Search

Introduction: Blood samples were collected to explore potential serum biomarkers associated with neurocognitive function in small-cell lung cancer (SCLC) patients who received prophylactic cranial irradiation (PCI)., Methods: This pre-specified study included patients with blood samples available, who participated in a phase III trial (NCT01780675). Blood samples were collected before PCI and 3-days post-initiating PCI. Neurocognitive decline was defined as a decrease of ≥ 5 points on total recall in the Hopkins Verbal Learning Test-Revised (HVLT-R) assessed from pre-PCI to 4-months post-PCI. Biomarkers were screened using univariate logistic regression analysis. P < .1 was considered statistically significant., Results: Forty-eight enrolled patients who had blood samples at baseline were included and 27 were available for analysis as the other 21 did not assess neurocognitive function at 4-months. Lower levels of Tie-2 (OR = 0.999, 90% CI 0.998-1.000, P = .062), and higher levels of MIP-1b (OR = 1.022, 90% CI 1.000-1.044, P = .093), CCL-17 (OR = 1.004, 90% CI 1.001-1.006, P = .029), and IL-1α (OR = 1.597, 90% CI 1.077-2.367, P = .05) before PCI were correlated with neurocognitive decline at 4-months. Decrease of VEGF-C (OR = 0.972, 90% CI 0.949-0.996, P = .055), CCL-17 (OR = 0.993, 90% CI 0.988-0.999, P = .036), IL-1α (OR = 0.788, 90% CI 0.635-0.979, P = .071), and VEGF (OR = 0.981, 90% CI 0.965-0.997, P = .051) 3-days post-initiating PCI were also associated with neurocognitive decline at 4-months., Conclusions: Biomarker levels before PCI and changes in their levels 3-days post-initiating PCI may be linked to subsequent neurocognitive decline at 4-months. If validated, these biomarkers could be used to predict the risk of neurocognitive decline and act as a decision aid for personalized PCI in SCLC., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Stereotactic body radiotherapy (SBRT) has firmly established its role in stage I NSCLC. Clinical trial results may not fully apply to real-world scenarios. This study aimed to uncover the real-world incidence of acute toxicity and 90-day mortality in patients with SBRT-treated stage I NSCLC and develop prediction models for these outcomes., Methods: Prospective data from the Dutch Lung Cancer Audit for Radiotherapy (DLCA-R) were collected nationally. Patients with stage I NSCLC (cT1-2aN0M0) treated with SBRT in 2017 to 2021 were included. Acute toxicity was assessed, defined as grade greater than or equal to 2 radiation pneumonitis or grade greater than or equal to 3 non-hematologic toxicity less than or equal to 90 days after SBRT. Prediction models for acute toxicity and 90-day mortality were developed and internally validated., Results: Among 7279 patients, the mean age was 72.5 years, with 21.6% being above 80 years. Most were male (50.7%), had WHO scores 0 to 1 (73.3%), and had cT1a-b tumors (64.6%), predominantly in the upper lobes (65.2%). Acute toxicity was observed in 280 (3.8%) of patients and 90-day mortality in 122 (1.7%). Predictors for acute toxicity included WHO greater than or equal to 2, lower forced expiratory volume in 1 second and diffusion capacity for carbon monoxide, no pathology confirmation, middle or lower lobe tumor location, cT1c-cT2a stage, and higher mean lung dose (c-statistic 0.68). Male sex, WHO greater than or equal to 2, and acute toxicity predicted higher 90-day mortality (c-statistic 0.73)., Conclusions: This nationwide study revealed a low rate of acute toxicity and an acceptable 90-day mortality rate in patients with SBRT-treated stage I NSCLC. Notably, advanced age did not increase acute toxicity or mortality risk. Our predictive models, with satisfactory performance, offer valuable tools for identifying high-risk patients., Competing Interests: Disclosure The authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Purpose: Stereotactic body radiation therapy (SBRT) in lung tumors has an excellent local control due to the high delivered dose. Proximity of the proximal bronchial tree (PBT) to the high dose area may result in pulmonary toxicity. Bronchial stenosis is an adverse event that can occur after high dose to the PBT. Literature on the risk of developing bronchial stenosis is limited. We therefore evaluated the risk of bronchial stenosis for tumors central to the PBT and correlated the dose to the bronchi., Methods and Materials: Patients with a planning tumor volume (PTV) ≤2 cm from PBT receiving SBRT (8 × 7.5 Gy) between 2015 to 2019 were retrospectively reviewed. Main bronchi and lobar bronchi were manually delineated. Follow-up computed tomography scans were analyzed for bronchial stenosis and atelectasis. Bronchial stenosis was assessed using Common Terminology Criteria for Adverse Events Version 4.0 (CTCAEv4). Patient, tumor, dosimetric factors and survival were evaluated between patients with and without stenosis using uni- and multivariate and Kaplan-Meier analysis., Results: Fifty-one patients were analyzed with a median age of 70 years and World Health Organization (WHO) performance status ≤1 in 92.2%. Median follow-up was 36 months (interquartile range [IQR], 19.6-45.4) and median overall survival 48 months (IQR 