Lung V20 Research Articles

Incidence of Pneumonitis in Consolidative Durvalumab Era and its Correlation with Lung Dose-Volumes Histograms in Stage III Nonresectable Non-Small Cell Lung Cancer (NCSLC)

<h3>Purpose/Objective(s)</h3> Durvalumab has been the standard of care following chemoradiation in stage III nonresectable NSCLC since the PACIFIC trial in 2017. Even though the incidence of any grade pneumonitis in the PACIFIC trial was only 9.1%, other studies have suggested that real world incidence of pneumonitis rate with consolidative Durvalumab is as high as 49%. We undertook this retrospective study to compare the incidence of pneumonitis in the pre and post Durvalumab era and its relationship with radiation dose parameters. <h3>Materials/Methods</h3> An IRB approved retrospective chart review study was conducted for patients with stage III nonresectable NSCLC who were diagnosed between January 1, 2012 and December 31, 2019 at our institution and received chemoradiation (CRT) alone or with consolidative Durvalumab. Patients who did not receive Durvalumab after it became standard of care were included in the CRT alone group. Patients with incomplete records were excluded. Radiotherapy data was collected from delivered radiation plans. Fisher's exact test was used to compare the difference in the rate of pneumonitis between CRT alone versus CRT with Durvalumab groups. Univariable logistic regression was performed to identify risk factors for pneumonitis and variables with p < 0.1 were included in a final multivariate logistic regression. Analysis was performed using R (version 4.1.2). <h3>Results</h3> 110 out of 166 patients were included in the final analysis. The median age of diagnosis was 64.5 years (range 39-86) with 56 being female (51%) gender. Fifty-eight patients were white (53%), while 41 African American (37%), and 11 unknown. Adenocarcinoma (50%, n=55) was most common histology followed by squamous cell carcinoma (44%, n=48), and others (6%, n=7). 94 (85%) patients received CRT alone and 16 (15%) received CRT with consolidative Durvalumab. 72 (65%) had right and 36 (33%) had left primary, and 2 mixed. There was a significant difference in the rate of symptomatic pneumonitis between CRT alone (21%) versus CRT with consolidative Durvalumab (56%) (p = 0.009). The mean lung V20 was 26% (1% - 50%), V10 was 36% (8% - 70%), and V5 47% (10% - 87%) with an average mean lung dose of 14 Gy. On univariable analysis, only V20 and Durvalumab were significant in predicting pneumonitis with p<0.05, lung mean dose with borderline significance (p<0.07) while V10, V5, age, sex, race and laterality were not. A multivariate model including Durvalumab, V20, and lung mean dose showed only Durvalumab to be significant (p = 0.01). <h3>Conclusion</h3> Our study showed compared to CRT alone, consolidative Durvalumab was associated with a significant increase in the rate of symptomatic pneumonitis. Further research is needed to understand the interaction between the radiation parameters of lung and Durvalumab.

Timing of Radiation Pneumonitis in Stage 3 Non-Small Cell Lung Cancer Patients by Receipt of Durvalumab

<h3>Purpose/Objective(s)</h3> Consolidation with Durvalumab is the standard of care in unresectable Stage 3 Non-Small Cell Lung cancer (NSCLC) following radical chemoradiation and pneumonitis is an independent side effect of these therapies. Literature has shown the peak time to development of radiation pneumonitis is 4-8 weeks. The purpose of this study was to describe the timing of radiation pneumonitis (RP) by receipt of Durvalumab in patients who received definitive chemoradiation. <h3>Materials/Methods</h3> In this single institution retrospective study, consecutive patients between 2016 and 2018 with unresectable Stage 3 treated with radical chemoradiation or radical chemoradiation followed by durvalumab were evaluated for development of at least grade 2 radiation pneumonitis based on clinical symptoms and characteristic radiology features. Descriptive analysis including the time from last fraction of radiotherapy to diagnosis of grade 2 radiation pneumonitis was determined. Diagnosis of RP within 2 months of completing radiotherapy was considered early diagnosis. Logistic regression analysis stratified by receipt of Durvalumab of clinical factors predictive of early diagnosis of radiation pneumonitis were evaluated. <h3>Results</h3> Of the 144 patients with unresectable stage III NSCLC, 31 (22%) developed at least grade 2 radiation pneumonitis after definitive chemoradiation. The median patient age was 67 years (range 41-87). Of these, 12 (39%) received consolidative Durvalumab and most patients over 65 years did not receive Durvalumab 13/20 (65%). The mean time to development of RP was 2.45 months (SD 2.06) in patients who did not receive Durvalumab and 3.90 months (SD 1.91) in patients who received Durvalumab. The mean V5 and V20 lung dose constraints were 60.14% (SD 2.73) and 29.96% (SD 1.82) respectively. By receipt of Durvalumab, age over 65, V5 and V20 lung dose constraints were not predictive of early onset radiation pneumonitis. <h3>Conclusion</h3> Patients on Durvalumab had later onset radiation pneumonitis compared to patients who did not. Traditional dosimetric predictors, i.e., V5 and 20, were not predictive of early onset radiation pneumonitis by receipt of Durvalumab. These results suggest that delaying initiation of Durvalumab may not be necessary in patients with unresectable NSCLC.

