25%) required re-planning for ART. Median age was 61 years (range 50 - 65). Twenty-six patients (75%) had upper lobe tumors. Fifteen (43%) patients had squamous carcinoma, 13 (37%) had adenocarcinoma, and 7 (20%) had small cell carcinoma. Requirement for ART was anticipated in 10/35 (28%) patients prior to CTRT. The triggers for ART were resolution of atelectasis in 7 (20%) patients, tumor response in 26 (74%) and progression in 2 (6%) patients. A median of 6 CBCTs prior to ART were acquired. A median of 26Gy (IQR 14-36Gy) was delivered prior to ART. While it required 5 days (IQR:3.5-7.5) for executing ART. There was a reduction in mean planning target volume of 23% (544cc - 418 cc; p = 0.003), mean GTV primary of 47% (153cc - 80.8cc; p = 0.024), and GTV nodes of 33.7% (8 cc - 5.3 cc; p = 0.033). The V20 of total lung minus PTV and the mean lung dose increased by 3.7% (18.8% - 19.5%; p = 0.158) and 4.5% (10.9Gy - 11.4Gy; p = 0.274) respectively whereas there was a reduction in heart V20 and Spinal cord Dmax by 18.3% (9.7 Gy to 8.2 Gy; p = 0.005) and 6.7% (36.6 Gy to 34.3 Gy; p = 0.100) respectively. At a median follow up of 14.7 months, the loco regional control rate was 70% and no patient experienced ³ grade 3 toxicity. In our practice approximately 25% patients of locally advanced lung cancer required ART, with tumor response and resolution of atelectasis being the most common triggers. Anticipation of clinically significant change, frequent use of on-board imaging and implementation of ART could prevent under dosage of the tumor and over dosage of OAR.

Volumetric Modulated Arc Therapy Versus Three-Dimensional Conformal Radiotherapy for Breast Cancer Patients Treated with Regional Nodal Irradiation

Locally advanced breast cancer is often treated with adjuvant radiotherapy to the chest wall or breast and the regional nodes following surgery. Intensity-modulated radiotherapy (IMRT) can improve target coverage and spare organ at risk, but the efficacy and safety of IMRT for locally advanced breast cancer have not been clarified. We aimed to compare the dosimetric parameters and clinical outcomes between 3D-CRT and volumetric modulated arc therapy (VMAT) for breast cancer. The hypothesis is that VMAT has better target coverage without increasing toxicities. Breast cancer patients who received adjuvant radiotherapy with regional nodes irradiation between July 2016 and December 2019 were included. Patients with a right-sided disease were treated with three-dimensional conformal radiotherapy (3D-CRT), whereas patients with a left-sided disease were treated with VMAT to reduce heart dose. Patients who received bilateral radiotherapy were excluded. Radiotherapy was delivered to the chest wall or breast, and supraclavicular region with or without internal mammary nodes. A dose of 50 Gy in 25 fractions was prescribed to the reference point for 3D-CRT, and to cover 75% of the PTV for VMAT. Single full or two partial arcs with 6MV were used for VMAT. Clinical outcome and dosimetric data were collected retrospectively from medical records. Toxicities were assessed by CTCAE ver.4.0. A total of 74 consecutive patients were included in this study. Thirty-five left-sided breast cancer patients received VMAT, and 39 right-sided breast cancer patients received 3D-CRT. The median follow-up was 591 days. The median age was 50 years. Grade 2 or higher acute dermatitis were observed in 10 patients (29%) with VMAT versus 17 patients (44%) with 3D-CRT (P = 0.18). Grade 3 acute dermatitis occurred in one patient in the 3D-CRT group. Grade 2 radiation pneumonitis occurred in one patient in each group (P = 1.0). Acute radiation esophagitis occurred in 25 patients only in the VMAT group. CTV coverage (CTV V47.5Gy, D95%, D75%) was significantly better for VMAT (86%, 42 Gy, 49 Gy) compared to 3D-CRT (72%, 29 Gy, 46 Gy) (all P < 0.01). Total lung V20 Gy was lower for VMAT versus 3D-CRT (11Gy versus 13 Gy, P < 0.01), whereas total lung V5 Gy and mean dose were higher for VMAT (34 Gy and 7.8 Gy) compared to 3D-CRT (22 Gy and 6.9 Gy) (P < 0.01, 0.01). Because of the laterality, the dose to the heart and esophagus was higher in the VMAT group (P < 0.01, 0.01). Five patients experienced recurrence (two distant metastases in the VMAT group and two distant and one local and distant metastases in the 3D-CRT group). VMAT for breast radiotherapy with regional nodal irradiation had better target coverage and lower lung V20 Gy at the expense of a small increase in the lung mean dose and V5 Gy. VMAT can be safely administered with similar toxicity to 3D-CRT.

