Thoracic Radiotherapy For Lung Cancer Research Articles

Cardiotoxicity following thoracic radiotherapy for lung cancer.

Radiotherapy is the standard of care treatment for unresectable NSCLC, combined with concurrent chemotherapy and adjuvant immunotherapy. Despite technological advances in radiotherapy planning and delivery, the risk of damage to surrounding thoracic tissues remains high. Cardiac problems, including arrhythmia, heart failure and ischaemic events, occur in 20% of patients with lung cancer who undergo radiotherapy. As survival rates improve incrementally for this cohort, minimising the cardiovascular morbidity of RT is increasingly important. Problematically, the reporting of cardiac endpoints has been poor in thoracic radiotherapy clinical trials, and retrospective studies have been limited by the lack of standardisation of nomenclature and endpoints. How baseline cardiovascular profile and cardiac substructure radiation dose distribution impact the risk of cardiotoxicity is incompletely understood. As Thoracic Oncology departments seek to expand the indications for radiotherapy, and as the patient cohort becomes older and more comorbid, there is a pressing need for cardiotoxicity to be comprehensively characterised with sophisticated oncology, physics and cardio-oncology evaluations. This review synthesises the evidence base for cardiotoxicity in conventional radiotherapy, focusing on lung cancer, including current data, unmet clinical needs, and future scientific directions.

Clinical predictors of severe radiation pneumonitis in patients undergoing thoracic radiotherapy for lung cancer

Clinical predictors of severe radiation pneumonitis in patients undergoing thoracic radiotherapy for lung cancer

A dynamic nomogram predicting symptomatic pneumonia in patients with lung cancer receiving thoracic radiation

PurposeThe most common and potentially fatal side effect of thoracic radiation therapy is radiation pneumonitis (RP). Due to the lack of effective treatments, predicting radiation pneumonitis is crucial. This study aimed to develop a dynamic nomogram to accurately predict symptomatic pneumonitis (RP ≥ 2) following thoracic radiotherapy for lung cancer patients.MethodsData from patients with pathologically diagnosed lung cancer at the Zhongshan People’s Hospital Department of Radiotherapy for Thoracic Cancer between January 2017 and June 2022 were retrospectively analyzed. Risk factors for radiation pneumonitis were identified through multivariate logistic regression analysis and utilized to construct a dynamic nomogram. The predictive performance of the nomogram was validated using a bootstrapped concordance index and calibration plots.ResultsAge, smoking index, chemotherapy, and whole lung V5/MLD were identified as significant factors contributing to the accurate prediction of symptomatic pneumonitis. A dynamic nomogram for symptomatic pneumonitis was developed using these risk factors. The area under the curve was 0.89(95% confidence interval 0.83–0.95). The nomogram demonstrated a concordance index of 0.89(95% confidence interval 0.82–0.95) and was well calibrated. Furthermore, the threshold values for high- risk and low- risk were determined to be 154 using the receiver operating curve.ConclusionsThe developed dynamic nomogram offers an accurate and convenient tool for clinical application in predicting the risk of symptomatic pneumonitis in patients with lung cancer undergoing thoracic radiation.

Predictive factors for severe radiation-induced lung injury in patients with lung cancer and coexisting interstitial lung disease

Background and purposeThis study aimed to investigate the predictive factors of severe radiation-induced lung injury (RILI) in patients with lung cancer and coexisting interstitial lung disease (ILD) undergoing conventionally fractionated thoracic radiotherapy. Materials and methodsThe study includes consecutive patients treated with thoracic radiotherapy for lung cancer at two tertiary centers between 2010 and 2021. RILI severity was graded using the National Cancer Institute Common Terminology Criteria version 5.0, with severe RILI defined as toxicity grade ≥4, and symptomatic RILI as grade ≥2. The absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and C-reactive protein were collected within 4 weeks before starting radiotherapy. Neutrophil–lymphocyte ratios (NLR) were calculated as ANC/ALC. The median follow-up was 9 (range, 6–114) months. ResultsAmong 54 patients, 22 (40.7 %) had severe RILI. On multivariate logistic regression analysis, high pretreatment ANC (p = 0.030, OR = 4.313), pretreatment NLR (p = 0.007, OR = 5.784), and ILD severity (p = 0.027, OR = 2.416) were significant predictors of severe RILI. Dosimetric factors were not associated with severe RP. Overall survival was significantly worse for patients with severe RILI than those without, with 1-year cumulative overall survival rates of 7.4 % and 62.8 %, respectively. ConclusionPretreatment blood NLR, ANC, and ILD severity were associated with severe RILI. Overall survival was dismal for patients with severe RILI.