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.

Proton Radiation Therapy After Chemotherapy in the Management of Aggressive Mediastinal Non-Hodgkin Lymphomas: A Particle Therapy Cooperative Group Lymphoma Subcommittee Collaboration

PurposeCombined modality therapy with multiagent chemotherapy and radiation therapy is a standard treatment option for aggressive mediastinal non-Hodgkin lymphomas (AMNHLs); however, concerns regarding acute and late radiation toxicities have fueled an effort to use systemic therapy alone. The use of proton therapy (PT) is a promising treatment option, but there are still limited data regarding clinical outcomes with this treatment modality. In this Particle Therapy Cooperative Group lymphoma subcommittee collaboration, we report outcomes of patients with AMNHL treated with pencil-beam scanning PT or double-scatter PT after chemotherapy. Methods and MaterialsThis was a multi-institutional retrospective observational cohort study of patients with AMNHL treated with PT following chemotherapy between 2011 and 2021. Progression-free survival (PFS), local recurrence–free survival (LRFS), and overall survival (OS) rates were estimated with the Kaplan-Meier method. PT toxicity was graded by the Common Terminology Criteria for Adverse Events version 5.0. A 2-tailed paired t test was used for dosimetric comparisons. ResultsTwenty-nine patients were identified. With a median follow-up time of 4.2 years (range, 0.2-8.9 years), the estimated 5-year PFS for all patients was 93%, 5-year LRFS was 96%, and estimated 5-year OS was 87%. Maximum acute grade 1 (G1) toxicities occurred in 18 patients, and 7 patients had maximum G2 toxicities. No G3+ radiation-related toxicities were observed. Average mean lung dose and lung V20 Gy were lower for patients treated with pencil-beam scanning PT compared with double-scatter PT (P = .016 and .006, respectively), while patients with lower mediastinal disease had higher doses for all evaluated dosimetric heart parameters. ConclusionsPT after chemotherapy for patients with AMNHL resulted in excellent outcomes with respect to 5-year PFS, LRFS, and OS without high-grade toxicities. Future work with larger sample sizes is warranted to further elucidate the role of PT in the treatment of AMNHL.

Integrating 18 F-FDG PET/CT with lung dose-volume for assessing lung inflammatory changes after arc-based radiotherapy for esophageal cancer: A pilot study.

The incidence of radiation pneumonitis (RP) has a highly linear relationship with low-dose lung volume. We previously established a volume-based algorithm (VBA) method to improve low-dose lung volume in radiotherapy (RT). This study assessed lung inflammatory changes by integrating fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) with VBA for esophageal cancer patients undergoing arc-based RT. Thirty esophageal cancer patients received 18 F-FDG PET/CT imaging pre-RT and post-RT were included in a retrospective pilot study. We fused lung doses and parameters of PET/CT in RT planning. Based on VBA, we used the 5Gy isodose curve to define high-dose (HD) and low-dose (LD) regions in the lung volume. We divided patients into non-RP (nRP) and RP groups. The maximum, mean standardized uptake value (SUVmax, SUVmean), global lung glycolysis (GLG), mean lung dose (MLD) and V5-30 in lungs were analyzed. Area under the curve values were utilized to identify optimal cut-off values for RP. Eleven patients in the nRP group and 19 patients in the RP group were identified. In 30 RP lungs, post-RT SUVmax, SUVmean and GLG of HD regions showed significant increases compared to values for pre-RT lungs. There were no significant differences in values of 22 nRP lungs. Post-RT SUVmax and SUVmean of HD regions, MLD, and lung V5 and V10 in RP lungs were significantly higher than in nRP lungs. For detecting RP, the optimal cut-off values were post-RT SUVmax > 2.28 and lung V5 > 47.14%. This study successfully integrated 18 F-FDG PET/CT with VBA to assess RP in esophageal cancer patients undergoing RT. Post-RT SUVmax > 2.28 and lung V5 > 47.14% might be potential indicators of RP.