21.5-59.3). In 15 patients (29.4%) bronchial stenosis was observed on follow-up computed tomography scan. Grade 1 stenosis was seen in 21.6% (n = 11), grade 2 in 7.8% (n = 4). No grade ≥3 stenosis was observed. Median time to stenosis was 9.6 months (IQR 4.4-19.2). Patients who developed stenosis had significantly larger gross tumor volume with a median of 19 cm 3 (IQR 7.7-63.2) versus 5.2 cm 3 (IQR 1.7-11.3, P <.01). Prognostic factors in multivariate analysis for stenosis were age (P = .03; odds ratio [OR] 1.1), baseline dyspnea (P = .02 OR 7.7), and the mean lobar bronchus dose (P = .01; OR 1.1)., Conclusions: Low-grade (≤2) lobar bronchial stenosis is a complication in approximately one-third of patients after SBRT for lung tumors with a PTV ≤2 cm from PBT. Prognostic risk factors were age, baseline dyspnea and mean dose on a lobar bronchus., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Toxicity concerns from thoracic radiation therapy in the treatment of lung cancers have changed substantially over the past few decades. Survival in the treatment of lung cancer has markedly improved and the introduction of advanced radiation and imaging techniques to treatment planning and delivery has made reducing toxicity possible. Phase 3 dose-escalation trials have revealed that excess dose to critical organs within the thorax can negatively impact overall survival. We summarize the existing literature on the known toxicities of thoracic radiation therapy, summarize the technological advances that have made toxicity reduction possible, and provide an overview of emerging technologies and biomarkers that are being evaluated to assess future toxicity reductions., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Background: The role of postoperative radiation therapy (PORT) in stage III N2 NSCLC is controversial. We analyzed decision-making for PORT among European radiation oncology experts in lung cancer., Methods: Twenty-two experts were asked before and after presentation of the results of the LungART trial to describe their decision criteria for PORT in the management of pN+ NSCLC patients. Treatment strategies were subsequently converted into decision trees and analyzed., Results: Following decision criteria were identified: extracapsular nodal extension, incomplete lymph node resection, multistation lymph nodes, high nodal tumor load, poor response to induction chemotherapy, ineligibility to receive adjuvant chemotherapy, performance status, resection margin, lung function and cardiopulmonary comorbidities. The LungART results had impact on decision-making and reduced the number of recommendations for PORT. The only clear indication for PORT was a R1/2 resection. Six experts out of ten who initially recommended PORT for all R0 resected pN2 patients no longer used PORT routinely for these patients, while four still recommended PORT for all patients with pN2. Fourteen experts used PORT only for patients with risk factors, compared to eleven before the presentation of the LungART trial. Four experts stated that PORT was never recommended in R0 resected pN2 patients regardless of risk factors., Conclusion: After presentation of the LungART trial results at ESMO 2020, 82% of our experts still used PORT for stage III pN2 NSCLC patients with risk factors. The recommendation for PORT decreased, especially for patients without risk factors. Cardiopulmonary comorbidities became more relevant in the decision-making for PORT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: To compare neurocognitive functioning in patients with SCLC who received prophylactic cranial irradiation (PCI) with or without hippocampus avoidance (HA)., Methods: In a multicenter, randomized phase 3 trial (NCT01780675), patients with SCLC were randomized to standard PCI or HA-PCI of 25 Gy in 10 fractions. Neuropsychological tests were performed at baseline and 4, 8, 12, 18, and 24 months after PCI. The primary end point was total recall on the Hopkins Verbal Learning Test-Revised at 4 months; a decline of at least five points from baseline was considered a failure. Secondary end points included other cognitive outcomes, evaluation of the incidence, location of brain metastases, and overall survival., Results: From April 2013 to March 2018, a total of 168 patients were randomized. The median follow-up time was 26.6 months. In both treatment arms, 70% of the patients had limited disease and baseline characteristics were well balanced. Decline on the Hopkins Verbal Learning Test-Revised total recall score at 4 months was not significantly different between the arms: 29% of patients on PCI and 28% of patients on HA-PCI dropped greater than or equal to five points (p = 1.000). Performance on other cognitive tests measuring memory, executive function, attention, motor function, and processing speed did not change significantly different over time between the groups. The overall survival was not significantly different (p = 0.43). The cumulative incidence of brain metastases at 2 years was 20% (95% confidence interval: 12%-29%) for the PCI arm and 16% (95% confidence interval: 7%-24%) for the HA-PCI arm., Conclusions: This randomized phase 3 trial did not find a lower probability