EP05.01-016 Radiation Recall Pneumonitis (RRP) Induced by Immune Checkpoint Inhibitors (ICIs) after Thoracic Radiotherapy for Lung Cancer

Radiation recall pneumonitis (RRP) describes inflammatory reactions at previously irradiated fields of pulmonary tissue after exposure to certain systemic agents. Immune checkpoint inhibitors (ICIs) have been reported as potential causal agents of RRP in lung cancer. Yet, the general characteristics and risk factors of ICI-related RRP remain unclear. This study investigates the incidence, characteristics, and risk factors of RRP induced by ICIs after thoracic radiotherapy in patients with lung cancer.

Estimating the Probability of Not Completing the Intended Course of Thoracic Radiotherapy for Lung Cancer.

In some patients with lung cancer scheduled for thoracic radiotherapy (RT), treatment is discontinued before reaching the planned dose. For optimal treatment personalization, a tool estimating whether a patient can complete radiotherapy would be helpful. Eleven pre-RT characteristics were analyzed in 170 patients receiving local RT for lung cancer. Characteristics included age, sex, tumor site, histology, tumor and nodal stage, distant metastasis, surgery, systemic treatment, pulmonary function, and smoking history. Age >75 years (p=0.038), distant metastasis (p=0.009), and forced expiratory volume in 1 second <1.2 l (p=0.038) were significantly associated with discontinuation of RT. A prognostic instrument was developed in 126 patients with complete data regarding these characteristics. It included three groups (0, 1, and 2-3 points) with non-completion rates of 33.3%, 55.0% and 75.0% (p=0.004). This new instrument can help estimating the probability that lung cancer patients assigned to local RT cannot complete the planned course of RT.

Tumour motion management in lung cancer: a narrative review.

Respiratory motion is one of the geometrical uncertainties that may affect the accuracy of thoracic radiotherapy in the treatment of lung cancer. Accounting for tumour motion may allow reducing treatment volumes, irradiated healthy tissue and possibly toxicity, and finally enabling dose escalation. Historically, large population-based margins were used to encompass tumour motion. A paradigmatic change happened in the last decades led to the development of modern imaging techniques during the simulation and the delivery, such as the 4-dimensional (4D) computed tomography (CT) or the 4D-cone beam CT scan, has contributed to a better understanding of lung tumour motion and to the widespread use of individualised margins (with either an internal tumour volume approach or a mid-position/ventilation approach). Moreover, recent technological advances in the delivery of radiotherapy treatments (with a variety of commercial solution allowing tumour tracking, gating or treatments in deep-inspiration breath-hold) conjugate the necessity of minimising treatment volumes while maximizing the patient comfort with less invasive techniques. In this narrative review, we provided an introduction on the intra-fraction tumour motion (in both lung tumours and mediastinal lymph-nodes), and summarized the principal motion management strategies (in both the imaging and the treatment delivery) in thoracic radiotherapy for lung cancer, with an eye on the clinical outcomes.

Initial Clinical Experience Treating Patients With Lung Cancer on a 6MV-Flattening-Filter-Free O-Ring Linear Accelerator.