Potential benefit of dose-escalated stereotactic body radiation therapy using CyberKnife for early-stage primary lung cancer.

The study aimed to evaluate the efficacy and safety of dose-escalated stereotactic body radiotherapy (SBRT) for primary lung cancer. Patients with peripherally located T1-2N0M0 primary lung cancer who underwent SBRT from April 2013 to December 2019 were included. Group A received 60Gy in five fractions with CyberKnife prescribed at 99% gross tumor volume. Group B received 48Gy in four fractions by a gantry-mounted linear accelerator, with isocenter prescription. Cumulative incidence of local failure (LF), progression free survival (PFS), overall survival (OS), and toxicity were retrospectively compared. Groups A and B comprised 39 and 36 patients, respectively. Group A had more patients without histological confirmation (p<.001) and showed lower V20 of bilateral lungs (p=.025). The median follow-up duration of Group A and B was 22.0 and 21.5 months, respectively, and the 2-year cumulative incidence of LF, PFS, and OS were .0%versus 11.6% (p=.065), 66.2%versus 62.7% (p=.694), 84.1%versus 81.1% (p=.827), respectively. There was no difference in Grade ≥ 2 toxicity rate between Groups A and B (7.7%vs. 11.1%; p=.704). Dose-escalated SBRT using CyberKnife showed reduced lung dose and potential benefits for improved local control with comparable toxicity.

Nomogram based on circulating lymphocyte subsets for predicting radiation pneumonia in esophageal squamous cell carcinoma.

PurposeCurrently, the relationship between radiation pneumonia (RP) and circulating immune cell in patients with esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to explore the relationship between RP and circulating lymphocyte subsets in patients with ESCC receiving chemoradiotherapy (CRT), and develop a nomogram model to predict RP. Since we should implement clinical intervention to ≥ grade 2 RP, a nomogram model for ≥ grade 2 RP was also established to provide an early warning.Patients and methodsThis study retrospectively included 121 patients with ESCC receiving CRT from Guangxi Medical University Cancer Hospital from 2013 to 2021. Independent factors associated with occurrence of RP and ≥ grade 2 RP were identified by univariate and multivariate logistic regression analysis in the training cohort, and incorporated into nomograms. The predictive accuracy and discrimination of the model was assessed using Concordance Index (C-index), calibration curve and decision curve analysis (DCA). And each model was internally validated. Additionally, to verify the optimized predictive performance of the nomograms, the area under the ROC curve (AUC) of each nomogram was compared to that of single independent risk factors, lung V10 and lung V20, respectively. Moreover, each model was further evaluated for risk stratification to identify populations at high risk of RP and ≥ grade 2 RP.ResultsMultivariate analysis suggested that TNM stage, post-RT percentage of CD8+ T cell, and lung V15 were independent predictive factors of RP. Besides, pre- and post-RT percentage of CD8+ T cell, and V15 were independent factors of ≥ grade 2 RP. The C-indexes of RP and ≥ grade 2 RP nomograms were 0.809 (95% CI: 0.715-0.903) and 0.787 (95% CI: 0.685-0.889) in the training cohort, respectively. And the C-indexes of RP and ≥ grade 2 RP nomograms were 0.718 (95% CI: 0.544-0.892) and 0.621 (95% CI: 0.404-0.837) in the validation cohort, respectively. The calibration curves showed that the predicted values of model agreed well with actual observations. Moreover, DCA results indicated the applicability and accuracy of the models to predict RP and ≥ grade 2 RP. After stratification, the incidence of the high-risk group was significantly higher than that of the low-risk group with respect to either RP or ≥ grade 2 RP.ConclusionTNM stage, post-RT percentage of CD8+ T cell, and lung V15 were the independent predictors of RP toxicity. Pre- and post-RT percentage of CD8+ T cell, and lung V15 were the independent factors of ≥ grade 2 RP toxicity. The nomograms based on circulating lymphocyte subsets can robustly predict RP and ≥ grade 2 RP, guiding clinicians in risk stratification and early intervention.