Osimertinib Greatly Increase the Risk of Radiotherapy Pneumonitis when Concurrent with Thoracic Radiotherapy

Osimertinib have prolonged the survival for NSCLC patients who harboring EGFR-TKI sensitizing or T790M resistance mutations. Osimetinib concurrent with thoracic radiotherapy is also a pattern for some people who experienced progression during the treatment of osimertinib or the transformation from first generation EGFR-TKI to osimertinib owe to the progression of primary lesion. But the risk of radiation pneumonitis (RP) for the concurrent osimertinib with thoracic radiotherapy have not been reported. We report a high rate of RP when concurrent osimertinib with thoracic radiotherapy. All patients from January 2017 to December 2019 at one institution were treated with concurrent osimertinib with thoracic radiotherapy were identified and all clinical records were reviewed. All people were treated with concurrent osimertinib with thoracic radiotherapy were included; the people who have a history of interstitial pneumonitis (ILD), immune checkpoint inhibitor therapy, thoracic radiotherapy was excluded. All patients were included treated with intensity-modulated radiotherapy, and osimertinib was administered orally at 80mg/d along with radiotherapy until the progression disease or intolerable toxicity. The diagnostic of RP was based on imaging manifestation of computed tomography, RP was graded from 1 to 5 according to CTCAE v5.0. Nine females and two males of lung adenocarcinoma patients harboring EGFR T790M treated with concurrent osimertinib and thoracic radiotherapy were included, nine of them experience progression disease of primary lesion during the treatment of first generation TKI and converted to osimertinib concurrent thoracic radiotherapy, two patients receive thoracic radiotherapy during the treatment of osimertinib because of the progression of primary lesion. The median age of 11 patients is 59 years old. The median follow time is 7.83 months, all 11 patients experience RP from grade 1 to grade 5. Seven patients (63.63%) developed to grade 2 or higher RP, 1 patient for grade 2, 5 patients for grade 3, 1 patient developed to fetal RP. The median dose for PTV is 60Gy (range 30-64Gy), the median fractioned dose is 2Gy (range 2-5Gy). The median volume for GTV is 11.70ml (range 2.50-247.71ml), PTV is 76.60ml (range 18.70-448.80ml). The median total-lung V5 is 29.92% (range 17.94-47.05%), V20 is 10.93% (range 6.26-28.06%), the median mean lung dose (MLD) is 6.40Gy (range 4.22-14.82Gy). We report up to 63.63% patients who receive concurrent osimertinib and thoracic radiotherapy developed to grade 2 or higher RP, and a patient developed to fetal RP, but they only have lower MLD and lesser V5, V20 compared to some patients who receive Concurrent Chemoradiation developed to RP. Compared with the 37.5% rate of RP for concurrent erlotinib and thoracic radiotherapy, our study pointed out a higher rate for osimertinib and come up with a warning for RP when concurrent osimertinib with thoracic radiotherapy.

An especially high rate of radiation pneumonitis observed in patients treated with thoracic radiotherapy and simultaneous osimertinib

Our study is the first to report an especially high rate of grade 2 or worse radiation pneumonitis in patients treated with thoracic radiotherapy and simultaneous Osimertinib, despite total lung V5, V20 and MLD seeming unlikely to induce radiation pneumonitis.