IntroductionModern technologies, like intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT), have improved the therapeutic ratio of thoracic radiotherapy (TRT) for lung cancer (LC). Halcyon™ (Varian Medical Systems, Palo Alto, CA, USA), a novel 6MV-flattening-filter-free O-ring linear accelerator (6X-FFF ORL), was designed to deliver IMRT and VMAT with greater speed than a C-arm linac. Herein, we report our initial clinical experience treating patients with LC on this linac.MethodsAll patients who received TRT for LC on the 6X-FFF ORL at our institution were retrospectively identified. Patients’ clinicopathologic data, radiotherapy details, early disease-control and toxicity outcomes, dosimetric data, couch corrections, and treatment times are reported.ResultsBetween 10/2018-12/2019, 30 consecutive patients (median age 66 years, range 54-94 years) received definitive or post-operative TRT for LC (median 66 Gy/33 fractions; range 5-70 Gy/2-37 fractions) following four-dimensional computed tomography (CT) simulation (97%) using daily kilovoltage KV cone-beam CT (CBCT) (100%) on a 6X-FFF ORL for non-small cell LC (84%) or small cell LC (16%), with 53% receiving VMAT, 43% receiving static-field IMRT, and 77% receiving concurrent systemic therapy. All plans were approved through institutional peer review. The average three-dimensional vector couch correction based on CBCT guidance was 0.90 ± 0.50 cm. The average beam-on and beam on plus CBCT times were 1.7 ± 1.1 min, and 5.0 ± 3.2 min, respectively. Grade 3 dyspnea and fatigue occurred in 3% and 3% of patients, respectively. There were no grade ≥4 toxicities.ConclusionIn this first clinical report of TRT for LC on a 6X-FFF ORL, daily CBCT-guided treatment was fast and safe with respect to dosimetry and clinical outcomes. Thus, use of this linac for TRT may increase LC patient throughput without a detriment in radiotherapy quality.

Clinical significance of radiation dose-volume parameters and functional status on the patient-reported quality of life changes after thoracic radiotherapy for lung cancer: a prospective study.

To date, limited data exist about the relationship between radiation dose-volume parameters and patient-reported quality of life (QOL) after thoracic radiotherapy (RT) for lung cancer. We conducted this prospective study to investigate which clinico-dosimetric factors have an impact on functional declines and symptom developments after thoracic RT for lung cancer. The study included 44 patients who had underwent thoracic three-dimensional conformal RT at our institution from 2016 to 2017. The health-related QOL was assessed using the EORTC QLQ-C30 and QLQ-LC13 questionnaires before RT (preRT), at the end of RT (endRT), and 3, 6, and 12months after the completion of RT. RT dose-volume parameters of adjacent normal organs such as the lung, heart, and esophagus were retrieved and used for regression analysis. Thoracic RT induced a temporary deterioration of many of the functional statuses and symptoms, but most of those improved and recovered to baseline levels 3months after RT. However, the role function (RF) decline persisted until 6months after RT (p < 0.05). Dysphagia showed the most noticeable change at the endRT (p < 0.001). In the multiple regression analysis, the absolute volume of body received at least 50Gy (p = 0.021) and a preRT RF score (p = 0.001) was significantly associated with the endRT RF scores. Dysphagia at the endRT was significantly associated with the V40 of the esophagus (p = 0.047), preRT emotional function (p = 0.029), and receipt of concurrent chemotherapy (p = 0.022). Both the dosimetric parameters and preRT functional status have an impact on the weak aspect of patient-reported QOL, which may cause poor treatment compliance during and after thoracic RT. For patients with a low preRT QOL score or those having large tumor which may result in higher dose volumes, careful RT planning could prevent the deterioration of QOL after RT.

EP1.01-75 Palliative Thoracic Radiotherapy for Lung Cancer: What Is the Most Appropriate Fractionation?