Dosimetric analysis of MR-LINAC treatment plans for salvage spine SBRT re-irradiation.

PurposeWe investigated the feasibility of thoracic spine stereotactic body radiotherapy (SBRT) using the Elekta Unity magnetic resonance‐guided linear accelerator (MRL) in patients who received prior radiotherapy. We hypothesized that Monaco treatment plans can improve the gross tumor volume minimum dose (GTVmin) with spinal cord preservation and maintain consistent plan quality during daily adaptation.MethodsPinnacle clinical plans for 10 patients who underwent thoracic spine SBRT (after prior radiotherapy) were regenerated in the Monaco treatment planning system for the Elekta Unity MRL using 9 and 13 intensity‐modulated radiotherapy (IMRT) beams. Monaco adapt‐to‐position (ATP) and adapt‐to‐shape (ATS) workflow plans were generated using magnetic resonance imaging with a simulated daily positional setup deviation, and these adaptive plans were compared with Monaco reference plans. Plan quality measures included target coverage, Paddick conformity index, gradient index, homogeneity index, spinal cord D0.01cc, esophagus D0.01cc, lung V10, and skin D0.01cc.ResultsGTVmin values from the Monaco 9‐beam and 13‐beam plans were significantly higher than those from Pinnacle plans (p < 0.01) with similar spinal cord dose. Spinal cord D0.01cc, esophagus D0.01cc, and lung V10 did not statistically differ among the three plans. The electron‐return effect did not induce remarkable dose effects around the lungs or skin. While in the ATP workflow, a large increase in GTVmin was observed at the cost of a 10%–50% increase in spinal cord D0.01cc, in the ATS workflow, the spinal cord dose increase was maintained within 3% of the reference plan.ConclusionThese findings show that MRL plans for thoracic spine SBRT are safe and feasible, allowing tumor dose escalation with spinal cord preservation and consistent daily plan adaptation using the ATS workflow. Careful plan review of hot spots and lung dose is necessary for safe MRL‐based treatment.

Prediction and clinical impact of delayed lymphopenia after chemoradiotherapy in locally advanced non-small cell lung cancer.

IntroductionThe dosimetric factors of radiotherapy have an acute impact on the host immune system during chemoradiotherapy (CRT) in locally advanced non-small cell lung cancer (NSCLC). However, even after CRT, a substantial number of patients remain immunosuppressed with delayed lymphopenia. Therefore, we aimed to evaluate clinical and dose-volumetric predictors of delayed lymphopenia after CRT in locally advanced NSCLC.Materials and methodsWe retrospectively reviewed 272 patients with locally advanced NSCLC who received definitive CRT from January 2012 to August 2020. Differential blood count data, including serum albumin values, were obtained at baseline, during and at first follow up after CRT. Acute and delayed lymphopenia events were defined as grade III/IV lymphopenia developed during or 4-12 weeks after CRT completion, which accounted for 84% and 10% of cases, respectively. Dose-volume histogram parameters for planned target volume, whole body, heart, lung, great vessels, spleen, esophagus and thoracic vertebral bodies were evaluated.ResultsMultivariate analysis revealed that patients with delayed lymphopenia were associated with inferior overall survival (HR 2.53, P = 0.001) and progression-free survival (HR 1.98, P = 0.006). However, there was no significant survival difference between groups stratified by acute lymphopenia. On multivariable logistic regression models, lung V5, baseline ALC, during-CRT ALC, and albumin nadir were significant predictors for delayed lymphopenia. Furthermore, the nomogram for delayed lymphopenia based on these variables had good discrimination (area under the curve, 0.905).ConclusionsIn this study, we investigated the prognostic significance of delayed lymphopenia and identified clinico-dosimetric parameters to predict delayed lymphopenia.

Imaging features of radiation-induced lung disease and its relationship with clinical and dosimetric factors in breast cancer patients.

