No abstract

Purpose To investigate the plasma dynamics of 5 proinflammatory/fibrogenic cytokines, including interleukin-1beta (IL-1β), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta1 (TGF-β1) to ascertain their value in predicting radiation-induced lung toxicity (RILT), both individually and in combination with physical dosimetric parameters. Methods and Materials Treatments of patients receiving definitive conventionally fractionated radiation therapy (RT) on clinical trial for inoperable stages I–III lung cancer were prospectively evaluated. Circulating cytokine levels were measured prior to and at weeks 2 and 4 during RT. The primary endpoint was symptomatic RILT, defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis. Minimum follow-up was 18 months. Results Of 58 eligible patients, 10 (17.2%) patients developed RILT. Lower pretreatment IL-8 levels were significantly correlated with development of RILT, while radiation-induced elevations of TGF-β1 were weakly correlated with RILT. Significant correlations were not found for any of the remaining 3 cytokines or for any clinical or dosimetric parameters. Using receiver operator characteristic curves for predictive risk assessment modeling, we found both individual cytokines and dosimetric parameters were poor independent predictors of RILT. However, combining IL-8, TGF-β1, and mean lung dose into a single model yielded an improved predictive ability (P<.001) compared to either variable alone. Conclusions Combining inflammatory cytokines with physical dosimetric factors may provide a more accurate model for RILT prediction. Future study with a larger number of cases and events is needed to validate such findings.

No abstract

Introduction Perfusion (Q) single photon emission computerized tomography (SPECT) has been used to divert dose away from higher-functioning lung during radiation therapy (RT) planning. This study aimed to 1) study regional lung function through co-registered pulmonary ventilation/perfusion (V/Q) SPECT-CT, and 2) classify these defects for its potential value in radiation planning in patients with non-small cell lung cancer (NSCLC). Methods Patients with stages I-III NSCLC requiring radiation-based therapy were eligible for this prospective study. V/Q SPECT performed within 2 weeks prior to radiation start was interpreted by nuclear medicine physicians and then measured by a semi-quantitative score. The potential mechanism of V, Q defect was analyzed; the potential impact of V/Q SPECT over Q SPECT alone was completed through classified applications (high dose RT versus RT avoidance) during planning. Results Images of 51 consecutive patients were analyzed. The V, Q defects were matched, reverse mismatched (V- defect greater than Q-defect), and mismatched (Q-defect greater than V-defect) in 61%, 31% and 8% patients, respectively. Tumor was the leading cause of the defects of ipsilateral lung in 73% patients. The defect scores of the ipsilateral lung were greater in patients with central primaries than those with peripheral primaries for both V- (2.3±1.1 vs. 1.5±0.8, p=0.017) and Q-SPECT (2.2±0.8 vs. 1.4±0.6, p=0.000). The patients with chronic obstructive pulmonary disease had greater defect scores in contralateral lung for both V- (1.5±0.7 vs. 1.0±0.8, p=0.006) and Q- SPECT (1.4±0.6 vs. 1.0±0.4, p=0.010). On assessing the potential value of SPECT on RT plan, 39% patients could have their RT plan if applying V/Q SPECT rather than Q SPECT alone. Conclusions V/Q SPECT provides a more comprehensive functional assessment, may provide additional value over Q-SPECT alone in assessing local pulmonary function and guide RT plan decisions in patients with NSCLC.

BackgroundYoung non-small cell lung cancer (NSCLC) patients under the age of 40 can further be categorized into different age subgroups. Whether they have homogeneous clinical features and survival outcomes remains unexplored.MethodsInformation of 4623 NSCLC patients up to 40 years old from 1988 to 2012 was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Clinicopathologic characteristics and survival outcomes were compared between patients diagnosed at 18–30 years old (younger group) and those at 31–40 years old (older group).ResultsThe proportion of patients in the younger group among all lung cancer patients was stable between 1988 and 2012. However, the proportion of patients in the older group decreased from 1.2% to 0.5%. The younger patients had a higher proportion of adenocarcinoma (P = 0.016), a lower proportion of large cell carcinoma (P = 0.008), a higher proportion of stage I disease (P = 0.002) and a lower proportion of stage III disease (P < 0.001). The younger patients had significantly better lung cancer-specific survival (LCSS) in the whole cohort (P < 0.001) and in the subgroup of patients with stage I (P = 0.038) or stage IV (P < 0.001) disease. Multivariate survival analysis showed that patients under 30 years old was an independent predictor of both better LCSS (P = 0.010) and overall survival (OS) (P = 0.018).ConclusionsAdult NSCLC patients under 30 years old had distinctive clinicopathologic characteristics and survival outcomes compared to patients diagnosed at 31–40 years old.

Purpose This study aimed to (1) examine changes in dyspnea, global pulmonary function test (PFT) results, and functional activity on ventilation (V)/perfusion (Q) single-photon emission computerized tomography (SPECT) scans during the course of radiation (RT), and (2) factors associated with the changes in patients with non-small-cell lung cancer (NSCLC). Methods and Materials Fifty-six stage I to III NSCLC patients treated with definitive RT with or without chemotherapy were enrolled prospectively. Dyspnea was graded according to Common Terminology Criteria for Adverse Events version 3.0 prior to and weekly during RT. V/Q SPECT-computed tomography (CT) and PFTs were performed prior to and during RT at approximately 45 Gy. Functions of V and Q activities were assessed using a semiquantitative scoring of SPECT images. Results Breathing improved significantly at the third week (mean dyspnea grade, 0.8 vs. 0.6; paired t-test p = 0.011) and worsened during the later course of RT (p > 0.05). Global PFT results did not change significantly, while regional lung function on V/Q SPECT improved significantly after ~45 Gy. The V defect score (DS) was 4.9 pre-RT versus 4.3 during RT (p = 0.01); Q DS was 4.3 pre-RT versus 4.0 during RT (p < 0.01). Improvements in V and Q functions were seen primarily in the ipsilateral lung (V DS, 1.9 pre-RT versus 1.4 during RT, p < 0.01; Q DS, 1.7 pre-RT versus 1.5 during RT, p < 0.01). Baseline primary tumor volume was significantly correlated with pre-RT V/Q DS (p < 0.01). Patients with central lung tumors had greater interval changes in V and Q than those with more peripheral tumors (p < 0.05 for both V and Q DS). Conclusions Regional ventilation and perfusion improved during RT at 45 Gy. This suggests that adaptive planning based on V/Q SPECT during RT may allow sparing of functionally recoverable lung tissue.

No abstract

Background: Inflammation plays a vital role in tumor growth and progression and can be affected by radiotherapy (RT) and chemotherapy. We sought to investigate the prognostic significance of neutrophilto-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and their associations with dosimetric factors in locally advanced non-small cell lung cancer (LA-NSCLC). Methods: In this retrospective study, subjects consisted of 244 patients who had received definitive RT ± chemotherapy for LA-NSCLC between 2012 and 2016. Absolute lymphocyte count (ALC), NLR and PLR recorded at pretreatment, during RT and post-RT were analyzed. Multivariable analysis (MVA) was performed to correlate clinical factors and inflammatory biomarkers with progression-free survival (PFS) and overall survival (OS) using a Cox regression model. Relationships between NLR or PLR with OS and PFS were evaluated with Kaplan-Meier analysis and compared with log-rank test results. Multiple stepwise linear regression was used to assess the associations between dosimetric factors and NLR or PLR.