Radiotherapy is the one of the most effective modalities to palliate the symptoms (hemoptysis, pain, breathlessness) of poor-prognosis patients with advanced non-small-cell lung cancer. Most appropriate dose schedule however remains debatable. We conducted a retrospective analysis that compared the efficacy of radiotherapy schedules consisting of 5 fractions of 4 Gy (5 x 4 Gy) versus 10 fractions of 3Gy (10 x 3 Gy) in advanced Non Small Cell Lung Cancer (NSCLC). The end point evaluated was symptomatic relief. Between July 2016 and September 2017, 60 patients with advanced NSCLC were randomised to either 5 fractions of 4 Gy (5 x 4 Gy): Arm A or 10 fractions of 3Gy (10 x 3 Gy):Arm B. The eligibility criteria was histologically or cytologically confirmed NSCLC, age ≥ 30, stage III or IV disease, Karnofsky performance status (PS) ≥ 40, expected survival ≥ 3 months. The quality-of-life was assessed using the patient records: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and the lung cancer–specific module QLQ-LC13. The primary study end points was control of symptoms viz cough, hemoptysis, pain and dyspnea, and the secondary end point was to evaluate Overall Survival (OS). 52 out of 60 patients were males,18/60 had lost to follow up. Majority of patients presented in 5th and 6th decade of their lives, mean age of presentation was 58.87 (Range31-80). Majority (69%) of patients had presented with poor KPS 70 or less. Most common presenting symptom was cough with expectoration (74.66%) followed by hemoptysis (47.33%). Post treatment 36% reported reduced cough, 44% reported reduced dyspnea, 57% reported reduced pain and 90% reported reduced hemoptysis within 20 weeks from start of treatment, with no statistical difference among the groups. Except for improved hemoptysis at week 5 in Arm A (P =0.03), there was no difference among the groups. Furthermore, the palliative effect of symptoms seemed to last throughout the planned follow-up period. Overall survival for all patients (n=42) revealed no significant survival difference among the treatment groups (P = 0.2). The median survival was 6.2 and 6.7 months in arm A and B, respectively. Hypofractionated regimen of 20Gy/5 fractions is atleast as effective at providing symptomatic relief and yields equivalent survival as 30Gy/10 fractions in patients with advanced non-small cell lung cancer and thoracic symptoms besides having the advantage of fewer visits to hospital as well.

Palliative Thoracic Radiotherapy for Lung Cancer: What Is the Most Appropriate Fractionation?

Palliative Thoracic Radiotherapy for Lung Cancer: What Is the Most Appropriate Fractionation?

The conditioned medium of human mesenchymal stromal cells reduces irradiation-induced damage in cardiac fibroblast cells.

Recently, multipotent mesenchymal stromal cell (MSC) treatment has attracted special attention as a new alternative strategy for stimulating regeneration. Irradiation myocardial fibrosis (IMF) is a major complication associated with total body irradiation for hematopoietic stem cell transplantation, nuclear accidents, and thoracic radiotherapy for lung cancer, esophageal cancer, proximal gastric cancer, breast cancer, thymoma, and lymphoma. The aim of the present study was to assess the therapeutic paracrine effects of human umbilical cord–derived mesenchymal stromal cells (UC-MSCs) in the cell model of IMF. For this purpose, primary human cardiac fibroblasts (HCF) cells were irradiated and cultured with the conditioned medium of UC-MSCs (MSCCM). MSCCM promoted cell viability, reduced collagen deposition as measured by Sircol assay and qPCR (Col1A1 and Col1A2), prevented oxidative stress and increased antioxidant status (as measured by malondialdehyde content and the activities and mRNA levels of antioxidant enzymes), and reduced pro-fibrotic TGF-β1, IL-6 and IL-8 levels (as examined by ELISA kit and qPCR). Pretreatment with inhibitor of NF-κB led to a decrease in the levels of TGF-β1 in cell lysate of HCF cells by ELISA kit. Furthermore, we also found that MSCCM prevented NF-κB signaling pathway activation for its proinflammatory actions induced by irradiation. Taken together, our data suggest that MSCCM could reduce irradiation-induced TGF-β1 production through inhibition of the NF-κB signaling pathway. These data provide new insights into the functional actions of MSCCM on irradiation myocardial fibrosis.

A Four-Tiered Prognostic Score for Patients Receiving Palliative Thoracic Radiotherapy for Lung Cancer

ABSTRACTPalliative radiotherapy improves lung cancer related symptoms. Prognosis should be taken into account when deciding about fractionation. In this study, prognostic factors derived from multivariate analysis were used to assign a point sum reflecting 6-month survival. Four prognostic groups were compared. Performance status, lactate dehydrogenase, C-reactive protein, liver/adrenal gland metastases, and extrathoracic disease status significantly predicted survival and formed the basis of the score. The four groups had a median survival of 0.8, 1.6, 3.3, and 10.5 months (6-month survival 0, 10, 30, 70%; 12-month survival 0, 0, 12, 40%; p = 0.0001), respectively. In the unfavorable group best supportive care might be preferable.