The aim is to extensively evaluate imaging features of radiation induced lung disease in breast cancer patients and to determine the relationship of imaging alterations with dosimetric parameters and patient related characteristics. A total of 76 breast cancer patients undergoing radiotherapy (RT) were studied retrospectively by case notes, treatment plans, dosimetric parameters, and chest computed tomography (CT) scans. Time intervals, that chest CT scans were acquired, were grouped as 1-6 months, 7-12 months, 13-18 months and more than 18 months after RT. Chest CTs (one or more for each patient) were assessed for the presence of ground glass opacity, septal thickening, consolidation/patchy pulmonary opacity/alveolar infiltrates, subpleural air cyst, air bronchogram, parenchymal bands, traction bronchiectasis, pleural/subpleural thickening and pulmonary volume loss. These alterations were scored by applying a system devised by Nishioka et al. Nishioka scores were analyzed for the relationship with clinical and dosimetric factors. IBM SPSS Statistics for Windows, version 22.0 (IBM Corp., Armonk, N.Y., USA) was used to analyze data. Median follow-up time was 49 months. Advanced age and aromatase inhibitor intake were correlated with higher Nishioka scores for 1-6 months' period. However, both were found nonsignificant in multivariate analysis. Nishioka scores of CT scans acquired more than 12 months after RT were positively correlated with mean lung dose, V5, V20, V30, and V40. Receiver operating characteristic analysis revealed that V5 for ipsilateral lung was the most robust dosimetric parameter predicting chronic lung injury. V5 >41% indicates the development of radiological lung changes. Keeping V5 ≤41% for ipsilateral lung could provide avoiding chronic lung sequelae.

Dosimetric evaluation of different radiotherapy techniques in mastectomized left-sided breast cancer.

Inclusion of internal mammary lymph nodes in mastectomized left breast cancer radiotherapy may lead to high dose receiving risk of the heart, lung, and contralateral breast. The aim of this study is to compare the dosimetric differences of field-in-field (FIF), volumetric-modulated arc therapy (VMAT), seven-field intensity-modulated radiotherapy (7F-IMRT), and helical tomotherapy (HT) planning techniques for mastectomized left breast cancer. Computed tomography images of ten patients treated with the FIF technique were used to compare four different treatment planning techniques. Planning target volume (PTV) included chest wall and regional lymph nodes. The heart, left anterior descending coronary artery (LAD), left and whole lung, thyroid, esophagus, and contralateral breast were identified as organs-at-risks (OARs). Except for HT, a single isocenter in PTV and bolus of thickness 0.3 cm on the chest wall was used. Complete and directional blocks were applied in HT, and the dosimetric parameters of PTV and OARs for four different techniques were analyzed using the Kruskal-Wallis test. 7F-IMRT, VMAT, and HT were superior to the FIF technique in providing homogeneous dose distribution covering the PTV (P < 0.0001). Mean doses (Dmean) of the contralateral breast and esophagus, lung, and body-PTV V5 (volume receiving 5 Gy) were reduced in FIF, whereas in the HT, Heart Dmean, LAD Dmean , Dmax, healthy tissue (body-PTV) Dmean , heart and left lung V20, and thyroid V30 were significantly reduced (P < 0.0001). FIF and HT techniques were found to be significantly advantageous over 7F-IMRT and VMAT for OARs. Using those three multiple-beam techniques reduced high-dose volumes of healthy tissues and organs in mastectomized left breast cancer radiotherapy but also increased low-dose volumes and contralateral lung and breast doses. Complete and directional blocks applied in HT reduce heart, lung, and contralateral breast doses.

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.

Association of T Cell Senescence with Radiation Pneumonitis in Patients with Non-small Cell Lung Cancer