of cognitive decline in patients with SCLC receiving HA-PCI compared with conventional PCI. No increase in brain metastases at 2 years was observed in the HA-PCI arm., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: The objective of this study was to determine the predictors and patterns of regional recurrence (RR) following stereotactic body radiotherapy (SBRT) for primary lung cancers., Material and Methods: Details of patient factors, treatment, and outcome factors were extracted from a multi-institutional (5) database. All events were calculated from the end of radiotherapy. Estimates of local recurrence, RR, and distant metastases (DM) were calculated using the competing risk method. Cause-specific and overall survival were calculated using the Kaplan-Meier method. Details of locations and number of simultaneous RRs were categorized by lymph node anatomic station., Results: A total of 734 patients were analyzed. The median follow-up was 3.0 years in surviving patients. Four hundred seventy-six (65%) patients had pathologic proof of disease. There were 64 patients with RR. The 2-year local recurrence, RR, and distant metastases rates were 5.6%, 9.0%, and 14.6% respectively. The 2-year cause-specific and overall survival were 89.9% and 63.7%, respectively. There were 136 simultaneous sites of RR. There were 21 recurrences in stations 4R (15.4%), 9 (6.6%) in 4L, 30 (22%) in 7, 19 (13.9%) in 10R, and 14 (10.3%) in 10L. The most common stations for isolated recurrence (n = 19) were station 7 (n = 5; 26.3%) and station 10R (n = 6; 31.6%). The most common RR levels were stations 4 and 7 for right and left upper lobe, stations 5, 7, and 10 for left lower lobe tumors, and stations 7 and 10 for right lower lobe tumors., Conclusion: Stations 4, 7, and 10 were the most common stations for RR. These patterns of recurrence may guide nodal staging procedures prior to SBRT., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Stereotactic body radiotherapy (SBRT) is the guideline-recommended treatment for medically inoperable patients with peripheral stage I non-small cell lung cancer (NSCLC). This study analyzed whether short-term (<6 months) death can be predicted reliably to select a subgroup of patients who will not have a benefit from SBRT., Methods: A total of 779 patients with early-stage NSCLC who had been treated with cone beam computed tomography-guided SBRT in five institutes and for whom information on overall survival during the first 6 months after treatment was available were included in this analysis. The probability of dying within 6 months after treatment was defined as the end point "early death" and modeled by multivariate logistic regression. Model fitting was performed using the least absolute shrinkage and selection operator method, and model test performance was estimated using double 10-fold cross validation. The variables age, sex, Eastern Cooperative Oncology Group performance status, operability, forced expiratory volume in 1 second, and Charlson comorbidity index were considered for model building., Results: Eastern Cooperative Oncology Group performance status and (to a lesser extent) operability were the most important predictors of early death, whereas the Charlson comorbidity index was associated only with the overall survival time. On the basis of the best expected test performance (area under the curve = 0.699), the risk for early death would be 8.8% (range 8.2%-13.7%) and 4.1% (3.0%-4.3%) for the 10% of patients with the highest and lowest risk, respectively. Overall, predictive performance was too low for clinical application., Conclusions: SBRT should be offered to all patients irrespective of their comorbidities, unless the performance status of the patients and the comorbidities prevent accurate SBRT planning and delivery., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Intensity modulated radiotherapy (IMRT) is increasingly used with concurrent chemotherapy but toxicity data are not well investigated. We correlated clinical and dosimetric parameters with acute toxicity grade ≥ 3 in patients with locally advanced NSCLC treated with IMRT and concurrent low-dose cisplatin., Patients and Methods: We analyzed age, PS, comorbidities, gross tumor volume, and the volume of the esophagus irradiated with 50 Gy (V50oes) in relation with acute toxicity. The mean lung dose (MLD) and pulmonary toxicity was described. Treatment consisted of 24 × 2, 75 Gy, and daily cisplatin 6 mg/m². Patients with an MLD ≥ 20 Gy or a PS > 2 were excluded from CCRT. Toxicity was prospectively scored using the Common Toxicity Criteria for adverse events version 3.0. The Charlson Comorbidity Index (CCI) was applied for scoring comorbidities. Multivariable logistic regressions for toxicity and survival estimates (Kaplan-Meier) were used for evaluation., Results: From 2008 to 2011, 188 patients received standard CCRT. In 35% of the patients, acute toxicity grade ≥ 3 was reported. Grade 5 toxicity was scored in 1% of the patients. V50oes (odds ratio [OR], 1.33 per 10% increase; P = .01) and PS ≥ 2 (OR, 3.45; P = .07) were significantly correlated with acute toxicity ≥ grade 3. No differences in toxicity were observed between