European Organization for Research and Treatment of Cancer (EORTC) recommendations for planning and delivery of high-dose, high precision radiotherapy for lung cancer

PurposeTo update literature-based recommendations for techniques used in high-precision thoracic radiotherapy for lung cancer, in both routine practice and clinical trials. MethodsA literature search was performed to identify published articles that were considered clinically relevant and practical to use. Recommendations were categorised under the following headings: patient positioning and immobilisation, Tumour and nodal changes, CT and FDG-PET imaging, target volumes definition, radiotherapy treatment planning and treatment delivery. An adapted grading of evidence from the Infectious Disease Society of America, and for models the TRIPOD criteria, were used. ResultsRecommendations were identified for each of the above categories. ConclusionRecommendations for the clinical implementation of high-precision conformal radiotherapy and stereotactic body radiotherapy for lung tumours were identified from the literature. Techniques that were considered investigational at present are highlighted.

External Validation of a Prognostic Score for Patients Receiving Palliative Thoracic Radiotherapy for Lung Cancer

BackgroundPalliative thoracic radiotherapy is a common treatment for patients with incurable lung cancer. A recent study suggested that a prognostic score based on performance status and N and M stage predicts survival and might support decision-making (eg, when deciding about fractionation). Our aim was to perform a validation study in an independent, larger dataset. Patients and MethodsThis was a retrospective single-institution study of 232 patients with small- or non–small-cell lung cancer, with methodology comparable with that of the original study. Three subgroups were created, based on the point sum resulting from assessment of performance status and N and M stage (10-11, 12-14, 15-17 points). ResultsPerformance status and N and M stage were significantly associated with overall survival after palliative radiotherapy in uni- and multivariate analyses. An unfavorable prognosis (10-11 points) was predicted in 56 patients (24%). Their median survival was 1.2 months. The intermediate group consisted of 137 patients (59%) with a median survival of 5.3 months. A favorable prognosis (15-17 points) was predicted in 39 patients (17%), whose median survival was 8.2 months. The difference between the intermediate and favorable subgroups did not reach statistical significance (P = .1, as compared with P = .0001 for the remaining 2 comparisons). ConclusionIn the original study, the median survival of patients in the 3 different prognostic strata was 2, 6, and 38 months. Except for the favorable subgroup, the validation study confirmed these results. Given the large, clinically highly relevant discrepancy (8 vs. 38 months), additional studies are needed in order to inform therapeutic decisions in patients with favorable point sum of 15 to 17.

Palliative Thoracic Radiotherapy for Lung Cancer: What Is the Impact of Total Radiation Dose on Survival?

BackgroundEffective symptom palliation can be achieved with low-dose palliative thoracic radiotherapy. In several studies, median survival was not improved with higher doses of radiation. More controversy exists regarding the impact of higher doses on 1- and 2-year survival rates. Therefore, a comparison of survival outcomes after radiotherapy with different biologically equivalent doses (equivalent dose in 2-Gy fractions, EQD2) was performed.MethodsThis was a retrospective single-institution study of 232 patients with small or non-small cell lung cancer. Most commonly 2 fractions of 8.5 Gy were prescribed (34%), followed by 10 fractions of 3 Gy or equivalent regimens (30%, EQD2 circa 33 Gy). The highest EQD2 consisted of 45 Gy. Intention-to-treat analyses were performed.ResultsSurvival was significantly shorter with regimens of intended EQD2 < 33 Gy, e.g., 2 fractions of 8.5 Gy (median 2.5 months compared to 5.0 and 7.5 months with EQD2 of circa 33 and 45 Gy, respectively). The 2-year survival rates were 0%, 7% and 11%, respectively. In 128 prognostically favorable patients, median survival was comparable for the three different dose levels (6 - 8.3 months). The 2-year survival rates were 0%, 10%, and 13%, respectively (not statistically significant).ConclusionAlthough most of the observed survival differences diminished after exclusion of poor prognosis patients with reduced performance status and/or progressive extrathoracic disease, a slight increase in 2-year survival rates with higher EQD2 cannot be excluded. Because of relatively small improvements, a confirmatory randomized trial in this subgroup would have to include a large number of patients.

Which Radiation Therapy Schedule in Combination With Chemotherapy For Locally Advanced NSCLC?