Associations between immunosenescence and radiation pneumonitis (RP) are largely unknown. We aimed to identify a peripheral blood T cell senescence biomarker to predict RP in patients with non-small cell lung cancer (NSCLC). Patients with locally advanced NSCLC who received definitive concurrent chemoradiotherapy (dCRT) were prospectively registered (cohort 1, n=23; cohort 2, n=31). Peripheral blood was collected at baseline, during dCRT, and at 1 month post-dCRT. Patients were dichotomized to grade ≥2 (G2+) RP and grade 0-1 (G0-1) RP. Flow cytometry was performed to assess phenotypes and functional properties of T cell subsets. RP incidence was estimated via competing risk analysis. Five and six patients exhibited G2+ RP following dCRT in cohorts 1 and 2, respectively. Patients with G2+ RP exhibited a more aged T cell pool and higher frequencies of senescent CD57+CD28-CD8+ T cells than patients with G0-1 RP at baseline, during dCRT, and at 1 month post-dCRT. These senescent cells exhibited increased granzyme B, IFN-γ, and TNF-α production. Higher baseline frequency of CD57+CD28-CD8+ T cells was an independent predictor of G2+ RP (hazard ratio, 8.42; 95% confidence interval, 2.58-27.45; P<0.001). Recursive partitioning analysis revealed three distinct risk groups stratified by baseline CD57+CD28-CD8+ T cell frequency and lung V20 Gy, with 1-year cumulative G2+ RP incidences of 50.0%, 16.7%, and 0% for high-, intermediate-, and low-risk groups, respectively (P=0.002). Higher baseline frequencies of CD57+CD28-CD8+ T cells correlated with increased G2+ RP risks. Our results suggest the need for further investigation of the role of T cell senescence on radiation-induced organ damage.

Dosimetric comparison of different intensity-modulated radiotherapy techniques for whole-breast irradiation of right-breast cancer

PurposeThis study compared the dosimetric parameters of field-in-field forward intensity-modulated radiotherapy (FIF-IMRT) and fixed-field inversely optimized intensity-modulated radiotherapy (FFIO-IMRT) for the whole-breast irradiation of patients undergoing right-breast lumpectomy. Material and methodsA total of 30 patients with pT1-2N0M0 right-breast invasive ductal carcinoma were enrolled in this study. Two different treatment plans, i.e., FIF-IMRT and FFIO-IMRT, were designed for each patient. The dosimetric parameters of the two treatment plans were compared including ipsilateral lung and heart, conformity index (CI), and the homogeneity index (HI) of the planning target volume (PTV). ResultsFixed-field inversely optimized intensity-modulated radiotherapy was found to significantly improve CI (83.302% vs. 60.146%) and HI (11.837% vs. 19.280%), and significantly reduced V25 (18.038% vs. 19.653%) and V30 (15.790% vs. 18.492%) of the ipsilateral lung. It also significantly increased V5 (69.791% vs. 32.615%) of the ipsilateral lung and V5 (61.579% vs. 3.829%), V10 (14.130% vs. 0.381%), V20 (1.843% vs. 0.051%), and Dmean (5.211Gy vs. 1.870Gy) of the heart. ConclusionRegardless of improving the conformity and homogeneity of PTV and reducing the ipsilateral lung irradiation volume at high doses, FFIO-IMRT significantly raised the ipsilateral lung irradiated volume at low doses, as well as the irradiation volume and mean radiation doses to the heart. This limits its use in patients with early-stage right breast cancer.

External Beam Accelerated Partial Breast Irradiation in Early Breast Cancer and the Risk for Radiogenic Pneumonitis.

Simple SummaryAccelerated partial breast irradiation represents a well-established and safe treatment alternative for selected patients with early stage breast cancer after breast-conserving surgery. In a prospective trial on external beam partial breast irradiation, the risk for radiogenic pneumonitis is analyzed. After a median follow-up of 56 (1–129) months, radiogenic pneumonitis grade 2 appeared in only 1/170 (0.6%) patients. Compared to standard whole breast irradiation, the radiation doses applied to the lungs were very low. The patient with the radiogenic pneumonitis was found to have a generally increased radiation susceptibility. Using accelerated partial breast irradiation, the risk of radiogenic pneumonitis appeared quite low and may be limited to very exceptional cases associated with innate risk factors with an increased radiation susceptibility.In order to evaluate the risk for radiation-associated symptomatic pneumonitis in a prospective external beam accelerated partial breast irradiation (APBI) trial, between 2011 and 2021, 170 patients with early stage breast cancer were enclosed in the trial. Patients were eligible for study participation if they had a histologically confirmed breast cancer or an exclusive ductal carcinoma in situ (DCIS), a tumor size ≤3 cm, free safety margins ≥2 mm, no involved axillary lymph nodes, tumor bed clips, and were ≥50 years old. Patients received APBI with 38 Gy with 10 fractions in 10 consecutive working days. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Median follow-up was 56 (1–129) months. Ipsilateral lung MLD, V20, and V30 were 4.3 ± 1.4 Gy, 3.0 ± 2.0%, and 1.0 ± 1.0%, respectively. Radiogenic pneumonitis grade 2 appeared in 1/170 (0.6%) patients two months after radiotherapy. Ipsilateral MLD, V20, and V30 were 6.1 Gy, 7, and 3% in this patient. Additionally, individual radiosensitivity was increased in this specific patient. Compared to WBI, APBI leads to lower lung doses. Using APBI, the risk of symptomatic radiogenic pneumonitis is very low and may be limited, with an ipsilateral V20 < 3% to very exceptional cases associated with innate risk factors with an increased radiation susceptibility.