age groups (< 70 and ≥ 70; P = .26), and those with a CCI score < 5 and ≥ 5, and acute severe toxicity (P = .36). Grade ≥ 3 pulmonary toxicity was seen in 7%. The 1- and 2-year overall survival in stage III disease were 78% and 52%, respectively. Patients with a poor PS or a high CCI score had similar survival outcomes., Conclusion: Concurrent low-dose cisplatin using IMRT is effective in a large cohort of consecutive patients with NSCLC and life threatening toxicity is rare (1%). PS ≥ 2 and V50oes are correlated with acute toxicity grade ≥ 3., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Concurrent radiochemotherapy (RCT) is the treatment of choice for patients with locally advanced non-small-cell lung cancer (NSCLC). Two meta-analyses were inconclusive in an attempt to define the optimal concurrent RCT scheme. Besides efficacy, treatment toxicity will influence the appointed treatment of choice. A systematic review of the literature was performed to record the early and late toxicities, as well as overall survival, of concurrent RCT regimens in patients with NSCLC. The databases of PubMed, Ovid, Medline, and the Cochrane Library were searched for articles on concurrent RCT published between January 1992 and December 2009. Publications of phase II and phase III trials with ≥ 50 patients per treatment arm were selected. Patient characteristics, chemotherapy regimen (mono- or polychemotherapy, high or low dose) and radiotherapy scheme, acute and late toxicity, and overall survival data were compared. Seventeen articles were selected: 12 studies with cisplatin-containing regimens and 5 studies using carboplatin. A total of 13 series with mono- or polychemotherapy schedules--as single dose or double or triple high-dose or daily cisplatin-containing (≤ 30 mg/m(2)/wk) chemotherapy were found. Acute esophagitis ≥ grade 3 was observed in up to 18% of the patients. High-dose cisplatin regimens resulted in more frequent and severe hematologic toxicity, nausea, and vomiting than did other schemes. The toxicity profile was more favorable in low-dose chemotherapy schedules. From phase II and III trials published between 1992 and 2010, it can be concluded that concurrent RCT with monochemotherapy consisting of daily cisplatin results in favorable acute and late toxicity compared with concurrent RCT with single high-dose chemotherapy, doublets, or triplets., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The prognosis of patients with lung cancer has improved over the past years. Patient selection, optimal sequencing of systemic and local treatments, and better surgical techniques, together with unprecedented improvements in imaging and computer technology and technical advances in radiation therapy planning and delivery has revolutionized radiation therapy in a short period of time. Among the most significant evolutions that have direct implications for daily practice are the more widespread use of stereotactic body radiation for stage I non-small-cell lung cancer (NSCLC), concurrent chemoradiation for stage III NSCLC, the implementation of 4-dimensional computed tomography and positron emission tomography, adaptive radiation therapy strategies, optimizing the timing of chest radiation therapy for limited disease small-cell lung cancer (SCLC) and prophylactic cranial irradiation for extensive disease SCLC. Molecular-based individualized radiation therapy dose prescription, which goes hand in hand with the realization of decision-support systems and the introduction of proton therapy centers give only a glimpse of what the future will bring., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: The aim of our study was to evaluate the clinical performance/ implementation of integrated F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) for differentiation of pulmonary pathology in an approach of outpatient fast track assessment., Methods: A prospective study was performed in 114 consecutive patients with pulmonary symptoms and/or abnormal chest x-ray were referred for fast track assessment to the Netherlands Cancer Institute from March 2005 to September 2007. The presence of malignancy was evaluated in a multidisciplinary setting, including F-fluorodeoxyglucose-PET, diagnostic CT, and bronchoscopy (including biopsy), with histopathological evaluation as the reference standard., Results: In 105 patients (92%), a final diagnosis was achieved. A malignancy was diagnosed in 84% of the patients; non-small cell lung cancer in 67%, small cell lung cancer in 7%, and metastases or other malignancies in 10%. Nonmalignant lesions were found in 16% of the patients. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value of positive PET/CT for the presence of malignancy were 97, 56, 90, 92, and 77%, respectively. PET/CT showed unexpected M1 disease (not detected on CT) in 10% of the patients. Almost half of the patients with a malignancy were scheduled for curative treatment, of whom 29 patients for surgery and 14 patients for chemoradiotherapy., Conclusion: In this outpatient fast track setting, PET/CT provides valuable information for diagnosing lung cancer, with a high positive predictive value, and is useful for clinical decision making.