Concurrent chemoradiotherapy is the standard of care in the management of locally advanced NSCLC, with disappointing results in terms of local tumor control and overall survival. Hystorically, it has been demonstrated a strict dose–response relationship in thoracic radiotherapy for lung cancer and, therefore, dose escalation was tested in many prospective trials. In this paper, we briefly review the most relevant publications focusing on dose management in terms of dose escalation with both conventional and altered fractionation schedules.

421PD Prospective monitoring of lung function tests with CO and NO diffusion during high dose thoracic radiotherapy for lung cancer: The CONORT study

421PD Prospective monitoring of lung function tests with CO and NO diffusion during high dose thoracic radiotherapy for lung cancer: The CONORT study

Risk Factors for Treatment-Related Death Associated with Chemotherapy and Thoracic Radiotherapy for Lung Cancer

The aim of the study is to evaluate the current status of treatment-related death (TRD) in lung cancer patients. We retrospectively analyzed the incidence and risk factors of TRD in lung cancer patients who received chemotherapy and/or thoracic radiotherapy using logistic regression analyses. Between January 2001 and December 2005, 1225 (222 small cell and 1003 non-small cell lung cancers) patients received chemotherapy and/or thoracic radiotherapy as the initial treatment. Of these, 43 patients receiving chemotherapy followed by thoracic radiotherapy were included into both the chemotherapy-alone and radiotherapy-alone groups. There were a total of 23 (1.9%) TRDs. Chemotherapy-related deaths occurred in 7 of 927 (0.8%) patients, including 4 from drug-induced lung injury, 2 from pneumonia, and 1 from unknown cause. Concurrent chemoradiotherapy-related deaths occurred in 12 of 245 (4.9%) patients, including 11 from radiation pneumonitis and 1 from pneumonia. Thoracic radiotherapy-related deaths occurred in 4 of 96 (4.2%) patients. The incidence of chemotherapy-related death was correlated with poor performance status (odds ratio [OR]: 11.4, 95% confidence interval [CI]: 3.53-37.1), the presence of hypoxia (OR: 19.3, CI: 6.06-61.7), hyponatremia (OR: 45.5, CI: 13.4-154), and treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (OR: 8.56, CI: 2.48-29.5), whereas the incidence of concurrent chemoradiotherapy-related death was correlated with pulmonary fibrosis (OR: 22.2, CI: 5.61-87.8). Radiotherapy results were not analyzed because there were too few patients. TRD occurred in 1.9% of the patients as a result of treatment-related lung injury in the majority of the cases.

Radiation recall pneumonitis induced by chemotherapy after thoracic radiotherapy for lung cancer

BackgroundRadiation recall pneumonitis (RRP) describes a rare reaction in previously irradiated area of pulmonary tissue after application of triggering agents. RRP remains loosely characterized and poorly understood since it has so far only been depicted in 8 cases in the literature. The objective of the study is to disclose the general characteristics of RRP induced by chemotherapy after thoracic irradiation for lung cancer, and to draw attention to the potential toxicity even after a long time interval from the previous irradiation.MethodsMedical records were reviewed. RRP induced by chemotherapy was diagnosed by the history of chemotherapy after radiotherapy, clinical presentation and radiographic abnormalities including ground-glass opacity, attenuation, or consolidation changes within the radiation field, plus that radiographic examination of the thorax before showed no radiation pneumonitis. RRP was graded according to Common Terminology Criteria for Adverse Events version 3.0. The characteristics of the 12 RRP cases were analyzed.ResultsTwelve patients were diagnosed of RRP, of who 8 received taxanes. The median time interval between end of radiotherapy and RRP, between end of radiotherapy and beginning of chemotherapy, and between beginning of chemotherapy and RRP was 95 days, 42 days and 47 days, respectively. Marked symptomatic and radiographic improvement was observed in the 12 patients after withdrawal of chemotherapy and application of systemic corticosteroids. Seven patients were rechallenged with chemotherapy, of whom four with the same kind of agents, and showed no recurrence with steroid cover.ConclusionsDoctors should pay attention to RRP even after a long time from the previous radiotherapy or after several cycles of consolidation chemotherapy. Taxanes are likely to be associated with radiation recall more frequently. Withdrawal of causative agent and application of steroids are the treatment of choice. Patients may be rechallenged safely with steroid cover and careful observation, which needs to be validated.