Examination of the dose distribution of volumetric modulated arc radiotherapy using a high-definition multi-leaf collimator for breast cancer patients with irradiated regional lymph nodes.

BackgroundA high-definition multi-leaf collimator (HD-MLC) with 5- and 10-mm fine MLCs is useful for radiotherapy. However, it is difficult to irradiate the mammary gland and supraclavicular region using a HD-MLC because of the narrow field of volumetric modulated arc radiotherapy (VMAT). Therefore, we aimed to evaluate the dose distribution of the VMAT dose using a HD-MLC in 15 patients with left breast cancer undergoing postoperative irradiation of breast and regional lymph nodes, including the internal mammary node.Materials and methodsThe following four plans were generated: three-arc VMAT using HD-MLC (HD-VMAT), two tangential arcs and one-arc VMAT using HD-MLC (tHD-VMAT), three-dimensional conformal radiotherapy (3DCRT) using HD-MLC, and two-arc VMAT using the Millennium 120-leaf MLC (M-VMAT). We assessed the doses to the target volume and organs at risk.ResultsThe target dose distributions were higher for HD-VMAT than 3DCRT. There were no significant differences in the heart mean dose (Dmean) or lung volume receiving 20 Gy (V20 Gy) between HD-VMAT and 3DCRT. The heart Dmean and lung V20 Gy of tHD-VMAT were higher than those of HD-VMAT, and the heart Dmean of M-VMAT was higher than that of HD-VMAT. However, the target doses of tHD-VMAT, M-VMAT, and HD-VMAT were equivalent.ConclusionsIn cases of the mammary gland and regional lymph node irradiation, including the internal mammary node in patients with left breast cancer, HD-VMAT was not inferior to M-VMAT and provided a better dose distribution to the target volume and organs at risk compared with 3DCRT and tHD-VMAT.

Prospective study to compare the dose distribution and acute toxicity of three-dimentional conformal radiation therapy with intensity-modulated radiation therapy for post-mastectomy radiotherapy in carcinoma breast

Though adjuvant radiotherapy has an established role in the treatment of carcinoma breast, there is concern regarding irradiation to heart and lung, more on left sided disease. Intensity Modulated Radiation Therapy (IMRT) modulates the intensity of the radiation beams with better accuracy, sparing surrounding normal organs. But it increases integral dose to normal healthy tissues compared to 3-Dimensional Conformal Radiation Therapy (3DCRT). So, our study was aimed at comparing the dosimetry and acute toxicity profile of 3DCRT and IMRT in post-mastectomy patients. In study arm patients received radiotherapy with IMRT and in control arm with 3DCRT, radiation dose being 50 Gy in 25 fractions for 5 weeks for both the arms. We compared the dosimetric data for Planning Target Volume (PTV) and Organ At-risk (OAR) by both techniques along with acute toxicity profile. Dosimetric parameter of PTV coverage V95 and V107 were significantly better in IMRT than 3DCRT (p-value &lt;0.0001). IMRT showed better homogeneity index (0.14 Gy vs 0.26 Gy) and conformity index was also better for IMRT (0.94 Gy vs 0.74 Gy, p-value 0.0028). The mean value of heart V25 in left sided disease was significantly lower in IMRT than 3DCRT (22.59 and 25.64, p value 0.01). V20 of ipsilateral lung was numerically less in IMRT though not significant (31.44 vs 35.3). But low dose volume was significantly more in IMRT, as seen by higher V5 of heart and ipsilateral lung. To conclude, IMRT has better PTV coverage and better sparing of organs at risk with more homogenous and conformal plans than 3DCRT. Keywords: adjuvant radiotherapy; IMRT; 3DCRT; carcinoma breast

Accelerated hypofractionated breast radiotherapy with simultaneous integrated boost: a feasibility study.

PurposeTo assess the feasibility of accelerated hypofractionated radiotherapy with simultaneous integrated boost (SIB) in patients with breast cancer.Materials and MethodsA total of 27 patients after breast-conserving surgery were included in this study. Patients were planned on a four-dimensional computerized tomogram, and contouring was done using RTOG guidelines. The dose was 34 Gy/10#/2 week to the breast and 40 Gy/10#/2 week to the tumor bed as SIB with volumetric modulated arc technique. The primary endpoint was grade 2 acute skin toxicity. Doses to the organs-at-risk were calculated. Toxicities and cosmesis were assessed using RTOG/LENT/SOMA and HARVARD/NSABP/RTOG grading scales, respectively. Disease-free survival (DFS) and overall survival (OS) were calculated with Kaplan-Meier curves.ResultsThe mean age of the patients was 42 years. Left and right breast cancers were seen in 17 (63%) and 10 (37%) patients, respectively. The mean values of ipsilateral lung V16 and contralateral lung V5 were 16.01% and 3.74%, respectively. The mean heart doses from the left and right breast were 7.25 Gy and 4.37 Gy, respectively. The mean doses to the contralateral breast, oesophagus, and Dmax to brachial plexus were 2.64 Gy, 3.69 Gy, and 26.95 Gy, respectively. The mean value of thyroid V25 was 19.69%. Grade 1 and 2 acute skin toxicities were observed in 9 (33%) and 5 (18.5%) patients, respectively. Grade 2 hyperpigmentation, edema, and induration were observed in 1 (3.7%), 2 (7.4%), and 4 (14.8%) patients, respectively. Mild breast pain and arm/shoulder discomfort were reported by 1 (3.4%) patient. The median follow-up was 51 months (range, 12 to 61 months). At four years, breast induration, edema, and fibrosis were observed in 1 (3.7%) patient. Cosmesis was excellent and good in 21 (78%) and 6 (22%) patients, respectively. Local recurrence and distant metastases occurred in 1 (3.7%) and 2 (7.4%) patients, respectively. DFS and OS at four years were 88% and 92%, respectively.ConclusionWith this radiotherapy schedule, acute and late toxicity rates were acceptable with no adverse cosmesis. Local control, DFS, and OS were good.

Impact of pretreatment clinical factors and DVH parameters on radiation pneumonitis and survival after intensity-modulated radiotherapy for lung cancer.

e20571 Background: The aim of this study was to investigate the relationship between clinical factors and dose-volume histogram parameters regarding Overall Survival (OS) and Radiation-Pneumonitis-Free Survival (RPFS) in lung cancer patients. Methods: We retrospectively reviewed clinical data of lung cancer patients from 2018 to 2020. Demographic, clinical, and treatment-related data were collected for all patients. OS was defined as the duration from pathological diagnosis to death or last follow-up. RPFS was defined as the duration from the start of radiation therapy to occurrence of grade≥3 Radiation-Pneumonitis, or final follow-up. RPFS and OS rates were estimated with the Kaplan-Meier method and compared using the log-rank test. The Cox regression model was used to estimate the hazard ratio (HR) and the corresponding 95% confidence interval (CI) for univariate and multivariate analysis. Results: A-hundred patients were included in this study. The median follow-up period after completion of radiotherapy was 42.9months (range: 2.0–152.1). In multivariate study, low serum sodium after RT, V5ipsi≥51%, V20ipsi≥28%, V30ipsi≥22% and MLDipsi≥15.99 Gy were independent predictive factors for poor OS, respectively ( p ＜0.05). MLD≥10.20 Gy suggested a poorer RPFS ( p ＜0.1) in this cohort. Conclusions: The independent significant risk factors of radiation pneumonitis were V20, V5 and MLD. In addition, the V20 and V5 of the ipsilateral lung should be more strictly limited to less than 28% and 51% when determining radiotherapy especially in this era of immunotherapy. Some blood indexes of low nutritional status were very important to determine the occurrence of high-risk radiation pneumonitis.

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.